Acute kidney injury (AKI), previously called acute renal failure (ARF) is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.[rx] Causes of AKI are classified as either prerenal (due to decreased blood flow to the kidney), intrinsic renal (due to damage to the kidney itself), or postrenal (due to blockage of urine flow).[rx] Prerenal causes of AKI include sepsis, dehydration, excessive blood loss, cardiogenic shock, heart failure, cirrhosis, and certain medications like ACE inhibitors or NSAIDs. Intrinsic renal causes of AKI include glomerulonephritis, lupus nephritis, acute tubular necrosis, certain antibiotics, chemotherapeutic agents, and contrast dye used for imaging. Postrenal causes of AKI include kidney stones, bladder cancer, neurogenic bladder, enlargement of the prostate, narrowing of the urethra, and certain medications like anticholinergics.[rx]
The most common cause of acute kidney injury (AKI) is acute tubular necrosis (ATN) when the pattern of injury lies within the kidney (intrinsic disease). The term tubular necrosis is a misnomer, as true cellular necrosis is usually minimal, and the alteration is not limited to the tubular structures. Acute tubular necrosis is most common in hospitalized patients and is associated with high morbidity and mortality. The pattern of injury that defines acute tubular necrosis includes renal tubular cell damage and death. Intrarenal vasoconstriction or a direct effect of drug toxicity is caused by an ischemic event, nephrotoxic mechanism, or a mixture of both.[rx]
Introduced by the KDIGO in 2012,[rx] specific criteria exist for the diagnosis of AKI.
AKI can be diagnosed if any one of the following is present:
Increase in SCr by ≥0.3 mg/dl (≥26.5 μmol/l) within 48 hours; or
Increase in SCr to ≥1.5 times baseline, which has occurred within the prior 7 days; or
Urine volume < 0.5 ml/kg/h for 6 hours.
Staging
The RIFLE criteria, proposed by the Acute Dialysis Quality Initiative (ADQI) group, aid in assessment of the severity of a person’s acute kidney injury. The acronym RIFLE is used to define the spectrum of progressive kidney injury seen in AKI:[rx][rx]
Pathophysiology of acute kidney injury in the proximal renal tubule
Risk: 1.5-fold increase in the serum creatinine, or glomerular filtration rate (GFR) decrease by 25 percent, or urine output <0.5 mL/kg per hour for six hours.
Injury: Two-fold increase in the serum creatinine, or GFR decrease by 50 percent, or urine output <0.5 mL/kg per hour for 12 hours.
Failure: Three-fold increase in the serum creatinine, or GFR decrease by 75 percent, or urine output of <0.3 mL/kg per hour for 24 hours, or no urine output (anuria) for 12 hours.
Loss: Complete loss of kidney function (e.g., need for renal replacement therapy) for more than four weeks.
End-stage kidney disease: Complete loss of kidney function (e.g., need for renal replacement therapy) for more than three months.
Causes of Acute Kidney Injury
Acute tubular necrosis is precipitated by an acute ischemic or toxic event or sepsis.
Ischemic-Induced Acute Tubular Necrosis – Prerenal azotemia and ischemic acute tubular necrosis have the same spectrum of causes. Any factor that leads to prerenal azotemia can lead to ischemic acute tubular necrosis. Some common causes include hypovolemic states such as diarrhea, vomiting, bleeding, dehydration, burns, renal losses via diuretics or osmotic diuresis, and third fluid sequestration. Edematous states such as heart failure and cirrhosis cause reduced kidney perfusion. Sepsis or anaphylaxis leads to systemic vasodilation. Coagulopathy, such as disseminated intravascular coagulation, can also cause acute tubular necrosis.[rx]
Nephrotoxic-Induced Acute Tubular Necrosis – The kidney clears and metabolizes many drugs. Some of these drugs behave as exogenous toxins and can cause direct renal tubular injury or crystal-induced acute kidney injury (AKI), leading to acute tubular necrosis. Drugs such as aminoglycoside, amphotericin B, radiocontrast media, sulfa drugs, acyclovir, cisplatin, calcineurin inhibitors (tacrolimus, cyclosporine), mammalian target of rapamycin mTOR inhibitors (everolimus, temsirolimus), foscarnet, ifosfamide, cidofovir, and intravenous immunoglobulin containing sucrose all can cause acute tubular necrosis.[rx]
Decreased blood flow
Some diseases and conditions can slow blood flow to your kidneys and cause AKI.
These diseases and conditions include:
Low blood pressure (called “hypotension”) or shock
Blood or fluid loss (such as bleeding, severe diarrhea)
Heart attack, heart failure, and other conditions leading to decreased heart function
Organ failure (e.g., heart, liver)
Overuse of pain medicines called “NSAIDs”, which are used to reduce swelling or relieve pain from headaches, colds, flu, and other ailments. Examples include ibuprofen, ketoprofen, and naproxen.
Severe allergic reactions
Burns
Injury
Major surgery
Direct Damage to the Kidneys
Some disease and conditions can damage your kidneys and lead to AKI. Some examples include:
A type of severe, life-threatening infection called “sepsis”
A type of cancer called “multiple myeloma”
A rare condition that causes inflammation and scarring to your blood vessels, making them stiff, weak, and narrow (called “vasculitis”)
An allergic reaction to certain types of drugs (called “interstitial nephritis”)
A group of diseases (called “scleroderma”) that affect the connective tissue that supports your internal organs
Conditions that cause inflammation or damage to the kidney tubules, to the small blood vessels in the kidneys, or to the filtering units in the kidneys (such as “tubular necrosis,” “glomerulonephritis, “vasculitis” or “thrombotic microangiopathy”).
Blockage of the urinary tract
In some people, conditions or diseases can block the passage of urine out of the body and can lead to AKI.
Blockage can be caused by:
Bladder, prostate, or cervical cancer
Enlarged prostate
Problems with the nervous system that affect the bladder and urination
Kidney stones
Blood clots in the urinary tract
Heme pigment-containing proteins such as hemoglobin and myoglobin can behave as endotoxins in 3 ways
Causing direct proximal tubular injury, tubular obstruction, or renal vasoconstriction.
Crystal-induced nephropathy due to high cell turnover such as uric acid, calcium phosphate crystals in the setting of ongoing malignancy treatment.
Light chain accumulation in multiple myeloma is directly toxic to the renal proximal and distal tubules.
Sepsis-Induced Acute Tubular Necrosis
Sepsis also plays a role in causing acute tubular necrosis because of systemic hypotension and renal hypoperfusion. Other mechanisms that are incompletely understood include endotoxemia leading to AKI by renal vasoconstriction and the release of inflammatory cytokines causing enhanced secretion of reactive oxygen species and leading to renal injury.[rx]
Decreased glomerular filtration rate (GFR) is associated with acute tubular necrosis, leading to 3 possible mechanisms of injury to the renal tubular epithelial cells:
Afferent arteriolar vasoconstriction in response to tubuloglomerular feedback
Backlink of glomerular filtrate
Tubular obstruction
Clinical Phases
These injury patterns lead to the following 4 phases clinically:
Initiation
The initiation phase is characterized by an acute decrease in GFR and a sudden increase in serum creatinine and BUN concentrations.
Extension
The extension phase consists of 2 major events:
Ongoing hypoxia following the ischemic event
An inflammatory response
These events are more pronounced in the corticomedullary junction of the kidney. In this phase, damage to the renal vascular endothelial cell is responsible for the ischemia of the renal tubular epithelial cell. The cells in the outer medulla continue to undergo injury and death with the combination of both necrosis and apoptosis. While in the outer cortex, the blood flow returns to near normal, leading to cellular repair. As the injury worsens in the cortico-medullary junction (CMJ), the GFR falls due to the continuous release of cytokines and chemokines enhancing the inflammatory cascade.
Maintenance
The maintenance phase is established by cellular repair, apoptosis, migration, and proliferation to maintain cellular and tubule integrity. The cellular function improves slowly as the cells repair and reorganize. The blood flow returns to the normal range, and the cells establish intracellular homeostasis.
Recovery
The recovery phase is the continuation of the maintenance phase in which cellular differentiation continues, and epithelial polarity is reestablished, improving the renal function.[rx][rx]
Symptoms of Acute Kidney Injury
Signs and symptoms of acute kidney injury differ depending on the cause and may include:
Too little urine leaving the body
Swelling in legs, ankles, and around the eyes
Fatigue or tiredness
Shortness of breath
Confusion
Nausea
Seizures or coma in severe cases
Chest pain or pressure
Not enough urine
Swelling in your legs, ankles or feet
Feeling tired
Trouble catching your breath
Feeling confused
Pain or pressure in your chest
In some cases, AKI causes no symptoms and is only found through other tests done by your healthcare provider.
Diagnosis of Acute Kidney Injury
Because it is a histological finding, acute tubular necrosis is diagnosed on a clinical basis. A biopsy is only performed when there is suspicion of an entity other than acute tubular necrosis causing AKI. Histopathological findings include:
Ischemic Acute Tubular Necrosis
Early:Changes range from swelling of the cell to focal tubular epithelial necrosis and apoptosis with desquamation of cells into the tubular lumen; dilated proximal tubules with loss or thinning of brush border; granular, hyaline, and pigmented cases especially in distal and collecting ducts; white blood cells in dilated vasa recta; interstitial edema; and eosinophilic hyaline casts of Tamm-Horsfall protein
Later:Regeneration of epithelia (dilated tubular lumina, flattened epithelium, large nuclei with prominent nucleoli and mitotic activity)
Nephrotoxic Acute Tubular Necrosis
The nephrotoxic agents that lead to acute tubular necrosis can manifest as different features of histological damage, including:
Ethylene glycol: Calcium oxalate crystals in tub[rx]
Hemoglobin/myoglobin: Deeply pigmented, red-brown cast in the distal and collecting tubule.
Carbon tetrachloride: Neutral lipid accumulation in injured cells followed by necrosis.
Indinavir:Clear intraluminal crystals with mononuclear reaction.
Lead:Intranuclear, dark inclusions, and necrosis.
Mercury: large acidophilic inclusions.
Tenofovir:Proximal tubular eosinophilic inclusions that represent giant mitochondria.
Vancomycin: Acute interstitial nephritis with eosinophilic and lymphocytic infiltrate and acute tubular necrosis.[rx]
History and Physical
The history and physical examination give a lot of clues in identifying a person with the prerenal disease and acute tubular necrosis which is caused by decreased renal perfusion. Events such as diarrhea, vomiting, sepsis, dehydration, or bleeding that leads to tissue hypoxia can indicate a risk of acute tubular necrosis. Hospitalized patients with events such as hypotension, sepsis, intraoperative events, use of nephrotoxic agents such as radiocontrast media or a nephrotoxic antibiotics help in identifying the clinical picture causing AKI and acute tubular necrosis.
Physical findings such as tachycardia, dry mucous membrane, decreased skin turgor, and cool extremities are findings that can be present in patients with volume depletion and hypotension. Fever and hypotension are common manifestations of sepsis. Muscle tenderness is present in the setting of rhabdomyolysis. Intraabdominal hypertension that causes abdominal distension due to abdominal compartment syndrome also impedes renal perfusion and raises the concern for acute tubular necrosis.
Lab Test and Imaging
The workup is usually to differentiate acute tubular necrosis from prerenal AKI and other causes of AKI. Major tests that help to differentiate include urinalysis (UA), response to fluid repletion, urinary sodium concentration, fractional excretion of sodium (FENa), and fractional excretion of urea in patients who get diuretics and novel biomarkers.
Urinalysis (UA) – In prerenal disease, the UA microscopy is normal or may contain hyaline casts. On the other hand, the UA of acute tubular necrosis shows muddy brown casts or renal tubular epithelial cells secondary to the sloughing of tubular cells into the lumen due to ischemia or toxic injury.
Blood tests – Blood tests will help find levels of creatinine, urea nitrogen phosphorus and potassium should be done in addition to blood tests for protein in order to look at kidney function.
Creatinine – is a waste product in your blood that’s made by muscle activity. Normally, it’s removed from your blood by your kidneys. But if your kidneys stop working, your creatinine level rises.
Urea nitrogen – is another waste product in your blood. It’s created when protein from the foods is broken down. Like creatinine, your kidneys remove this from your blood. When your kidneys stop working, your urea nitrogen levels rise.
Serum potassium – is a substance found in your blood that balances water levels in your bloodstream. Kidney disease can cause either high or low potassium levels.
Serum sodium – is another substance in your blood that helps with fluid balance in your body. High sodium levels can mean that your kidneys aren’t working properly because your body can’t get rid of the right amount of sodium.
GFR – Your blood test will also help find your GFR (glomerular filtration rate) to estimate the decrease in kidney function
Fractional excretion of sodium (FENa) – This is a good test to differentiate between acute tubular necrosis and prerenal disease with a value less than 1% favoring prerenal disease and more than 2%, acute tubular necrosis. However, these values are not always accurate as in chronic prerenal states such as congestive heart failure and cirrhosis in which there is an overlap between both (ATN and prerenal AKI) having a value of less than 1%.[rx]
Urine sodium concentration – This test determines that the kidney is sodium avid in hypovolemic states (prerenal) where kidneys try to conserve sodium or lose sodium due to tubular injury with values more than 40 to 50 mEq/L indicating acute tubular necrosis and less than 20 mEq/L suggestive of prerenal disease. [rx]
Novel Biomarkers – Numerous biomarkers have evolved to detect AKI/acute tubular necrosis early as compared to serum creatinine. These biomarkers include serum cystatin C to be an early and reliable marker of renal injury as compared to serum creatinine which is often witnessed 48 to 72 hours after the initial insult. Other markers include urinary alpha one microglobulin, beta-2 microglobulin, urinary liver-type fatty acid-binding protein (L-FABP), and kidney injury molecule 1 (KIM-1) for the detection of proximal tubular damage, urinary interleukin-18 (IL-18) is known to differentiate ATN from CKD, urinary tract infection (UTI), and prerenal azotemia. Urinary biomarker neutrophil gelatinase-associated lipocalin (NGAL) is upregulated in renal ischemia after distal tubular injury.[rx][rx]
Urine output measurement. This measures how much urine you pass in 24 hours. You will get a container to take home, pee into, and then return to the lab after a full 24 hours. It can help your doctor determine why you’re having kidney failure.
Removing a sample of kidney tissue for testing. In some situations, your doctor may recommend a kidney biopsy to remove a small sample of kidney tissue for lab testing. Your doctor inserts a needle through your skin and into your kidney to remove the sample.
Treatment of Acute Kidney Injury
The mainstay of management is the prevention of acute tubular necrosis by identifying the patients undergoing high-risk procedures and having comorbidities such as diabetes mellitus, heart failure, advanced malignancy, atherosclerosis, and CKD that can potentiate the effects of acute tubular necrosis. The following are some of the high-risk procedures and conditions:
Cardiogenic shock
Hemorrhagic shock
Pancreatitis
Severe burns
Sepsis
Hypovolemia
Major surgery (cardiac bypass, vascular surgery such as abdominal aortic aneurysm peripheral limb surgery, hepatobiliary surgery, emergent surgical exploration)
Interventions to decrease the risk of acute tubular necrosis in the above conditions include prevention of hypovolemia or hypotension including cessation of ACEI or angiotensin II receptor blocker in patients with low blood pressure, and optimization of volume status via intravenous (IV) fluids, such as crystalloids, to ensure adequate renal perfusion. Nephrotoxic medications that can lead to acute tubular necrosis should be avoided, including NSAIDs, antibiotics such as amphotericin B, aminoglycosides, vancomycin, piperacillin/tazobactam, and radiocontrast agents.
Diuretics are used only to manage the volume status but are not recommended for the treatment of acute tubular necrosis in the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines. Other pharmacological agents such as dopamine, fenoldopam, and atrial natriuretic peptide do not provide any survival benefit in patients with acute tubular necrosis.
Renal replacement therapy (RRT) has the same indications and is used in volume overload refractory to diuretics, hyperkalemia, signs of uremia, and metabolic acidosis. In critically ill hemodynamically unstable patients, the use of continuous renal replacement therapy (CRRT) is the preferred option.[rx]
Diet. Your doctor will limit the amount of salt and potassium you get until your kidneys heal. That’s because both of these substances are removed from your body through your kidneys. Changing how and what you eat won’t reverse acute kidney failure. But your doctor may change your diet while they treat the conditions that caused it. This may mean treating a health problem like heart failure, taking you off certain medications, or giving you fluids through an IV if you’re dehydrated. If your doctor has put you on a low potassium diet, you’ll need to cut back on high-potassium foods like bananas, spinach, oranges, potatoes, and tomatoes. On the other hand, you can eat more low-potassium foods like apples, strawberries, grapes, and cauliflower.
Dialysis. If your kidney damage is severe enough, you may require hemodialysis until your kidneys can heal. Dialysis does not help kidneys heal but takes over the work of kidneys until they do. If your kidneys don’t heal, dialysis could be long-term.
Treating complications until your kidneys recover
Your doctor will also work to prevent complications and allow your kidneys time to heal. Treatments that help prevent complications include:
Treatments to balance the amount of fluids in your blood. If your acute kidney failure is caused by a lack of fluids in your blood, your doctor may recommend intravenous (IV) fluids. In other cases, acute kidney failure may cause you to have too much fluid, leading to swelling in your arms and legs. In these cases, your doctor may recommend medications (diuretics) to cause your body to expel extra fluids.
Medications to control blood potassium. If your kidneys aren’t properly filtering potassium from your blood, your doctor may prescribe calcium, glucose or sodium polystyrene sulfonate (Kionex) to prevent the accumulation of high levels of potassium in your blood. Too much potassium in the blood can cause dangerous irregular heartbeats (arrhythmias) and muscle weakness.
Medications to restore blood calcium levels. If the levels of calcium in your blood drop too low, your doctor may recommend an infusion of calcium.
Dialysis to remove toxins from your blood. If toxins build up in your blood, you may need temporary hemodialysis — often referred to simply as dialysis — to help remove toxins and excess fluids from your body while your kidneys heal. Dialysis may also help remove excess potassium from your body. During dialysis, a machine pumps blood out of your body through an artificial kidney (dialyzer) that filters out waste. The blood is then returned to your body.
Lifestyle and home remedies
During your recovery from acute kidney failure, your doctor may recommend a special diet to help support your kidneys and limit the work they must do. Your doctor may refer you to a dietitian who can analyze your current diet and suggest ways to make your diet easier on your kidneys.
Depending on your situation, your dietitian may recommend that you:
Choose lower potassium foods. Your dietitian may recommend that you choose lower potassium foods. High-potassium foods include bananas, oranges, potatoes, spinach and tomatoes. Examples of low-potassium foods include apples, cauliflower, peppers, grapes and strawberries.
Avoid products with added salt. Lower the amount of sodium you eat each day by avoiding products with added salt, including many convenience foods, such as frozen dinners, canned soups and fast foods. Other foods with added salt include salty snack foods, canned vegetables, and processed meats and cheeses.
Limit phosphorus. Phosphorus is a mineral found in foods, such as whole-grain bread, oatmeal, bran cereals, dark-colored colas, nuts and peanut butter. Too much phosphorus in your blood can weaken your bones and cause skin itchiness. Your dietitian can give you specific recommendations on phosphorus and how to limit it in your particular situation.
As your kidneys recover, you may no longer need to eat a special diet, although healthy eating remains important.
Complications
Potential complications of acute kidney failure include:
Fluid buildup. Acute kidney failure may lead to a buildup of fluid in your lungs, which can cause shortness of breath.
Chest pain. If the lining that covers your heart (pericardium) becomes inflamed, you may experience chest pain.
Muscle weakness. When your body’s fluids and electrolytes — your body’s blood chemistry — are out of balance, muscle weakness can result.
Permanent kidney damage. Occasionally, acute kidney failure causes permanent loss of kidney function, or end-stage renal disease. People with end-stage renal disease require either permanent dialysis — a mechanical filtration process used to remove toxins and wastes from the body — or a kidney transplant to survive.
Death. Acute kidney failure can lead to loss of kidney function and, ultimately, death.
Prevention
Acute kidney failure is often difficult to predict or prevent. But you may reduce your risk by taking care of your kidneys. Try to:
Pay attention to labels when taking over-the-counter (OTC) pain medications. Follow the instructions for OTC pain medications, such as aspirin, acetaminophen (Tylenol, others), ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve, others). Taking too much of these medications may increase your risk of kidney injury. This is especially true if you have pre-existing kidney disease, diabetes or high blood pressure.
Work with your doctor to manage kidney and other chronic conditions. If you have kidney disease or another condition that increases your risk of acute kidney failure, such as diabetes or high blood pressure, stay on track with treatment goals and follow your doctor’s recommendations to manage your condition.
Make a healthy lifestyle a priority. Be active; eat a sensible, balanced diet; and drink alcohol only in moderation — if at all.
Electrolyte balance is one of the key issues in maintaining homeostasis in the body, and it also plays important roles in protecting cellular function, tissue perfusion, and acid-base balance. Fluid and electrolyte balance must also be maintained for the management of many clinical conditions. Electrolyte imbalances are common findings in many diseases.[rx,rx] Imbalances in every electrolyte must be considered in a combined and associated fashion, and examinations must aim to clarify the clinical scenario for an effective and successful treatment. Most of the important and prevailing electrolyte imbalances are hypo- and hyper-states of sodium, potassium, calcium, and magnesium.
Electrolytes are essential for basic life functioning, such as maintaining electrical neutrality in cells, generating and conducting action potentials in the nerves and muscles. Sodium, potassium, and chloride are significant electrolytes along with magnesium, calcium, phosphate, and bicarbonates. Electrolytes come from our food and fluids.
These electrolytes can have an imbalance, leading to either high or low levels. High or low levels of electrolytes disrupt normal bodily functions and can lead to even life-threatening complications. This article reviews the basic physiology of electrolytes and their abnormalities, and the consequences of electrolyte imbalance.
Electricity and your body
Electrolytes take on a positive or negative charge when they dissolve in your body fluid. This enables them to conduct electricity and move electrical charges or signals throughout your body. These charges are crucial to many functions that keep you alive, including the operation of your brain, nerves, and muscles, and the creation of new tissue.
Each electrolyte plays a specific role in your body. The following are some of the most important electrolytes and their primary functions:
Sodium
helps control fluids in the body, impacting blood pressure
necessary for muscle and nerve function
Chloride
helps balance electrolytes
helps balance electrolytes
balances acidity and alkalinity, which helps maintain a healthy pH
essential to digestion
Potassium
regulates your heart and blood pressure
helps balance electrolytes
aids in transmitting nerve impulses
contributes to bone health
necessary for muscle contraction
Magnesium
important to the production of DNA and RNA
contributes to nerve and muscle function
helps maintain heart rhythm
helps regulate blood glucose levels
enhances your immune system
Calcium
key component of bones and teeth
important to the movement of nerve impulses and muscle movement
contributes to blood clotting
Phosphate
strengthens bones and teeth
helps cells produce the energy needed for tissue growth and repair
Bicarbonate
helps your body maintain a healthy pH
regulates heart function
Sodium, Electrolytes, and Fluid Balance
Electrolytes play a vital role in maintaining homeostasis within the body.
Key Points
Electrolytes help to regulate myocardial and neurological functions, fluid balance, oxygen delivery, acid-base balance, and much more.
The most serious electrolyte disturbances involve abnormalities in the levels of sodium, potassium, and/or calcium.
Kidneys work to keep the electrolyte concentrations in the blood constant despite changes in the body.
Key Terms
homeostasis: The ability of a system or living organism to adjust its internal environment to maintain a stable equilibrium; such as the ability of warm-blooded animals to maintain a constant temperature.
electrolyte: Any of the various ions (such as sodium or chloride) that regulate the electric charge on cells and the flow of water across their membranes.
sodium: A chemical element with the symbol Na (from Latin: natrium) and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals.
Importance of Electrolyte Balance
Electrolytes play a vital role in maintaining homeostasis within the body. They help regulate myocardial and neurological function, fluid balance, oxygen delivery, acid-base balance, and other biological processes.
Electrolytes are important because they are what cells (especially those of the nerve, heart, and muscle ) use to maintain voltages across their cell membranes and to carry electrical impulses (nerve impulses, muscle contractions) across themselves and to other cells.
Electrolyte imbalances can develop from excessive or diminished ingestion and from the excessive or diminished elimination of an electrolyte. The most common cause of electrolyte disturbances is renal failure. The most serious electrolyte disturbances involve abnormalities in the levels of sodium, potassium, and/or calcium.
Other electrolyte imbalances are less common and often occur in conjunction with major electrolyte changes. Chronic laxative abuse or severe diarrhea or vomiting (gastroenteritis) can lead to electrolyte disturbances combined with dehydration. People suffering from bulimia or anorexia nervosa are especially at high risk for an electrolyte imbalance.
Kidneys work to keep the electrolyte concentrations in blood constant despite changes in your body. For example, during heavy exercise electrolytes are lost through sweating, particularly sodium and potassium, and sweating can increase the need for electrolyte (salt) replacement. It is necessary to replace these electrolytes to keep their concentrations in the body fluids constant.
Dehydration
There are three types of dehydration:
Hypotonic or hyponatremic (primarily a loss of electrolytes, sodium in particular).
Hypertonic or hypernatremic (primarily a loss of water).
Isotonic or hyponatremic (an equal loss of water and electrolytes).
In humans, the most common type of dehydration by far is isotonic (isonatraemic) dehydration; which effectively equates with hypovolemia; but the distinction of isotonic from hypotonic or hypertonic dehydration may be important when treating people with dehydration.
Physiologically, and despite the name, dehydration does not simply mean loss of water, as both water and solutes (main sodium) are usually lost in roughly equal quantities as to how they exist in blood plasma. In hypotonic dehydration, intravascular water shifts to the extravascular space and exaggerates the intravascular volume depletion for a given amount of total body water loss.
Neurological complications can occur in hypotonic and hypertonic states. The former can lead to seizures, while the latter can lead to osmotic cerebral edema upon rapid rehydration.
In more severe cases, the correction of a dehydrated state is accomplished by the replenishment of necessary water and electrolytes (through oral rehydration therapy or fluid replacement by intravenous therapy). As oral rehydration is less painful, less invasive, less expensive, and easier to provide, it is the treatment of choice for mild dehydration. Solutions used for intravenous rehydration must be isotonic or hypotonic.
Cell electrolytes: This diagram illustrates the mechanism for the transportation of water and electrolytes across the epithelial cells in the secretory glands.
Sodium Balance Regulation
Sodium is an important cation that is distributed primarily outside the cell.
Key Points
The body has a potent sodium-retaining mechanism: the renin-angiotensin system.
In states of sodium depletion, aldosterone levels increase; in states of sodium excess, aldosterone levels decrease.
The major physiological controller of aldosterone secretion is the plasma angiotensin II level that increases aldosterone secretion.
Key Terms
sodium: A chemical element with the symbol Na (from Latin: natrium) and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals.
aldosterone: A mineralocorticoid hormone that is secreted by the adrenal cortex and regulates the balance of sodium and potassium in the body.
angiotensin: Any of several polypeptides that narrow the blood vessels and regulate arterial pressure.
Sodium Regulation
Sodium is an important cation that is distributed primarily outside the cell. The cell sodium concentration is about 15 mmol/l, but it varies in different organs; it has an intracellular volume of 30 liters and about 400 mmol are inside the cell.
The plasma and interstitial sodium is about 140 mmol/l with an extracellular volume of about 13 liters, 1,800 mmol are in the extracellular space. The total body sodium, however, is about 3,700 mmol as there is about 1,500 mmol stored in bones.
The body has potent sodium-retaining mechanisms and even if a person is on five mmol Na+/day they can maintain sodium balance. Extra sodium is lost from the body by reducing the activity of the renin –angiotensin system that leads to increased sodium loss from the body. Sodium is lost through the kidneys, sweat, and feces.
In states of sodium depletion, the aldosterone levels increase. In states of sodium excess, aldosterone levels decrease. The major physiological controller of aldosterone secretion is the plasma angiotensin II level that increases aldosterone secretion.
A high plasma potassium level also increases aldosterone secretion because, besides retaining Na+, high plasma aldosterone causes K+ loss by the kidney. Plasma Na+ levels have little effect on aldosterone secretion.
Renin-angiotensin system: The regulation of sodium via the hormones renin, angiotensin, and aldosterone. In states of sodium depletion, the aldosterone levels increase, and in states of sodium excess, the aldosterone levels decrease.
A low renal perfusion pressure stimulates the release of renin, which forms angiotensin I that is converted to angiotensin II. Angiotensin II will correct the low perfusion pressure by causing the blood vessels to constrict, and increase sodium retention by its direct effect on the proximal renal tubule and by an effect operated through aldosterone. The perfusion pressure to the adrenal gland has a little direct effect on aldosterone secretion and the low blood pressure operates to control aldosterone via the renin-angiotensin system.
Aldosterone also acts on the sweat ducts and colonic epithelium to conserve sodium. When aldosterone is activated to retain sodium the plasma sodium tends to rise. This immediately causes the release of ADH, which causes water to be retained, thus balancing Na+ and H2O in the right proportion to restore plasma volume.
In addition to aldosterone and angiotensin II, other factors influence sodium excretion.
Atrial peptide causes the loss of sodium by the kidneys: it is secreted from the heart in high sodium states due to excess intake or cardiac disease.
Elevated blood pressure will also cause Na+ loss, and low blood pressure usually leads to sodium retention.
Potassium Balance Regulation
Potassium is mainly an intracellular ion.
Key Points
Most of the total body potassium is inside the cells and the next largest proportion is in the bones.
In an unprocessed diet, potassium is much more plentiful than sodium and it is present as an organic salt, while sodium is added as NaCl.
High potassium intake can potentially increase the extracellular K+ level two times before the kidney can excrete the extra potassium.
High plasma potassium increases aldosterone secretion and this increases the potassium loss from the body to restore balance.
Key Terms
alkalotic: A condition that reduces the hydrogen ion concentration of arterial blood plasma (alkalemia). Generally, alkalosis is said to occur when the blood pH exceeds 7.45.
Potassium: A chemical element with the symbol K and the atomic number 19. Elemental potassium is a soft, silvery-white, alkali metal that oxidizes rapidly in the air and is very reactive with water—it can generate sufficient heat to ignite the hydrogen emitted in the reaction.
acidosis: An increase in acidity of the blood and other body tissue (i.e., an increased hydrogen ion concentration). If not further qualified, it usually refers to the acidity of the blood plasma.
Potassium Balance
Potassium is predominantly an intracellular ion. Most of the total body potassium of about 4,000 mmol is inside the cells, and the next largest proportion (300–500 mmol) is in the bones. Cell K+ concentration is about 150 mmol/l but varies in different organs. Extracellular potassium is about 4.0 mmol/l, with an extracellular value of about 13 liters, 52 mmol (i.e., less than 1.5%) is present here and only 12 mmol is in the plasma.
In an unprocessed diet, potassium is much more plentiful than sodium. It is present as an organic salt, while sodium is added as NaCl. In a hunter-gatherer, K+ intake may be as much as 400 mmol/d while in the Western diet it is 70 mmol/d or less if a person has a minimal amount of fresh fruit and vegetables.
The processing of foods replaces K+ with NaCl. While the body can excrete a large K+ load, it is unable to conserve K+. On a zero K+ intake, or in a person with K+ depletion, there will still be a loss of K+ of 30–50 mmol/d in the urine and feces.
Acid-Base Status Control
If there is a high potassium intake, for example, 100 mmol, this would potentially increase the extracellular K+ level two times before the kidney could excrete the extra potassium. The body buffers the extra potassium by equilibrating it within the cells.
The acid-base status controls the distribution between plasma and cells. A high pH (i.e., alkalosis >7.4) favors the movement of K+ into the cells, and a low pH (i.e., acidosis ) causes movement out of the cell. A high plasma potassium level increases aldosterone secretion and this increases the potassium loss from the body to restore balance.
This change of distribution with the acid-base status means that the plasma K+ may not reflect the total body content. Therefore, a person with acidosis (pH 7.1) and a plasma K+ of 6.5 mmol/l could be depleted of total body potassium. This occurs in diabetic acidosis. Conversely, a person who is alkalotic with a plasma K+ of 3.4 mmol/l may have a normal level of total body potassium.
Calcium and Phosphate Balance Regulation
Calcium is a key electrolyte: 99% is deposited in the bones and the remainder is associated with hormone release and cell signaling.
Key Points
Calcium absorption is controlled by vitamin D, and calcium excretion is controlled by the parathyroid hormones.
There is a constant loss of calcium by the kidney even if there is none in the diet.
Calcium in plasma exists in three forms: ionized, nonionized and protein-bound.
Key Terms
calcium: A chemical element, atomic number 20, that is an alkaline earth metal and occurs naturally as carbonate in limestone and as silicate in many rocks.
parathyroid hormone: A polypeptide hormone that is released by the chief cells of the parathyroid glands and is involved in raising the levels of calcium ions in the blood.
vitamin D: A fat-soluble vitamin that is required for normal bone development and that prevents rickets; it can be manufactured in the skin on exposure to sunlight.
Calcium is a very important electrolyte. Ninety-nine percent or more is deposited in the bones and the remainder plays a vital role in nerve conduction, muscle contraction, hormone release, and cell signaling.
The plasma concentration of Ca++ is 2.2 mmol/l, and phosphate is 1.0 mmol/l. The solubility product of Ca and P is close to saturation in plasma. The concentration of Ca++ in the cytoplasm is < 10–6 mmol/l but the concentration of Ca++ in the cell is much higher as calcium is taken up (and is able to be released from) cell organelles.
In the typical Australian diet, there is about 1200 mg/d of calcium. Even if it was all soluble it is not all absorbed as it combines with phosphates in the intestinal secretions. In addition, absorption is regulated by the active vitamin D; increased amounts of vitamin D increase Ca++ absorption.
Absorption is controlled by vitamin D while excretion is controlled by parathyroid hormones. However, the distribution from bone to plasma is controlled by both the parathyroid hormones and vitamin D.
There is also a constant loss of calcium via the kidneys even if there is none in the diet. This excretion of calcium by the kidneys and its distribution between bone and the rest of the body is primarily controlled by the parathyroid hormone.
The calcium in plasma exists in three forms:
Ionized.
Nonionized.
Protein-bound.
It is the ionized calcium concentration that is monitored by the parathyroid gland —if it is low, parathyroid hormone secretion is increased. This increases the ionized calcium levels by increasing bone re-absorption, decreasing renal excretion, and acting on the kidney to increase the rate of formation of active vitamin D, thereby increasing the gut’s absorption of calcium.
The usual amount of phosphate in the diet is about 1 g/d but not all of it is absorbed. Any excess is excreted by the kidney and this excretion is increased by the parathyroid hormone.
This hormone also causes phosphate to leach out of the bones. Plasma phosphate has no direct effect on parathyroid hormone secretion; however, if it is elevated it combines with Ca++ to decrease ionized Ca++ in plasma, and thereby increase parathyroid hormone secretion.
Calcium regulation: This is an illustration of how the parathyroid hormone regulates the levels of calcium in the blood.
Anion Regulation
The anions chloride, bicarbonate, and phosphate have important roles in maintaining the balance and neutrality of vital body mechanisms.
Key Points
Chloride is needed to maintain proper hydration, as well as to balance cations, and maintain the electrical neutrality of the extracellular fluid.
Bicarbonate‘s main role is to maintain the body’s acid-base balance through a buffer system.
Phosphate is a major constituent of the intracellular fluid, and it is important in the regulation of metabolic processes and as a buffering agent in animal cells.
The kidneys regulate the salt balance in the blood by controlling the excretion and the reabsorption of various ions.
Key Terms
anion: An negatively charged ion.
hyperphosphatemia: An elevated amount of phosphate in the blood.
hypochloremia: An electrolyte disturbance caused by an abnormally depleted level of chloride ions in the blood.
hypophosphatemia: An electrolyte disturbance caused by an abnormally low level of phosphate in the blood.
Anion Regulation
The excretion of ions occurs mainly through the kidneys, with lesser amounts of ions being lost in sweat and in feces. In addition, excessive sweating may cause a significant loss, especially of the anion chloride. Severe vomiting or diarrhea will also cause a loss of chloride and bicarbonate ions.
Adjustments in the respiratory and renal functions allow the body to regulate the levels of these ions in the extracellular fluid (ECF).
Chloride
Chloride is the predominant extracellular anion and it is a major contributor to the osmotic pressure gradient between the intracellular fluid (ICF) and extracellular fluid (ECF). Chloride maintains proper hydration and functions to balance the cations in the ECF to keep the electrical neutrality of this fluid. The paths of secretion and reabsorption of chloride ions in the renal system follow the paths of sodium ions.
Hypochloremia, or lower-than-normal blood chloride levels, can occur because of defective renal tubular absorption. Vomiting, diarrhea, and metabolic acidosis can also lead to hypochloremia.
In contrast, hyperchloremia, or higher-than-normal blood chloride levels, can occur due to dehydration, excessive intake of dietary salt (NaCl) or the swallowing of sea water, aspirin intoxication, congestive heart failure, and the hereditary, chronic lung disease cystic fibrosis. In people who have cystic fibrosis, the chloride levels in their sweat are two to five times those of normal levels; therefore, analysis of their sweat is often used to diagnose the disease.
Bicarbonate
Bicarbonate is the second-most abundant anion in the blood. Its principal function is to maintain your body’s acid–base balance by being part of buffer systems.
Bicarbonate ions result from a chemical reaction that starts with the carbon dioxide (CO2) and water (H2O) molecules that are produced at the end of aerobic metabolism. Only a small amount of CO2 can be dissolved in body fluids; thus, over 90 percent of the CO2 is converted into bicarbonate ions, HCO3-, through the following reactions:
CO2 + H2O ↔ H2CO3 ↔ H2CO3– + H+
The bidirectional arrows indicate that the reactions can go in either direction depending on the concentrations of the reactants and products. Carbon dioxide is produced in large amounts in tissues that have a high metabolic rate, and is converted into bicarbonate in the cytoplasm of the red blood cells through the action of an enzyme called carbonic anhydrase.
Bicarbonate is transported in the blood and once in the lungs, the reactions reverse direction, and CO2 is regenerated from the bicarbonate to be exhaled as metabolic waste.
Bicarbonate as a buffering system: In the lungs, CO2 is produced from bicarbonate and removed as metabolic waste through the reverse reaction of the bicarbonate bidirectional equation.
Phosphate
Phosphate is present in the body in three ionic forms:
H2PO4−
HPO42−
PO43−
The addition and removal of phosphate from the proteins in all cells is a pivotal strategy in the regulation of metabolic processes. Phosphate is useful in animal cells as a buffering agent, and the most common form is HPO2−4. Bone and teeth bind up 85 percent of the body’s phosphate as part of calcium phosphate salts. In addition, phosphate is found in phospholipids, such as those that make up the cell membrane, and in ATP, nucleotides, and buffers.
Hypophosphatemia, or abnormally low phosphate blood levels, occurs with the heavy use of antacids, during alcohol withdrawal, and during malnourishment. In the face of phosphate depletion, the kidneys usually conserve phosphate, but during starvation, this conservation is impaired greatly.
Hyperphosphatemia, or abnormally increased levels of phosphates in the blood, occurs if there is decreased renal function or in cases of acute lymphocytic leukemia. Additionally, because phosphate is a major constituent of the ICF, any significant destruction of cells can result in the dumping of phosphate into the ECF.
Normal and Critical Findings
Laboratory Values:
Serum Sodium:
Normal Range: 135 to 145 mmol/L
Mild-moderate Hyponatremia: 125 to 135 mmol/L, Severe: less than 125 mmol/L
Hypernatremia: Mild-moderate: 145 to 160 mmol/L, Severe: over 160 mmol/L
Serum Potassium:
Normal Range: 3.6 to 5.5 mmol/L
Hypokalemia: Mild Hypokalemia under 3.6 mmol/L, Moderate: 2.5 mmol/L, Severe : greater than 2.5 mmol/L
Hyperkalemia: Mild hyperkalemia: 5 to 5.5 mmol/L, Moderate- 5.5 to 6.5, Severe: 6.5 to 7 mmol/L
Serum Calcium:
Normal Range: 8.8 to 10.7 mg/dl
Hypercalcemia: greater than 10.7 mg/dl , Severe: over 11.5 mg/dl
Hypocalcemia: less than 8.8 mg/dl
Serum Magnesium:
Normal Range: 1.46 to 2.68 mg/dl
Hypomagnesemia: under 1.46 mg/dl
Hypermagenesemia: over 2.68
Bicarbonate:
Normal Range: 23 to 30 mmol/L\
It increases or decreases depending on the acid-base status.
Phosphorus:
Normal Range: 3.4 to 4.5 mg/dl
Hypophosphatemia: less than 2.5 mg/dl
Hyperphosphatemia: greater than 4.5 mg/dl
Complications
Both hyponatremia and hypernatremia, as well as hypomagnesemia, can lead to neurological consequences such as seizure disorders.
Hypokalemia and hyperkalemia, as well as hypocalcemia, are more responsible for arrhythmias.
Bicarbonate imbalance can lead to metabolic acidosis or alkalosis.
Patient Safety and Education
A piece of valuable advice to the patients would be to take the medications exactly as prescribed by the clinicians to avoid electrolyte imbalance as a consequence of not taking the prescribed dose.
One should call for immediate medical help when the patient feels weak, has muscle ache, or has altered consciousness.
Clinical Significance
Some of the common causes of electrolyte disorders seen in clinical practices are:
Hypernatremia: unreplaced fluid loss through the skin and gastrointestinal tract, osmotic diuresis, hypertonic saline administration
Hypokalemia: hyperaldosteronism, loop diuretics
Hyperkalemia: increase release from cells as in metabolic acidosis, insulin deficiency, beta-blocker or decreased potassium excretion as in acute or chronic kidney disease, aldosterone deficiency or resistance
Hypocalcemia: acute pancreatitis, parathyroid hormone deficiency after thyroidectomy, neck dissection, resistance to parathormone, hypomagnesemia, sepsis
Hypermagnesemia: increase oral magnesium intake
Hypomagnesemia: renal losses as in diuretics, alcohol use disorder or GI losses as in diarrhea
Bicarbonate level: increases in primary metabolic alkalosis or compensation to primary respiratory acidosis – decreases in primary metabolic acidosis or compensation to primary respiratory alkalosis.
Hyperchloremia: normal saline infusion
Hypochloremia: GI loss as in diarrhea, renal losses with diuretics
Hypophosphatemia: refeeding syndrome, vitamin D deficiency, hyperparathyroidism
Xanthogranulomatous pyelonephritis is a rare and aggressive variant of chronic pyelonephritis. It usually occurs due to chronic nephrolithiasis and infection. The diagnosis is often confused with renal cell carcinoma, and a CT scan, as well as histology of the mass, helps to confirm the diagnosis. Since it can involve adjacent structures or organs, early diagnosis and treatment with nephrectomy have an excellent prognosis. This activity describes the evaluation and management of xanthogranulomatous pyelonephritis and highlights the role of the interprofessional team in evaluating and treating patients with this condition.
Xanthogranulomatous pyelonephritis (XGP) is a rare and aggressive variant of chronic pyelonephritis resulting in a non-functioning kidney. It is most often associated with chronic obstruction and stones with ongoing infection.[rx] It is also referred to as a pseudotumor due to an enlarged kidney resembling a tumor and the ability of local invasion and destruction. The disease is characterized by the destruction and replacement of renal or peri-renal tissue with granulomatous tissue containing lipid-laden macrophages. The term “xantho” (Greek meaning yellow) is used in its name due to the infiltration of lipid-laden macrophages that appear yellow in the pathological section. XGP was first described by Schlagenhaufer in 1916 and was named as xanthogranuloma by Osterlin in 1944.[rx][rx][rx][rx]
Xanthogranulomatous pyelonephritis is often confused with a true neoplasm, most commonly renal cell carcinoma due to its similarity in clinical and radiographic features, as well as the ability to involve the adjacent structures or organs. Therefore, early identification and treatment are required to decrease the morbidity and mortality associated with this condition. Although antibiotics can be given in acute infection, the treatment of choice for XGP is nephrectomy.[rx]
Classification
(a) Diffuse: Kidney involvement is diffuse.
(b) Segmental: Kidney involvement is segmental.
(c) Focal: Involvement within the cortex of the kidney.
Staging
Xanthogranulomatous pyelonephritis is classified as focal, segmental, and diffuse. The diffuse form is more common, which is further staged by Malek and Elder into three different stages according to the extent of involvement in the nearby tissues.
Stage 1 (Nephric): Disease limited to the kidney.
Stage 2 (Perinephric): Disease involving the renal pelvis or the peri-renal fat within Gerota fascia.
Stage 3 (Paranephric): Disease involving the wider area, including the adjacent organs or retroperitoneum.[rx]
Causes of Xanthogranulomatous Pyelonephritis
The etiology of XGP remains unknown. However, most of the cases result from chronic urinary obstruction and infection. The organisms most commonly associated with XGP are Escherichia coli, Proteus mirabilis, Pseudomonas, Enterococcus faecalis, and Klebsiella, etc. Urinary obstruction occurs as a result of calculus, most commonly, staghorn calculus (in almost 80% of patients), which serves as a nidus for infection resulting in the destruction of the renal parenchyma. However, in children, congenital ureteropelvic abnormalities may result in chronic urinary obstruction.[rx][rx]
Risk factors for XGP:
Diabetes mellitus
Hypertension
Immunocompromised individuals
Abnormal lipid metabolism
Renal transplantation
Brachydactyly mental retardation syndrome in children[rx]
The exact pathophysiology of XGP is unclear. The mechanism involved in the pathogenesis of XGP is nephrolithiasis leading to chronic obstruction and infection. It is an inflammatory disorder that may occur due to a defect in the degradation of bacteria by a macrophage. The disease is characterized by the destruction and replacement of renal or peri-renal tissue with granulomatous tissue containing lipid-laden macrophages. However, the accumulation of lipids and cholesterol in the lesion is not well understood. It starts from the renal pelvis and calyces spreading to the renal parenchyma and finally to the adjacent organs if left untreated. Adjacent organs such as liver, spleen, duodenum, pancreas, and great vessels can be involved in a severe form of XGP.[rx]
Diagnosis of Xanthogranulomatous Pyelonephritis
The microscopic examination of xanthogranulomatous pyelonephritis lesion shows three distinct zones centered by a calyx with the following findings in each zone:
Inner zone – Consists of leukocytes, lymphocytes, plasma cells, histiocytes or macrophages, and necrosis.
Middle zone – Consists of granulation tissues surrounded by hemorrhage. The pathognomonic feature is the presence of lipid-laden foamy macrophages (xanthoma cells) that gives a yellow color to the tissue.
Outer zone – Consists of giant cells, cholesterol clefts, and fibrous tissues.
The gross pathology of the mass may show yellow tissue with necrosis and hemorrhage.
History and Physical
The typical history of a patient with XGP is a middle-aged female presenting with recurrent urinary tract infections most commonly due to Escherichia coli and Proteus mirabilis. In children, the presenting complaint may be fever, flank or abdominal pain, and growth retardation.
The presentation is similar to renal tuberculosis. Hence, the history of travel to the endemic region should be evaluated.
The adult patient with XGP may present with the following symptoms:
Unilateral flank pain and fever: The most common presenting complaints in a patient with XGP. Flank pain is usually unilateral, and the nature of the pain is dull and persistent.
Urinary symptoms like dysuria, hematuria, and increased urinary frequency
Anorexia, chills, and weight loss in a few cases[rx]
Physical findings
High temperature
Conjunctival pallor due to anemia
Unilateral or bilateral renal mass on palpation
Costovertebral angle tenderness on palpation
Cutaneous draining of fistula due to neurocutaneous fistula formation
Hepatomegaly in a few cases when there is an invasion of the liver
Lab Test and Imaging
Evaluation of a patient with XGP requires appropriate history, physical examination, and comprehensive lab work. The detailed laboratory and radiographic findings are explained below:
Blood examination – Includes CBC with a differential that may show anemia and leukocytosis in a patient with XGP. Erythrocyte sedimentation rate (ESR) and C-Reactive protein (CRP) are often elevated. Renal function tests may show elevated blood urea nitrogen and creatinine levels. The liver function test is often abnormal due to mild biliary retention.
Urine examination – Urinalysis may show signs of a urinary tract infection (UTI) that includes pyuria, bacteriuria, and hematuria. Urine culture shows the growth of organisms like Escherichia coli, Proteus mirabilis, Pseudomonas, Enterococcus faecalis, Klebsiella, etc.
Radiographic imaging – Plain X-ray of the abdomen may show calculi, especially staghorn calculi. Renal ultrasonography may reveal hydronephrosis and loss of normal renal architecture. Computed tomography (CT) scan findings are most useful for diagnosing a case of XGP. CT scan with contrast may show replacement of the normal renal tissue by multiple, hypoechoic areas of the dilated collecting system that is surrounded by an enhanced rim of contrast medium that results in a multiloculated appearance (known as the “bear paw” sign).[rx][rx] It can also identify renal stones within the collecting system. CT scan can also determine the extent and local invasion of the lesion and can be used to stage the disease. Magnetic resonance imaging (MRI) can be done in patients who are allergic to contrast. Intravenous urography and DTPA (diethylenetriamine pentaacetic acid) renal scan may show a poorly functioning kidney.
Biopsy – The pathognomonic finding is the lipid-laden foamy macrophages, which can be challenging to differentiate from clear cell carcinoma of the kidney.
Immunohistochemical staining – In cases where differentiation between XGP and renal cell carcinoma is difficult, it has been found that patients with XGP stained positive for PAS (periodic acid Schiff) stain.[rx][rx]
The preoperative diagnosis of XGP can be difficult due to the similar findings associated with renal cell carcinoma. CT scan helps differentiate these two conditions as well as knowing the extension of the disease. However, confirmatory diagnosis of XGP is made by pathological examination.
Treatment of Xanthogranulomatous Pyelonephritis
Individuals with a clinical presentation and pre-operative diagnosis of focal or segmental XGP can be treated with antibiotics and percutaneous drainage. With no improvement, partial nephrectomy or nephrectomy can be done.
In patients with a diagnosis of diffuse or advanced stage XGP, the treatment of choice is nephrectomy. The use of antibiotics before and after surgery controls the local infection and avoids septic complications. The aim of surgery is to remove all granulomatous tissue so that there is no fistula formation in the future. Sinuses or fistulas should be repaired if found.[rx]
Rare cases of bilateral XGP should be treated with bilateral nephrectomy and long-term dialysis.
There has been debate regarding open versus laparoscopic nephrectomy. Because of the inflammatory nature of the disease, laparoscopic nephrectomy is often challenging, and the conversion rate from laparoscopic to open nephrectomy is 50%. Laparoscopic nephrectomy can be done in selected patients by a surgeon with advanced laparoscopic experience and skills. Laparoscopic nephrectomy is associated with less blood loss and reduced hospital stay in patients with XGP.[rx]
Differential Diagnosis
The differential diagnosis for xanthogranulomatous pyelonephritis includes:
The clinical presentation and radiographic appearance of XPG and renal cell carcinoma are similar, however, fever and raised inflammatory markers (CRP and ESR) are most commonly associated with XPG. If present, the “bear paw” signis a pathognomonic feature of XPG. However, histology gives the confirmatory diagnosis for XGP.
Complications
The complications of xanthogranulomatous pyelonephritis are due to the involvement of adjacent organs and are as follows:
Cystinuria is a condition characterized by the buildup of the amino acid cysteine, a building block of most proteins, in the kidneys and bladder. As the kidneys filter blood to create urine, cystine is normally absorbed back into the bloodstream.
Cystine stones are due to an inherited defect in the transport of the amino acid cystine leading to excessive excretion in the kidney causing cystinuria. Cystinuria causes supersaturation in the kidney predisposing to the development of stones. This activity outlines the evaluation and management of cystine stones and explains the role of the interprofessional team in improving care for patients with this condition. Cystine stones account for only about 1% to 2% of all kidney stones but represent about 6% to 8% of all pediatric calculi. The name “cystine” comes from its original description as “bladder calculi” in 1833.
Kidney stones are the primary clinical manifestation of this condition. The primary treatment is the optimization of urinary volume and pH with hydration and oral alkalinizing drugs. Medical therapy consists of thiol-based drugs and is used in patients where conservative measures alone are insufficient.
While most cystine stone formers will make pure cystine stones, up to 40% may develop mixed calculi that will also contain calcium oxalate, calcium phosphate, or struvite.[rx]
Compared to calcium stone formers, cystine nephrolithiasis patients will tend to make larger stones, require more urological procedures, and will start making stones at an earlier age. They also face a greater risk of eventual kidney damage and chronic renal failure compared to calcium nephrolithiasis patients.[rx][rx][rx][rx]
Causes of Cystinuria
The cause of cystinuria is an inheritable, autosomal recessive genetic defect that affects the proximal renal tubular reabsorption of cystine. This same problem also affects lysine, ornithine, and arginine (COLA), but only cystine is clinically significant as it is the only amino acid in this group that will form stones. Cystine is the least soluble of all the essential amino acids. Interestingly, intestinal transport and absorption of cystine, in patients with cystinuria, tends to be impaired, but other factors offset this benefit.[rx][rx]
Cystinuria would not be a problem except for its relative insolubility in urine at physiological pH levels. Cystine solubility is highly pH-dependent because it substantially increases as the urine becomes more alkaline.
Cystine solubility is also affected by urinary macromolecules and ions, both of which increase cystine’s solubility.
Symptoms of Cystinuria
Cystinuria is primarily characterized by a buildup of the amino acid, cystine, in the kidneys and bladder. This leads to the formation of cystine crystals and/or stones which may block the urinary tract. Signs and symptoms of cystinuria are a consequence of stone formation and may include:[rx][rx][rx]
Nausea
Blood in the urine (hematuria)
Flank pain
Frequent urinary tract infections
Chronic or acute renal failure (rare)
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.
The initial presentation of a patient with cystine stones is identical to any patient with obstructing urolithiasis. They typically will develop acute flank pain with hematuria, often associated with nausea and vomiting. The pain will radiate around the flank towards the groin, and they often have CVA tenderness. Microscopic or gross hematuria is frequently present, but up to 15% of patients with obstructing stones may not have even microscopic hematuria. The strongest element in the patient’s history is a strong personal or family history of cystinuria and cystine stone formation.
Lab Test and Imaging
Since cysteine contains sulfur, the urine of hypercystinuric individuals may have a rotten egg odor. Typical hexagonal cystine crystals can sometimes be seen on urinalysis in affected patients. When these hexagonal crystals appear on urinalysis, it suggests supersaturation of the urine with cystine.[rx][rx]
The sodium cyanide-nitroprusside test is often the initial laboratory screening test for cystinuria as it is fast, simple, and provides a reasonably reliable, qualitative assessment of urinary cystine levels. The cyanide converts cystine to cysteine, which then binds to the nitroprusside creating an intense purple color in just a few minutes. The test typically turns positive at cystine levels above 75 mg/gm creatinine.[rx] It is not recommended in known cystine stone-forming patients as it is necessary to have a more reliable 24 hour total.
The ability of a patient’s urine to dissolve cystine can be determined by a “cystine capacity” test. A pre-determined amount of solid cystine is added to a measured sample of the patient’s urine. The sample is incubated and then all solid cystine is removed. If the recoverable cystine weighs less than the original solid sample, the urine is undersaturated. If it weighs more, then it is supersaturated. While it is a reasonable test for cystine supersaturation, it is relatively insensitive which limits its clinical usefulness. But it does allow a reasonably accurate measurement of cystine supersaturation even for patients who are on medical therapy.[rx]
The definitive diagnosis of obstructing calculi will require imaging, which includes CT scans, KUB X-rays, and/or ultrasound. CT scans without contrast remain the “gold standard” for the diagnosis of urolithiasis and will demonstrate cystine stones clearly as will an ultrasound for renal calculi, but they cannot distinguish cystine from other stone chemicals constituents. Plain x-rays of the abdomen will not show cystine stones well as they are only faintly radiopaque and will tend to have a ground-glass appearance.[rx]
Regular renal ultrasounds are recommended in all cystine stone-forming patients every 6 to 12 months.[rx]
Treatment of Cystinuria
Surgical treatment of cystine stones is similar to that of other stones except that cystine is notoriously resistant to extracorporeal shock wave lithotripsy (ESWL) unless the stones are less than 1 cm in size. Retrograde pyelography and the use of indwelling ureteral catheters will help to visualize stones that otherwise would be difficult to localize for ESWL therapy. Even then, the stones are relatively difficult to see and target reliably. They also will likely require more shocks than calcium oxalate or calcium phosphate stones. For these reasons, ureteroscopy with laser lithotripsy is preferable for most cystinuria patients with obstructing cystine stones that require surgery.
Total removal of all cystine stones and fragments has demonstrated reduced recurrence rates and better preservation of renal function. Stone surgery has not caused any measurable decrease in overall renal function.[rx][rx][rx]
Medical Management
Acceptable levels of urinary cystine are 250 mg/L or less at a urinary pH of 6.5 to 7. This level can often be reached through increased fluid intake and urinary alkalinization. The use of thiol-based medications to reduce urinary cystine levels is discouraged unless hydration therapy and alkalinization treatment are insufficient to achieve the desired “optimal” cystine concentration levels (less than 250 mg/L) at an acceptable pH (6.5 to 7). A sustained urinary pH of 7.5 can be useful to dissolve existing cystine stones. Some experts have recommended lower cystine concentrations of 150 mg/L and possibly even lower at 90 mg/L as “optimal”.[rx]
Hydration is usually the first step in medical management. Increasing fluid intake sufficiently to reliably generate 2,500 to 3,00 ml or more of urine per day is often necessary. The goal is to dilute the urine sufficiently to get the urinary cystine content to the recommended concentration level of 250 mg/L or less; this frequently requires having the patient wake up in the middle of the night to void and drink extra water. Drinking 240 ml of water every hour during the day and 480 ml before bed and at least once overnight is a standard strategy for maximizing oral hydration therapy and urinary volume. Hydration can be monitored by following the specific gravity, which should always be 1.010 or less. Since some cystinuric patients can generate up to 1400 mg of cystine per day, hydration alone may not be sufficient, but it is always the first step in management. Up to one-third of cystine stone patients can manage their stone recurrences with fluid management. Optimal hydration will depend on the patient’s individual cystine excretion.[rx]
Urinary alkalinization can not only prevent cystine precipitation and stone formation but may also dissolve existing cystine stones. For prophylaxis, the urinary pH should be targeted at 7.0 to 7.5, but for stone dissolution, a urinary pH higher than 7.5 needs to be maintained. At this high pH level (above 7.5), calcium phosphate stones can precipitate. In such cases, hypercalciuria needs to be controlled tightly with diet and thiazides. Mineral water and citrus juices can help increase pH levels, but potassium citrate supplementation is the mainstay of urinary alkalinization therapy. The usual daily potassium citrate dosage in cystinuria is 60 to 90 mEq total in 3 or 4 divided doses and then titrated as needed to optimize the pH. Serum potassium should also be checked periodically in patients on high dosages of potassium citrate to detect hyperkalemia.[rx] Unfortunately, potassium citrate is notorious for poor long-term patient compliance as it requires frequent daily dosing, tends to have significant gastrointestinal side effects and liquid formulations often have exceedingly bad taste.[rx] If hyperkalemia is limiting potassium citrate administration, lower potassium urinary alkalinizing medications are available.
Sodium bicarbonate can also be used to help with pH issues, especially in patients at risk for hyperkalemia with potassium citrate therapy; but it tends to have a relatively short-term alkalinizing effect and the extra sodium intake may increase urinary cystine excretion. High animal protein diets are also discouraged in cystinuric patients for the same reason.[rx]
Acetazolamide is a carbonic anhydrase inhibitor that increases urinary bicarbonate excretion and raises urinary pH levels. While not a first-line therapy (it can cause hypocitraturia and metabolic acidosis), it may occasionally be of some help in maintaining high urinary pH levels in addition to the other therapies mentioned. It can be particularly useful in maintaining a high nighttime urinary pH without the need for multiple awakenings or additional overnight alkalinization dosing.[rx]
When conservative measures, as outlined above, are insufficient after a 3 month trial period, a thiol-based drug regimen is usually the next step in treatment for active cystine stone formers.[rx]
Thiol-Based Agents
Cystine is composed of two cysteine molecules bound together by a disulfide bond. Thiol-based drugs have sulfhydryl groups that can reduce this disulfide bond, producing a mixed cysteine disulfide compound that is far more soluble than the original cysteine molecule. As a general guide, most patients with a 24-hour urinary cystine excretion of 500 mg or more are likely to need a thiol medication in addition to hydration therapy and alkalinization.[rx]
Thiol-based treatment is thought to have the extra benefit of possibly making cystine stones more amenable to ESWL treatment. This may occur because of the mixing of calcium phosphate along with the cystine creating a more fragile stone that is more easily fragmented with ESWL therapy. All patients on thiol-based drug therapy should have routine blood counts, platelet counts, serum albumin, liver function tests, and 24-hour urine tests for cystine and protein.[rx]
Penicillamine, a penicillin derivative,was the first thiol drug used for cystinuria. Penicillamine-cysteine disulfide is 50 times more soluble in urine than cystine. Each 250 mg penicillamine tablet can reduce urinary cystine levels by about 75 mg to 100 mg per day. The problem with penicillamine is that there is a high incidence of side effects, including fever, rash, loss of taste, arthritis, leukopenia, aplastic anemia, gastrointestinal (GI) disturbances, renal membranous nephropathy with proteinuria, and pyridoxine deficiency. The incidence of significant side effects is about 50%, which limits long-term compliance. Almost 70% of patients discontinued the drug due to adverse effects in one study. For these reasons, penicillamine use is limited in favor of other thiol-based drugs.[rx]
Tiopronin (Thiola, alpha-mercapto propionyl glycine, or alpha-MPG) is a second-generation thiol drug that works similarly to penicillamine but is roughly 30% more effective with significantly fewer side effects. It received approval for use in the United States in 1988, so there is ample experience with the medication. The typical dose is 300 mg three times per day. Long-term compliance is about 70%. For these reasons, tiopronin is currently the thiol drug of choice for cystinuria when hydration and urinary alkalinization therapy fail to achieve optimal cystine concentration levels at an acceptable pH.[rx]
Captopril is an ACE inhibitor normally used for hypertension, but it is also a unique thiol-based drug that can form captopril-cysteine mixed disulfides that are highly soluble in cystinuric patients. While safe with few side effects, captopril’s clinical effectiveness in cystinuric stone-forming patients is uncertain as various studies provide conflicting results. It should be considered a reasonable treatment option in cystinuric patients who are also hypertensive or where other thiols are overly toxic or unavailable.[rx][rx]
Bucillamine is a third-generation, thiol-based drug that is currently available only in Japan and South Korea but is approved only for use in rheumatoid arthritis. As a di-thiol compound, it would theoretically be more effective than tiopronin and better tolerated since lower dosages of the drug would be needed. Experience in Asia over 30 years has demonstrated a low toxicity profile and bucillamine has been shown to be more effective than tiopronin in at least one small cystinuria study.[rx] Phase 2 studies are currently underway in the United States to determine its potential clinical usefulness in treating hypercystinuria.
Tiopronin(Brand name: Thiola) – Manufactured by Retrophin, Inc.
FDA-approved indication: Prevention of cystine nephrolithiasis in patients with homozygous cystinuria.
Other Issues
Besides bucillamine, other new cystine binding agents or crystal growth inhibitors are under evaluation. For example, L-cystine dimethyl esters (L-CDME) and L-cystine methyl esters (L-CME) have shown promising results with good therapeutic effects at relatively low concentrations, which suggest better tolerability and fewer side effects than similar agents.[rx][rx] Some new, investigational thiol compounds, such as thiophosphate and meso-2-3-dimercaptosuccinic acid, are undergoing testing and appear promising.[rx]
Most urinary dipsticks do not have any clear color differentiation between a pH of 6 and 7.5. A small Indianapolis company, Urodynamics (317-915-7896, 317-257-1302), makes an FDA-approved dipstick for home and patient use that has such differentiation as well as a specific gravity reading that is ideal for urine pH and hydration monitoring in cystine stone-forming patients on medical therapy.
A combination of potassium citrate and potassium bicarbonate is being evaluated for efficacy and safety in cystine stone-forming children.
Experimentally, real-time in situ atomic force microscopy has shown that L-cystine dimethyl ester (L-CDME) and L-cystine methyl ester (L-CME) can dramatically reduce the growth rate of cystine stones and crystals. They interfere with specific receptor sites on crystal surfaces that block cystine molecule binding.[rx][rx]
Selenium, at a dosage of 200 mg/day for six weeks, was shown in a 2018 double-blinded study to significantly reduce cystine crystal volume, but this finding has not yet been confirmed.[rx]
Stem cell transplants have shown positive activity in reducing cystinuria in the mouse model and a human phase 1 and 2 study is currently underway.[rx]
Alpha-lipoic acid has been shown to increase urinary cystine solubility in mice. It also has prevented cystine stones in 2 human patients.[rx] A phase 2 clinical trial is assessing the effectiveness of a daily administration of 1200 mg of alpha-lipoic acid over a 3 year period in controlling stone formation in hypercystinuric patients.[rx]
A new vasopressin receptor antagonist (Tolvaptan) has been shown to prevent the growth of cystine stones in animal models.[rx] A pilot study is currently underway to evaluate its safety and tolerability in human subjects.[rx]
Crystal growth inhibitors may be the next new wave of prophylactic treatments for cystine stone patients. L-cystine bismorpholide and L-cystine bis(N’-methylpiperazide) appear to be the most potent potential cystine crystalization inhibitors but they have not yet been tested in any clinical trials.[rx]
A recombinant human enzyme (ACN00107) that is able to degrade cysteine and cystine, as well as reduce urinary cystine levels while inhibiting cystine stone formation, has been shown to be effective in mice and is awaiting human trials.[rx]
Chaperone therapy, where various agents are used to correcting protein and enzymatic misfolding, is a new approach to various heritable diseases. Since several mutations result in protein misfolding in cystinuria, chaperone therapy is a potentially promising alternative treatment for cystinuric patients in the future.[rx]
About 25% of cystine stone formers will have non-cystine chemical components in their stones. For this reason, complete stone composition analyses and 24-hour urine tests are recommended for optimal stone prophylaxis.[rx]
Surgery
If the stones are very large and painful or block one of the tubes leading from the kidney, they might need to be removed surgically. There are a few different types of surgeries to break up the stones. These include the following procedures:
Extracorporeal shock wave lithotripsy (ESWL) – This procedure uses shock waves to break up large stones into smaller pieces. It’s not as effective for cystine stones as for other types of kidney stones.
Percutaneous nephrolithotomy (or nephrolithotomy) – This procedure involves passing a special instrument through your skin and into your kidney to take out the stones or break them apart.
Acute Kidney Colic/Acute renal colic is severe pain resulting from the presence of a stone in the urinary system. The stone can be present anywhere along the path between the kidneys and the urethra. Nephrolithiasis refers to kidney stones, or renal calculi, and, in conjunction with ureteral calculi, are the primary cause of acute renal colic. Nephrolithiasis has a lifetime prevalence of five to fifteen percent and an incidence of 0.5% in North America and Europe. This activity reviews the evaluation and management of nephrolithiasis and highlights the role of the interprofessional team in caring for patients affected by this condition.
Renal colic is a type of abdominal pain commonly caused by obstruction of the ureter from dislodged kidney stones. The most frequent site of obstruction is the vesicoureteric junction (VUJ), the narrowest point of the upper urinary tract. Acute obstruction and the resultant urinary stasis (disruption of urine flow) can distend the ureter (hydroureter) and cause a reflexive peristaltic smooth muscle spasm, which leads to a very intense visceral pain transmitted via the ureteric plexus.
An acute renal colic is a severe form of sudden flank pain that typically originates over the costovertebral angle and extends anteriorly and inferiorly towards the groin or testicle. It is often caused by acute obstruction of the urinary tract by calculus and is frequently associated with nausea and vomiting. The degree of pain is related to the degree of obstruction and not the size of the stone, although stone size can be a reasonable predictor of the likelihood of spontaneous passage. While kidney stones are not the only cause of flank pain, their frequency, and the severity of the pain they cause make nephrolithiasis the most likely presumptive diagnosis when sudden flank pain occurs.
Nephrolithiasis, also known as kidney stones, is a common condition affecting 5% to 15% of the population at some point, with a yearly incidence of 0.5% in North America and Europe, and is usually caused by a crystal or crystalline aggregate traveling from the kidney through the genitourinary system and becoming stuck creating an obstruction to urinary flow, typically in the ureter. This obstruction results in proximal ureteral and renal pelvic dilation which is the immediate cause of the intense pain known as renal colic.[rx][rx][rx][rx]
Causes of Acute Kidney Colic
Renal colic is caused by dilation of the renal pelvis and ureteral segments. While usually colic is from an acute obstruction such as a ureteral calculus, it may also be due to a variety of other problems and disorders such as ureteral spasms immediately after double J stent removal or ureteroscopy. Similar ureteral blockages from chronic sources (such as ureteropelvic junction obstructions, prostate, cervical or pelvic cancer, scarring, and retroperitoneal fibrosis among others), do not generally cause acute pain or colic.
Ureteral calculi are a common cause of the most acute and severe level of flank pain. The bulk of this review will therefore focus on renal colic from obstruction by a ureteral stone.
There are multiple predictors and risk factors for kidney stone formation.
The following are the most common:
Inadequate urinary volume – Patients with extremely low urine volumes (usually less than 1 liter per day) increase the concentration of solutes (indicated by urine with an osmolarity greater than 600 mOsm/kg) and promote urinary stasis, which can cause supersaturation of solutes and lead to stone formation. The optimal daily urine volume for stone formers is 2,500 ml with a minimum acceptable level of 2,000 ml.[rx][rx]
Hypercalciuria – Most often, this is an idiopathic finding. It can be secondary to increased intestinal absorption of calcium, higher circulating serum calcium, reduced renal calcium reabsorption (renal calcium leak), hypervitaminosis D, hyperparathyroidism, high protein load, or systemic acidosis. Hypercalciuria increases the urinary saturation of calcium salts like oxalate and phosphate, causing the formation of crystals and calculi. Calcium-containing stones form approximately 80% of all renal calculi. Hypercalciuria is usually defined as urinary calcium of 250 mg or more per 24 hours. Treatment involves minimizing excessive daily oral calcium intake, correcting phosphate deficiencies that lead to increased Vitamin D activity, and the use of thiazides to increase calcium reabsorption in the nephron.
Hyperoxaluria – Oxalate naturally occurs in plants where it binds tightly to calcium in the plant’s tissue fluid. Ingestion of vegetable material results in intestinal oxalate absorption and urinary excretion. As oxalate has no nutritional or beneficial role in human physiology, it is excreted in the urine where it can form crystals and stones with calcium. Oxalate is considered the strongest chemical promotor of stones. Normal urinary oxalate is up to about 40 mg per day but optimal 24-hour urine levels are generally at 25 mg/day or less. Green leafy vegetables like spinach, rhubarb, and collard greens are particularly high in oxalate.
Hyperuricosuria – High urinary uric acid levels can promote both calcium oxalate and uric acid stone formation. Uric acid stones account for 5% to 10% of all renal calculi. Hyperuricosuria can be secondary to a high animal protein diet or a genetic defect causing increased uric acid excretion. Most pure uric acid stones are caused by high total urinary acid levels and not by elevated urinary uric acid levels. Allopurinol or febuxostat (Uloric) can be used to reduce uric acid production and potassium citrate is used for aciduria.
Infection stones – These are caused by urea-splitting organisms (Proteus or Klebsiella spp but not Escherichia coli) that break down urea in the urine, increasing concentrations of ammonia and pH which promote struvite stone formation and growth. Infection stones are also called struvite or triple (Magnesium, Ammonium, Calcium) phosphate calculi. Treatment includes control of infection with total surgical removal of all stones which are considered infected. A specific urease inhibitor, acetohydroxamic acid, may be useful in selected cases.[rx]
Hypocitraturia – Inadequate urinary citrate levels can contribute to new nephrolithiasis formation. Citrate is the urinary equivalent of serum bicarbonate. It increases urinary pH, but it also acts as a specific inhibitor of crystal aggregation and stone formation by forming soluble complexes with calcium and magnesium. Optimal levels are approximately 300 mg (or more)/L of urine. Potassium citrate supplements are also recommended to optimize urine pH in cases of uric acid stones and aciduria.
Symptoms of Acute Kidney Colic
Small stones may not cause any symptoms. Larger stones can cause renal colic, especially if they block a ureter. This is the tube urine travels through on its way from your kidney to your bladder.
Symptoms of renal colic include:
intense pain along the side of your body between your ribs and hip, or in your lower abdomen
pain that spreads to your back or groin
nausea or vomiting
Renal colic pain often comes in waves. These waves can last from 20 to 60 minutes.
pain when you urinate
blood in your urine, which may be pink, red, or brown
cloudy or foul-smelling urine
gravel — tiny pieces of stones in your urine
urgent need to urinate
urinating more or less than usual
fever and chills (if you have an infection)
Diagnosis of Acute Kidney Colic
History and Physical
Patients with renal colic typically present with sudden onset of flank pain radiating laterally to the abdomen and/or to the groin. Patients often report a dull constant level of pain with colicky episodes of increased pain. The constant pain is often due to stretching of the renal capsule due to obstruction, whereas colicky pain can be caused by peristalsis of the ureteral smooth muscle. Many patients report associated nausea or vomiting, and some may report gross hematuria. As the stone migrates distally and approaches the bladder, the patient may experience dysuria, urinary frequency, urgency, or difficulty in urination.
Patients experiencing renal colic may present in very severe pain. Classically, these patients are unable to find a comfortable position and are often writhing or constantly pacing around the examination table. The exam may reveal flank pain more commonly than abdominal pain, and the skin may be cool or diaphoretic. There is often a prior personal or family history history of stones, recent ureteroscopic surgery, or just after removal of a double J stent.
In the case of a recent ureteroscopy or immediately after removal of a double J stent, the history alone can provide the diagnosis. In these cases, the renal colic is due to a ureteral spasm which effectively causes an obstruction with resultant proximal ureteral and renal dilation even without a stone. The pain can be just as intense as from an obstructing ureteral stone.
Diagnosis is made through a combination of history and physical exams, laboratory testing, and imaging studies. Urinalysis shows some degree of microscopic or gross hematuria in 85% of stone patients, but should also be evaluated for signs of infection (e.g., white blood cells, bacteria). Urinary pH greater than 7.5 may be suggestive of a urease-producing bacterial infection, while pH values less than 5.5 may indicate the presence of uric acid calculi.
A basic metabolic panel (BMP) should be obtained to assess for renal function, dehydration, acid-base status, and electrolyte balance. Serum calcium should be checked. A complete blood count (CBC) can be considered to evaluate for leukocytosis if there is a concern for infection although a mild elevation of WBCs is commonly secondary to white blood cell emargination.
Hematuria is present in 85% of acute renal colic cases caused by calculi. While the presence of hematuria is suggestive of a stone, it is not definitive and neither does the absence of hematuria conclusively prove that a stone is not present.
Consider obtaining a parathyroid hormone (PTH) level if hypercalcemia is present and therefore primary hyperparathyroidism is suspected. If possible, urine should be strained to capture stones for chemical analysis to help determine optimal preventive prophylactic measures. Further metabolic testing, such as a 24-hour urine collection for volume, pH, calcium, oxalate, uric acid, citrate, sodium, magnesium, and potassium concentrations, should be considered in high-risk first-time stone formers, pediatric patients, or recurrent stone formers. It is highly recommended in nephrolithiasis patients with solitary kidneys, renal failure, renal transplants, gastrointestinal (GI) bypass, and any patient with high or increased anesthesia risk.
Renal ultrasonography can be used to establish hydronephrosis and measure resistive index and track larger renal stones (especially uric acid), but it will often miss stones smaller than 5 mm in size and is not a reliable imaging modality for visualizing ureteral calculi. The degree of perinephric fluid can be a predictor of the degree of obstruction.[rx] Resistive index can be useful in diagnosing ureteral obstructions. It is defined as (peak systolic velocity – end-diastolic velocity)/ peak systolic velocity) where normal is typically 0.7 or less. Higher levels indicate either obstruction or intrinsic renal disease.[rx][rx]
Unenhanced (or helical) CT is the gold standard for the initial diagnosis of suspected renal colic; with a sensitivity of 98%, the specificity of 100%, and a negative predictive value of 97%. This modality allows rapid identification of stone, provides information as to the location and size of the stone, and any associated hydroureter, hydronephrosis, or ureteral edema, and can give information regarding potential other etiologies of pain (e.g., abdominal aortic aneurysm, malignancy). In those patients with no previous history of nephrolithiasis, CT should be performed to guide management. CT scans may underestimate stone size in comparison with an intravenous pyelogram or abdominal x-ray.
However, CT scans expose patients to a significant radiation burden and they can be costly. In some patients with a history of renal colic that present with pain similar to previous obstructing urolithiasis, it may be sufficient to perform ultrasonography (US). While the US is less sensitive (60% to 76%) than CT for detecting calculi less than 5 mm, it can reliably detect hydronephrosis and evidence of obstruction (increased resistive index in the affected kidney). It is also the modality of choice for evaluating a pregnant patient with concern for renal colic. Studies have shown that using ultrasonography as a primary imaging modality does not lead to an increase in complications in comparison to CT. Ultrasound is also a good way to follow a patient known to have uric acid urinary stones.
A plain abdominal x-ray (KUB) can identify many stones, but 10% to 20% of renal calculi are radiolucent and provide little information regarding hydronephrosis, obstruction, or renal anatomy. Additionally, bowel gas, the bony pelvis, and abdominal organs may obstruct stone visualization. The KUB is recommended in kidney stone cases when the CT scan is positive, and the exact location of the stone is known. This helps in clearly identifying those stones that can be tracked by follow-up KUB and those that might be amenable to lithotripsy.
Combining renal ultrasound (which can easily demonstrate hydronephrosis but is less reliable in detecting stones) with a KUB (which has good sensitivity for imaging calculi but no dilation), can be very cost-effective as an alternative to CT scans with lower cost and reduced radiation. Symptomatic stones are likely to produce hydronephrosis or obstruction (visible on ultrasound) or will be seen directly on the KUB. The combination of KUB radiography with renal ultrasonography provides a reported diagnostic accuracy for an obstructing stone of 90%, specificity of 93%, and a sensitivity of 88%.[rx]
If the stone should pass before imaging can be performed, some evidence of residual inflammation may remain, such as hydronephrosis or pain, even if no stone is specifically or definitively identified.
Treatment of Acute Kidney Colic
Most small stones are passed spontaneously and only pain management is required. Above 5 mm (0.20 in) the rate of spontaneous stone passage decreases. NSAIDs (non-steroidal anti-inflammatory drugs), such as diclofenac[rx] or ibuprofen, and antispasmodics like butylscopolamine are used. Although morphine may be administered to assist with emergency pain management, it is often not recommended as morphine is addictive and raises ureteral pressure, worsening the condition. Vomiting is also considered an important adverse effect of opioids, mainly with pethidine.[rx] Oral narcotic medications are also often used.
Treatment includes the following:
Immediate intervention with analgesia and antiemetics. NSAIDs and opiates are first-line therapies for analgesia. NSAIDs work in two ways in renal colic. First, NSAIDs decrease the production of arachidonic acid metabolites, which mediate pain receptors, alleviating pain caused by distension of the renal capsule. Additionally, they cause contraction of the efferent arterioles to the glomerulus, causing a reduction in glomerular filtration, and reducing hydrostatic pressure across the glomerulus. Because patients are frequently unable to tolerate oral medications, parenteral NSAIDs such as ketorolac (15 mg to 30 mg intravenously (IV) or intramuscularly (IM)) or diclofenac (37.5 mg IV) are most commonly used.[rx][rx][rx]
Successful use of intravenous lidocaine for renal colic has been reported. The protocol is to inject lidocaine 120 mg in 100 mL normal saline intravenously over 10 minutes for pain management. It has been quite effective for intractable renal colic unresponsive to standard therapy and typically starts to work in 3-5 minutes. No adverse events have been reported.[rx]
Opiate pain medication, such as morphine sulfate (0.1 mg/kg IV or IM) or hydromorphone (0.02 mg/kg IV or IM), can also be used effectively for analgesia, especially when other measures have failed. However, opiates are associated with respiratory depression and sedation, and there is a risk of dependence associated with prolonged opiate use.
Fluid hydration. Although there is no evidence to support that empiric fluid will help “flush out” a stone, many patients are dehydrated secondary to decreased oral intake or vomiting and can benefit from adequate hydration.
Medical expulsive therapy. Alpha 1 adrenergic receptors exist in increasing concentration in the distal ureter. The use of alpha blockade medications (for example, tamsulosin or nifedipine) is theorized to facilitate stone passage by decreasing intra-ureteral pressure and dilating the distal ureter. However, data from randomized control trials are somewhat mixed as to whether these medications improved stone passage. The consensus opinion is they may be helpful in smaller stones in the lower or distal ureter. They are probably of little use in larger stones in the proximal ureter. Silodosin (Rapaflo) 4 and 8 mg was compared to standard tamsulosin 0.4 mg. The higher dose of silodosin (8 mg) was comparable to the tamsulosin, but the lower dose of 4 mg was clearly inferior with reduced expulsion rates and increased pain reported.[rx]
Definitive management of impacted stones. There are several invasive methods to improve the stone passage. These include shock wave lithotripsy, in which high energy shock waves are used to fragment stones, ureteroscopy with either laser or electrohydraulic stone fragmentation, or in rare cases, open surgery. In the presence of infection, a double J stent or percutaneous nephrostomy may be used to help with urinary drainage of the affected renal unit with definitive stone therapy postponed until the patient is stable.
The optimal timing of intervention for renal colic depends on the underlying etiology. For an obstructing stone, intervention is suggested even in asymptomatic patients after 30 days due to the increased risk of scarring and other complications.
Behavior modification and preventative management. Increase fluid intake to optimize urine output with a goal of 2 L to 2.5 L of urine daily. Patients with calcium stones and high urine calcium concentrations should limit sodium intake and have a goal of moderate calcium intake of 1000 mg to 1200 mg dietary calcium daily. Those with calcium stones and low urinary citrate or those with uric acid stones and high urinary uric acid should increase intake of fruits and vegetables and decrease non-dairy animal protein. They may benefit from potassium citrate supplementation. Uric acid stone formers are usually best treated with potassium citrate (urinary alkalinize) to a pH of 6.5. Hyperuricosuria calcium stone formers can benefit from allopurinol. Thiazide diuretics are indicated in those with high urinary calcium and recurrent calcium stones to reduce the amount of urinary calcium. Patients with hyperoxaluria should be encouraged to lower their oxalate intake (spinach, nuts, chocolate, green leafy vegetables). [rx][rx][rx]
Nerve blocks can often be helpful, especially in chronic cases of flank pain. An anesthetic injection is typically an injection proximal to the area of the 11th or 12th intercostal nerve. Good efficacy of a nerve block suggests a musculoskeletal or neuropathic etiology. Paravertebral, splanchnic, and intercostal nerve blocks have all shown varying degrees of efficacy in relief from flank pain.[rx][rx][rx]
24-hour urine testing for kidney stone prophylaxis is now recommended for all high-risk and recurrent stone formers. The American Urological Association Guidelines recommend informing even first-time stone formers about 24-hour urine testing and prophylactic therapy. Good guidelines for the interpretation of 24-hour urine tests and optimal treatment selection have been published and are now available for free download.[rx]
There is typically no antalgic position for the patient (lying down on the non-aching side and applying a hot bottle or towel to the area affected may help). Larger stones may require surgical intervention for their removal, such as shockwave lithotripsy, laser lithotripsy, ureteroscopy or percutaneous nephrolithotomy. Patients can also be treated with alpha blockers[rx] in cases where the stone is located in the ureter.
Surgery
Ureteroscopy guided stone extraction – This invasive surgical procedure involves a doctor inserting a thin scope with a light and attached camera into the urinary tract. Using this allows them to locate and remove the stone.
Extracorporeal shock wave lithotripsy (ESWL) – ESWL is a non-invasive treatment. It is the process of aiming small sound waves at the kidneys to break up stones into tiny pieces. A person can then pass these fragments in the urine.
Percutaneous nephrolithotomy – Doctors typically perform this procedure under general anesthesia. They will make a small incision in the person’s back to access the kidney and will remove the stone using a lighted scope and small surgical instruments.
Stent placement – Sometimes, doctors place a thin tube into a person’s ureter to help relieve the obstruction and promote the passing of stones.
Ureteroscopy – Your doctor inserts a thin, lighted scope up through your urethra and bladder to remove the stone.
Percutaneous nephrolithotomy – This procedure uses tiny instruments inserted through a small cut in your back to remove a stone. You will be asleep during this procedure.
Acute renal colic is severe pain resulting from the presence of a stone in the urinary system. The stone can be present anywhere along the path between the kidneys and the urethra. Nephrolithiasis refers to kidney stones, or renal calculi, and, in conjunction with ureteral calculi, are the primary cause of acute renal colic. Nephrolithiasis has a lifetime prevalence of five to fifteen percent and an incidence of 0.5% in North America and Europe. This activity reviews the evaluation and management of nephrolithiasis and highlights the role of the interprofessional team in caring for patients affected by this condition.
Renal colic is a type of abdominal pain commonly caused by obstruction of the ureter from dislodged kidney stones. The most frequent site of obstruction is the vesicoureteric junction (VUJ), the narrowest point of the upper urinary tract. Acute obstruction and the resultant urinary stasis (disruption of urine flow) can distend the ureter (hydroureter) and cause a reflexive peristaltic smooth muscle spasm, which leads to a very intense visceral pain transmitted via the ureteric plexus.
An acute renal colic is a severe form of sudden flank pain that typically originates over the costovertebral angle and extends anteriorly and inferiorly towards the groin or testicle. It is often caused by acute obstruction of the urinary tract by calculus and is frequently associated with nausea and vomiting. The degree of pain is related to the degree of obstruction and not the size of the stone, although stone size can be a reasonable predictor of the likelihood of spontaneous passage. While kidney stones are not the only cause of flank pain, their frequency, and the severity of the pain they cause make nephrolithiasis the most likely presumptive diagnosis when sudden flank pain occurs.
Nephrolithiasis, also known as kidney stones, is a common condition affecting 5% to 15% of the population at some point, with a yearly incidence of 0.5% in North America and Europe, and is usually caused by a crystal or crystalline aggregate traveling from the kidney through the genitourinary system and becoming stuck creating an obstruction to urinary flow, typically in the ureter. This obstruction results in proximal ureteral and renal pelvic dilation which is the immediate cause of the intense pain known as renal colic.[rx][rx][rx][rx]
Causes of Acute Renal Colic
Renal colic is caused by dilation of the renal pelvis and ureteral segments. While usually colic is from an acute obstruction such as a ureteral calculus, it may also be due to a variety of other problems and disorders such as ureteral spasms immediately after double J stent removal or ureteroscopy. Similar ureteral blockages from chronic sources (such as ureteropelvic junction obstructions, prostate, cervical or pelvic cancer, scarring, and retroperitoneal fibrosis among others), do not generally cause acute pain or colic.
Ureteral calculi are a common cause of the most acute and severe level of flank pain. The bulk of this review will therefore focus on renal colic from obstruction by a ureteral stone.
There are multiple predictors and risk factors for kidney stone formation.
The following are the most common:
Inadequate urinary volume – Patients with extremely low urine volumes (usually less than 1 liter per day) increase the concentration of solutes (indicated by urine with an osmolarity greater than 600 mOsm/kg) and promote urinary stasis, which can cause supersaturation of solutes and lead to stone formation. The optimal daily urine volume for stone formers is 2,500 ml with a minimum acceptable level of 2,000 ml.[rx][rx]
Hypercalciuria – Most often, this is an idiopathic finding. It can be secondary to increased intestinal absorption of calcium, higher circulating serum calcium, reduced renal calcium reabsorption (renal calcium leak), hypervitaminosis D, hyperparathyroidism, high protein load, or systemic acidosis. Hypercalciuria increases the urinary saturation of calcium salts like oxalate and phosphate, causing the formation of crystals and calculi. Calcium-containing stones form approximately 80% of all renal calculi. Hypercalciuria is usually defined as urinary calcium of 250 mg or more per 24 hours. Treatment involves minimizing excessive daily oral calcium intake, correcting phosphate deficiencies that lead to increased Vitamin D activity, and the use of thiazides to increase calcium reabsorption in the nephron.
Hyperoxaluria – Oxalate naturally occurs in plants where it binds tightly to calcium in the plant’s tissue fluid. Ingestion of vegetable material results in intestinal oxalate absorption and urinary excretion. As oxalate has no nutritional or beneficial role in human physiology, it is excreted in the urine where it can form crystals and stones with calcium. Oxalate is considered the strongest chemical promotor of stones. Normal urinary oxalate is up to about 40 mg per day but optimal 24-hour urine levels are generally at 25 mg/day or less. Green leafy vegetables like spinach, rhubarb, and collard greens are particularly high in oxalate.
Hyperuricosuria – High urinary uric acid levels can promote both calcium oxalate and uric acid stone formation. Uric acid stones account for 5% to 10% of all renal calculi. Hyperuricosuria can be secondary to a high animal protein diet or a genetic defect causing increased uric acid excretion. Most pure uric acid stones are caused by high total urinary acid levels and not by elevated urinary uric acid levels. Allopurinol or febuxostat (Uloric) can be used to reduce uric acid production and potassium citrate is used for aciduria.
Infection stones – These are caused by urea-splitting organisms (Proteus or Klebsiella spp but not Escherichia coli) that break down urea in the urine, increasing concentrations of ammonia and pH which promote struvite stone formation and growth. Infection stones are also called struvite or triple (Magnesium, Ammonium, Calcium) phosphate calculi. Treatment includes control of infection with total surgical removal of all stones which are considered infected. A specific urease inhibitor, acetohydroxamic acid, may be useful in selected cases.[rx]
Hypocitraturia – Inadequate urinary citrate levels can contribute to new nephrolithiasis formation. Citrate is the urinary equivalent of serum bicarbonate. It increases urinary pH, but it also acts as a specific inhibitor of crystal aggregation and stone formation by forming soluble complexes with calcium and magnesium. Optimal levels are approximately 300 mg (or more)/L of urine. Potassium citrate supplements are also recommended to optimize urine pH in cases of uric acid stones and aciduria.
Symptoms of Acute Renal Colic
Small stones may not cause any symptoms. Larger stones can cause renal colic, especially if they block a ureter. This is the tube urine travels through on its way from your kidney to your bladder.
Symptoms of renal colic include:
intense pain along the side of your body between your ribs and hip, or in your lower abdomen
pain that spreads to your back or groin
nausea or vomiting
Renal colic pain often comes in waves. These waves can last from 20 to 60 minutes.
pain when you urinate
blood in your urine, which may be pink, red, or brown
cloudy or foul-smelling urine
gravel — tiny pieces of stones in your urine
urgent need to urinate
urinating more or less than usual
fever and chills (if you have an infection)
Diagnosis of Acute Renal Colic
History and Physical
Patients with renal colic typically present with sudden onset of flank pain radiating laterally to the abdomen and/or to the groin. Patients often report a dull constant level of pain with colicky episodes of increased pain. The constant pain is often due to stretching of the renal capsule due to obstruction, whereas colicky pain can be caused by peristalsis of the ureteral smooth muscle. Many patients report associated nausea or vomiting, and some may report gross hematuria. As the stone migrates distally and approaches the bladder, the patient may experience dysuria, urinary frequency, urgency, or difficulty in urination.
Patients experiencing renal colic may present in very severe pain. Classically, these patients are unable to find a comfortable position and are often writhing or constantly pacing around the examination table. The exam may reveal flank pain more commonly than abdominal pain, and the skin may be cool or diaphoretic. There is often a prior personal or family history history of stones, recent ureteroscopic surgery, or just after removal of a double J stent.
In the case of a recent ureteroscopy or immediately after removal of a double J stent, the history alone can provide the diagnosis. In these cases, the renal colic is due to a ureteral spasm which effectively causes an obstruction with resultant proximal ureteral and renal dilation even without a stone. The pain can be just as intense as from an obstructing ureteral stone.
Diagnosis is made through a combination of history and physical exams, laboratory testing, and imaging studies. Urinalysis shows some degree of microscopic or gross hematuria in 85% of stone patients, but should also be evaluated for signs of infection (e.g., white blood cells, bacteria). Urinary pH greater than 7.5 may be suggestive of a urease-producing bacterial infection, while pH values less than 5.5 may indicate the presence of uric acid calculi.
A basic metabolic panel (BMP) should be obtained to assess for renal function, dehydration, acid-base status, and electrolyte balance. Serum calcium should be checked. A complete blood count (CBC) can be considered to evaluate for leukocytosis if there is a concern for infection although a mild elevation of WBCs is commonly secondary to white blood cell emargination.
Hematuria is present in 85% of acute renal colic cases caused by calculi. While the presence of hematuria is suggestive of a stone, it is not definitive and neither does the absence of hematuria conclusively prove that a stone is not present.
Consider obtaining a parathyroid hormone (PTH) level if hypercalcemia is present and therefore primary hyperparathyroidism is suspected. If possible, urine should be strained to capture stones for chemical analysis to help determine optimal preventive prophylactic measures. Further metabolic testing, such as a 24-hour urine collection for volume, pH, calcium, oxalate, uric acid, citrate, sodium, magnesium, and potassium concentrations, should be considered in high-risk first-time stone formers, pediatric patients, or recurrent stone formers. It is highly recommended in nephrolithiasis patients with solitary kidneys, renal failure, renal transplants, gastrointestinal (GI) bypass, and any patient with high or increased anesthesia risk.
Renal ultrasonography can be used to establish hydronephrosis and measure resistive index and track larger renal stones (especially uric acid), but it will often miss stones smaller than 5 mm in size and is not a reliable imaging modality for visualizing ureteral calculi. The degree of perinephric fluid can be a predictor of the degree of obstruction.[rx] Resistive index can be useful in diagnosing ureteral obstructions. It is defined as (peak systolic velocity – end-diastolic velocity)/ peak systolic velocity) where normal is typically 0.7 or less. Higher levels indicate either obstruction or intrinsic renal disease.[rx][rx]
Unenhanced (or helical) CT is the gold standard for the initial diagnosis of suspected renal colic; with a sensitivity of 98%, the specificity of 100%, and a negative predictive value of 97%. This modality allows rapid identification of stone, provides information as to the location and size of the stone, and any associated hydroureter, hydronephrosis, or ureteral edema, and can give information regarding potential other etiologies of pain (e.g., abdominal aortic aneurysm, malignancy). In those patients with no previous history of nephrolithiasis, CT should be performed to guide management. CT scans may underestimate stone size in comparison with an intravenous pyelogram or abdominal x-ray.
However, CT scans expose patients to a significant radiation burden and they can be costly. In some patients with a history of renal colic that present with pain similar to previous obstructing urolithiasis, it may be sufficient to perform ultrasonography (US). While the US is less sensitive (60% to 76%) than CT for detecting calculi less than 5 mm, it can reliably detect hydronephrosis and evidence of obstruction (increased resistive index in the affected kidney). It is also the modality of choice for evaluating a pregnant patient with concern for renal colic. Studies have shown that using ultrasonography as a primary imaging modality does not lead to an increase in complications in comparison to CT. Ultrasound is also a good way to follow a patient known to have uric acid urinary stones.
A plain abdominal x-ray (KUB) can identify many stones, but 10% to 20% of renal calculi are radiolucent and provide little information regarding hydronephrosis, obstruction, or renal anatomy. Additionally, bowel gas, the bony pelvis, and abdominal organs may obstruct stone visualization. The KUB is recommended in kidney stone cases when the CT scan is positive, and the exact location of the stone is known. This helps in clearly identifying those stones that can be tracked by follow-up KUB and those that might be amenable to lithotripsy.
Combining renal ultrasound (which can easily demonstrate hydronephrosis but is less reliable in detecting stones) with a KUB (which has good sensitivity for imaging calculi but no dilation), can be very cost-effective as an alternative to CT scans with lower cost and reduced radiation. Symptomatic stones are likely to produce hydronephrosis or obstruction (visible on ultrasound) or will be seen directly on the KUB. The combination of KUB radiography with renal ultrasonography provides a reported diagnostic accuracy for an obstructing stone of 90%, specificity of 93%, and a sensitivity of 88%.[rx]
If the stone should pass before imaging can be performed, some evidence of residual inflammation may remain, such as hydronephrosis or pain, even if no stone is specifically or definitively identified.
Treatment of Acute Renal Colic
Most small stones are passed spontaneously and only pain management is required. Above 5 mm (0.20 in) the rate of spontaneous stone passage decreases. NSAIDs (non-steroidal anti-inflammatory drugs), such as diclofenac[rx] or ibuprofen, and antispasmodics like butylscopolamine are used. Although morphine may be administered to assist with emergency pain management, it is often not recommended as morphine is addictive and raises ureteral pressure, worsening the condition. Vomiting is also considered an important adverse effect of opioids, mainly with pethidine.[rx] Oral narcotic medications are also often used.
Treatment includes the following:
Immediate intervention with analgesia and antiemetics. NSAIDs and opiates are first-line therapies for analgesia. NSAIDs work in two ways in renal colic. First, NSAIDs decrease the production of arachidonic acid metabolites, which mediate pain receptors, alleviating pain caused by distension of the renal capsule. Additionally, they cause contraction of the efferent arterioles to the glomerulus, causing a reduction in glomerular filtration, and reducing hydrostatic pressure across the glomerulus. Because patients are frequently unable to tolerate oral medications, parenteral NSAIDs such as ketorolac (15 mg to 30 mg intravenously (IV) or intramuscularly (IM)) or diclofenac (37.5 mg IV) are most commonly used.[rx][rx][rx]
Successful use of intravenous lidocaine for renal colic has been reported. The protocol is to inject lidocaine 120 mg in 100 mL normal saline intravenously over 10 minutes for pain management. It has been quite effective for intractable renal colic unresponsive to standard therapy and typically starts to work in 3-5 minutes. No adverse events have been reported.[rx]
Opiate pain medication, such as morphine sulfate (0.1 mg/kg IV or IM) or hydromorphone (0.02 mg/kg IV or IM), can also be used effectively for analgesia, especially when other measures have failed. However, opiates are associated with respiratory depression and sedation, and there is a risk of dependence associated with prolonged opiate use.
Fluid hydration. Although there is no evidence to support that empiric fluid will help “flush out” a stone, many patients are dehydrated secondary to decreased oral intake or vomiting and can benefit from adequate hydration.
Medical expulsive therapy. Alpha 1 adrenergic receptors exist in increasing concentration in the distal ureter. The use of alpha blockade medications (for example, tamsulosin or nifedipine) is theorized to facilitate stone passage by decreasing intra-ureteral pressure and dilating the distal ureter. However, data from randomized control trials are somewhat mixed as to whether these medications improved stone passage. The consensus opinion is they may be helpful in smaller stones in the lower or distal ureter. They are probably of little use in larger stones in the proximal ureter. Silodosin (Rapaflo) 4 and 8 mg was compared to standard tamsulosin 0.4 mg. The higher dose of silodosin (8 mg) was comparable to the tamsulosin, but the lower dose of 4 mg was clearly inferior with reduced expulsion rates and increased pain reported.[rx]
Definitive management of impacted stones. There are several invasive methods to improve the stone passage. These include shock wave lithotripsy, in which high energy shock waves are used to fragment stones, ureteroscopy with either laser or electrohydraulic stone fragmentation, or in rare cases, open surgery. In the presence of infection, a double J stent or percutaneous nephrostomy may be used to help with urinary drainage of the affected renal unit with definitive stone therapy postponed until the patient is stable.
The optimal timing of intervention for renal colic depends on the underlying etiology. For an obstructing stone, intervention is suggested even in asymptomatic patients after 30 days due to the increased risk of scarring and other complications.
Behavior modification and preventative management. Increase fluid intake to optimize urine output with a goal of 2 L to 2.5 L of urine daily. Patients with calcium stones and high urine calcium concentrations should limit sodium intake and have a goal of moderate calcium intake of 1000 mg to 1200 mg dietary calcium daily. Those with calcium stones and low urinary citrate or those with uric acid stones and high urinary uric acid should increase intake of fruits and vegetables and decrease non-dairy animal protein. They may benefit from potassium citrate supplementation. Uric acid stone formers are usually best treated with potassium citrate (urinary alkalinize) to a pH of 6.5. Hyperuricosuria calcium stone formers can benefit from allopurinol. Thiazide diuretics are indicated in those with high urinary calcium and recurrent calcium stones to reduce the amount of urinary calcium. Patients with hyperoxaluria should be encouraged to lower their oxalate intake (spinach, nuts, chocolate, green leafy vegetables). [rx][rx][rx]
Nerve blocks can often be helpful, especially in chronic cases of flank pain. An anesthetic injection is typically an injection proximal to the area of the 11th or 12th intercostal nerve. Good efficacy of a nerve block suggests a musculoskeletal or neuropathic etiology. Paravertebral, splanchnic, and intercostal nerve blocks have all shown varying degrees of efficacy in relief from flank pain.[rx][rx][rx]
24-hour urine testing for kidney stone prophylaxis is now recommended for all high-risk and recurrent stone formers. The American Urological Association Guidelines recommend informing even first-time stone formers about 24-hour urine testing and prophylactic therapy. Good guidelines for the interpretation of 24-hour urine tests and optimal treatment selection have been published and are now available for free download.[rx]
There is typically no antalgic position for the patient (lying down on the non-aching side and applying a hot bottle or towel to the area affected may help). Larger stones may require surgical intervention for their removal, such as shockwave lithotripsy, laser lithotripsy, ureteroscopy or percutaneous nephrolithotomy. Patients can also be treated with alpha blockers[rx] in cases where the stone is located in the ureter.
Surgery
Ureteroscopy guided stone extraction – This invasive surgical procedure involves a doctor inserting a thin scope with a light and attached camera into the urinary tract. Using this allows them to locate and remove the stone.
Extracorporeal shock wave lithotripsy (ESWL) – ESWL is a non-invasive treatment. It is the process of aiming small sound waves at the kidneys to break up stones into tiny pieces. A person can then pass these fragments in the urine.
Percutaneous nephrolithotomy – Doctors typically perform this procedure under general anesthesia. They will make a small incision in the person’s back to access the kidney and will remove the stone using a lighted scope and small surgical instruments.
Stent placement – Sometimes, doctors place a thin tube into a person’s ureter to help relieve the obstruction and promote the passing of stones.
Ureteroscopy – Your doctor inserts a thin, lighted scope up through your urethra and bladder to remove the stone.
Percutaneous nephrolithotomy – This procedure uses tiny instruments inserted through a small cut in your back to remove a stone. You will be asleep during this procedure.
Acute pyelonephritis is a bacterial infection causing inflammation of the kidneys. Pyelonephritis occurs as a complication of an ascending urinary tract infection that spreads from the bladder to the kidneys. Symptoms usually include fever, flank pain, nausea, vomiting, burning with urination, increased frequency, and urgency. This activity outlines the clinical presentation, diagnosis, and management of acute pyelonephritis, and highlights the role of the interprofessional team in caring for patient with the condition.
Acute pyelonephritis is a bacterial infection causing inflammation of the kidneys and is one of the most common diseases of the kidney. Pyelonephritis occurs as a complication of an ascending urinary tract infection (UTI) which spreads from the bladder to the kidneys and their collecting systems. The 2 most common symptoms are usually fever and flank pain. Acute pyelonephritis can be divided into uncomplicated and complicated. Complicated pyelonephritis includes pregnant patients, patients with uncontrolled diabetes, kidney transplants, urinary anatomical abnormalities, acute or chronic kidney failure, as well as immunocompromised patients and those with hospital-acquired bacterial infections. It is important to make a distinction between complicated and uncomplicated pyelonephritis, as patient management and disposition depend on it.
Causes of Acute Pyelonephritis
The main cause of acute pyelonephritis is gram-negative bacteria, the most common being Escherichia coli. Other gram-negative bacteria which cause acute pyelonephritis include Proteus, Klebsiella, and Enterobacter. In most patients, the infecting organism will come from their fecal flora. Bacteria can reach the kidneys in 2 ways: hematogenous spread and through ascending infection from the lower urinary tract. Hematogenous spread is less common and usually occurs in patients with ureteral obstructions or immunocompromised and debilitated patients. Most patients will get acute pyelonephritis through ascending infection. Ascending infection happens through several steps. Bacteria will first attach to urethral mucosal epithelial cells and will then travel to the bladder via the urethra either through either instrumentation or urinary tract infections which occur more frequently in females. UTIs are more common in females than in males due to shorter urethras, hormonal changes, and close distance to the anus. Urinary tract obstruction caused by something such as a kidney stone can also lead to acute pyelonephritis. An outflow obstruction of urine can lead to incomplete emptying and urinary stasis which causes bacteria to multiply without being flushed out. A less common cause of acute pyelonephritis is vesicoureteral reflux, which is a congenital condition where urine flows backward from the bladder into the kidneys.
E. coli is the most common bacteria causing acute pyelonephritis due to its unique ability to adhere to and colonize the urinary tract and kidneys. E.coli has adhesive molecules called P-fimbriae which interact with receptors on the surface of uroepithelial cells. Kidneys infected with E. coli can lead to an acute inflammatory response which can cause scarring of the renal parenchyma. Though the mechanism in which renal scarring occurs is still poorly understood, it has been hypothesized that the adhesion of bacteria to the renal cells disrupts the protective barriers, which lead to localized infection, hypoxia, ischemia, and clotting in an attempt to contain the infection. Inflammatory cytokines, bacterial toxins, and other reactive processes further lead to complete pyelonephritis and in many cases systemic symptoms of sepsis and shock.
Mechanical – any structural abnormalities in the urinary tract, vesicoureteral reflux (urine from the bladder flowing back into the ureter), kidney stones, urinary tract catheterization, ureteral stents or drainage procedures (e.g., nephrostomy), pregnancy, neurogenic bladder (e.g., due to spinal cord damage, spina bifida or multiple sclerosis) and prostate disease (e.g., benign prostatic hyperplasia) in men
Constitutional – diabetes mellitus, immunocompromised states
Behavioral – change in sexual partner within the last year, spermicide use
Being female – The urethra is shorter in women than it is in men, which makes it easier for bacteria to travel from outside the body to the bladder. The nearness of the urethra to the vagina and anus also creates more opportunities for bacteria to enter the bladder. Once in the bladder, an infection can spread to the kidneys. Pregnant women are at even higher risk of a kidney infection.
Having a urinary tract blockage – This includes anything that slows the flow of urine or reduces your ability to empty your bladder when urinating — including a kidney stone, something abnormal in your urinary tract’s structure or, in men, an enlarged prostate gland.
Having a weakened immune system – This includes medical conditions that impair your immune systems, such as diabetes and HIV. Certain medications, such as drugs taken to prevent rejection of transplanted organs, have a similar effect.
Having damage to nerves around the bladder – Nerve or spinal cord damage can block the sensations of a bladder infection so that you’re unaware when it’s advancing to a kidney infection.
Using a urinary catheter for a time – Urinary catheters are tubes used to drain urine from the bladder. You might have a catheter placed during and after some surgical procedures and diagnostic tests. You might use one continuously if you’re confined to a bed.
Having a condition that causes urine to flow the wrong way – In vesicoureteral reflux, small amounts of urine flow from your bladder back up into your ureters and kidneys. People with this condition are at higher risk of kidney infection during childhood and adulthood. Positive family history (close family members with frequent urinary tract infections)
Symptoms of Acute Pyelonephritis
Symptoms usually appear within two days of infection. Common symptoms include:
a fever greater than 102°F (38.9°C)
pain in the abdomen, back, side, or groin
painful or burning urination
cloudy urine
pus or blood in the urine
urgent or frequent urination
fishy-smelling urine
shaking or chills
nausea – vomiting
general aching or ill feeling
fatigue
moist skin
mental confusion
Frequent urination
Strong, persistent urge to urinate
Burning sensation
Urine that smells bad or is cloudy
Symptoms may be different in children and older adults than they are in other people. For example, mental confusion is common in older adults and is often their only symptom. People with chronic pyelonephritis may experience only mild symptoms or may even lack noticeable symptoms altogether.
Diagnosis of Acute Pyelonephritis
Histopathology will usually reveal necrosis or putrid abscess formation within the renal parenchyma. The renal tissues are infiltrated with neutrophils, macrophages, and plasma cells. However, the architecture is not completely disorganized.
History and Physical
Acute pyelonephritis will classically present as a triad of fever, flank pain, and nausea or vomiting, but not all symptoms have to be present. Symptoms will usually develop within several hours or over the course of a day. Symptoms of cystitis such as dysuria and hematuria will be present in women usually. In children, common symptoms of acute pyelonephritis can be absent. Symptoms such as failure to thrive, fever, and feeding difficulty are most common in neonates and children under 2 years old. Elderly patients may present with altered mental status, fever, deterioration, and damage to other organ systems. On physical examination, the patient’s general appearance will be variable. Some patients will appear ill and uncomfortable, while others may appear healthy. Patients will usually not appear toxic. When a patient is febrile, fever may be high, often over 103 F. Costovertebral angle tenderness is commonly unilateral over the affected kidney, but in some cases, bilateral costovertebral angle tenderness may be present. Suprapubic tenderness during the abdominal examination will vary from mild to moderate with or without rebound tenderness.
Lab Test and Imaging
A good history and physical is the mainstay of evaluating acute pyelonephritis, but laboratory and imaging studies can be helpful. A urinary specimen should be obtained for a urinalysis.
Blood Test – work such as a complete blood cell count (CBC) is sent to look for an elevation in white blood cells. The complete metabolic panel can be used to search for aberrations in creatinine and BUN to assess kidney function.
Urinalysis – For a urinalysis, you will collect a urine sample in a special container at a doctor’s office or at a lab. On urinalysis, one should look for pyuria as it is the most common finding in patients with acute pyelonephritis. Nitrite production will indicate that the causative bacteria is E.coli. Proteinuria and microscopic hematuria may be present as well on urinalysis. If hematuria is present, then other causes may be considered such as kidney stones. All patients with suspected acute pyelonephritis should also have urine cultures sent for proper antibiotic management. A health care professional will look at the sample under a microscope for bacteria and white blood cells, which the body produces to fight infection. Bacteria also can be found in the urine of healthy people, so a kidney infection is diagnosed based both on your symptoms and a lab test.
Urine culture – A health care professional may culture your urine to find out what type of bacteria is causing the infection. A health care professional can see how the bacteria have multiplied, usually in 1 to 3 days, and can then determine the best treatment.
Ultrasonography – can be used to detect pyelonephritis, but a negative study does not exclude acute pyelonephritis. Regardless, ultrasound can still be a useful study when evaluating for acute pyelonephritis because it can be done bedside, has no radiation exposure, and may reveal renal abnormalities, which can prompt further testing or definitive treatment.
FBC – this shows elevated white cell count with neutrophilia.
Blood cultures – these are positive in approximately 15-30% of cases.
Imaging
X-Ray – Imaging is useful if the clinical picture or biochemical markers are ambivalent, as structural problems are not uncommon. Ultrasonography is usually the first-line investigation. Whether advised for all varies between guidelines. Imaging is normally recommended in men and children; it is mandatory in patients with recurrent pyelonephritis and may help to identify obstruction or stones.
CT Scan – The imagining study of choice for acute pyelonephritis is abdominal/pelvic CT with contrast. Imaging studies will usually not be required for the diagnosis of acute pyelonephritis but are indicated for patients with a renal transplant, patients in septic shock, those patients with poorly controlled diabetes, complicated UTIs, immunocompromised patients, or those with toxicity persisting for longer than 72 hours.
Dimercaptosuccinic acid (DMSA) scan – is mainly used for detailed renal cortical views in recurrent cases, to detect scarring.
MRI – is also useful in detecting scarring but may require sedation in children. In adults, it is increasingly used where renal infection, masses, and urinary obstruction are suspected but its use is limited by cost and availability.
Renal biopsy – is occasionally employed to exclude papillary necrosis.
Recent studies identified procalcitonin as a biological marker in diagnosing acute pyelonephritis in children, potentially more useful than white cell count or CRP. National Institute for Health and Care Excellence (NICE) guidance advises CRP alone is not useful in differentiating lower UTI from pyelonephritis in children. Cochrane review in 2015 came to the conclusion that although procalcitonin seemed the most helpful, there was not enough evidence to recommend routine use of any of these blood tests in clinical practice at this time.
Treatment of Acute Pyelonephritis
Acute pyelonephritis can be managed as either outpatient or inpatient. Healthy, young, non-pregnant women who present with uncomplicated pyelonephritis can be treated as outpatients. Inpatient treatment is usually required for those who are very young, elderly, immunocompromised, those with poorly controlled diabetes, renal transplant, patients, patients with structural abnormalities of the urinary tract, pregnant patients, or those who cannot tolerate oral intake. The mainstay of treatment of acute pyelonephritis is antibiotics, analgesics, and antipyretics. Nonsteroidal anti-inflammatory drugs (NSAIDs) work well to treat both pain and fever associated with acute pyelonephritis. The initial selection of antibiotics will be empiric and should be based on the local antibiotic resistance. Antibiotic therapy should then be adjusted based on the results of the urine culture. Most uncomplicated cases of acute pyelonephritis will be caused by E. coli for which patients can be treated with oral cephalosporins or TMP-SMX for 14 days. Complicated cases of acute pyelonephritis require intravenous (IV) antibiotic treatment until there are clinical improvements. Examples of IV antibiotics include piperacillin-tazobactam, fluoroquinolones, meropenem, and cefepime. For patients who have allergies to penicillin, vancomycin can be used. Follow-up for non-admitted patients for resolution of symptoms should be in 1 to 2 days. Follow-up urine culture results should be obtained only in patients who had a complicated course and are usually not needed in healthy, non-pregnant women. Any patient that had a complicated UTI should be sent for follow-up imaging to identify any abnormalities that predispose the patient to further infections.
Complications
If left untreated, a kidney infection can lead to potentially serious complications, such as:
Kidney scarring – This can lead to chronic kidney disease, high blood pressure, and kidney failure.
Blood poisoning (septicemia) – Your kidneys filter waste from your blood and return your filtered blood to the rest of your body. Having a kidney infection can cause the bacteria to spread through your bloodstream.
Pregnancy complications – Women who develop a kidney infection during pregnancy may have an increased risk of delivering low birth weight babies.
Prevention
Reduce your risk of kidney infection by taking steps to prevent urinary tract infections. Women, in particular, may reduce their risk of urinary tract infections if they:
Drink fluids, especially water – Fluids can help remove bacteria from your body when you urinate.
Urinate as soon as you need to – Avoid delaying urination when you feel the urge to urinate.
Empty the bladder after intercourse – Urinating as soon as possible after intercourse helps clear bacteria from the urethra, reducing your risk of infection.
Wipe carefully – Wiping from front to back after urinating and after a bowel movement helps prevent bacteria from spreading to the urethra.
Avoid using feminine products in the genital area – Using products such as deodorant sprays in your genital area or douches can be irritating.
A 24-hour urinalysis is a timed urine collection used in the metabolic evaluation of urinary stone disease, proteinuria evaluation, and estimation of renal function via creatinine clearance, estimating residual renal function in end-stage renal disease with urea and creatinine clearance. The testing is usually performed in an outpatient setting while the patient consumes their usual diet. Results are combined with detailed medical and dietary history, serum chemistry, and stone composition to guide prophylactic stone-reducing treatment. A 24-hour urine study can also be used in the pediatric population when inherited conditions such as primary hyperoxaluria and cystinuria are involved. [rx][rx]
A 24-hour urine collection is a simple lab test that measures what’s in your urine. The test is used to check kidney function. A 24-hour urine collection is done by collecting your urine in a special container over a full 24-hour period. The container must be kept cool until the urine is returned to the lab.
Alternative Names
Urine protein – 24 hours;
Chronic kidney disease – urine protein;
Kidney failure – urine protein
Indications of 24-Hour Urinalysis
Diabetic nephropathy. This happens when someone has uncontrolled diabetes. It causes high levels of protein (albumin) in the urine and can lead to kidney damage.
High blood pressure. Abnormally high blood pressure can lead to lasting (permanent) kidney damage.
Lupus nephritis. Lupus is an autoimmune disease where the immune system attacks the kidneys and damages them.
Frequent urinary tract infections.
Prolonged urinary tract blockage.
Alport syndrome. This health problem causes vision and hearing problems, as well as progressive scarring of the kidneys. The syndrome is passed down through families.
Nephrotic syndrome. This health problem has several different causes. Symptoms include protein in the urine, low protein in the blood, high cholesterol levels, and tissue swelling.
Polycystic kidney disease. This health problem causes the growth of many fluid-filled cysts in the kidneys. This makes the kidneys larger. Over time, it takes over and destroys working kidney tissue.
Interstitial nephritis or pyelonephritis. This is an inflammation in the small structures in the kidney. It’s often caused by infection.
Screening for preeclampsia in pregnancy. Preeclampsia is a dangerous health problem that sometimes occurs in pregnancy. It causes high blood pressure and can lead to organ failure.
Kidney stones (nephrolithiasis). Kidney stones form because of an imbalance of minerals, salts and water in the urine.
There may be other reasons for your healthcare provider to recommend 24-hour urine collection.
What are the risks of a 24-hour urine collection?
A 24-hour urine collection is a safe, easy test. People can collect urine on their own. Certain factors may affect the accuracy of a 24-hour urine collection. These include:
Forgetting to collect some of your urine
Going beyond the 24-hour collection period and collecting too much urine
Losing urine from the specimen container through spilling
Not keeping urine cold while collecting it
Acute stress
Vigorous exercise
Certain foods, such as coffee, tea, cocoa, bananas, citrus fruits, and vanilla
There may be other risks depending on your specific health problems. Be sure to discuss any concerns with your healthcare provider before the collection.
How do I get ready for a 24-hour urine collection?
Your healthcare provider will explain the procedure and you can ask questions.
Make sure you understand if you need to stay away from certain foods while collecting your urine.
You will be given large containers to store your urine and a container to urinate into. Make sure you know how to use them. Have a cold place to store the urine while you’re collecting it. For instance, a refrigerator or in a cooler on ice.
You may be told to start the collection at a specific time.
If possible, choose a 24-hour period when you will be at home so you do not have to transport your urine.
If you are pregnant or think you may be, tell your healthcare provider.
Make sure your provider has a list of all medicines (prescription and over-the-counter), herbs, vitamins, and supplements that you are taking.
Based on your health condition, your healthcare provider may request other specific preparation.
What happens during a 24-hour urine collection?
A 24-hour urine collection may be done on an outpatient basis. This means you go home the same day. Or it may be done during a hospital stay. Procedures may vary depending on your condition and your healthcare provider’s practices.
Generally, a 24-hour urine collection follows this process:
You will be given 1 or more containers for collecting and storing your urine. A brown plastic container is typically used. A special pan that fits in the toilet or a urinal may be used to collect the urine. You will need to transfer the urine from the collecting container to the storage container. You will need to keep it cold.
The 24-hour collection may start at any time during the day after you urinate. But your healthcare provider may tell you when to start. It is common to start the collection the first thing in the morning. It is important to collect all urine in the following 24-hour period.
Don’t save the urine from your first time urinating. Flush this first specimen, but note the time. This is the start time of the 24-hour collection.
All urine, after the first flushed specimen, must be saved, stored, and kept cold. This means keeping it either on ice or in a refrigerator for the next 24 hours.
Try to urinate again at the same time, 24 hours after the start time, to finish the collection process. If you can’t urinate at this time, it is OK.
Once the urine collection has been completed, the urine containers need to be taken to the lab as soon as possible. If you are doing the urine collection at home, you will be given instructions on how and where to take it.
Depending on your specific health problem, you may be asked to repeat the collection over several days.
Specimen Requirements and Procedure
Instructions for collecting a 24-hour urine sample vary by the laboratory. Typically, the patient’s first voided morning urine is discarded. Subsequent urine produced for the next 24 hours including the next morning’s first voided specimen, is collected in containers that are provided by the laboratory. A preservative solution is added to the urine collection to stabilize the sample for later analysis. Once a full 24 hours of urine is collected, the total volume is recorded. A representative sample from the total collection is then submitted to the laboratory for analysis. Serum samples, usually calcium, potassium, uric acid, and phosphorus, are sometimes also included in the study. It is important for patients to adhere to their normal diet and activities during the collection.[rx][rx]
Once the analysis is complete, a detailed report of the results is provided to the ordering clinician. These results are used to direct prophylactic medical management. Collecting a sample for a full 24 hours can be difficult for some patients and is certainly inconvenient. However, it is necessary to accurately and reliably identify urinary chemistry risk factors for calculus formation as spot urine chemistry is inadequate.
A chemical composition analysis of any stone material is very helpful if available.
Diagnostic Tests
Various labs offer 24-hour urine testing which provides clinicians a detailed laboratory report stratifying stone risk based on the laboratory data points. Typically, 24-hour urine tests for nephrolithiasis prophylaxis will include urinary volume, pH, calcium, citrate, magnesium, phosphate, sulfate, oxalate, and uric acid. Supersaturation ratios for various stone types can then be calculated. In patients with a history of cystine stones or a positive cystine cyanide test, 24-hour cystine levels can also be measured.[rx][rx]
Finding or selecting a laboratory for processing 24-hour urine chemistries can sometimes be challenging. Optimally, all the testing is done in a single laboratory, and the results are presented clearly on just 1 or 2 pages. The 24-hour totals and the relative concentrations should both be given. Be aware that “normal” values are not necessarily “optimal” values for urinary chemical constituents. Optimal urinary chemistry reference values are not reported which makes interpretation a little more complicated. Try to use a laboratory that performs a lot of 24-hour urine testing and reports all the results together. When multiple reports from several laboratories have to be combined to retrieve all the data, it is far more difficult to correlate and analyze.
Key Components of The 24-hour Urinalysis and Their Importance.
Urine Volume and Creatinine
Decreased urine volume is a major risk factor for stone disease as concentrated urine raises the supersaturation of all stone-forming salts. A prospective trial by Borghi et al. in 1999 helped define a goal urinary volume level of 2500 mL per day to reduce stone risk. Furthermore, urine volumes over this amount can decrease stone risk even further.
Urine creatinine excretion is used to determine the accuracy of a timed urine collection. As a byproduct of muscle metabolism, the excretion of creatinine is relatively stable based on muscle mass. The average daily excretion of creatinine for males is 18 to 24 mg/kg and 15 to 20 mg/kg for females. Thus, a lower than expected creatinine excretion suggests an incomplete collection.
pH
Human urine has a pH typically between 4.5 and 8.0. Urine pH is a critical data point as changes in urine pH can drive the crystallization of certain salts. Crystallization of calcium phosphate, calcium oxalate, uric acid, cystine, and struvite are all pH-dependent. Calcium oxalate precipitation is typically not as pH-dependent as the others. Uric acid stone risk is greatest in the acidic range below 5.5. Calcium phosphate crystals form in an alkaline environment of 6.5 and above. Average urine pH over a 24-hour period should fall between 5.7 to 6.3, which limits pH-dependent stone formation.
Sodium and Potassium
Urinary sodium excretion roughly equates to dietary sodium intake. As urinary sodium increases, urinary calcium excretion increases. Because of this relationship, control of dietary sodium is key to controlling hypercalciuria. Lower sodium diets typically allow for up to 1500 mg of dietary sodium per day. Urinary potassium concentration is most useful in monitoring compliance of treatments such as potassium citrate. Potassium citrate supplements should result in marked increases in urinary potassium secretion.
Magnesium
Magnesium is an inhibitor of urinary crystallization thus decreasing stone risk. Roughly half of the dietary magnesium is excreted in the urine. Low urine magnesium is typically dietary in origin.
Calcium
Elevated urinary calcium concentration can be found in nearly half of patients forming calcium stones. Urine calcium concentration is dependent on dietary calcium, sodium intake, and protein intake. Moderate calcium intake is typically recommended to limit urinary excretion while maintaining bone health. Diets low in calcium can be lithogenic, due to increased oxalate absorption in a low calcium diet. Modulation of urine calcium is often accomplished with diet changes or medications depending on etiology.
Citrate
Citrate is a potent inhibitor of calcium salt crystallization. Hypocitraturia is a common risk factor for stone disease and can be found in up to a third of calcium stone formers. Low urinary citrate can be from a variety of factors including diet, metabolic acidosis, or hypokalemia. Hypocitraturia can also be idiopathic. Citrate can be found in foods such as citrus juice. Most patients with low urinary citrate require supplementation as dietary means alone is insufficient.
Concentrated citrate supplements such as potassium citrate are commonly available. Optimal urinary citrate levels are roughly 300 mg per 1000 mL of urine. Low urinary citrate levels in the setting of thiazide therapy may correlate with hypokalemia. A 24-hour urine study is used to monitor urinary citrate concentration and resultant urinary pH level. Over alkalinizing, the urine can predispose to calcium phosphate stones if the pH consistently exceeds 7.0.
Oxalate
High urine oxalate is another common abnormality in the urine of calcium stone formers. Roughly a third of calcium stone formers will have elevated urine oxalate. Oxalate is both endogenous and dietary. Dietary oxalate is absorbed in the colon and distal portions of the ileum. Normal oxalate excretion ranges from around 40 to 50 mg per day. Reductions in excretion can have goals as low as 25 mg per day. Dietary sources of oxalate include black tea, nuts, chocolate, and green leafy vegetables like spinach. Excessive vitamin C supplements are also metabolized to oxalate in the urine. For this reason, vitamin C supplements should be limited to 1000 mg or less daily. Enteric hyperoxaluria can be a significant risk factor for patients with inflammatory bowel disease, cystic fibrosis, pancreatic insufficiency, or previous bariatric bowel surgery.
A more detailed review of 24-hour urine chemistry interpretation and treatment guide for kidney stone prevention can be found in our companion review article 24-Hour Urine Testing for Nephrolithiasis: Guide to Interpretation by Leslie and Bashir.
Results, Reporting, Critical Findings for 24-Hour Urinalysis
Components of 24-hour urine exams vary by the laboratory. Components included in most standard 24-hour analyses include urine volume, the concentration of urine calcium, oxalate, citrate, and uric acid, urine pH level, and supersaturation values. Supersaturation of calcium oxalate, calcium phosphate, and uric acid are commonly reported. Other analytes include urine potassium, magnesium, phosphorus, ammonium, chloride, sulfate, and nitrogen in the form of urea. Reports typically include reference range values that help stratify the risk of stone formation. Specialized testing is also available for pediatric patients and patients with cystinuria. These tests include cysteine excretion, supersaturation, and urine pH. The interpretation of urine chemistry requires reference ranges. Urine chemistry is a continuous variable making the strict cut-off points and abnormal values somewhat arbitrary. As urinary constituents reach outside of normal or optimal ranges, the lithogenic risk increases.[rx]
What do the test results mean?
Test results should be available after a couple of days, depending on the lab schedule. A normal test result shows less than 150 milligrams of protein per day. Test results may vary slightly between laboratories. Ask your doctor about the exact meaning of your test results.
Protein in the urine may signify kidney damage or disease. Protein levels may also rise temporarily due to factors such as infection, stress, or excess exercise.
If the protein is caused by kidney damage, the test results will help to determine the extent of that damage. The protein amount can also be used to monitor any disease progression or measure your response to therapy.
Proteinuria is associated with many other conditions. These include:
amyloidosis, an abnormal presence of amyloid proteins in organs and tissues
bladder cancer tumors
congestive heart failure
diabetes
urinary tract infection
use of medications that damage the kidneys
Waldenström’s macroglobulinemia, a rare plasma cell cancer
glomerulonephritis, inflammation of the blood vessels in the kidneys
Goodpasture syndrome, a rare autoimmune disease
heavy metal poisoning
hypertension
kidney infection
multiple myeloma, a cancer of the plasma cells
lupus, an inflammatory autoimmune disease
polycystic kidney disease
Your doctor may order more tests to make a diagnosis.
Nephrolithiasis/Kidney stone disease, also known as nephrolithiasis or urolithiasis, is when a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine stream.[rx] A small stone may pass without causing symptoms.[rx] If a stone grows to more than 5 millimeters (0.2 in), it can cause blockage of the ureter, resulting in severe pain in the lower back or abdomen.[rx][rx] A stone may also result in blood in the urine, vomiting, or painful urination.[rx] About half of people who have had a kidney stone will have another within ten years.[rx]
Urolithiasis is a common condition, and it accounts for a large number of hospital visits. It is frequently preventable by modification of risk factors and has numerous treatment options. This activity outlines the etiology, management, and treatment of urolithiasis and highlights the role of the interprofessional team in evaluating and treating patients with this condition.
Renal stones are formed within the kidneys, and this is called nephrolithiasis. Urolithiasis is a condition that occurs when these stones exit the renal pelvis and move into the remainder of the urinary collecting system, which includes the ureters, bladder, and urethra. Many patients with urolithiasis can be managed with expectant management, analgesic, and anti-emetic medications; however, stones that are associated with obstruction, renal failure, and infection require further increasingly critical interventions.[rx]
Types of Nephrolithiasis
Calcium stones – Small asymptomatic stones in the kidney can be safely ignored, and if patients maintain good states of hydration, the risk of recurrent symptoms can be dramatically reduced 10. In all settings, a search for a possible underlying cause of hyperoxaluria/hypercalciuria should be sought and if present corrected when possible. Larger stones may be treated with extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrostomy
Struvite stones – Struvite stones are usually large (staghorn calculi) and result from infection. These stones need to be treated surgically and the entire stone removed, including small fragments, as otherwise, these residual fragments act as a reservoir for infection and recurrent stone formation.
Uric acid stones – Uric acid stones usually are the result of low urinary pH, and hydration and elevation of urinary pH to approximately 6 are usually sufficient (note rendering the urine too alkali (e.g. pH >6.5) may result in calcium stone formation).
Cystine stones – Cystine stones may be difficult to treat and are difficult to shatter with ESWL. Hydration and alkalinization are usually first-line therapy.
Causes of Nephrolithiasis
There are multiple types of kidney stones; however, 80% of stones are composed of calcium oxalate or phosphate. Other stone types include uric acid (9%), struvite (10%), and cysteine (1%) stones and are significantly less common than stones composed of calcium oxalate or phosphate (80%).[rx] The different types of stones occur due to varying risk factors such as diet, prior personal and family history of stones, environmental factors, medications, and the patient’s medical history.
Common risk factors for stone formation include poor oral fluid intake, high animal-derived protein intake, high oxalate intake (found in foods such as beans, beer, berries, coffee, chocolate, some nuts, some teas, soda, spinach, potatoes), and high salt intake.[rx] Oral hydration is recommended at a rate that produces approximately 2.5 L of urine per day, and acceptable choices for fluids include water, coffee, tea, beer, and low sugar fruit juices except for tomato (high sodium content), grapefruit and cranberry (high oxalate content). Consumption of citrate helps to prevent stone formation as it inhibits crystal aggregation by forming complexes with calcium salts within the urine. 60% of patients with calcium stones have been found to have hypocitraturia.[rx][rx] Low calcium intake has been shown to increase the risk of kidney stone formation, contrary to common belief. Decreased oral calcium intake will reduce calcium levels within the GI tract, which would otherwise be available to bind to oxalate. This, in turn, will increase oxalate absorption and excretion, increasing the risk of stone formation. Vitamin C intake and fish oil have also been shown to increase the risk of calcium stones.
A prior personal and family history of kidney stones will increase the patient’s risk of developing subsequent stones substantially. Procedures such as Roux-en-Y gastric bypass and sleeve gastrectomy have shown a three-fold increase in calcium oxalate stone formation secondary to the malabsorptive post-surgical state, resulting in increased urinary oxalate levels, decreased production of urine, and decreased urine citrate.[rx]
The presence of medical conditions such as chronic kidney disease, hypertension, gout, diabetes mellitus, hyperlipidemia, obesity, endocrine, and malignancies increase the risk of development of kidney stones. Obesity, hyperlipidemia, and type 2 diabetes mellitus have a strong association with calcium oxalate and uric acid stones. Patients with histories of hyperlipidemia, hypertension, and type 2 diabetes mellitus often have diets that are high in animal-derived proteins, salt, and sugar, placing them at higher risk for stone formation. Insulin resistance in obesity and type 2 diabetes mellitus promotes metabolic changes that increase the risk of stone formation secondary to increased urinary calcium and uric acid excretion. A recent study evaluating 4500 patients with a history of kidney stones and insulin resistance showed increased urinary pH and decreased urinary acid excretion, promoting nephrolithiasis/urolithiasis. A prospective, large study followed participants over the years and assessed initial weight, weight gain, dietary exposure, BMI, and waist circumference and strongly showed that while increased BMI does raise the risk of symptomatic stone formation, increased weight due to adiposity in adulthood plays a very key role.[rx][rx]
Drug-induced urolithiasis is rare, and only compromises 2% of stones. Common drugs include protease inhibitors used for the treatment of HIV (atazanavir and indinavir) and sulfadiazine. Protease inhibitor stones are poorly visualized on unenhanced CT scans and are gelatinous in material, making them often unsusceptible to lithotripsy. They typically cause a high-grade urinary obstruction requiring ureteral stenting.[rx] Ceftriaxone has been shown to increase the risk of stone formation in patients who are on long-term therapy.[rx]
Certain risk factors have been identified including
low fluid intake
urinary tract malformations:
Horseshoe kidney
duplex collecting system
urinary tract infections
especially with urease producing bacteria (see below)
urease hydrolyzes urea to ammonium thus increasing urinary pH
cystinuria: congenital disorder
hypercalciuria: most common metabolic abnormality
high sodium intake
primary hyperparathyroidism
hypervitaminosis D
Cushing syndrome
sarcoidosis
milk-alkali syndrome
hyperoxaluria
high dietary oxalate (vegetarians)
low gut absorption of calcium, leading to increased absorption of oxalate
Most renal calculi contain calcium, usually in the form of calcium oxalate (CaC2O4) and often mixed with calcium phosphate (CaPO4). In most instances, no specific cause can be identified, although most patients have idiopathic hypercalciuria without hypercalcemia.
Brushite is a unique form of calcium phosphate stones that tends to recur quickly if patients are not treated aggressively with stone prevention measures and are resistant to treatment with shock wave lithotripsy.
Interestingly hyperuricosuria is also associated with the increased calcium-containing stone formation and is thought to be related to the uric acid crystals acting as a nidus on which calcium oxalate and calcium phosphate can precipitate.
Rarely the underlying cause is primary oxaluria, a liver enzyme deficiency leading to massive cortical and medullary nephrocalcinosis, and renal failure.
Certain medications can predispose to calcium oxalate or calcium phosphate calculi, including:
loop diuretics
acetazolamide
topiramate
zonisamide
Struvite stones
Struvite (magnesium ammonium phosphate or “triple phosphate”) stones are usually seen in the setting of infection with urease-producing bacteria (e.g. Proteus, Klebsiella, Pseudomonas, and Enterobacter), resulting in hydrolysis of urea into ammonium and increase in the urinary pH.
They can grow very large and form a cast of the renal pelvis and calyces resulting in so-called staghorn calculi. The struvite accounts for ~70% of these calculi and is usually mixed with calcium phosphate thus rendering them radiopaque. Uric acid and cystine are also found as minor components.
Uric acid
Hyperuricosuria is not always associated with hyperuricemia and is seen in a variety of settings (see above), although in most instances uric acid stones occur in patients with no identifiable underlying etiology. Uric acid crystals form and remain insoluble at acidic urinary pH.
Cystine stones
Cystine stones are also formed in acidic urine and are seen in patients with congenital cystinuria.
Others
Medication stones
indinavir stones are typically radiolucent
indinavir is a protease inhibitor, a class of antiretroviral drugs used in HIV treatment
the formation of renal tract stones has since been described with other members of the protease inhibitor class
magnesium trisilicate stones which are poorly radiopaque
ciprofloxacin stones which are radiolucent
sulphonamides stones which are radiolucent
triamterene stones which are poorly radiopaque
guaifenesin/ephedrine stones which are radiolucent
pure/protein matrix stones mostly (~65%) made of organic proteins, carbohydrates, and glucosamines (cf. with other stones which are crystalline with only a minor organic element)
Symptoms of Nephrolithiasis
The exact symptoms of urolithiasis depend on the location and size of the calculi in the urinary system. General signs and symptoms may include:
Renal or ureteral colic
Blood in the urine (hematuria)
Urinary tract infection
Abdominal pain
This pain, known as renal colic, is often described as one of the strongest pain sensations known.[rx]
Renal colic caused by kidney stones is commonly accompanied by urinary urgency, restlessness, hematuria, sweating, nausea, and vomiting.
It typically comes in waves lasting 20 to 60 minutes caused by peristaltic contractions of the ureter as it attempts to expel the stone.[rx]
The classical features of renal colic are sudden severe pain. It is usually caused by stones in the kidney, renal pelvis or ureter, causing dilatation, stretching, and spasm of the ureter.
Pain starts in the loin about the level of the costovertebral angle (but sometimes lower) and moves to the groin, with the tenderness of the loin or renal angle, sometimes with haematuria.
If the stone is high and distends the renal capsule then pain will be in the flank but as it moves down pain will move anteriorly and down towards the groin.
A stone that is moving is often more painful than a stone that is static.
The pain radiates down to the testis, scrotum, labia or anterior thigh.
Whereas the pain of biliary or intestinal colic is intermittent, the pain of renal colic is more constant but there are often periods of relief or just a dull ache before it returns. The pain may change as the stone moves. The patient is often able to point to the place of maximal pain and this has a good correlation with the current site of the stone.
Other symptoms which may be present include:
Rigors and fever.
Dysuria.
Haematuria.
Urinary retention.
Nausea and vomiting.
Stones in the kidneys can obstruct the urinary flow in the kidneys or the ureters, which can lead to severe flank pain and possibly blood in the urine. Stones in the bladder can lead to symptoms such as pain, as well as an increased urge and frequency of urination.
Diagnosis of Nephrolithiasis
History and Physical
Regardless of the type of stone, patients present with a similar array of symptoms, ranging from asymptomatic to critically ill. The presentation includes sudden to gradual onset, unilateral colicky abdominal/flank pain that often waxes/wanes, hematuria (90% microscopic on UA), nausea, vomiting, and fever.
The abdominal exam typically shows a soft, non-distended abdomen. Depending on the location of the pain within the urinary tract, pain can range from flank pain when near the ureteropelvic junction to groin/scrotal/labial pain if the stone is at the ureterovesical junction. Pediatric patients may present with irritability, crying, fevers, and vomiting. Awake and alert patients are often restless due to the pain and shift around incessantly to find a position of comfort.
In severe cases, stones can cause urinary obstruction and/or can become a source of sepsis. In these patients, symptoms are more severe and include mild confusion to obtundation secondary to severe metabolic abnormalities. In patients that do present with severe infection or sepsis, hemodynamic instability is often present.
Lab Test and Imaging
Laboratory investigations typically carried out include[rx]
microscopic examination of the urine, which may show red blood cells, bacteria, leukocytes, urinary casts, and crystals;
urine culture to identify any infecting organisms present in the urinary tract and sensitivity to determine the susceptibility of these organisms to specific antibiotics;
complete blood count, looking for neutrophilia (increased neutrophil granulocyte count) suggestive of bacterial infection, as seen in the setting of struvite stones;
renal function tests to look for abnormally high blood calcium levels (hypercalcemia);
24-hour urine collection to measure total daily urinary volume, magnesium, sodium, uric acid, calcium, citrate, oxalate, and phosphate;
collection of stones (by urinating through a StoneScreen kidney stone collection cup or a simple tea strainer) is useful. Chemical analysis of collected stones can establish their composition, which in turn can help to guide future preventive and therapeutic management.
Appropriate labwork to be ordered in the initial evaluation of a patient with suspected urolithiasis is as follows:
Urine analysis (UA)
It is done with microscopy (can show gross blood or + microscopic hematuria, +/-leukocyte esterase, +/- nitrites +WBC), urine HCG (all women of reproductive age), CBC, CMP, lactic acid, lipase, amylase, blood cultures (if the patient has +SIRS criteria). The choice of imaging modality can be selected using factors such as the patient’s body habitus, pregnant state, cost, and consideration of radiation exposure.
Radiographic features
These depend on the stone composition and vary according to modality. The much greater sensitivity of CT to tissue attenuation means that some stones radiolucent on plain radiography are nonetheless radiopaque on CT.
Plain radiograph
X-ray of kidney, ureter, and bladder (KUB) can be used to assess for radiopaque stones (calcium phosphate and oxalate), but not radiolucent stones (uric acid and cystine), and it has a sensitivity and specificity of 45% and 85%, respectively. Despite low yield in an acute setting, KUB is most helpful in monitoring for stone growth over time.
Calcium-containing stones are radiopaque:
calcium oxalate +/- calcium phosphate
struvite (triple phosphate) – usually opaque but variable
pure calcium phosphate
Lucent stones include:
uric acid
cystine
medication (indinavir is best known) stones
pure matrix stones (although may have a radiodense rim or center)
Fluoroscopy
Intravenous urography (IVU) is a traditional radiographic study of the renal parenchyma, pelvicalyceal system, ureters, and urinary bladder. It involves the administration of intravenous contrast. This exam has been largely replaced by non-contrast CT.
Ultrasound
Renal ultrasound is a method that can be used to assess urolithiasis and is an ideal initial imaging study of choice in pediatric and pregnant patients to avoid radiation.[rx] This form of imaging will identify stones within the kidneys, pyeloureteric, and vesicoureteric junctions, and identify hydronephrosis secondary to obstructive urolithiasis. Doppler jet can also be used to assess urinary flow. The sensitivity and specificity of ureteric stones are 57% and 97.5%. Stones will appear echogenic (bright white) on ultrasound. A large body habitus can significantly limit the visualization of stones. Assessment of the size of the stone can also be operator-dependent.
Ultrasound is frequently the first investigation of the urinary tract, and although by no means as sensitive as CT, it is often able to identify calculi. Small stones and those close to the corticomedullary junction can be difficult to reliably identify. Ultrasound compared to CT KUB reference showed a sensitivity of only 24% in identifying calculi. Nearly 75% of calculi not visualized were <3 mm. Features include
echogenic foci
acoustic shadowing
twinkle artifact on color Doppler
color comet-tail artifact
Pulsed wave (PWD) and color flow Doppler (CFD) are further sonographic modalities that may act as a diagnostic aid, and assess for the presence of complications;
ureteric jets in obstructive uropathy tend to be shorter, slower, and occur less often suggested cutoff values vary; the combination of fewer than 1.5 jets per minute, with peak velocities below 19.5 cm/s and jet durations less than 2.5 seconds have specificities ranging between 87 and 97%
the renal resistive index (RI) is significantly higher in obstructed kidneys contralateral unaffected renal RI comparison useful elevation in RI may precede pelvicalyceal dilation
CT Scan
CT abdomen/pelvis without contrast has become the ideal study of choice to assess for ureterolithiasis if the patient can tolerate radiation, with sensitivity and specificity of 95% and 98%.
It is possible that stones less than 3 mm in size might not be detected, as they may slip through the imaging slices of the CT scanner. CT will provide visualization of every type of stone, except for stones that are formed secondary to HIV medications (protease inhibitors).
CT scan is also useful in that it can help to predict therapeutic response to shock wave lithotripsy, as stones that have higher attenuation on CT will likely require an increased number of shocks and less successful response to the treatment itself.
BMI must be taken into consideration when selecting a standard dose vs. low dose CT scan, and current guidelines state that a low dose CT scan is not recommended for patients with a BMI of more than 30
On CT almost all stones are opaque but vary considerably in density.
calcium oxalate +/- calcium phosphate: 400-600 HU
struvite (triple phosphate): usually opaque but variable
pure calcium phosphate: 400-600 HU
uric acid: 100-200 HU
cystine: opaque
Two radiolucent stones are worth mentioning
medication (protease inhibitor (indinavir)) stones radiolucent and usually undetectable on non-contrast CT characterized on delayed phase as a filling defect in the ureter
pure matrix stones 99% of renal tract calculi are visible on a non-contrast CT. Given that one of the commonest sites for a stone to become lodged is the vesicoureteric junction, some centers perform the study in the prone position to establish if the stone is retained within the intravesical component of the ureter or has already passed into the bladder itself.
Dual-energy CT
Dual-energy CT is a technique allowing the composition of the calculus to be determined, by assessing stone attenuation at two different kVp levels. Each CT vendor has its own algorithms for the use of dual-energy CT for assessing stone composition. Dual-energy CT may be useful in detecting stones concealed by the opacification of the collecting system. Dual-energy CT has also been shown to predict the success of extracorporeal shock wave lithotripsy.
MRI
It is another option for imaging urolithiasis. It is better in sensitivity (82%) and specificity (98%) than ultrasound and KUB but is inferior to CT. MRI is reliable for determining hydronephrosis, but a stone may not always be visualized because it relies on identifying calcifications and signal voids.
The benefit of MRI is that it provides 3D imaging without radiation, and it is a good second-line imaging option for pregnant and pediatric patients to be used adjunctively to ultrasound.
The cons of MRI with respect to the diagnosis of urolithiasis are that it is three times as expensive as CT, time-consuming, and not readily available in the ED where the majority of these patients will present.[rx]
A validated risk assessment tool has been derived and validated called the STONE score, which stratifies patients in a low, moderate, or high probability of having a stone using five criteria; sex, timing origin, nausea, and erythrocytes.[rx]
Treatment of Nephrolithiasis
The treatment of urolithiasis is based upon the patient’s acute presentation and includes both conservative medical therapies and surgical interventions. Often when patients present, pain control is an important intervention. Oral and IV anti-inflammatory medications (NSAIDs) are indicated as first-line treatments for pain. Opioids can be used, but are reserved for refractory pain. IV lidocaine has also been studied as an effective pain control option.[rx] Nausea and vomiting should be treated with IV antiemetic medications such as ondansetron, metoclopramide, promethazine, to name a few. Medical expulsive therapy, or MET, includes alpha-blockers, such as doxazosin and tamsulosin, have been shown to be a useful adjunct to facilitate passage of larger (5-10 mm) stones but has not shown to be beneficial in the passage of smaller ones. IV crystalloid fluids can be given to patients who appear dehydrated due to persistent vomiting, but have not been shown to facilitate stone passage.
Approximately 86% of stones will pass spontaneously within 30-40 days.[rx][rx][rx] Overall, the size of the stone largely contributes to how long the stone will take to pass, and its likelihood of passing spontaneously.
Less than or equal to 2 mm stones, 8 days for mean passage and passage rate of 87%
3 mm stones, 12 days for mean passage and passage rate of 76%
Between 4 – 6 mm, 22 days for mean passage and passage rate of 60%
7 mm stone with a passage rate of 48%
8-9 mm stone with a passage rate of 25%
Patients with urolithiasis can present with varying degrees of illness/complications associated with the condition. Patients with small stones, physiologic bloodwork, no signs of infection, or acute obstruction can be managed using MET.
Patients presenting with large stones, or if the presentation is consistent with acute renal failure, oliguria/anuria, SIRS criteria, associated infection, or a history of the solitary kidney is present, may require urgent/emergent urologic intervention. Intractable pain or vomiting, inability to tolerate oral intake, pregnancy, or pediatric patients may require hospitalization for closer observation.
Further interventions should be discussed with urology emergently, and an appropriate plan of care should be made according to the patient’s risk factors, medical history, acute presentation, and urologist’s comfort and preference. There are various methods of acute urologic interventions, including extracorporeal shockwave lithotripsy (ESWL), flexible ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL).
Flexible URS is the most common method used and involves an endoscopic approach passed through the lower urinary tract system into the ureters and calyces. This technique allows for the visualization of the urinary tract and the retrieval of an obstructing stone.[rx] Flexible ureteroscopy is a good option for lower pole stones between 1.5 and 2 cm in size.[rx] Additionally, it is an ideal choice of treatment for patients taking anticoagulant/antiplatelet medications.
ESWL is a technique in which an x-ray is used to target stone location, and shockwaves from an energy source are used to fragment the stone into smaller pieces that can be passed into the urine. This technique may require to follow up ureteral stent placement to facilitate fragment passage. This technique typically requires IV sedation or general anesthesia but can be performed on an outpatient basis. Cystine stones may be resistant to treatment.
PCNL is often reserved for patients that fail or have contraindications to URS or ESWL. This method is preferred for stones greater than 20 mm in size, staghorn calculi, and stones in patients with a history of chronic kidney disease. Large stones located in the kidney and proximal ureter are often treated using this technique. General or spinal anesthesia is used, and a small puncture wound is placed in the flank skin overlying the stone, followed by a ureteroscope to retrieve the stone. Contraindications to PCNL include current pregnancy, bleeding disorders, and active urinary tract infections.[rx]
Acute renal obstruction with signs of urinary tract infection is a urologic emergency. This will require emergent decompression to prevent permanent renal damage and worsening of infection. The two options currently present for this are indwelling ureteral catheter and placement of a nephrostomy tube.
In patients who have calcium urolithiasis, medications such as thiazide diuretics, citrate salts (potassium citrate), and lifestyle modifications are beneficial in long-term management.[rx] Struvite stones will largely require surgical intervention and close follow-up with urology. The cornerstone of cystine stone urolithiasis is lifestyle modification, including increasing fluid intake to optimize urinary output to ~3 liters per day and minimizing animal protein and sodium intake. Potassium citrate and thiol drugs have also been beneficial in patients with a history of cystine stones. Uric acid stones can be managed with increased fruit, and vegetable intake decreased animal protein intake and initiation of potassium citrate and uric acid lowering medications such as allopurinol to prevent recurrence of stones.[rx]
Outpatient management can be assisted by testing to determine the etiology of urolithiasis which includes testing focused on abnormalities in the serum (serum calcium, phosphorus, oxalate, sulfate, magnesium, citrate, cysteine, ammonium, vitamin D levels, lactate dehydrogenase, and parathyroid hormone) and the urine (urine electrolytes, pH, uric acid, creatinine, and calcium). These tests allow for further stone analysis to improve further management.[rx]
Initial management of acute presentation
Non-steroidal anti-inflammatory drugs (NSAIDs), usually in the form of diclofenac IM or PR, should be offered first-line for the relief of the severe pain of renal colic. NSAIDs are more effective than opioids for this indication and have less tendency to cause nausea. However, if parenteral morphine is required in severe renal colic pain, this works quickly and can provide pain relief in the time taken for an NSAID to work. If opioids are needed then a Cochrane review concluded that it should not be pethidine.
Provide antiemetics and rehydration therapy if needed.
The majority of stones will pass spontaneously but may take 1-3 weeks; patients who have not passed a stone or who have continuing symptoms should have the progress of the stone monitored at a minimum of weekly intervals to assess the progression of the stone.
Conservative management may be continued for up to three weeks unless the patient is unable to manage the pain, or if he or she develops signs of infection or obstruction.
Medical expulsive therapy may be used to facilitate the passage of the stone. It is useful in cases where there is no obvious reason for immediate surgical removal. Calcium-channel blockers (eg, nifedipine) or alpha-blockers (eg, tamsulosin) are given. A corticosteroid such as prednisolone is occasionally added when an alpha-blocker is used but should not be given as monotherapy.[rx]
Managing patients at home
All patients managed at home should drink a lot of fluids and, if possible, void urine into a container or through a tea strainer or gauze to catch any identifiable calculus.
Analgesia: paracetamol is safe and effective for mild-to-moderate pain; codeine can be added if more pain relief is required. Paracetamol and codeine should be prescribed separately so they can be individually titrated.
Patients managed at home should be offered fast-track investigation initiated by the hospital on receipt of a letter or email completed by the general practitioner.
Patients should ideally receive an appointment for radiology within seven days of the onset of symptoms.
An urgent urology outpatient appointment should be arranged for within one week if renal imaging shows a problem requiring intervention.
Slaked lime
It decreases urinary calcium when combined with food rich in oxalic acid such as green leafy vegetables.[rx]
Diuretics
One of the recognized medical therapies for the prevention of stones is thiazide and thiazide-like diuretics, such as chlorthalidone or indapamide. These drugs inhibit the formation of calcium-containing stones by reducing urinary calcium excretion.[rx] Sodium restriction is necessary for the clinical effect of thiazides, as sodium excess promotes calcium excretion. Thiazides work best for renal leak hypercalciuria (high urine calcium levels), a condition in which high urinary calcium levels are caused by a primary kidney defect. Thiazides are useful for treating absorptive hypercalciuria, a condition in which high urinary calcium is a result of excess absorption from the gastrointestinal tract.[rx]
Allopurinol
For people with hyperuricosuria and calcium stones, allopurinol is one of the few treatments that have been shown to reduce kidney stone recurrences. Allopurinol interferes with the production of uric acid in the liver. The drug is also used in people with gout or hyperuricemia (high serum uric acid levels).[rx] Dosage is adjusted to maintain a reduced urinary excretion of uric acid. Serum uric acid level at or below 6 mg/100 ml) is often a therapeutic goal. Hyperuricemia is not necessary for the formation of uric acid stones; hyperuricosuria can occur in the presence of normal or even low serum uric acid. Some practitioners advocate adding allopurinol only in people in whom hyperuricosuria and hyperuricemia persist, despite the use of a urine-alkalinizing agent such as sodium bicarbonate or potassium citrate.[rx]
Surgery
Most stones under 5 mm (0.2 in) pass spontaneously.[rx][rx] Prompt surgery may, nonetheless, be required in persons with only one working kidney, bilateral obstructing stones, a urinary tract infection, and thus, it is presumed, an infected kidney, or intractable pain.[rx] Beginning in the mid-1980s, less invasive treatments such as extracorporeal shock wave lithotripsy, ureteroscopy, and percutaneous nephrolithotomy began to replace open surgery as the modalities of choice for the surgical management of urolithiasis.[rx] More recently, flexible ureteroscopy has been adapted to facilitate retrograde nephrostomy creation for percutaneous nephrolithotomy. This approach is still under investigation, though early results are favorable.[rx] Percutaneous nephrolithotomy or, rarely, atrophic nephrolithotomy, is the treatment of choice for large or complicated stones (such as calyceal staghorn calculi) or stones that cannot be extracted using less invasive procedures.[rx][rx]
Procedures to remove stones include
Extracorporeal shock wave lithotripsy (ESWL) – shock waves are directed over the stone to break it apart. The stone particles will then pass spontaneously.
Percutaneous nephrolithotomy (PCNL) – used for large stones (>2 cm), staghorn calculi and also cystine stones. Stones are removed at the time of the procedure using a nephroscope.
Ureteroscopy – this involves the use of laser to break up the stone and has an excellent success rate in experienced hands.
Open surgery – rarely necessary and usually reserved for complicated cases or for those in whom all the above have failed – eg, multiple stones.
Several options are available for the treatment of bladder stones. The percutaneous approach has lower morbidity, with similar results to transurethral surgery while ESWL has the lowest rate of elimination of bladder stones and is reserved for patients at high surgical risk.
Ureteroscopic surgery
Ureteroscopy has become increasingly popular as flexible and rigid fiberoptic ureteroscopes have become smaller. One ureteroscopic technique involves the placement of a ureteral stent (a small tube extending from the bladder, up the ureter and into the kidney) to provide immediate relief of an obstructed kidney. Stent placement can be useful for saving a kidney at risk for postrenal acute kidney failure due to the increased hydrostatic pressure, swelling and infection (pyelonephritis and pyonephrosis) caused by an obstructing stone. Ureteral stents vary in length from 24 to 30 cm (9.4 to 11.8 in) and most have a shape commonly referred to as a “double-J” or “double pigtail”, because of the curl at both ends. They are designed to allow urine to flow past an obstruction in the ureter. They may be retained in the ureter for days to weeks as infections resolve and as stones are dissolved or fragmented by ESWL or by some other treatment. The stents dilate the ureters, which can facilitate instrumentation, and they also provide a clear landmark to aid in the visualization of the ureters and any associated stones on radiographic examinations. The presence of indwelling ureteral stents may cause minimal to moderate discomfort, frequency or urgency incontinence, and infection, which in general resolves on removal. Most ureteral stents can be removed cystoscopically during an office visit under topical anesthesia after resolution of urolithiasis.[rx] Research is currently uncertain if placing a temporary stent during ureteroscopy leads to different outcomes than not placing a stent in terms of a number of hospital visits for post-operative problems, short or long term pain, need for narcotic pain medication, risk of UTI, need for a repeat procedure or narrowing of the ureter from scarring.[rx]
More definitive ureteroscopic techniques for stone extraction (rather than simply bypassing the obstruction) include basket extraction and ultrasound ureterolithotripsy. Laser lithotripsy is another technique, which involves the use of a holmium yttrium aluminum garnet (Ho: YAG) laser to fragment stones in the bladder, ureters, and kidneys.[rx]
Ureteroscopic techniques are generally more effective than ESWL for treating stones located in the lower ureter, with success rates of 93–100% using Ho YAG laser lithotripsy.[rx] Although ESWL has been traditionally preferred by many practitioners for treating stones located in the upper ureter, more recent experience suggests ureteroscopic techniques offer distinct advantages in the treatment of upper ureteral stones. Specifically, the overall success rate is higher, fewer repeat interventions and postoperative visits are needed, and treatment costs are lower after ureteroscopic treatment when compared with ESWL. These advantages are especially apparent with stones greater than 10 mm (0.4 in) in diameter. However, because ureteroscopy of the upper ureter is much more challenging than ESWL, many urologists still prefer to use ESWL as a first-line treatment for stones of less than 10 mm, and ureteroscopy for those greater than 10 mm in diameter.[rx] Ureteroscopy is the preferred treatment in pregnant and morbidly obese people, as well as those with bleeding disorders.[rx]
Prevention
Recurrence of renal stones is common and therefore patients who have had a renal stone should be advised to adapt and adopt several lifestyle measures which will help to prevent or delay recurrence:
Increase fluid intake to maintain urine output at 2-3 litres per day.
Reduce salt intake.
Reduce the amount of meat and animal protein eaten.
Reduce oxalate intake (foods rich in oxalate include chocolate, rhubarb, nuts) and urate-rich foods (eg, offal and certain fish).
Drink regular cranberry juice: increases citrate excretion and reduces oxalate and phosphate excretion.
Maintain calcium intake at normal levels (lowering intake increases excretion of calcium oxalate).
Depending on the composition of the stone, medication to prevent further stone formation is sometimes given – eg, thiazide diuretics (for calcium stones), allopurinol (for uric acid stones) and calcium citrate (for oxalate stones).
Urolithiasis is a term used to describe calculi or stones that form the urinary tract. This condition involves the formation of calcifications in the urinary system, usually in the kidneys or ureters, but may also affect the bladder and/or urethra.
Urolithiasis is a common condition, and it accounts for a large number of hospital visits. It is frequently preventable by modification of risk factors and has numerous treatment options. This activity outlines the etiology, management, and treatment of urolithiasis and highlights the role of the interprofessional team in evaluating and treating patients with this condition.
Renal stones are formed within the kidneys, and this is called nephrolithiasis. Urolithiasis is a condition that occurs when these stones exit the renal pelvis and move into the remainder of the urinary collecting system, which includes the ureters, bladder, and urethra. Many patients with urolithiasis can be managed with expectant management, analgesic, and anti-emetic medications; however, stones that are associated with obstruction, renal failure, and infection require further increasingly critical interventions.[rx]
Types of Urolithiasis
Calcium stones – Small asymptomatic stones in the kidney can be safely ignored, and if patients maintain good states of hydration, the risk of recurrent symptoms can be dramatically reduced 10. In all settings, a search for a possible underlying cause of hyperoxaluria/hypercalciuria should be sought and if present corrected when possible. Larger stones may be treated with extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrostomy
Struvite stones – Struvite stones are usually large (staghorn calculi) and result from infection. These stones need to be treated surgically and the entire stone removed, including small fragments, as otherwise, these residual fragments act as a reservoir for infection and recurrent stone formation.
Uric acid stones – Uric acid stones usually are the result of low urinary pH, and hydration and elevation of urinary pH to approximately 6 are usually sufficient (note rendering the urine too alkali (e.g. pH >6.5) may result in calcium stone formation).
Cystine stones – Cystine stones may be difficult to treat and are difficult to shatter with ESWL. Hydration and alkalinization are usually first-line therapy.
Causes of Urolithiasis
There are multiple types of kidney stones; however, 80% of stones are composed of calcium oxalate or phosphate. Other stone types include uric acid (9%), struvite (10%), and cysteine (1%) stones and are significantly less common than stones composed of calcium oxalate or phosphate (80%).[rx] The different types of stones occur due to varying risk factors such as diet, prior personal and family history of stones, environmental factors, medications, and the patient’s medical history.
Common risk factors for stone formation include poor oral fluid intake, high animal-derived protein intake, high oxalate intake (found in foods such as beans, beer, berries, coffee, chocolate, some nuts, some teas, soda, spinach, potatoes), and high salt intake.[rx] Oral hydration is recommended at a rate that produces approximately 2.5 L of urine per day, and acceptable choices for fluids include water, coffee, tea, beer, and low sugar fruit juices except for tomato (high sodium content), grapefruit and cranberry (high oxalate content). Consumption of citrate helps to prevent stone formation as it inhibits crystal aggregation by forming complexes with calcium salts within the urine. 60% of patients with calcium stones have been found to have hypocitraturia.[rx][rx] Low calcium intake has been shown to increase the risk of kidney stone formation, contrary to common belief. Decreased oral calcium intake will reduce calcium levels within the GI tract, which would otherwise be available to bind to oxalate. This, in turn, will increase oxalate absorption and excretion, increasing the risk of stone formation. Vitamin C intake and fish oil have also been shown to increase the risk of calcium stones.
A prior personal and family history of kidney stones will increase the patient’s risk of developing subsequent stones substantially. Procedures such as Roux-en-Y gastric bypass and sleeve gastrectomy have shown a three-fold increase in calcium oxalate stone formation secondary to the malabsorptive post-surgical state, resulting in increased urinary oxalate levels, decreased production of urine, and decreased urine citrate.[rx]
The presence of medical conditions such as chronic kidney disease, hypertension, gout, diabetes mellitus, hyperlipidemia, obesity, endocrine, and malignancies increase the risk of development of kidney stones. Obesity, hyperlipidemia, and type 2 diabetes mellitus have a strong association with calcium oxalate and uric acid stones. Patients with histories of hyperlipidemia, hypertension, and type 2 diabetes mellitus often have diets that are high in animal-derived proteins, salt, and sugar, placing them at higher risk for stone formation. Insulin resistance in obesity and type 2 diabetes mellitus promotes metabolic changes that increase the risk of stone formation secondary to increased urinary calcium and uric acid excretion. A recent study evaluating 4500 patients with a history of kidney stones and insulin resistance showed increased urinary pH and decreased urinary acid excretion, promoting nephrolithiasis/urolithiasis. A prospective, large study followed participants over the years and assessed initial weight, weight gain, dietary exposure, BMI, and waist circumference and strongly showed that while increased BMI does raise the risk of symptomatic stone formation, increased weight due to adiposity in adulthood plays a very key role.[rx][rx]
Drug-induced urolithiasis is rare, and only compromises 2% of stones. Common drugs include protease inhibitors used for the treatment of HIV (atazanavir and indinavir) and sulfadiazine. Protease inhibitor stones are poorly visualized on unenhanced CT scans and are gelatinous in material, making them often unsusceptible to lithotripsy. They typically cause a high-grade urinary obstruction requiring ureteral stenting.[rx] Ceftriaxone has been shown to increase the risk of stone formation in patients who are on long-term therapy.[rx]
Certain risk factors have been identified including
low fluid intake
urinary tract malformations:
Horseshoe kidney
duplex collecting system
urinary tract infections
especially with urease producing bacteria (see below)
urease hydrolyzes urea to ammonium thus increasing urinary pH
cystinuria: congenital disorder
hypercalciuria: most common metabolic abnormality
high sodium intake
primary hyperparathyroidism
hypervitaminosis D
Cushing syndrome
sarcoidosis
milk-alkali syndrome
hyperoxaluria
high dietary oxalate (vegetarians)
low gut absorption of calcium, leading to increased absorption of oxalate
Most renal calculi contain calcium, usually in the form of calcium oxalate (CaC2O4) and often mixed with calcium phosphate (CaPO4). In most instances, no specific cause can be identified, although most patients have idiopathic hypercalciuria without hypercalcemia.
Brushite is a unique form of calcium phosphate stones that tends to recur quickly if patients are not treated aggressively with stone prevention measures and are resistant to treatment with shock wave lithotripsy.
Interestingly hyperuricosuria is also associated with the increased calcium-containing stone formation and is thought to be related to the uric acid crystals acting as a nidus on which calcium oxalate and calcium phosphate can precipitate.
Rarely the underlying cause is primary oxaluria, a liver enzyme deficiency leading to massive cortical and medullary nephrocalcinosis, and renal failure.
Certain medications can predispose to calcium oxalate or calcium phosphate calculi, including:
loop diuretics
acetazolamide
topiramate
zonisamide
Struvite stones
Struvite (magnesium ammonium phosphate or “triple phosphate”) stones are usually seen in the setting of infection with urease-producing bacteria (e.g. Proteus, Klebsiella, Pseudomonas, and Enterobacter), resulting in hydrolysis of urea into ammonium and increase in the urinary pH.
They can grow very large and form a cast of the renal pelvis and calyces resulting in so-called staghorn calculi. The struvite accounts for ~70% of these calculi and is usually mixed with calcium phosphate thus rendering them radiopaque. Uric acid and cystine are also found as minor components.
Uric acid
Hyperuricosuria is not always associated with hyperuricemia and is seen in a variety of settings (see above), although in most instances uric acid stones occur in patients with no identifiable underlying etiology. Uric acid crystals form and remain insoluble at acidic urinary pH.
Cystine stones
Cystine stones are also formed in acidic urine and are seen in patients with congenital cystinuria.
Others
Medication stones
indinavir stones are typically radiolucent
indinavir is a protease inhibitor, a class of antiretroviral drugs used in HIV treatment
the formation of renal tract stones has since been described with other members of the protease inhibitor class
magnesium trisilicate stones which are poorly radiopaque
ciprofloxacin stones which are radiolucent
sulphonamides stones which are radiolucent
triamterene stones which are poorly radiopaque
guaifenesin/ephedrine stones which are radiolucent
pure/protein matrix stones mostly (~65%) made of organic proteins, carbohydrates, and glucosamines (cf. with other stones which are crystalline with only a minor organic element)
Symptoms of Urolithiasis
The exact symptoms of urolithiasis depend on the location and size of the calculi in the urinary system. General signs and symptoms may include:
Renal or ureteral colic
Blood in the urine (hematuria)
Urinary tract infection
Abdominal pain
This pain, known as renal colic, is often described as one of the strongest pain sensations known.[rx]
Renal colic caused by kidney stones is commonly accompanied by urinary urgency, restlessness, hematuria, sweating, nausea, and vomiting.
It typically comes in waves lasting 20 to 60 minutes caused by peristaltic contractions of the ureter as it attempts to expel the stone.[rx]
The classical features of renal colic are sudden severe pain. It is usually caused by stones in the kidney, renal pelvis or ureter, causing dilatation, stretching, and spasm of the ureter.
Pain starts in the loin about the level of the costovertebral angle (but sometimes lower) and moves to the groin, with the tenderness of the loin or renal angle, sometimes with haematuria.
If the stone is high and distends the renal capsule then pain will be in the flank but as it moves down pain will move anteriorly and down towards the groin.
A stone that is moving is often more painful than a stone that is static.
The pain radiates down to the testis, scrotum, labia or anterior thigh.
Whereas the pain of biliary or intestinal colic is intermittent, the pain of renal colic is more constant but there are often periods of relief or just a dull ache before it returns. The pain may change as the stone moves. The patient is often able to point to the place of maximal pain and this has a good correlation with the current site of the stone.
Other symptoms which may be present include:
Rigors and fever.
Dysuria.
Haematuria.
Urinary retention.
Nausea and vomiting.
Stones in the kidneys can obstruct the urinary flow in the kidneys or the ureters, which can lead to severe flank pain and possibly blood in the urine. Stones in the bladder can lead to symptoms such as pain, as well as an increased urge and frequency of urination.
Diagnosis of Urolithiasis
History and Physical
Regardless of the type of stone, patients present with a similar array of symptoms, ranging from asymptomatic to critically ill. The presentation includes sudden to gradual onset, unilateral colicky abdominal/flank pain that often waxes/wanes, hematuria (90% microscopic on UA), nausea, vomiting, and fever.
The abdominal exam typically shows a soft, non-distended abdomen. Depending on the location of the pain within the urinary tract, pain can range from flank pain when near the ureteropelvic junction to groin/scrotal/labial pain if the stone is at the ureterovesical junction. Pediatric patients may present with irritability, crying, fevers, and vomiting. Awake and alert patients are often restless due to the pain and shift around incessantly to find a position of comfort.
In severe cases, stones can cause urinary obstruction and/or can become a source of sepsis. In these patients, symptoms are more severe and include mild confusion to obtundation secondary to severe metabolic abnormalities. In patients that do present with severe infection or sepsis, hemodynamic instability is often present.
Lab Test and Imaging
Laboratory investigations typically carried out include[rx]
microscopic examination of the urine, which may show red blood cells, bacteria, leukocytes, urinary casts, and crystals;
urine culture to identify any infecting organisms present in the urinary tract and sensitivity to determine the susceptibility of these organisms to specific antibiotics;
complete blood count, looking for neutrophilia (increased neutrophil granulocyte count) suggestive of bacterial infection, as seen in the setting of struvite stones;
renal function tests to look for abnormally high blood calcium levels (hypercalcemia);
24-hour urine collection to measure total daily urinary volume, magnesium, sodium, uric acid, calcium, citrate, oxalate, and phosphate;
collection of stones (by urinating through a StoneScreen kidney stone collection cup or a simple tea strainer) is useful. Chemical analysis of collected stones can establish their composition, which in turn can help to guide future preventive and therapeutic management.
Appropriate labwork to be ordered in the initial evaluation of a patient with suspected urolithiasis is as follows:
Urine analysis (UA)
It is done with microscopy (can show gross blood or + microscopic hematuria, +/-leukocyte esterase, +/- nitrites +WBC), urine HCG (all women of reproductive age), CBC, CMP, lactic acid, lipase, amylase, blood cultures (if the patient has +SIRS criteria). The choice of imaging modality can be selected using factors such as the patient’s body habitus, pregnant state, cost, and consideration of radiation exposure.
Radiographic features
These depend on the stone composition and vary according to modality. The much greater sensitivity of CT to tissue attenuation means that some stones radiolucent on plain radiography are nonetheless radiopaque on CT.
Plain radiograph
X-ray of kidney, ureter, and bladder (KUB) can be used to assess for radiopaque stones (calcium phosphate and oxalate), but not radiolucent stones (uric acid and cystine), and it has a sensitivity and specificity of 45% and 85%, respectively. Despite low yield in an acute setting, KUB is most helpful in monitoring for stone growth over time.
Calcium-containing stones are radiopaque:
calcium oxalate +/- calcium phosphate
struvite (triple phosphate) – usually opaque but variable
pure calcium phosphate
Lucent stones include:
uric acid
cystine
medication (indinavir is best known) stones
pure matrix stones (although may have a radiodense rim or center)
Fluoroscopy
Intravenous urography (IVU) is a traditional radiographic study of the renal parenchyma, pelvicalyceal system, ureters, and urinary bladder. It involves the administration of intravenous contrast. This exam has been largely replaced by non-contrast CT.
Ultrasound
Renal ultrasound is a method that can be used to assess urolithiasis and is an ideal initial imaging study of choice in pediatric and pregnant patients to avoid radiation.[rx] This form of imaging will identify stones within the kidneys, pyeloureteric, and vesicoureteric junctions, and identify hydronephrosis secondary to obstructive urolithiasis. Doppler jet can also be used to assess urinary flow. The sensitivity and specificity of ureteric stones are 57% and 97.5%. Stones will appear echogenic (bright white) on ultrasound. A large body habitus can significantly limit the visualization of stones. Assessment of the size of the stone can also be operator-dependent.
Ultrasound is frequently the first investigation of the urinary tract, and although by no means as sensitive as CT, it is often able to identify calculi. Small stones and those close to the corticomedullary junction can be difficult to reliably identify. Ultrasound compared to CT KUB reference showed a sensitivity of only 24% in identifying calculi. Nearly 75% of calculi not visualized were <3 mm. Features include
echogenic foci
acoustic shadowing
twinkle artifact on color Doppler
color comet-tail artifact
Pulsed wave (PWD) and color flow Doppler (CFD) are further sonographic modalities that may act as a diagnostic aid, and assess for the presence of complications;
ureteric jets in obstructive uropathy tend to be shorter, slower, and occur less often suggested cutoff values vary; the combination of fewer than 1.5 jets per minute, with peak velocities below 19.5 cm/s and jet durations less than 2.5 seconds have specificities ranging between 87 and 97%
the renal resistive index (RI) is significantly higher in obstructed kidneys contralateral unaffected renal RI comparison useful elevation in RI may precede pelvicalyceal dilation
CT Scan
CT abdomen/pelvis without contrast has become the ideal study of choice to assess for ureterolithiasis if the patient can tolerate radiation, with sensitivity and specificity of 95% and 98%.
It is possible that stones less than 3 mm in size might not be detected, as they may slip through the imaging slices of the CT scanner. CT will provide visualization of every type of stone, except for stones that are formed secondary to HIV medications (protease inhibitors).
CT scan is also useful in that it can help to predict therapeutic response to shock wave lithotripsy, as stones that have higher attenuation on CT will likely require an increased number of shocks and less successful response to the treatment itself.
BMI must be taken into consideration when selecting a standard dose vs. low dose CT scan, and current guidelines state that a low dose CT scan is not recommended for patients with a BMI of more than 30
On CT almost all stones are opaque but vary considerably in density.
calcium oxalate +/- calcium phosphate: 400-600 HU
struvite (triple phosphate): usually opaque but variable
pure calcium phosphate: 400-600 HU
uric acid: 100-200 HU
cystine: opaque
Two radiolucent stones are worth mentioning
medication (protease inhibitor (indinavir)) stones radiolucent and usually undetectable on non-contrast CT characterized on delayed phase as a filling defect in the ureter
pure matrix stones 99% of renal tract calculi are visible on a non-contrast CT. Given that one of the commonest sites for a stone to become lodged is the vesicoureteric junction, some centers perform the study in the prone position to establish if the stone is retained within the intravesical component of the ureter or has already passed into the bladder itself.
Dual-energy CT
Dual-energy CT is a technique allowing the composition of the calculus to be determined, by assessing stone attenuation at two different kVp levels. Each CT vendor has its own algorithms for the use of dual-energy CT for assessing stone composition. Dual-energy CT may be useful in detecting stones concealed by the opacification of the collecting system. Dual-energy CT has also been shown to predict the success of extracorporeal shock wave lithotripsy.
MRI
It is another option for imaging urolithiasis. It is better in sensitivity (82%) and specificity (98%) than ultrasound and KUB but is inferior to CT. MRI is reliable for determining hydronephrosis, but a stone may not always be visualized because it relies on identifying calcifications and signal voids.
The benefit of MRI is that it provides 3D imaging without radiation, and it is a good second-line imaging option for pregnant and pediatric patients to be used adjunctively to ultrasound.
The cons of MRI with respect to the diagnosis of urolithiasis are that it is three times as expensive as CT, time-consuming, and not readily available in the ED where the majority of these patients will present.[rx]
A validated risk assessment tool has been derived and validated called the STONE score, which stratifies patients in a low, moderate, or high probability of having a stone using five criteria; sex, timing origin, nausea, and erythrocytes.[rx]
Treatment of Urolithiasis
The treatment of urolithiasis is based upon the patient’s acute presentation and includes both conservative medical therapies and surgical interventions. Often when patients present, pain control is an important intervention. Oral and IV anti-inflammatory medications (NSAIDs) are indicated as first-line treatments for pain. Opioids can be used, but are reserved for refractory pain. IV lidocaine has also been studied as an effective pain control option.[rx] Nausea and vomiting should be treated with IV antiemetic medications such as ondansetron, metoclopramide, promethazine, to name a few. Medical expulsive therapy, or MET, includes alpha-blockers, such as doxazosin and tamsulosin, have been shown to be a useful adjunct to facilitate passage of larger (5-10 mm) stones but has not shown to be beneficial in the passage of smaller ones. IV crystalloid fluids can be given to patients who appear dehydrated due to persistent vomiting, but have not been shown to facilitate stone passage.
Approximately 86% of stones will pass spontaneously within 30-40 days.[rx][rx][rx] Overall, the size of the stone largely contributes to how long the stone will take to pass, and its likelihood of passing spontaneously.
Less than or equal to 2 mm stones, 8 days for mean passage and passage rate of 87%
3 mm stones, 12 days for mean passage and passage rate of 76%
Between 4 – 6 mm, 22 days for mean passage and passage rate of 60%
7 mm stone with a passage rate of 48%
8-9 mm stone with a passage rate of 25%
Patients with urolithiasis can present with varying degrees of illness/complications associated with the condition. Patients with small stones, physiologic bloodwork, no signs of infection, or acute obstruction can be managed using MET.
Patients presenting with large stones, or if the presentation is consistent with acute renal failure, oliguria/anuria, SIRS criteria, associated infection, or a history of the solitary kidney is present, may require urgent/emergent urologic intervention. Intractable pain or vomiting, inability to tolerate oral intake, pregnancy, or pediatric patients may require hospitalization for closer observation.
Further interventions should be discussed with urology emergently, and an appropriate plan of care should be made according to the patient’s risk factors, medical history, acute presentation, and urologist’s comfort and preference. There are various methods of acute urologic interventions, including extracorporeal shockwave lithotripsy (ESWL), flexible ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL).
Flexible URS is the most common method used and involves an endoscopic approach passed through the lower urinary tract system into the ureters and calyces. This technique allows for the visualization of the urinary tract and the retrieval of an obstructing stone.[rx] Flexible ureteroscopy is a good option for lower pole stones between 1.5 and 2 cm in size.[rx] Additionally, it is an ideal choice of treatment for patients taking anticoagulant/antiplatelet medications.
ESWL is a technique in which an x-ray is used to target stone location, and shockwaves from an energy source are used to fragment the stone into smaller pieces that can be passed into the urine. This technique may require to follow up ureteral stent placement to facilitate fragment passage. This technique typically requires IV sedation or general anesthesia but can be performed on an outpatient basis. Cystine stones may be resistant to treatment.
PCNL is often reserved for patients that fail or have contraindications to URS or ESWL. This method is preferred for stones greater than 20 mm in size, staghorn calculi, and stones in patients with a history of chronic kidney disease. Large stones located in the kidney and proximal ureter are often treated using this technique. General or spinal anesthesia is used, and a small puncture wound is placed in the flank skin overlying the stone, followed by a ureteroscope to retrieve the stone. Contraindications to PCNL include current pregnancy, bleeding disorders, and active urinary tract infections.[rx]
Acute renal obstruction with signs of urinary tract infection is a urologic emergency. This will require emergent decompression to prevent permanent renal damage and worsening of infection. The two options currently present for this are indwelling ureteral catheter and placement of a nephrostomy tube.
In patients who have calcium urolithiasis, medications such as thiazide diuretics, citrate salts (potassium citrate), and lifestyle modifications are beneficial in long-term management.[rx] Struvite stones will largely require surgical intervention and close follow-up with urology. The cornerstone of cystine stone urolithiasis is lifestyle modification, including increasing fluid intake to optimize urinary output to ~3 liters per day and minimizing animal protein and sodium intake. Potassium citrate and thiol drugs have also been beneficial in patients with a history of cystine stones. Uric acid stones can be managed with increased fruit, and vegetable intake decreased animal protein intake and initiation of potassium citrate and uric acid lowering medications such as allopurinol to prevent recurrence of stones.[rx]
Outpatient management can be assisted by testing to determine the etiology of urolithiasis which includes testing focused on abnormalities in the serum (serum calcium, phosphorus, oxalate, sulfate, magnesium, citrate, cysteine, ammonium, vitamin D levels, lactate dehydrogenase, and parathyroid hormone) and the urine (urine electrolytes, pH, uric acid, creatinine, and calcium). These tests allow for further stone analysis to improve further management.[rx]
Initial management of acute presentation
Non-steroidal anti-inflammatory drugs (NSAIDs), usually in the form of diclofenac IM or PR, should be offered first-line for the relief of the severe pain of renal colic. NSAIDs are more effective than opioids for this indication and have less tendency to cause nausea. However, if parenteral morphine is required in severe renal colic pain, this works quickly and can provide pain relief in the time taken for an NSAID to work. If opioids are needed then a Cochrane review concluded that it should not be pethidine.
Provide antiemetics and rehydration therapy if needed.
The majority of stones will pass spontaneously but may take 1-3 weeks; patients who have not passed a stone or who have continuing symptoms should have the progress of the stone monitored at a minimum of weekly intervals to assess the progression of the stone.
Conservative management may be continued for up to three weeks unless the patient is unable to manage the pain, or if he or she develops signs of infection or obstruction.
Medical expulsive therapy may be used to facilitate the passage of the stone. It is useful in cases where there is no obvious reason for immediate surgical removal. Calcium-channel blockers (eg, nifedipine) or alpha-blockers (eg, tamsulosin) are given. A corticosteroid such as prednisolone is occasionally added when an alpha-blocker is used but should not be given as monotherapy.[rx]
Managing patients at home
All patients managed at home should drink a lot of fluids and, if possible, void urine into a container or through a tea strainer or gauze to catch any identifiable calculus.
Analgesia: paracetamol is safe and effective for mild-to-moderate pain; codeine can be added if more pain relief is required. Paracetamol and codeine should be prescribed separately so they can be individually titrated.
Patients managed at home should be offered fast-track investigation initiated by the hospital on receipt of a letter or email completed by the general practitioner.
Patients should ideally receive an appointment for radiology within seven days of the onset of symptoms.
An urgent urology outpatient appointment should be arranged for within one week if renal imaging shows a problem requiring intervention.
Slaked lime
It decreases urinary calcium when combined with food rich in oxalic acid such as green leafy vegetables.[rx]
Diuretics
One of the recognized medical therapies for the prevention of stones is thiazide and thiazide-like diuretics, such as chlorthalidone or indapamide. These drugs inhibit the formation of calcium-containing stones by reducing urinary calcium excretion.[rx] Sodium restriction is necessary for the clinical effect of thiazides, as sodium excess promotes calcium excretion. Thiazides work best for renal leak hypercalciuria (high urine calcium levels), a condition in which high urinary calcium levels are caused by a primary kidney defect. Thiazides are useful for treating absorptive hypercalciuria, a condition in which high urinary calcium is a result of excess absorption from the gastrointestinal tract.[rx]
Allopurinol
For people with hyperuricosuria and calcium stones, allopurinol is one of the few treatments that have been shown to reduce kidney stone recurrences. Allopurinol interferes with the production of uric acid in the liver. The drug is also used in people with gout or hyperuricemia (high serum uric acid levels).[rx] Dosage is adjusted to maintain a reduced urinary excretion of uric acid. Serum uric acid level at or below 6 mg/100 ml) is often a therapeutic goal. Hyperuricemia is not necessary for the formation of uric acid stones; hyperuricosuria can occur in the presence of normal or even low serum uric acid. Some practitioners advocate adding allopurinol only in people in whom hyperuricosuria and hyperuricemia persist, despite the use of a urine-alkalinizing agent such as sodium bicarbonate or potassium citrate.[rx]
Surgery
Most stones under 5 mm (0.2 in) pass spontaneously.[rx][rx] Prompt surgery may, nonetheless, be required in persons with only one working kidney, bilateral obstructing stones, a urinary tract infection, and thus, it is presumed, an infected kidney, or intractable pain.[rx] Beginning in the mid-1980s, less invasive treatments such as extracorporeal shock wave lithotripsy, ureteroscopy, and percutaneous nephrolithotomy began to replace open surgery as the modalities of choice for the surgical management of urolithiasis.[rx] More recently, flexible ureteroscopy has been adapted to facilitate retrograde nephrostomy creation for percutaneous nephrolithotomy. This approach is still under investigation, though early results are favorable.[rx] Percutaneous nephrolithotomy or, rarely, atrophic nephrolithotomy, is the treatment of choice for large or complicated stones (such as calyceal staghorn calculi) or stones that cannot be extracted using less invasive procedures.[rx][rx]
Procedures to remove stones include
Extracorporeal shock wave lithotripsy (ESWL) – shock waves are directed over the stone to break it apart. The stone particles will then pass spontaneously.
Percutaneous nephrolithotomy (PCNL) – used for large stones (>2 cm), staghorn calculi and also cystine stones. Stones are removed at the time of the procedure using a nephroscope.
Ureteroscopy – this involves the use of laser to break up the stone and has an excellent success rate in experienced hands.
Open surgery – rarely necessary and usually reserved for complicated cases or for those in whom all the above have failed – eg, multiple stones.
Several options are available for the treatment of bladder stones. The percutaneous approach has lower morbidity, with similar results to transurethral surgery while ESWL has the lowest rate of elimination of bladder stones and is reserved for patients at high surgical risk.
Ureteroscopic surgery
Ureteroscopy has become increasingly popular as flexible and rigid fiberoptic ureteroscopes have become smaller. One ureteroscopic technique involves the placement of a ureteral stent (a small tube extending from the bladder, up the ureter and into the kidney) to provide immediate relief of an obstructed kidney. Stent placement can be useful for saving a kidney at risk for postrenal acute kidney failure due to the increased hydrostatic pressure, swelling and infection (pyelonephritis and pyonephrosis) caused by an obstructing stone. Ureteral stents vary in length from 24 to 30 cm (9.4 to 11.8 in) and most have a shape commonly referred to as a “double-J” or “double pigtail”, because of the curl at both ends. They are designed to allow urine to flow past an obstruction in the ureter. They may be retained in the ureter for days to weeks as infections resolve and as stones are dissolved or fragmented by ESWL or by some other treatment. The stents dilate the ureters, which can facilitate instrumentation, and they also provide a clear landmark to aid in the visualization of the ureters and any associated stones on radiographic examinations. The presence of indwelling ureteral stents may cause minimal to moderate discomfort, frequency or urgency incontinence, and infection, which in general resolves on removal. Most ureteral stents can be removed cystoscopically during an office visit under topical anesthesia after resolution of urolithiasis.[rx] Research is currently uncertain if placing a temporary stent during ureteroscopy leads to different outcomes than not placing a stent in terms of a number of hospital visits for post-operative problems, short or long term pain, need for narcotic pain medication, risk of UTI, need for a repeat procedure or narrowing of the ureter from scarring.[rx]
More definitive ureteroscopic techniques for stone extraction (rather than simply bypassing the obstruction) include basket extraction and ultrasound ureterolithotripsy. Laser lithotripsy is another technique, which involves the use of a holmium yttrium aluminum garnet (Ho: YAG) laser to fragment stones in the bladder, ureters, and kidneys.[rx]
Ureteroscopic techniques are generally more effective than ESWL for treating stones located in the lower ureter, with success rates of 93–100% using Ho YAG laser lithotripsy.[rx] Although ESWL has been traditionally preferred by many practitioners for treating stones located in the upper ureter, more recent experience suggests ureteroscopic techniques offer distinct advantages in the treatment of upper ureteral stones. Specifically, the overall success rate is higher, fewer repeat interventions and postoperative visits are needed, and treatment costs are lower after ureteroscopic treatment when compared with ESWL. These advantages are especially apparent with stones greater than 10 mm (0.4 in) in diameter. However, because ureteroscopy of the upper ureter is much more challenging than ESWL, many urologists still prefer to use ESWL as a first-line treatment for stones of less than 10 mm, and ureteroscopy for those greater than 10 mm in diameter.[rx] Ureteroscopy is the preferred treatment in pregnant and morbidly obese people, as well as those with bleeding disorders.[rx]
Prevention
Recurrence of renal stones is common and therefore patients who have had a renal stone should be advised to adapt and adopt several lifestyle measures which will help to prevent or delay recurrence:
Increase fluid intake to maintain urine output at 2-3 litres per day.
Reduce salt intake.
Reduce the amount of meat and animal protein eaten.
Reduce oxalate intake (foods rich in oxalate include chocolate, rhubarb, nuts) and urate-rich foods (eg, offal and certain fish).
Drink regular cranberry juice: increases citrate excretion and reduces oxalate and phosphate excretion.
Maintain calcium intake at normal levels (lowering intake increases excretion of calcium oxalate).
Depending on the composition of the stone, medication to prevent further stone formation is sometimes given – eg, thiazide diuretics (for calcium stones), allopurinol (for uric acid stones) and calcium citrate (for oxalate stones).
Kidney Calculi are a common cause of blood in the urine (hematuria) and pain in the abdomen, flank, or groin. They occur in one in 11 people at some time in their lifetimes with men affected 2 to 1 over women. Development of the stones is related to decreased urine volume or increased excretion of stone-forming components such as calcium, oxalate, uric acid, cystine, xanthine, and phosphate. Calculi may also be caused by low urinary citrate levels or excessive urinary acidity. This activity reviews the cause, pathophysiology, and presentation of renal calculi and highlights the role of the interprofessional team in its management.
Renal calculi are a common cause of blood in the urine (hematuria) and pain in the abdomen, flank, or groin. They occur in one in 11 people at some time in their lifetimes with men affected 2 to 1 over women. Development of the stones is related to decreased urine volume or increased excretion of stone-forming components such as calcium, oxalate, uric acid, cystine, xanthine, and phosphate. Calculi may also be caused by low urinary citrate levels or excessive urinary acidity.[rx][rx][rx]
Renal calculi present with excruciating pain and most patients present to the emergency department in agony. A single event does not cause kidney failure but recurrent renal calculi can damage the tubular epithelial cells, which can lead to functional loss of the renal parenchyma.
Causes of Kidney Calculi
Urolithiasis occurs when solutes crystallize out of urine to form stones. Urolithiasis may occur due to anatomic features leading to urinary stasis, low urine volume, dietary factors (e.g., high oxalate or high sodium), urinary tract infections, systemic acidosis, medications, or uncommonly genetic factors such as cystinuria. The most common cause of stone disease is inadequate hydration and subsequent low urine volume. The other four most common factors contributing to urinary stone formation are hypercalciuria, hyperoxaluria, hyperuricosuria, and hypocitraturia.[rx][rx]
The four major types of renal calculi include
Calcium stones (due to hyperparathyroidism, renal calcium leak, hyperoxaluria, hypomagnesemia and hypocitraturia)
Uric acid stones are associated with pH less than 5, high intake of purine foods (fish, legumes, meat), or cancer. These stones may also be associated with gout
Struvite stones (caused by gram negative-urease positive organisms that breakdown urea into ammonia. Common organisms include pseudomonas, proteus, and klebsiella. E coli is not associated with struvite stones)
Cystine stones are due to an intrinsic metabolic defect causing the failure of the renal tubules to reabsorb cystine, lysine, ornithine, and arginine.
Many drugs are known to cause stones and include the following:
Atazanavir
Indinavir
Triamterene
Guaifenesin
Overuse of silicate
Sulfonamide
There also appears to be a genetic association to renal calculi. In some families, there may be mutations that cause a defect in the renal tubular handling of calcium and other substrates.
Most urinary stones start as Randall’s plaque at the junction of the nephron’s collecting tubule and the renal pelvis in the papilla. These plaques start suburothelial and then gradually grow until they break through into the renal pelvis. Once in continuous contact with urine, layers of calcium oxalate typically start to form on the calcium phosphate nidus (all Randall’s plaques are composed of calcium phosphate). Calcium oxalate stones tend to form when the urinary pH is under 7.2 while calcium phosphate will form in the more alkaline urine. Hyperparathyroidism and similar metabolic disturbances like renal tubular acidosis typically form stones that are primarily or significantly composed of calcium phosphate. Overly acidic urine is the primary cause of uric acid stones (not hyperuricosuria).[rx][rx]
The majority of renal calculi are made of calcium, followed by urare crystals. Supersaturation of the urine is the common denominator in all cases of renal calculi. In some cases, calcium oxalate stones may deposit in the renal papilla. Calcium phosphate stones usually precipitate in the basement membrane of the thin loop of Henle and may erode into the interstitium. The colicky pain s usually due to the dilatation and spasm of the ureter.
Symptoms of Kidney Calculi
Large calculi remaining in the renal parenchyma or renal collecting system are often asymptomatic unless they cause obstruction and/or infection. Severe pain, often accompanied by nausea and vomiting, usually occurs when calculi pass into the ureter and cause acute obstruction. Sometimes gross hematuria also occurs.
Pain (renal colic) is of variable intensity but is typically excruciating and intermittent, often occurs cyclically, and lasts 20 to 60 minutes. Nausea and vomiting are common. Pain in the flank or kidney area that radiates across the abdomen suggests upper ureteral or renal pelvic obstruction. Pain that radiates along the course of the ureter into the genital region suggests lower ureteral obstruction. Suprapubic pain along with urinary urgency and frequency suggests a distal ureteral, ureterovesical, or bladder calculus.
On examination, patients may be in obvious extreme discomfort, often ashen and diaphoretic. Patients with renal colic may be unable to lie still and may pace, writhe, or constantly shift position. The abdomen may be somewhat tender on the affected side as palpation increases pressure in the already-distended kidney (costovertebral angle tenderness), but peritoneal signs (guarding, rebound, rigidity) are lacking.
For some patients, the first symptom is hematuria or either gravel or calculus in the urine. Other patients may have symptoms of a urinary tract infection, such as fever, dysuria, or cloudy or foul-smelling urine.
Diagnosis of Kidney Calculi
Patients with a stone disease will most commonly present with acute, severe flank pain that will often radiate to the abdomen and especially to the groin, testicle, and labia. It is often sharp and severe in nature. It may also be colicky. The pain is often associated with nausea and vomiting which is due to the embryological origins of the urogenital tract.
Renal colic usually peaks within 90-120 minutes and the pain radiation follows dermatomes T10-S4. The first phase may wake the patient up from sleep and the pain is steady, followed by waves of excruciating pain. The second phase is characterized by constant pain and may last 3-4 hours. The third phase is associated with mild pain relief but waves of pain may still persist. This phase may last 4-16 hours.
If infected, patients may also present with fever, chills, or other systemic signs of infection. This condition, called pyonephrosis or obstructive pyelonephritis, is potentially severe and life-threatening, requiring emergency decompression surgery.[rx]
Patients often present with hematuria as 85% of patients demonstrate at least microscopic hematuria on urinalysis.
The physical exam may reveal costovertebral tenderness and hypoactive bowel sounds. The testis and pubic area may also be tender to touch. Fever is rarely seen in renal colic but the presence of fever, pyuria, and leucocytosis may be indicative of pyelonephritis.
Lab Test and Imaging
A urinalysis should be obtained on every patient with a suspected kidney stone. Hematuria is usually present, but up to 15% of kidney stone patients will not demonstrate even microscopic hematuria. The presence of urinary crystals may suggest urolithiasis. Positive nitrites, leukocytes, and bacteria suggest infection which should be cultured and treated aggressively.[rx]
A KUB can be obtained to screen for the presence of significant nephrolithiasis, but may often miss stones that are small, hidden by bowel or uncalcified. Ultrasound may be very useful for assessing obstruction and resultant hydronephrosis, especially in pregnancy where x-ray studies are discouraged. It can also be used to measure the resistive index which can suggest ureteral obstruction.
Values of 0.70 or less are considered normal while higher values suggest obstructive uropathy. Bilateral high resistive indices suggest medical renal disease while a unilateral high resistive index (0.75 or higher) suggests an obstruction such as from a stone. Once a ureteral stone has been identified, the lower the resistive index, the more likely the stone will pass spontaneously. [rx]
Ultrasound can also identify uric acid and other non-calcific stones if they are large enough (usually greater than 4 mm), but it can also miss the presence of stones that are less than 5 mm.
The most sensitive and reliable test to diagnose urolithiasis is a non-contrast abdominal and pelvic CT scan, which will also provide information regarding obstruction with resultant hydronephrosis or concerns for infection.[rx][rx][rx][rx][rx] Other labs to obtain would include a WBC with differential, and a urine culture if the patient is febrile or has a urinalysis suggestive of a possible infection. The initial use of IV contrast for CT scans in patients with abdominal pain is not recommended. In many cases, an atypical abdominal pain will ultimately turn out to be a kidney stone that has moved or the presence of a urological anatomical variant such as a horseshoe kidney. Even without IV contrast, in most cases, the correct diagnosis can be made. If contrast is absolutely necessary, doing the non-contrast study first eliminates urinary stones from consideration. Certainly, if the urinalysis is abnormal for blood or possible infection, a non-contrast abdominal and pelvic CT should be performed prior to using contrast which will make identification of any urinary stones far more difficult. If this recommendation is not followed, sooner or later contrast will be given to a patient who will ultimately be diagnosed with urinary stones. Obscuring urinary stones with IV contrast can make it much more difficult to determine optimum treatment and possible surgery.[rx][rx][rx][rx][rx]
If the CT is positive for stones, a simultaneous KUB should be done. This will provide information useful in tracking or following the progress of the stone, its degree of calcification, and its shape which cannot always be identified from the CT scan alone.[rx]
Treatment of Kidney Calculi
Many stones may be watched conservatively as an outpatient, with intervention planned as an outpatient. Smaller stones (less than 5 mm) have a greater chance (90%) of passing on their own with medical expulsion therapy (usually tamsulosin, nifedipine or alfuzosin). Any hint of a urinary tract infection should be treated aggressively with antibiotics.[rx][rx][rx]
Acute management requires IV hydration, analgesia, and antiemetic medications. Studies show that desmopressin can lower the pain of renal calculi. Anecdotal reports indicate that the use of calcium channel blockers can provide pain relief due to relaxation of the ureter and helps passage of the stone distally. Others recommend the use of alpha-blockers. The urine should be strained for stones.
There are several cases where urgent intervention is required.
An obstructing stone in a patient with a urinary tract infection, fever or sepsis. (This is called pyonephrosis or obstructive pyelonephritis and requires urgent surgical decompression by urology or interventional radiology)
Nausea or pain uncontrolled with outpatient management
An obstructing stone in a solitary kidney
Any degree of simultaneous bilateral obstruction which can easily lead to renal failure
Any degree of obstruction with a rising creatinine
In the case of urinary tract infection or urosepsis with an obstructing stone, the obstruction should first be relieved with either a ureteral double J stent or nephrostomy tube placement. The decision of which treatment modality is most appropriate should be made by urology. In general, the more severely ill the patient, the greater the benefit from a nephrostomy tube. Definitive stone management can then occur once the infection is no longer active. Morbidly obese patients and those who cannot be safely taken off of their blood thinners may require double J stent, regardless.
Electively, stones can be surgically managed in several ways. Extracorporeal shockwave lithotripsy (ESWL) can be used to break up stones anywhere in the urinary tract but is primarily used in the kidney and upper ureter. Ureteroscopy with laser lithotripsy can be used to manage stones endoscopically and is preferred for ureteral stones in the lower ureter. For large (greater than 2 cm) stones in the renal pelvis, percutaneous nephrolithotomy can be performed.
Once the patient has had his or her acute stone episode treated, it is recommended to evaluate the patient for the underlying cause for their stone episode, particularly if he or she has had stones in the past. This would involve obtaining a basic metabolic panel as well as a 24-hour urine collection for stone prevention analysis. Patients need to understand that this represents a commitment from them to follow a long-term course of therapy for stone prevention and that no treatment plan is foolproof so an occasional stone may still be produced but is much less likely on therapy than off. Physicians evaluating 24-hour kidney stone results should not only look at the normal ranges but also at what may be optimal. For example, in general, optimal 24-hour urinary calcium should be no more than 250 mg, oxalate less than 25 mg, citrate more than 600 mg, urinary volume more than 2,000 cc and urinary uric acid at 600 mg or less. While these levels may not be realistically obtainable in every patient, they are used as goals for treatment where the intention is to get as many chemistry levels optimal as possible even if they are all technically normal.[rx][rx][rx]
Analysis of 24-hour urine tests can be complicated. A companion piece “24 Hour Urine Testing for Nephrolithiasis: Guide to Interpretation” by Leslie S and Bashir K is recommended for more details on 24-hour urine interpretation and preventive therapy.
Admission is recommended in the following cases:
Inadequate pain relief with oral analgesics
Patient with a transplanted kidney and renal calculi
Presence of renal calculi and pyelonephritis
Dissolution therapy
Dissolution therapy does not work for calcium stones but it may be used to manage uric acid and cystine stones. Uric acids can be dissolved by making the urine alkaline with sodium bicarbonate. In addition, allopurinol can be used to reduce uric acid excretion. Thiazide diuretics are recommended for patients with recurrent stones. Cystine stones can be managed with D-penicillamine, aggressive fluid intake, and alkalinization.
Analgesia
Renal colic may be relieved with opioids, such as morphine and, for a rapid onset, fentanyl. Ketorolac 30 mg IV is rapidly effective and nonsedating. Vomiting usually resolves as pain decreases, but persistent vomiting can be treated with an antiemetic (eg, ondansetron 10 mg IV).
Expulsive therapy
Although increasing fluids (either oral or IV) has traditionally been recommended, increased fluid administration has not been proven to speed the passage of calculi. Patients with calculi <1 cm in diameter who have no infection or obstruction, whose pain is controlled with analgesics, and who can tolerate liquids can be treated at home with analgesics and alpha-receptor blockers (eg, tamsulosin 0.4 mg orally once a day) to facilitate calculus passage. Calculi that have not passed within 6 to 8 weeks typically require removal. In patients with suspected infection and obstruction, initial treatment is the relief of obstruction as soon as possible with a cystoscopically placed ureteral stent or percutaneous nephrostomy tube and treatment of the infection followed by removal of calculi as soon as possible.
Calculus removal
The technique used for removal depends on the location and size of the calculus. Techniques include extracorporeal shock wave lithotripsy and, to ensure complete removal or for larger calculi, endoscopic techniques. Endoscopic techniques may involve rigid or flexible ureteroscopes (endoscopes) and may involve direct-vision removal (basketing), fragmentation with some sort of lithotripsy device (eg, pneumatic, ultrasonic, laser), or both. Short-term ureteral stenting (eg, 2 weeks) is commonly used until the resolution of any inflammation or edema caused by the stone or the procedure.
For symptomatic calculi< 1 cm in diameter in the renal collecting system or proximal ureter, shock wave lithotripsy is a reasonable first option for therapy.
For larger calculi or if shock wave lithotripsy is unsuccessful, ureteroscopy (done in a retrograde fashion) with holmium laser lithotripsy is usually used. Sometimes removal is possible using an endoscope inserted anterograde through the kidney. For renal stones >2 cm, percutaneous nephrolithotomy, with insertion of a nephroscope directly into the kidney, is the treatment of choice.
For mid ureteral calculi, ureteroscopy with holmium laser lithotripsy is usually the treatment of choice. Shock wave lithotripsy is an alternative.
For distal ureteral calculi, endoscopic techniques (ureteroscopy), such as direct removal and use of intracorporeal lithotripsy (eg, holmium laser, pneumatic), are considered by many to be the procedures of choice. Shock wave lithotripsy can also be used.
Calculus dissolution
Uric acid calculi in the upper or lower urinary tract occasionally may be dissolved by prolonged alkalinization of the urine with potassium citrate 20 mEq (20 mmol/L) orally 2 to 3 times a day, but the chemical dissolution of calcium calculi is not possible and of cystine calculi is difficult.
Prevention of Urinary Calculi
In a patient who has passed a first calcium calculus, the likelihood of forming the 2nd calculus is about 15% at 1 year, 40% at 5 years, and 80% at 10 years. Drinking large amounts of fluids—8 to 10 ten-ounce (300-milliliter) glasses a day—is recommended for the prevention of all stones. Patients who form stones (those with a history of recurrent stones and those with stones newly diagnosed via imaging) should drink enough fluid to produce at least 2.5 liters of urine daily. Recovery and analysis of the calculus, measurement of calculus-forming substances in the urine, and the clinical history are needed to plan other prophylactic measures.
In < 3% of patients, no metabolic abnormality is found. These patients seemingly cannot tolerate normal amounts of calculus-forming salts in their urine without crystallization. Thiazide diuretics, potassium citrate, and increased fluid intake may reduce their calculus production rate.
For hypercalciuria, patients may receive thiazide diuretics (eg, chlorthalidone 25 mg orally once a day or indapamide 1.25 mg orally once a day) to lower urine calcium excretion and thus prevent urinary supersaturation with calcium oxalate. Patients are encouraged to increase their fluid intake to ≥ 3 L/day. A diet that is low in sodium and high in potassium is recommended. Even with a high potassium intake, supplementation with potassium citrate is recommended to prevent hypokalemia. Restriction of dietary animal protein is also recommended.
For patients with hypocitraturia, potassium citrate (20 mEq [20 mmol/L] orally twice a day) enhances citrate excretion. A normal calcium intake (eg, 1000 mg or about 2 to 3 dairy servings per day) is recommended, and calcium restriction is avoided. Oral orthophosphate has not been thoroughly studied. Alternative alkaline agents (eg, sodium or potassium bicarbonate) can be used to enhance citrate excretion if potassium citrate cannot be tolerated.
Hyperoxaluria prevention varies. Patients with small-bowel disease can be treated with a combination of high fluid intake, calcium loading (usually in the form of calcium citrate 400 mg orally twice a day with meals), cholestyramine, and a low-oxalate, low-fat diet. Hyperoxaluria may respond to pyridoxine 100 to 200 mg orally once a day, possibly by increasing transaminase activity, because this activity is responsible for the conversion of glyoxylate, the immediate oxalate precursor, to glycine.
In hyperuricosuria, intake of animal protein should be reduced. If the diet cannot be changed, allopurinol 300 mg each morning lowers uric acid production. For uric acid calculi, the urine pH must be increased to between 6 and 6.5 by giving an oral alkalinizing drug that contains potassium (eg, potassium citrate 20 mEq [20 mmol/L] twice a day) along with increased fluid intake.
Infection with urea-splitting bacteria requires culture-specific antibiotics and complete removal of all calculi. If eradication of infection is impossible, long-term suppressive therapy (eg, with nitrofurantoin) may be necessary. In addition, acetohydroxamic acid can be used to reduce the recurrence of struvite calculi.
To prevent recurrent cystine calculi, urinary cystine levels must be reduced to < 250 mg cystine/L of urine. Any combination of increasing urine volume along with reducing cystine excretion (eg, with alpha-mercapto propionyl glycine [tiopronin] or penicillamine) should reduce the urinary cystine concentration.
Renal calculi are a common cause of blood in the urine (hematuria) and pain in the abdomen, flank, or groin. They occur in one in 11 people at some time in their lifetimes with men affected 2 to 1 over women. Development of the stones is related to decreased urine volume or increased excretion of stone-forming components such as calcium, oxalate, uric acid, cystine, xanthine, and phosphate. Calculi may also be caused by low urinary citrate levels or excessive urinary acidity. This activity reviews the cause, pathophysiology, and presentation of renal calculi and highlights the role of the interprofessional team in its management.
Renal calculi are a common cause of blood in the urine (hematuria) and pain in the abdomen, flank, or groin. They occur in one in 11 people at some time in their lifetimes with men affected 2 to 1 over women. Development of the stones is related to decreased urine volume or increased excretion of stone-forming components such as calcium, oxalate, uric acid, cystine, xanthine, and phosphate. Calculi may also be caused by low urinary citrate levels or excessive urinary acidity.[rx][rx][rx]
Renal calculi present with excruciating pain and most patients present to the emergency department in agony. A single event does not cause kidney failure but recurrent renal calculi can damage the tubular epithelial cells, which can lead to functional loss of the renal parenchyma.
Causes of Renal Calculi
Urolithiasis occurs when solutes crystallize out of urine to form stones. Urolithiasis may occur due to anatomic features leading to urinary stasis, low urine volume, dietary factors (e.g., high oxalate or high sodium), urinary tract infections, systemic acidosis, medications, or uncommonly genetic factors such as cystinuria. The most common cause of stone disease is inadequate hydration and subsequent low urine volume. The other four most common factors contributing to urinary stone formation are hypercalciuria, hyperoxaluria, hyperuricosuria, and hypocitraturia.[rx][rx]
The four major types of renal calculi include
Calcium stones (due to hyperparathyroidism, renal calcium leak, hyperoxaluria, hypomagnesemia and hypocitraturia)
Uric acid stones are associated with pH less than 5, high intake of purine foods (fish, legumes, meat), or cancer. These stones may also be associated with gout
Struvite stones (caused by gram negative-urease positive organisms that breakdown urea into ammonia. Common organisms include pseudomonas, proteus, and klebsiella. E coli is not associated with struvite stones)
Cystine stones are due to an intrinsic metabolic defect causing the failure of the renal tubules to reabsorb cystine, lysine, ornithine, and arginine.
Many drugs are known to cause stones and include the following:
Atazanavir
Indinavir
Triamterene
Guaifenesin
Overuse of silicate
Sulfonamide
There also appears to be a genetic association to renal calculi. In some families, there may be mutations that cause a defect in the renal tubular handling of calcium and other substrates.
Most urinary stones start as Randall’s plaque at the junction of the nephron’s collecting tubule and the renal pelvis in the papilla. These plaques start suburothelial and then gradually grow until they break through into the renal pelvis. Once in continuous contact with urine, layers of calcium oxalate typically start to form on the calcium phosphate nidus (all Randall’s plaques are composed of calcium phosphate). Calcium oxalate stones tend to form when the urinary pH is under 7.2 while calcium phosphate will form in the more alkaline urine. Hyperparathyroidism and similar metabolic disturbances like renal tubular acidosis typically form stones that are primarily or significantly composed of calcium phosphate. Overly acidic urine is the primary cause of uric acid stones (not hyperuricosuria).[rx][rx]
The majority of renal calculi are made of calcium, followed by urare crystals. Supersaturation of the urine is the common denominator in all cases of renal calculi. In some cases, calcium oxalate stones may deposit in the renal papilla. Calcium phosphate stones usually precipitate in the basement membrane of the thin loop of Henle and may erode into the interstitium. The colicky pain s usually due to the dilatation and spasm of the ureter.
Symptoms of Renal Calculi
Large calculi remaining in the renal parenchyma or renal collecting system are often asymptomatic unless they cause obstruction and/or infection. Severe pain, often accompanied by nausea and vomiting, usually occurs when calculi pass into the ureter and cause acute obstruction. Sometimes gross hematuria also occurs.
Pain (renal colic) is of variable intensity but is typically excruciating and intermittent, often occurs cyclically, and lasts 20 to 60 minutes. Nausea and vomiting are common. Pain in the flank or kidney area that radiates across the abdomen suggests upper ureteral or renal pelvic obstruction. Pain that radiates along the course of the ureter into the genital region suggests lower ureteral obstruction. Suprapubic pain along with urinary urgency and frequency suggests a distal ureteral, ureterovesical, or bladder calculus.
On examination, patients may be in obvious extreme discomfort, often ashen and diaphoretic. Patients with renal colic may be unable to lie still and may pace, writhe, or constantly shift position. The abdomen may be somewhat tender on the affected side as palpation increases pressure in the already-distended kidney (costovertebral angle tenderness), but peritoneal signs (guarding, rebound, rigidity) are lacking.
For some patients, the first symptom is hematuria or either gravel or calculus in the urine. Other patients may have symptoms of a urinary tract infection, such as fever, dysuria, or cloudy or foul-smelling urine.
Diagnosis of Renal Calculi
Patients with a stone disease will most commonly present with acute, severe flank pain that will often radiate to the abdomen and especially to the groin, testicle, and labia. It is often sharp and severe in nature. It may also be colicky. The pain is often associated with nausea and vomiting which is due to the embryological origins of the urogenital tract.
Renal colic usually peaks within 90-120 minutes and the pain radiation follows dermatomes T10-S4. The first phase may wake the patient up from sleep and the pain is steady, followed by waves of excruciating pain. The second phase is characterized by constant pain and may last 3-4 hours. The third phase is associated with mild pain relief but waves of pain may still persist. This phase may last 4-16 hours.
If infected, patients may also present with fever, chills, or other systemic signs of infection. This condition, called pyonephrosis or obstructive pyelonephritis, is potentially severe and life-threatening, requiring emergency decompression surgery.[rx]
Patients often present with hematuria as 85% of patients demonstrate at least microscopic hematuria on urinalysis.
The physical exam may reveal costovertebral tenderness and hypoactive bowel sounds. The testis and pubic area may also be tender to touch. Fever is rarely seen in renal colic but the presence of fever, pyuria, and leucocytosis may be indicative of pyelonephritis.
Lab Test and Imaging
A urinalysis should be obtained on every patient with a suspected kidney stone. Hematuria is usually present, but up to 15% of kidney stone patients will not demonstrate even microscopic hematuria. The presence of urinary crystals may suggest urolithiasis. Positive nitrites, leukocytes, and bacteria suggest infection which should be cultured and treated aggressively.[rx]
A KUB can be obtained to screen for the presence of significant nephrolithiasis, but may often miss stones that are small, hidden by bowel or uncalcified. Ultrasound may be very useful for assessing obstruction and resultant hydronephrosis, especially in pregnancy where x-ray studies are discouraged. It can also be used to measure the resistive index which can suggest ureteral obstruction.
Values of 0.70 or less are considered normal while higher values suggest obstructive uropathy. Bilateral high resistive indices suggest medical renal disease while a unilateral high resistive index (0.75 or higher) suggests an obstruction such as from a stone. Once a ureteral stone has been identified, the lower the resistive index, the more likely the stone will pass spontaneously. [rx]
Ultrasound can also identify uric acid and other non-calcific stones if they are large enough (usually greater than 4 mm), but it can also miss the presence of stones that are less than 5 mm.
The most sensitive and reliable test to diagnose urolithiasis is a non-contrast abdominal and pelvic CT scan, which will also provide information regarding obstruction with resultant hydronephrosis or concerns for infection.[rx][rx][rx][rx][rx] Other labs to obtain would include a WBC with differential, and a urine culture if the patient is febrile or has a urinalysis suggestive of a possible infection. The initial use of IV contrast for CT scans in patients with abdominal pain is not recommended. In many cases, an atypical abdominal pain will ultimately turn out to be a kidney stone that has moved or the presence of a urological anatomical variant such as a horseshoe kidney. Even without IV contrast, in most cases, the correct diagnosis can be made. If contrast is absolutely necessary, doing the non-contrast study first eliminates urinary stones from consideration. Certainly, if the urinalysis is abnormal for blood or possible infection, a non-contrast abdominal and pelvic CT should be performed prior to using contrast which will make identification of any urinary stones far more difficult. If this recommendation is not followed, sooner or later contrast will be given to a patient who will ultimately be diagnosed with urinary stones. Obscuring urinary stones with IV contrast can make it much more difficult to determine optimum treatment and possible surgery.[rx][rx][rx][rx][rx]
If the CT is positive for stones, a simultaneous KUB should be done. This will provide information useful in tracking or following the progress of the stone, its degree of calcification, and its shape which cannot always be identified from the CT scan alone.[rx]
Treatment of Renal Calculi
Many stones may be watched conservatively as an outpatient, with intervention planned as an outpatient. Smaller stones (less than 5 mm) have a greater chance (90%) of passing on their own with medical expulsion therapy (usually tamsulosin, nifedipine or alfuzosin). Any hint of a urinary tract infection should be treated aggressively with antibiotics.[rx][rx][rx]
Acute management requires IV hydration, analgesia, and antiemetic medications. Studies show that desmopressin can lower the pain of renal calculi. Anecdotal reports indicate that the use of calcium channel blockers can provide pain relief due to relaxation of the ureter and helps passage of the stone distally. Others recommend the use of alpha-blockers. The urine should be strained for stones.
There are several cases where urgent intervention is required.
An obstructing stone in a patient with a urinary tract infection, fever or sepsis. (This is called pyonephrosis or obstructive pyelonephritis and requires urgent surgical decompression by urology or interventional radiology)
Nausea or pain uncontrolled with outpatient management
An obstructing stone in a solitary kidney
Any degree of simultaneous bilateral obstruction which can easily lead to renal failure
Any degree of obstruction with a rising creatinine
In the case of urinary tract infection or urosepsis with an obstructing stone, the obstruction should first be relieved with either a ureteral double J stent or nephrostomy tube placement. The decision of which treatment modality is most appropriate should be made by urology. In general, the more severely ill the patient, the greater the benefit from a nephrostomy tube. Definitive stone management can then occur once the infection is no longer active. Morbidly obese patients and those who cannot be safely taken off of their blood thinners may require double J stent, regardless.
Electively, stones can be surgically managed in several ways. Extracorporeal shockwave lithotripsy (ESWL) can be used to break up stones anywhere in the urinary tract but is primarily used in the kidney and upper ureter. Ureteroscopy with laser lithotripsy can be used to manage stones endoscopically and is preferred for ureteral stones in the lower ureter. For large (greater than 2 cm) stones in the renal pelvis, percutaneous nephrolithotomy can be performed.
Once the patient has had his or her acute stone episode treated, it is recommended to evaluate the patient for the underlying cause for their stone episode, particularly if he or she has had stones in the past. This would involve obtaining a basic metabolic panel as well as a 24-hour urine collection for stone prevention analysis. Patients need to understand that this represents a commitment from them to follow a long-term course of therapy for stone prevention and that no treatment plan is foolproof so an occasional stone may still be produced but is much less likely on therapy than off. Physicians evaluating 24-hour kidney stone results should not only look at the normal ranges but also at what may be optimal. For example, in general, optimal 24-hour urinary calcium should be no more than 250 mg, oxalate less than 25 mg, citrate more than 600 mg, urinary volume more than 2,000 cc and urinary uric acid at 600 mg or less. While these levels may not be realistically obtainable in every patient, they are used as goals for treatment where the intention is to get as many chemistry levels optimal as possible even if they are all technically normal.[rx][rx][rx]
Analysis of 24-hour urine tests can be complicated. A companion piece “24 Hour Urine Testing for Nephrolithiasis: Guide to Interpretation” by Leslie S and Bashir K is recommended for more details on 24-hour urine interpretation and preventive therapy.
Admission is recommended in the following cases:
Inadequate pain relief with oral analgesics
Patient with a transplanted kidney and renal calculi
Presence of renal calculi and pyelonephritis
Dissolution therapy
Dissolution therapy does not work for calcium stones but it may be used to manage uric acid and cystine stones. Uric acids can be dissolved by making the urine alkaline with sodium bicarbonate. In addition, allopurinol can be used to reduce uric acid excretion. Thiazide diuretics are recommended for patients with recurrent stones. Cystine stones can be managed with D-penicillamine, aggressive fluid intake, and alkalinization.
Analgesia
Renal colic may be relieved with opioids, such as morphine and, for a rapid onset, fentanyl. Ketorolac 30 mg IV is rapidly effective and nonsedating. Vomiting usually resolves as pain decreases, but persistent vomiting can be treated with an antiemetic (eg, ondansetron 10 mg IV).
Expulsive therapy
Although increasing fluids (either oral or IV) has traditionally been recommended, increased fluid administration has not been proven to speed the passage of calculi. Patients with calculi <1 cm in diameter who have no infection or obstruction, whose pain is controlled with analgesics, and who can tolerate liquids can be treated at home with analgesics and alpha-receptor blockers (eg, tamsulosin 0.4 mg orally once a day) to facilitate calculus passage. Calculi that have not passed within 6 to 8 weeks typically require removal. In patients with suspected infection and obstruction, initial treatment is the relief of obstruction as soon as possible with a cystoscopically placed ureteral stent or percutaneous nephrostomy tube and treatment of the infection followed by removal of calculi as soon as possible.
Calculus removal
The technique used for removal depends on the location and size of the calculus. Techniques include extracorporeal shock wave lithotripsy and, to ensure complete removal or for larger calculi, endoscopic techniques. Endoscopic techniques may involve rigid or flexible ureteroscopes (endoscopes) and may involve direct-vision removal (basketing), fragmentation with some sort of lithotripsy device (eg, pneumatic, ultrasonic, laser), or both. Short-term ureteral stenting (eg, 2 weeks) is commonly used until the resolution of any inflammation or edema caused by the stone or the procedure.
For symptomatic calculi< 1 cm in diameter in the renal collecting system or proximal ureter, shock wave lithotripsy is a reasonable first option for therapy.
For larger calculi or if shock wave lithotripsy is unsuccessful, ureteroscopy (done in a retrograde fashion) with holmium laser lithotripsy is usually used. Sometimes removal is possible using an endoscope inserted anterograde through the kidney. For renal stones >2 cm, percutaneous nephrolithotomy, with insertion of a nephroscope directly into the kidney, is the treatment of choice.
For mid ureteral calculi, ureteroscopy with holmium laser lithotripsy is usually the treatment of choice. Shock wave lithotripsy is an alternative.
For distal ureteral calculi, endoscopic techniques (ureteroscopy), such as direct removal and use of intracorporeal lithotripsy (eg, holmium laser, pneumatic), are considered by many to be the procedures of choice. Shock wave lithotripsy can also be used.
Calculus dissolution
Uric acid calculi in the upper or lower urinary tract occasionally may be dissolved by prolonged alkalinization of the urine with potassium citrate 20 mEq (20 mmol/L) orally 2 to 3 times a day, but the chemical dissolution of calcium calculi is not possible and of cystine calculi is difficult.
Prevention of Urinary Calculi
In a patient who has passed a first calcium calculus, the likelihood of forming the 2nd calculus is about 15% at 1 year, 40% at 5 years, and 80% at 10 years. Drinking large amounts of fluids—8 to 10 ten-ounce (300-milliliter) glasses a day—is recommended for the prevention of all stones. Patients who form stones (those with a history of recurrent stones and those with stones newly diagnosed via imaging) should drink enough fluid to produce at least 2.5 liters of urine daily. Recovery and analysis of the calculus, measurement of calculus-forming substances in the urine, and the clinical history are needed to plan other prophylactic measures.
In < 3% of patients, no metabolic abnormality is found. These patients seemingly cannot tolerate normal amounts of calculus-forming salts in their urine without crystallization. Thiazide diuretics, potassium citrate, and increased fluid intake may reduce their calculus production rate.
For hypercalciuria, patients may receive thiazide diuretics (eg, chlorthalidone 25 mg orally once a day or indapamide 1.25 mg orally once a day) to lower urine calcium excretion and thus prevent urinary supersaturation with calcium oxalate. Patients are encouraged to increase their fluid intake to ≥ 3 L/day. A diet that is low in sodium and high in potassium is recommended. Even with a high potassium intake, supplementation with potassium citrate is recommended to prevent hypokalemia. Restriction of dietary animal protein is also recommended.
For patients with hypocitraturia, potassium citrate (20 mEq [20 mmol/L] orally twice a day) enhances citrate excretion. A normal calcium intake (eg, 1000 mg or about 2 to 3 dairy servings per day) is recommended, and calcium restriction is avoided. Oral orthophosphate has not been thoroughly studied. Alternative alkaline agents (eg, sodium or potassium bicarbonate) can be used to enhance citrate excretion if potassium citrate cannot be tolerated.
Hyperoxaluria prevention varies. Patients with small-bowel disease can be treated with a combination of high fluid intake, calcium loading (usually in the form of calcium citrate 400 mg orally twice a day with meals), cholestyramine, and a low-oxalate, low-fat diet. Hyperoxaluria may respond to pyridoxine 100 to 200 mg orally once a day, possibly by increasing transaminase activity, because this activity is responsible for the conversion of glyoxylate, the immediate oxalate precursor, to glycine.
In hyperuricosuria, intake of animal protein should be reduced. If the diet cannot be changed, allopurinol 300 mg each morning lowers uric acid production. For uric acid calculi, the urine pH must be increased to between 6 and 6.5 by giving an oral alkalinizing drug that contains potassium (eg, potassium citrate 20 mEq [20 mmol/L] twice a day) along with increased fluid intake.
Infection with urea-splitting bacteria requires culture-specific antibiotics and complete removal of all calculi. If eradication of infection is impossible, long-term suppressive therapy (eg, with nitrofurantoin) may be necessary. In addition, acetohydroxamic acid can be used to reduce the recurrence of struvite calculi.
To prevent recurrent cystine calculi, urinary cystine levels must be reduced to < 250 mg cystine/L of urine. Any combination of increasing urine volume along with reducing cystine excretion (eg, with alpha-mercapto propionyl glycine [tiopronin] or penicillamine) should reduce the urinary cystine concentration.
