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
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Calcium stones (due to hyperparathyroidism, renal calcium leak, hyperoxaluria, hypomagnesemia and hypocitraturia)
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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
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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)
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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:
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Atazanavir
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Indinavir
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Triamterene
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Guaifenesin
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Overuse of silicate
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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.
Resistive Index = (peak systolic velocity – end-diastolic velocity)/peak systolic velocity
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.
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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)
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Nausea or pain uncontrolled with outpatient management
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An obstructing stone in a solitary kidney
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Any degree of simultaneous bilateral obstruction which can easily lead to renal failure
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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:
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Inadequate pain relief with oral analgesics
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Patient with a transplanted kidney and renal calculi
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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.
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