About 1/1000 adults in the US is hospitalized annually because of urinary calculi, which are also found in about 1% of all autopsies. Up to 12% of men and 10% of women will develop a urinary calculus by age 70. Calculi vary from microscopic crystalline foci to calculi several centimeters in diameter. A large calculus, called a staghorn calculus, can fill an entire renal calyceal system.
Etiology of Urinary Calculi
About 85% of calculi in the US are composed of calcium, mainly calcium oxalate (see table Composition of Urinary Calculi Composition of Urinary Calculi Urinary calculi are solid particles in the urinary system. They may cause pain, nausea, vomiting, hematuria, and, possibly, chills and fever due to secondary infection. Diagnosis is based on... read more ); 10% are uric acid; 2% are cystine; most of the remainder are magnesium ammonium phosphate (struvite).
General risk factors include disorders that increase urinary salt concentration, either by increased excretion of calcium or uric acid salts, or by decreased excretion of urinary citrate.
For calcium calculi, risk factors vary by population. The main risk factor in the US is hypercalciuria, a hereditary condition present in 50% of men and 75% of women with calcium calculi; thus, patients with a family history of calculi are at increased risk of recurrent calculi. These patients have normal serum calcium, but urinary calcium is elevated > 250 mg/day (> 6.2 mmol/day) in men and > 200 mg/day (> 5.0 mmol/day) in women.
Hypocitruria (urinary citrate < 350 mg/day [1820 micromol/day]), present in about 40 to 50% of calcium calculi–formers, promotes calcium calculi formation because citrate normally binds urinary calcium and inhibits the crystallization of calcium salts.
About 5 to 8% of calculi are caused by renal tubular acidosis Renal Tubular Acidosis Renal tubular acidosis (RTA) is acidosis and electrolyte disturbances due to impaired renal hydrogen ion excretion (type 1), impaired bicarbonate resorption (type 2), or abnormal aldosterone... read more . About 1 to 2% of patients with calcium calculi have primary hyperparathyroidism. Rare causes of hypercalciuria are sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more , vitamin D intoxication Vitamin D Toxicity Usually, vitamin D toxicity results from taking excessive amounts. In vitamin D toxicity, resorption of bone and intestinal absorption of calcium is increased, resulting in hypercalcemia. Marked... read more , hyperthyroidism Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms are many and include tachycardia, fatigue, weight loss, nervousness, and tremor... read more , multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing... read more , metastatic cancer, and hyperoxaluria.
Hyperoxaluria (urinary oxalate > 40 mg/day [> 440 micromol/day]) can be primary or caused by excess ingestion of oxalate-containing foods (eg, rhubarb, spinach, cocoa, nuts, pepper, tea) or by excess oxalate absorption due to various enteric diseases (eg, bacterial overgrowth syndromes, Crohn disease, ulcerative colitis, chronic pancreatic or biliary disease) or ileojejunal (eg, bariatric) surgery.
Other risk factors include taking high doses of vitamin C (ie, > 2000 mg/day), a calcium-restricted diet (possibly because dietary calcium binds dietary oxalate), and mild hyperuricosuria. Mild hyperuricosuria, defined as urinary uric acid > 800 mg/day (> 5 mmol/day) in men or > 750 mg/day (> 4 mmol/day) in women, is almost always caused by excess intake of purine (in proteins, usually from meat, fish, and poultry); it may cause calcium oxalate calculus formation (hyperuricosuric calcium oxalate nephrolithiasis).
Uric acid calculi most commonly develop as a result of increased urine acidity (urine pH < 5.5), or rarely with severe hyperuricosuria (urinary uric acid > 1500 mg/day [> 9 mmol/day]), which crystallizes undissociated uric acid. Uric acid crystals may comprise the entire calculus or, more commonly, provide a nidus on which calcium or mixed calcium and uric acid calculi can form.
Cystine calculi occur only in the presence of cystinuria Cystinuria Cystinuria is an inherited defect of the renal tubules in which reabsorption of cystine (the homodimer of the amino acid cysteine) is impaired, urinary excretion is increased, and cystine stones... read more .
Magnesium ammonium phosphate calculi (struvite, infection calculi) indicate the presence of a urinary tract infection Introduction to Urinary Tract Infections (UTIs) Urinary tract infections (UTIs) can be divided into upper tract infections, which involve the kidneys (pyelonephritis), and lower tract infections, which involve the bladder (cystitis), urethra... read more caused by urea-splitting bacteria (eg, Proteus species, Klebsiella species). The calculi must be treated as infected foreign bodies and removed in their entirety. Unlike other types of calculi, magnesium ammonium phosphate calculi occur 3 times more frequently in women.
Rare causes of urinary calculi include indinavir, melamine, triamterene, and xanthine.
Pathophysiology of Urinary Calculi
Urinary calculi may remain within the renal parenchyma or renal collecting system or be passed into the ureter and bladder. During passage, calculi may irritate the ureter and may become lodged, obstructing urine flow and causing hydroureter and sometimes hydronephrosis. How rapidly obstruction develops determines the severity of renal colic. Common areas of lodgment include the following:
Distal ureter (at the level of the iliac vessels)
Larger calculi are more likely to become lodged. Typically, a calculus must have a diameter > 5 mm to become lodged. Calculi ≤ 5 mm are more likely to pass spontaneously.
Even partial obstruction causes decreased glomerular filtration, which may persist briefly after the calculus has passed. With hydronephrosis and elevated glomerular pressure, renal blood flow declines, further worsening renal function. Generally, however, in the absence of infection, permanent renal dysfunction occurs only after about 28 days of complete obstruction.
Secondary infection can occur with long-standing obstruction, but most patients with calcium-containing calculi do not have infected urine.
Symptoms and Signs of Urinary 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 (see Symptoms and Signs of Obstructive Uropathy Symptoms and Signs Obstructive uropathy is structural or functional hindrance of normal urine flow, sometimes leading to renal dysfunction (obstructive nephropathy). Symptoms, less likely in chronic obstruction... read more ).
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 a calculus in the urine. Other patients may have symptoms of a urinary tract infection Bacterial Urinary Tract Infections Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain... read more , such as fever, dysuria Dysuria Dysuria is painful or uncomfortable urination, typically a sharp, burning sensation. Some disorders cause a painful ache over the bladder or perineum. Dysuria is an extremely common symptom... read more , or cloudy or foul-smelling urine.
Diagnosis of Urinary Calculi
Clinical differential diagnosis
Determination of calculus composition
The symptoms and signs may suggest other diagnoses, such as
Peritonitis (eg, due to appendicitis Appendicitis Appendicitis is acute inflammation of the vermiform appendix, typically resulting in abdominal pain, anorexia, and abdominal tenderness. Diagnosis is clinical, often supplemented by CT or ultrasonography... read more , ectopic pregnancy Ectopic Pregnancy In ectopic pregnancy, implantation occurs in a site other than the endometrial lining of the uterine cavity—ie, in the fallopian tube, uterine cornua, cervix, ovary, or abdominal or pelvic cavity... read more , or pelvic inflammatory disease Pelvic Inflammatory Disease (PID) Pelvic inflammatory disease (PID) is a polymicrobial infection of the upper female genital tract: the cervix, uterus, fallopian tubes, and ovaries; abscess may occur. PID may be sexually transmitted... read more ): Pain is usually constant, and patients lie still because movement worsens pain; patients often also have rebound tenderness or rigidity.
Cholecystitis Acute Cholecystitis Acute cholecystitis is inflammation of the gallbladder that develops over hours, usually because a gallstone obstructs the cystic duct. Symptoms include right upper quadrant pain and tenderness... read more : May cause colicky pain, usually in the epigastrium or right upper quadrant, often with Murphy sign.
Bowel obstruction Intestinal Obstruction Intestinal obstruction is significant mechanical impairment or complete arrest of the passage of contents through the intestine due to pathology that causes blockage of the bowel. Symptoms include... read more : May cause colicky abdominal pain and vomiting, but the pain is usually bilateral and not located primarily in the flank or along the ureter.
Pancreatitis Overview of Pancreatitis Pancreatitis is classified as either acute or chronic. Acute pancreatitis is inflammation that resolves both clinically and histologically. Chronic pancreatitis is characterized by histologic... read more : May cause upper abdominal pain and vomiting, but the pain is usually constant, may be bilateral, and is usually not along the flank or ureter.
With most of these disorders, urinary symptoms are uncommon and other symptoms may suggest which organ system is actually involved (eg, vaginal discharge or bleeding in pelvic disorders among females). Dissecting aortic aneurysm must be considered, particularly in older patients, because, if a renal artery is affected, it can cause hematuria, pain that radiates along a ureteral distribution, or both. Other considerations in the general evaluation of acute abdominal pain are discussed elsewhere (see Evaluation of Acute Abdominal Pain: Evaluation Abdominal pain is common and often inconsequential. Acute and severe abdominal pain, however, is almost always a symptom of intra-abdominal disease. It may be the sole indicator of the need... read more ).
Pearls & Pitfalls
Patients suspected of having a calculus causing colic require urinalysis and usually an imaging study. If a calculus is confirmed, evaluation of the underlying disorder, including calculus composition testing, is required.
Macroscopic or microscopic hematuria is common, but urine may be normal despite multiple calculi. Pyuria with or without bacteria may be present. Pyuria suggests infection, particularly if combined with suggestive clinical findings, such as foul-smelling urine or a fever. A calculus and various crystalline substances may be present in the sediment. If so, further testing via 24-hour urine collections is usually necessary to identify the cause because the composition of the calculus and crystals cannot be determined conclusively by microscopy. The only exception is when typical hexagonal crystals of cystine are found in a concentrated, acidified specimen, confirming cystinuria.
Noncontrast helical CT is the most common initial imaging study. This study can detect the location of a calculus as well as the degree of obstruction. Moreover, helical CT may also reveal other causes of the pain (eg, aortic aneurysm). For patients who have recurrent calculi, cumulative radiation exposure from multiple CT scans is a concern. However, the routine use of low-dose renal CT can meaningfully reduce cumulative radiation dose with little loss of sensitivity (1 Diagnosis references Urinary calculi are solid particles in the urinary system. They may cause pain, nausea, vomiting, hematuria, and, possibly, chills and fever due to secondary infection. Diagnosis is based on... read more ). For patients with typical symptoms, ultrasonography or plain abdominal x-rays can usually confirm presence of a calculus with minimal or no radiation exposure. MRI may not identify calculi.
Although most urinary calculi are demonstrable on plain x-ray, neither their presence nor their absence obviates the need for more definitive imaging, so this study can be avoided except in some patients with suspected recurrent calculi. Both renal ultrasonography Ultrasonography Imaging tests are often used to evaluate patients with renal and urologic disorders. Abdominal x-rays without radiopaque contrast agents may be done to check for positioning of ureteral stents... read more and excretory urography IV urography (IVU) Imaging tests are often used to evaluate patients with renal and urologic disorders. Abdominal x-rays without radiopaque contrast agents may be done to check for positioning of ureteral stents... read more (previously called intravenous urography) can identify calculi and hydronephrosis. However, ultrasonography is less sensitive for small or ureteral calculi in patients without hydronephrosis, and excretory urography is time consuming and exposes the patient to the risk of IV contrast agents. These studies are generally used when helical CT is unavailable.
Identifying the cause
The calculus is obtained by straining the urine (or, if necessary, during operative removal) and sent to the laboratory for stone analysis. Some calculi are brought in by patients. Urine specimens that show microscopic crystals are sent for crystallography.
In patients with a single calcium calculus and no additional risk factors for calculi, evaluation to exclude hyperparathyroidism is sufficient. Evaluation entails urinalysis and determination of plasma calcium concentration on 2 separate occasions. Predisposing factors, such as recurrent calculi, a diet high in animal protein, or use of vitamin C or D supplements, should be sought.
Patients with a strong family history of calculi, conditions that might predispose to calculi formation (eg, sarcoidosis Sarcoidosis Sarcoidosis is an inflammatory disorder resulting in noncaseating granulomas in one or more organs and tissues; etiology is unknown. The lungs and lymphatic system are most often affected, but... read more , bone metastases, multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing... read more ), or conditions that would make it difficult to treat calculi (eg, solitary kidney, urinary tract anomalies) require evaluation for all possible causative disorders and risk factors. This evaluation should include serum electrolytes, uric acid, and calcium on 2 separate occasions. Follow-up determination of parathyroid hormone levels is done if necessary. Urine tests should include routine urinalysis and 2 separate 24-hour urine collections with the patient on a routine diet to determine urine volume, pH, and excretion of calcium, uric acid, citrate, oxalate, sodium, and creatinine. For further information on the medical management of kidney stones, see the guideline of the American Urological Association (2 Diagnosis references Urinary calculi are solid particles in the urinary system. They may cause pain, nausea, vomiting, hematuria, and, possibly, chills and fever due to secondary infection. Diagnosis is based on... read more ).
1. Zilberman DE, Tsivian M, Lipkin ME, et al: Low dose computerized tomography for detection of urolithiasis—its effectiveness in the setting of the urology clinic. J Urol 185(3):910-914, 2011. doi: 10.1016/j.juro.2010.10.052
2. Pearle MS, Goldfarb DS, Assimos DG, et al: Medical management of kidney stones—AUA guideline. doi: 10.1016/j.juro.2014.05.006J Urology 92(2):316-24, 2014. doi: 10.1016/j.juro.2014.05.006
Treatment of Urinary Calculi
Facilitate calculus passage, eg, with alpha-receptor blockers such as tamsulosin (described as medical expulsive therapy)
For persistent or infection-causing calculi, complete removal using primarily endoscopic techniques
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).
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 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.
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 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 midureteral 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.
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 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 a 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 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 Hypokalemia Hypokalemia is serum potassium concentration 3.5 mEq/L ( 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common cause is... read more . Restriction of dietary animal protein is also recommended.
For patients with hypocitruria, 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-mercaptopropionylglycine [tiopronin] or penicillamine) should reduce the urinary cystine concentration.
85% of urinary calculi are calcium, mainly calcium oxalate (see table Composition of Urinary Calculi Composition of Urinary Calculi Urinary calculi are solid particles in the urinary system. They may cause pain, nausea, vomiting, hematuria, and, possibly, chills and fever due to secondary infection. Diagnosis is based on... read more ); 10% are uric acid; 2% are cystine; and most of the remainder are magnesium ammonium phosphate (struvite).
Larger calculi are more likely to obstruct; however, obstruction can occur even with small ureteral calculi (ie, 2 to 5 mm).
Symptoms include hematuria, symptoms of infection, and renal colic.
Test usually with urinalysis, imaging, and—if the calculus can later be retrieved—determination of calculus composition.
Give analgesics and drugs to facilitate calculus passage (eg, alpha-receptor blockers) acutely and remove calculi that cause infection or persist endoscopically.
Decrease the risk of subsequent calculus formation by treating with measures such as thiazide diuretics, potassium citrate, increases in fluid intake, and decreases in dietary animal protein, depending on calculus composition.