Urinary Calculi

About 85% of calculi in the United States are composed of calcium, mainly calcium oxalate (see table ); 10% are composed of uric acid; 2% are composed of cystine; most of the remainder are mainly composed of 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 United States 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 include palpitations, fatigue, weight loss, heat intolerance, anxiety, 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 primary hyperoxaluria.

Elevated urinary oxalate levels (hyperoxaluria, urinary oxalate > 40 mg/day [> 440 micromol/day]) may cause calcium oxalate calculus formation (hyperuricosuric calcium oxalate nephrolithiasis). Hyperoxaluria 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).

Uric acid calculi most commonly develop as a result of increased urine acidity (urine pH < 5.5), or very 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 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). These 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.

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. Common areas of lodgment include the following:

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.

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. Gross hematuria also occurs, but not in all patients with urinary tract stones.

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.

The symptoms and signs may suggest other diagnoses, such as

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 ).

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.

See also

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 long-acting 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... read more . Restriction of dietary animal protein is also recommended (1 General reference 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 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 medication 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.