All iLive content is medically reviewed or fact checked to ensure as much factual accuracy as possible.
We have strict sourcing guidelines and only link to reputable media sites, academic research institutions and, whenever possible, medically peer reviewed studies. Note that the numbers in parentheses ([1], [2], etc.) are clickable links to these studies.
If you feel that any of our content is inaccurate, out-of-date, or otherwise questionable, please select it and press Ctrl + Enter.
Cystinuria
Medical expert of the article
Last reviewed: 05.07.2025
Cystinuria is a hereditary defect of the renal tubules in which the resorption of the amino acid cystine is impaired, its excretion in the urine increases, and cystine stones form in the urinary tract. Symptoms include the development of renal colic due to stone formation and, possibly, urinary tract infection or manifestations of renal failure. Diagnosis is based on determining the excretion of cystine in the urine. Treatment of cystinuria includes increasing the daily volume of fluid consumed and alkalinization of the urine.
Causes of Cystinuria
Cystinuria is inherited in an autosomal recessive manner. In heterozygous carriers, increased urinary excretion of cystine may be observed, but rarely sufficient to form stones.
[ 3 ], [ 4 ], [ 5 ], [ 6 ], [ 7 ]
Pathophysiology of cystinuria
The primary defect is a limitation of tubular reabsorption of cystine in the kidneys, which increases its concentration in the urine. Cystine is poorly soluble in acidic urine, so if its concentration in the urine exceeds its solubility, cystine crystals form in the urine, which then form cystine stones.
The reabsorption of two essential amino acids (lysine, ornithine, arginine) is also impaired, which does not cause significant problems, since these amino acids have an alternative transport system independent of the cystine transport system. Moreover, these amino acids are more soluble in urine than cystine, and their increased excretion does not lead to crystal precipitation and stone formation. Their absorption in the small intestine (and the absorption of cystine) is also reduced.
Symptoms of Cystinuria
Symptoms of cystinuria, most commonly renal colic, usually appear between the ages of 10 and 30. UTI and renal failure due to obstructive uropathy may develop.
Radiopaque cystine stones form in the renal pelvis or urinary bladder. Staghorn calculi are common. Cystine may be present in the urine as yellow-brown hexagonal crystals. Excessive amounts of cystine in the urine can be detected using the cyanide nitroprusside test. The diagnosis is confirmed by detecting daily excretion of cystine greater than 400 mg/day (normally less than 30 mg/day).
Treatment of cystinuria
Eventually, end-stage renal failure usually develops. Lowering urinary cystine concentrations reduces renal damage. This is accomplished by increasing urine volume. Fluid intake should be sufficient to produce a urine output of approximately 3 to 4 liters per day. Hydration is especially important at night when urine pH decreases. Alkalinization of the urine to a pH greater than 7.4 with sodium or potassium bicarbonate 1 mEq/kg orally twice daily and acetazolamide 5 mg/kg (up to 250 mg) orally at night significantly increases cystine solubility. If high fluid intake and urine alkalinization do not reduce stone formation, other agents may be tried. Penicillamine (7.5 mg/kg 4 times daily and 250 to 1000 mg orally 4 times daily in older children) is effective, but toxic effects limit its use. Approximately 1/2 of patients develop toxic manifestations such as fever, rash, arthralgia, or less commonly nephrotic syndrome, pancytopenia, or SLE-like reactions. Cystinuria can be treated with captopril (0.3 mg/kg orally 3 times daily), but it is not as effective as penicillamine, but is significantly less toxic.