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Cystinuria
is an inherited defect of the renal tubules in which resorption
of the amino acid cystine is impaired, urinary excretion is increased,
and cystine stones form in the urinary tract. Symptoms are colic
from stones and perhaps urinary infection or the sequelae of renal
failure. Diagnosis is by measurement of cystine excretion in the
urine. Treatment is with increased fluid intake and alkalinization
of the urine.
Cystinuria is inherited as an autosomal recessive trait. Heterozygotes may excrete increased quantities of cystine in the urine but seldom enough to form stones.
Pathophysiology
The primary defect is diminished renal tubular resorption of cystine, which increases cystine concentration in the urine. Cystine is poorly soluble in acidic urine, so that when its urinary concentration exceeds its solubility, crystals precipitate and stones form.
Resorption of dibasic amino acids (lysine, ornithine, arginine ) is also impaired, which causes no problems because these amino acids have an alternative transport system separate from that shared with cystine. Furthermore, they are more soluble than cystine in urine, and their increased excretion does not result in crystal or stone formation. Their absorption (and that of cystine) is also decreased in the small bowel.
Symptoms,
Signs, and Diagnosis
Symptoms, most commonly renal colic, usually appear between ages 10 and 30. UTI and renal failure due to obstruction may develop.
Radiopaque cystine stones form in the renal pelvis or bladder. Staghorn stones are common. Cystine may appear in the urine as yellow-brown hexagonal crystals. Excessive cystine in the urine may be detected with the nitroprusside cyanide test. Diagnosis is confirmed by observing a cystine excretion of > 400 mg/day (normal, < 30 mg/day).
Prognosis
and Treatment
Eventually, end-stage renal disease usually develops. Decreasing the urinary concentration of cystine decreases renal toxicity. This is accomplished by increasing urine volume. Fluid intake must be sufficient to provide a urine flow rate of 3 to 4 L/day. Hydration is particularly important at night when urinary pH drops. Alkalinization of the urine to pH > 7.4 with NaHCO3 or KHCO3 1 mEq/kg po bid to tid and acetazolamide 5 mg/kg (up to 250 mg) po at bedtime increases the solubility of cystine significantly. When high fluid intake and alkalinization do not reduce stone formation, other drugs may be tried. Penicillamine (7.5 mg/kg qid and 250 mg to 1 g po qid in older children) is effective, but toxicity limits its usefulness. About ½ of all patients develop some toxic manifestation, such as fever, rash, arthralgias, or, less commonly, nephrotic syndrome, pancytopenia, or SLE-like reaction. Captopril (0.3 mg/kg po tid) is not as effective as penicillamine but is much less toxic.
Last full review/revision November 2005
Content last modified November 2005
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