Captopril Reduces Urinary Cystine Excretion in Cystinuria

Cystinuria is characterized by cystine stone formation and loss of renal function. Conservative therapy is generally ineffective and penicillamine therapy can be complicated by serious side effects. To our knowledge, we report the first clinical use of captopril in the treatment of homozygous cystinuria in two siblings. In the first patient, a 70% reduction in cystine excretion was observed after 26 weeks of therapy with 150 mg/d of captopril. Discontinuation of use of the drug resulted in a return to baseline cystine excretion, further loss of renal function, and nephrotic range proteinuria. Repeated treatment with captopril stabilized renal function, reduced proteinuria, and returned cystine excretion to near normal levels. In the second patient, cystine excretion was reduced by 93% after nine weeks of therapy with 75 mg/d of captopril. No adverse side effects were observed in either patient. Formation of the captopril–cysteine disulfide accounts for part of the reduction in cystine excretion but other mechanisms probably contribute. Because captopril–cysteine disulfide is 200 times more soluble than cystine, long-term captopril therapy may be useful in the treatment of cystinuria.