Captopril reduces urinary cystine excretion in cystinuria

Area of Science:

• Nephrology
• Medical Genetics
• Pharmacology

Background:

• Cystinuria is a rare inherited disorder causing kidney stones due to excessive cystine excretion.
• Current treatments for cystinuria, including conservative measures and penicillamine, have limitations and potential side effects.
• Homozygous cystinuria presents a severe form of the disease, necessitating effective therapeutic strategies.

Observation:

• This study reports the first clinical application of captopril for treating homozygous cystinuria in two siblings.
• Captopril administration led to significant reductions in urinary cystine excretion in both patients.
• Discontinuation of captopril resulted in a return of elevated cystine excretion and renal function decline, which reversed upon re-initiation of therapy.

Findings:

• The first patient experienced a 70% decrease in cystine excretion with captopril, alongside stabilized renal function and reduced proteinuria.
• The second patient showed a 93% reduction in cystine excretion with captopril, with no observed adverse effects.
• The formation of a captopril-cysteine disulfide complex is proposed as a mechanism for reduced cystine excretion, enhancing solubility.

Implications:

• Captopril demonstrates potential as a novel therapeutic agent for managing cystinuria, particularly the homozygous form.
• The enhanced solubility of the captopril-cysteine disulfide complex suggests a favorable long-term treatment outcome.
• Further research into captopril's efficacy and safety in a larger cystinuria cohort is warranted.