Nephrotic Syndrome Induced by Tiopronin in a Male Patient with Cystinuria

Cystinuria is a rare, lifelong, autosomal recessive disorder characterized by high urine cystine excretion, leading to chronic and recurrent kidney stone formation. This inherited metabolic disorder occurs due to defective cystine, lysine, ornithine, and arginine reabsorption in the brush border membrane of the proximal renal tubule (S3 segment) and the gastrointestinal epithelial cells. Tiopronin is a thiol agent used in the treatment of severe homozygous cystinuria in patients who are resistant to conservative measures. We report an 18-year-old male with cystinuria confirmed by genetic testing, who was treated with conservative measures such as high fluid intake, low sodium diet, and oral potassium citrate since the diagnosis was made at four years of age. However, due to the recurrence of several calculi in both kidneys, tiopronin treatment was initiated at the dose of 250 mg three times a day. After three months of therapy, the patient developed nephrotic syndrome with proteinuria of 6.6 g/l, hypoproteinemia, hyperlipidemia, and edema. Considering the adverse effect of tiopronin, the drug was immediately withdrawn and the patient was managed with human albumin substitution, diuretics, and angiotensin receptor blocker, without corticosteroids. Complete clinical and biochemical remission was achieved within 7 days. Clinicians should be aware of this rare but serious adverse effect of tiopronin, and monitor patients receiving tiopronin carefully for the possible occurrence of edema, proteinuria, with the aim of timely intervention and tiopronin discontinuation.