D-Penicillamine; A Valuable and Tolerable Long-Term Rescue Therapy for Cystinuric Urolithiasis

Abstract

Background: Cystinuric urolithiasis (CyU) is a rare autosomal recessive disorder due to defective proximal tubule reabsorption of cystine. It is associated with rapid and recurrent formation of large stones at an early age. Most patients are treated conservatively with adequate hydration (3 liters/day), alkalization of the urine with citrate to a pH between 7 - 8, and dietary modification to reduce salt and protein intake. Thiol, viz., D-penicillamine (DPA), is a drug that acts to form a complex with cystine that is 50 times more soluble than cystine itself, yet its use is limited by fear of its adverse effects and induction of membranous glomerulopathy. Patients and Methods: A total of 17 (1/3) of our CyU patients had failed such a conservative approach despite confirmed adequate compliance and had large and recurrent CyU. After their initial urological intervention (percutaneous nephrolithotomy or endoscopic laser lithotripsy), they received DPA 250 mg thrice daily. Results: Subsequent to DPA therapy, stone load (yearly urological intervention for large stones) decreased from 3 ± 1 to 0.4/year over a period of 93 ± 21 months ( p < 0.001), with only 2 patients requiring minimal laser endoscopic lithotripsy. Moreover, their initial daily cystine output decreased from 1.9 ± 0.1 mmol to 0.55 ± 0.1 after 2 months of DPA therapy ( p < 0.001) and remained low at the same level in all patients after 48 months and by the end of the study. Overall, the drug was well tolerated and none of the patients had significant proteinuria or blood dyskaryosis requiring drug discontinuation. Conclusion: Our data show that DPA can be an efficacious and safe long-term therapy for patients with high-load CyU.