Medical treatment of cystinuria: Critical reappraisal of long-term results

Purpose: We evaluated long-term results of a contemporary medical therapeut ic regimen in patients with cystinuria and analyzed factors predictive of t herapeutic success. Materials and Methods: A total of 27 adults with cystine urolithiasis were treated at our institution for 1.3 to 32 years (mean 11.6, overall 312 pati ent-years). We obtained data on the pre-referral period for 274 patient-yea rs overall. Basic therapy included hyperdiuresis and alkalization. The thio ls D-penicillamine or tiopronin were added when standard therapy failed to prevent new stones and stone growth or dissolve preexisting stones. X-ray a nd echography were performed every 4 months during the initial 2 years and every 6 months thereafter. Results: In the pre-referral period 256 stone episodes occurred and 81 urol ogical procedures were performed in 24 patients (0.93 and 0.29 per patient- year, respectively). Nine patients were treated with added thiols. During t he therapeutic period the incidence of stone episodes decreased to 66 (0.20 per patient-year, p <0.001), while the need for urological procedures decr eased to 44 (0.14 per patient-year, p <0.001). No further urological proced ures were required in 15 patients, including 4 treated with thiols. However , the remaining 12 patients, including 5 treated with thiols, underwent 1 t o 7 procedures each (mean 0.26 per patient-year). In the 2 groups mean dail y cystine excretion plus or minus standard deviation at baseline (863 +/- 2 53 versus 761 +/- 270 mg. daily) and mean urinary pH of about 7.4 did not d iffer significantly. However, daily urine volume was significantly higher i n patients with arrested stone formation (3,151 +/- 587 versus 2,446 +/- 65 4 ml./24 hours, p = 0.006). Conclusions: Our study provides evidence that a regularly followed medical program based on high diuresis and alkalization with second line addition o f thiols may arrest or markedly decrease cystine stone formation and preclu de the need for urological procedures in more than half of the patients. Ho wever, patients poorly compliant with hyperdiuresis remain at risk for recu rrence. We suggest that maintaining a daily urine volume of greater than 3 l. is essential for therapeutic success regardless of whether thiol derivat ives are administered.