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    Cystinuria is an inherited disease characterized by increased urinary cystine excretion and recurrent cystine stones. Current treatment regimens have limited effectiveness in preventing stone recurrence and are often poorly tolerated. The aim of this study was to evaluate the effect of tolvaptan, a vasopressin receptor 2 (V2) antagonist, on cystine stone volume in mice with cystinuria. Tolvaptan (0.4 mg per mouse) or placebo was delivered by gavage daily for 30 days. Urinary amino acids and cystine stones were analyzed to assess drug efficacy in preventing L-cystine stone growth using several analytical methods. Data were entered into SPSS and analyzed by paired sample T test. p value < 0.05 was considered significant. Compared with control group, the liquid intake and urine volume in tolvaptan-treated mice were significantly increased. The urinary cystine concentrations in group tolvaptan was lower than the baseline concentration before the experiment. After treatment, mice treated with tolvaptan had significantly delayed stone growth, exhibited lower overall stone volume accumulation, compared with control group. The increased stone volume of tolvaptan group was less than control group (8.00 ± 4.93 mm3 vs 27.90 ± 4.48 mm3, p < 0.001). The serum creatinine in the control group (11.75 ± 1.634 μmol/L) was higher than that in the tolvaptan group (7.625 ± 1.401 μmol/L) (p = 0.0759). In addition, tolvaptan significantly inhibited the formation and growth of stones in mice after cystolithotomy. The present study indicated that tolvaptan's efficacy in preventing L-cystine stone growth through increased liquid intake and urine volume of cystinuric mice.

    Citation

    Yunjin Bai, Yin Tang, Jiahao Wang, Xiaoming Wang, Zhenghao Wang, Dehong Cao, Ping Han, Jia Wang. Tolvaptan treatment of cystine urolithiasis in a mouse model of cystinuria. World journal of urology. 2021 Jan;39(1):263-269

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    PMID: 32189089

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