Abstract
Introduction
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.
Materials and methods
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.
Results
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.
Conclusion
The present study indicated that tolvaptan’s efficacy in preventing l-cystine stone growth through increased liquid intake and urine volume of cystinuric mice.
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Acknowledgements
This work was financed by grants from the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZY2016104) and Department of Science and Technology of Sichuan Province (2018SZ0168).
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JW and PH: protocol/project development, data management, and manuscript writing/editing. YJB and YT: protocol/project development, data analysis, and manuscript writing/editing. YJB, YT, JHW, XMW, DHC and ZHW: data collection or management; JW, YJB, YT, XMW, JHW, and ZHW: revised the manuscript. All authors read and approved the final manuscript.
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The authors of this study disclose no conflicts of interest. This study was no funded in anyway by the manufacturers of tolvaptan.
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Bai, Y., Tang, Y., Wang, J. et al. Tolvaptan treatment of cystine urolithiasis in a mouse model of cystinuria. World J Urol 39, 263–269 (2021). https://doi.org/10.1007/s00345-020-03166-3
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DOI: https://doi.org/10.1007/s00345-020-03166-3