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.

中文翻译：

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托伐普坦治疗胱氨酸尿症小鼠模型中的胱氨酸尿石症

摘要

介绍

胱氨酸尿症是一种遗传性疾病，其特征是尿胱氨酸排泄增加和胱氨酸结石复发。当前的治疗方案在预防结石复发方面的效果有限，并且通常耐受性差。本研究的目的是评估托伐普坦（一种加压素受体 2 (V2) 拮抗剂）对胱氨酸尿症小鼠胱氨酸结石体积的影响。

材料和方法

托伐普坦（每只小鼠 0.4 毫克）或安慰剂每天通过灌胃给药，持续 30 天。氨基酸尿和胱氨酸结石进行分析，以评估在防止药效升使用几种分析方法-cystine石增长。数据录入SPSS，采用配对样本T检验进行分析。p值 < 0.05 被认为是显着的。

结果

与对照组相比，托伐普坦治疗组小鼠的液体摄入量和尿量均显着增加。托伐普坦组尿胱氨酸浓度低于实验前基线浓度。治疗后，与对照组相比，托伐普坦治疗的小鼠结石生长显着延迟，总体结石体积积累量较低。托伐普坦组增加的结石体积小于对照组（8.00 ± 4.93 mm ³对 27.90 ± 4.48 mm ³，p  < 0.001）。对照组血清肌酐（11.75±1.634 μmol/L）高于托伐普坦组（7.625±1.401 μmol/L）（p = 0.0759）。此外，托伐普坦可显着抑制膀胱镜取石术后小鼠结石的形成和生长。

结论

本研究表明，托伐普坦通过增加胱氨酸尿症小鼠的液体摄入量和尿量来预防l-胱氨酸结石的生长。