Effectiveness of Tolvaptan in the Treatment for Patients with Autosomal Dominant Polycystic Kidney Disease: A Meta-analysis

Author(s): Xuan Xie, Qian Cai, Xiao-Yuan Guo, Dong-Hai Bai, Hai-Zhong Sheng, Bao-Kui Wang*, Kai Yan, An-Ming Lu, Xin-Ran Wang

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 23 , Issue 1 , 2020

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Abstract:

Aims and Objective: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common chronic kidney disease that leads to End-Stage Renal Disease (ESRD). The key target of this therapy is to prevent the progression of kidney failure. Tolvaptan could slow kidney cyst growth and are proven highly effective. The aims of this analysis are to perform a systematic review, estimate and evaluate the efficacy and safety of tolvaptan in ADPKD patients.

Materials and Methods: Randomized controlled trials of tolvaptan in ADPKD were identified in PubMed, Ovid, Web of Science and the Cochrane Library electronic database. The changes observed in kidney function, treatment efficiency and the incidence of adverse events between the tolvaptan and placebo groups were compared. Data were analyzed by the RevMan software.

Results: Eight trials, including 7 double-blinded randomised controlled trials and 1 quasi RCT involving 1,536 patients were extracted. Significant differences in the annual rate of change in the total kidney volume TKV at any stages of CKD (MD = -3.32, 95%CI =-4.57,-2.07, I2 =70%) and the glomerular filtration rate (MD = 1.4, 95%CI = 0.83,1.97, I2 =0%) were observed between the tolvaptan group and the placebo group. Subgroup analysis of patients in different CKD stages also showed the same conclusion. There was an increase in the urine osmolality, and 24-hour urine volume in patients receiving tolvaptan. Tolvaptan reduced the rate of serious hypertension and kidney pain events in ADPKD patients. At higher doses, it increased the rate of adverse events (liver injuries, thirst, pollakiuria, and nocturia). There was no significant risk of bias in the included studies.

Conclusion: Tolvaptan has a beneficial effect on ADPKD, but is associated with an increase in adverse events at high doses when compared with the placebo. Further RCTs on tolvaptan may be required to support this conclusion.

Keywords: ADPKD, tolvaptan, meta-analysis, vasopressinv2-receptor antagonist, CK, kidney disease.

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VOLUME: 23
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Year: 2020
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DOI: 10.2174/1386207322666191203092715
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