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

Abstract

Aim 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. Conclusions: 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.

Recent updates in therapeutic approach using tolvaptan for autosomal dominant polycystic kidney disease

“…In the subgroup analysis, the effect of preserving kidney function was prominent in patients with more severe clinical phenotypes, similar to changes in TKV. Although there have been no reports considering ESKD as an outcome, the positive effect of preserving kidney function has been maintained in most studies [22,23]. Extrapolations from the results of the TEMPO 3:4 suggested that [24].…”

An Overview of In Vivo and In Vitro Models for Autosomal Dominant Polycystic Kidney Disease: A Journey from 3D-Cysts to Mini-Pigs

“…In addition, numerous extra-renal manifestations of the disease, such as pancreatic and liver cysts, increased blood pressure, and a higher risk of cerebral aneurisms have been reported [ 9 ]. As of today, the selective vasopressin V 2 receptor antagonist tolvaptan (Jinarc ® (EU, UK, Canada), Jynarque ® (USA), Samsca ® (Japan)) is the only available treatment that can slow cyst growth in ADPKD patients [ 10 , 11 ]. Through the inhibition of the binding of the antidiuretic hormone arginine vasopressin (AVP) to its receptor, tolvaptan diminishes cAMP production and thus cAMP-associated cyst cell proliferation and cyst fluid secretion.…”