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

Abstract

As a genetic disease, there has been a long-standing effort to identify therapeutic options for autosomal dominant polycystic kidney disease (ADPKD). Following the development of tolvaptan, a vasopressin 2 receptor antagonist, the treatment strategy for ADPKD patients with rapid disease progression has been changed with a disease-targeted approach. Tolvaptan showed significant efficacy in preserving kidney function and reducing the total kidney volume (TKV) growth rate. These effects were especially pronounced in patients with more severe clinical phenotypes, such as higher TKV and rapidly declining kidney function. Despite the therapeutic effects of tolvaptan, aquaretic symptoms are unavoidable side effects related to the mechanism of the drug and are also directly related to the quality of life. A shared decision-making process could be a valuable strategy for reducing the incidence of side effects and improving medication adherence. Herein, we aimed to review overall clinical trials for applying tolvaptan and suggest important factors during the shared decision-making process.

Keywords: Decision making, shared; Polycystic kidney, autosomal dominant; Tolvaptan.

Figure 1.

History of tolvaptan development from bench to clinical application. The first row shows the discovery of vasopressin V1/V2 receptors and the role of cyclic adenosine monophosphate in the development of polycystic kidney disease [57-59]. The second row shows the development of the first nonpeptide vasopressin 1 receptor (V1R) and V2R antagonists [60]. The third row and below represent the overall trials from the experimental to a clinical trial for the application of V2R antagonists and the approval status worldwide [[11,12,19,61-66]]. cAMP, cyclic AMP; PKD, polycystic kidney disease; TEMPO, Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes; REPRISE, Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD.