Dietary Aspects and Drug-Related Side Effects in Autosomal Dominant Polycystic Kidney Disease Progression

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most commonly inherited kidney disease. In the absence of targeted therapies, it invariably progresses to advanced chronic kidney disease. To date, the only approved treatment is tolvaptan, a vasopressin V2 receptor antagonist that has been demonstrated to reduce cyst growth and attenuate the decline in kidney function. However, it has various side effects, the most frequent of which is aquaresis, leading to a significant discontinuation rate. The strategies proposed to combat aquaresis include the use of thiazides or metformin and a reduction in the dietary osmotic load. Beyond the prescription of tolvaptan, which is limited to those with a rapid and progressive decline in kidney function, dietary interventions have been suggested to protect against disease progression. Moderate sodium restriction, moderate protein intake (up to 0.8 g/kg/day), avoidance of being overweight, and increased water consumption are recommended in ADPKD guidelines, though all with low-grade evidence. The aim of the present review is to critically summarize the evidence on the effect of dietary modification on ADPKD and to offer some strategies to mitigate the adverse aquaretic effects of tolvaptan.

Metabolism-based approaches for autosomal dominant polycystic kidney disease

“…Trial testing metformin in ADPKD should be completed by 2026 and provide valuable information ( Testa and Magistroni, 2020 ). Weight loss targeting metabolic alterations has the potential to be a disease modifying intervention in ADPKD, but behavioral dietary interventions are limited by long-term adherence ( Quiroga and Torra, 2022 ) so it will be important to explore the potential of bariatric surgery and pharmacological approaches. Therefore, it is tempting to speculate that interventions targeting downstream events such as metabolic reprogramming may retain and improve on the tolerability and efficacy reported with Tolvaptan offering potential new therapeutic opportunities.…”