Pharmacotherapy in kidney disease: what it takes to move from general guidance to specific recommendations to stratified subgroups of patients - the tale of autosomal dominant polycystic kidney disease (ADPKD).

Abstract

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary condition that leads to a range of systemic manifestations. Many of them require pharmacological interventions. Most patients receive multidrug therapy.

Areas covered: The review summarizes prevalent ADPKD manifestations that might require pharmacological intervention and the most common drug therapies. It lists 2 to 3 prescribed drugs for each manifestation of ADPKD. The review identifies the drug transporters and drug-metabolizing enzymes associated with these drugs, as well as potential drug-drug interactions. To fulfill these aims, a literature search was conducted on PubMed, covering the period from 2021 to July 2024.

Expert opinion: ADPKD therapy often focuses on treating a single manifestation of the disease. However, ADPKD is a complex condition that requires multidrug treatment. While doses of renally eliminated drugs are adjusted in ADPKD patients to account for renal function decline, the condition may change the expression and function of renal and hepatic drug-metabolizing enzymes and transporters, which could result in misevaluations in drug dosing in ADPKD patients and result in under- or overdosing, as well as drug-drug interactions. PBPK modeling offers a valuable tool to predict drug-drug interactions, preventing overdosing, and support precision dosing in patients with ADPKD.