How to individualise renoprotective therapy in obese patients with chronic kidney disease: a commentary by the Diabesity Working Group of the ERA.

Abstract

The inter-related pandemics of obesity and type 2 diabetes mellitus (T2DM) are fueling a rise in the prevalence of chronic kidney disease (CKD), which amplifies the risk of cardiovascular events and which may progress to end-stage kidney disease (ESKD). Treatment options for such patients have rapidly expanded over the past decade, and continue to evolve. Herein, we primarily focus on glucagon-like peptide-1 receptor agonists (GLP-1RAs) and their role in the management of CKD in the setting of overweight/obesity and T2DM. Recommendations from the recent KDIGO CKD guidelines are summarised, and new evidence arising since publication of these guidelines is highlighted. We review clinical studies supporting the role of GLP-1RAs in patients with diabesity and CKD, including the FLOW trial, as well as exploring potential mechanisms of their nephroprotective effects. Their role in the management of patients with ESKD on maintenance dialysis and after kidney transplantation, while less evidence-based, is also discussed. The potential for other gut hormone-based therapies including GLP-1/GIP dual agonists (tirzepatide), triple agonists (incorporating glucagon agonism), and amylin analogues to improve cardiovascular and kidney outcomes in patients with CKD is explored. We highlight the role of novel therapies distinct from the gut-kidney axis, including nsMRAs. We outline the potential for multi-target therapy incorporating RAASis, SGLT2is, incretin-based treatments and nsMRAs to improve cardiovascular and kidney outcomes in patients with overweight/obesity and T2DM. Current unknowns in the timing and sequence of multi-target therapy in patients with CKD are emphasised. Priority research questions for the future are highlighted throughout the review.