Mineralocorticoid receptor antagonist use in chronic kidney disease with type 2 diabetes: a clinical practice document by the European Renal Best Practice (ERBP) board of the European Renal Association (ERA)

Abstract

Chronic kidney disease (CKD) in individuals with type 2 diabetes (T2D) represents a major public health issue; it develops in about 30-40% of patients with diabetes mellitus and is the commonest cause of CKD worldwide. Patients with CKD and T2D are at high risk of both developing kidney failure and of cardiovascular events. Renin-angiotensin system (RAS) blockers were considered the cornerstone of treatment of albuminuric CKD in T2D for more than 20 years. However, the residual risk of progression to more advanced CKD stages under RAS blockade remains high, while in major studies with these agents in patients with CKD and T2D no significant reductions in cardiovascular events and mortality were evident. Steroidal mineralocorticoid receptor antagonists (MRAs) are known to reduce albuminuria in individuals on RAS monotherapy, but their wide clinical use has been curtailed by the significant risk of hyperkalemia and absence of trials with hard renal outcomes. In recent years, non-steroidal MRAs have received increasing interest due to better pharmacologic profile. Finerenone, the first compound of this class, was shown to effectively reduce the progression of kidney disease and of cardiovascular outcomes in participants with T2D in phase 3 trials. This clinical practice document prepared from a task force of the European Renal Best Practice (ERBP) board summarizes current knowledge on the role of MRAs in the treatment of CKD in T2D aiming to support clinicians in decision-making and everyday management of patients with this condition.

Diabetische Nephropathie und Progressionsverlangsamung der CKD

“…Über den Mineralokortikoid-Rezeptor werden Entzündungs-und Fibroseprozesse an Herzen und Nieren unterhalten, was zu einer CKD-Progression durch Albuminurie und Glomerulosklerose führt [27]. Auch steroidale MRA hatten bereits zuvor einen albuminuriesenkenden Effekt gezeigt, weswegen ein progressionsverlangsamender Effekt nahelag [28]. Dies konnte später ebenso für Finerenon belegt werden [26].…”

Finerenone: From the Mechanism of Action to Clinical Use in Kidney Disease

“…Three randomized studies evaluated the effect of esaxerenone on albuminuria in patients with CKD and type 2 diabetes. A dose-dependent reduction in albuminuria was present in all three studies, and clinically significant hyperkalemia was rarely reported (4–9% of patients) [ 61 ]. A meta-analysis by Jiang et al (2022) showed that the use of nonsteroidal MRAs (finerenone, apararenone, and esaxerenone) in patients with type 2 diabetes and CKD reduced albuminuria and systolic blood pressure without an excess risk of serious adverse events.…”

Novel cardioprotective and nephroprotective combination in patients with type 2 diabetes and chronic kidney disease: perspectives of use

“…1). Основным принципом нефропротекции у пациентов с СД2 и ХБП в настоящее время является совокупное назначение трех классов «болезнь-модифицирующих» препаратов (иАПФ/БРА, иНГЛТ-2, финеренон) [35][36][37][38][39][40][41].…”