Finerenone in Predominantly Advanced CKD and Type 2 Diabetes With or Without Sodium-Glucose Cotransporter-2 Inhibitor Therapy.

Abstract

INTRODUCTION:

FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) investigated the nonsteroidal, selective mineralocorticoid receptor (MR) antagonist finerenone in patients with CKD and type 2 diabetes (T2D). This analysis explores the impact of use of sodium-glucose cotransporter-2 inhibitor (SGLT-2i) on the treatment effect of finerenone.

METHODS:

Patients (N = 5674) with T2D, urine albumin-to-creatinine ratio (UACR) of 30 to 5000 mg/g and estimated glomerular filtration rate (eGFR) of 25 to <75 ml/min per 1.73 m2 receiving optimized renin-angiotensin system (RAS) blockade were randomized to finerenone or placebo. Endpoints were change in UACR and a composite kidney outcome (time to kidney failure, sustained decrease in eGFR ≥40% from baseline, or renal death) and key secondary cardiovascular outcomes (time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) (ClinicalTrials.gov, NCT02540993).

RESULTS:

Of 5674 patients, 259 (4.6%) received an SGLT-2i at baseline. Reduction in UACR with finerenone was found with or without use of SGLT-2i at baseline, with ratio of least-squares means of 0.69 (95% CI = 0.66-0.71) and 0.75 (95% CI -= 0.62-0.90), respectively (P interaction = 0.31). Finerenone also significantly reduced the kidney and key secondary cardiovascular outcomes versus placebo; there was no clear difference in the results by SGLT-2i use at baseline (P interaction = 0.21 and 0.46, respectively) or at any time during the trial. Safety was balanced with or without SGLT-2i use at baseline, with fewer hyperkalemia events with finerenone in the SGLT-2i group (8.1% vs. 18.7% without).

CONCLUSION:

UACR improvement was observed with finerenone in patients with CKD and T2D already receiving SGLT-2is at baseline, and benefits on kidney and cardiovascular outcomes appear consistent irrespective of use of SGLT-2i.

• Authors: Peter Rossing, Gerasimos Filippatos, Rajiv Agarwal, Stefan D Anker, Bertram Pitt, Luis M Ruilope, Juliana C N Chan, Adriaan Kooy, Kieran McCafferty, Guntram Schernthaner, Christoph Wanner, Amer Joseph, Markus F Scheerer, Charlie Scott, George L Bakris, FIDELIO-DKD Investigators
• Journal: Kidney international reports (Kidney Int Rep) Vol. 7 Issue 1 Pg. 36-45 (Jan 2022) ISSN: 2468-0249 [Electronic] United States
• PMID: 35005312 (Publication Type: Journal Article)
• Copyright: © 2021 International Society of Nephrology. Published by Elsevier Inc.