Efficacy and safety of finerenone in patients with chronic kidney disease: an individual participant data pooled analysis (INFINITY)

Abstract

Background: Overactivation of the mineralocorticoid receptor is a common pathway for chronic kidney disease (CKD) progression across multiple disease aetiologies. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, has shown kidney and cardiovascular benefits in CKD due to type 2 diabetes, but its efficacy and safety across disease aetiologies, and levels of glycaemia, estimated glomerular filtration rate (eGFR), and albuminuria have not been evaluated. The aim of this study was to evaluate the efficacy and safety of finerenone across the spectrum of CKD.

Methods: We conducted an individual participant data meta-analysis of three randomised, double-blind, placebo-controlled trials of finerenone in patients with CKD: FIDELIO-DKD (NCT02540993; Sept 17, 2015, to April 14, 2020), FIGARO-DKD (NCT02545049; Sept 17, 2015, to Feb 2, 2021), and FIND-CKD (NCT05047263; Sept 21, 2021, to Feb 2, 2026). We used Cox regression models to evaluate relative effects on kidney and cardiovascular outcomes. The main kidney outcome was kidney failure or sustained 57% or more decline in eGFR; the main cardiovascular outcome was hospitalisation for heart failure or cardiovascular death. This study was registered with PROSPERO, CRD420251269149.

Findings: Across the three trials enrolling 14 574 participants, the mean age was 63·7 years (SD 10·6), 4467 (30·7%) were female, 10 107 (69·3%) were male, mean eGFR was 56·4 mL/min per 1·73 m2 (SD 21·4), and median urinary albumin-to-creatinine ratio was 567·4 mg/g (IQR 233·6-1164·7). Finerenone reduced the risk of the composite kidney outcome by 24% versus placebo (22·3 vs 28·8 events per 1000 patient-years; hazard ratio 0·76 [95% CI 0·68-0·86]) and kidney failure alone (0·85 [0·74-0·99]). Finerenone reduced the risk of the composite cardiovascular outcome versus placebo (19·1 vs 23·9 events per 1000 patient-years; 0·80 [0·70-0·91]), including heart failure hospitalisation (0·78 [0·66-0·92]) and cardiovascular death (0·82 [0·67-0·999]). Finerenone also reduced the risk of all-cause death (0·88 [0·79-0·99]). Treatment effects on the composite kidney outcome were consistent irrespective of glycaemic status, CKD aetiology, baseline eGFR, albuminuria, and use of sodium-glucose co-transporter-2 inhibitors. Hyperkalaemia occurred more frequently with finerenone than with placebo, but the absolute incidence of hyperkalaemia leading to hospitalisation was low.

Interpretation: In the studied populations with CKD, finerenone reduced the risk of CKD progression, including kidney failure alone, and reduced heart failure hospitalisation, cardiovascular death, and all-cause death. These findings support finerenone as a foundational therapy for CKD across a broad range of disease aetiologies and levels of glycaemia, eGFR, and albuminuria.