Physicians' Academy for Cardiovascular Education

CV benefits and safety with nonsteroidal MRA in stage 4 CKD

Outcomes with Finerenone in Participants with Stage 4 CKD and Type 2 Diabetes: A FIDELITY Subgroup Analysis

Literature - Sarafidis P, Agarwal R, Pitt B, et al. - Clin J Am Soc Nephrol. 2023 Mar 17 [Online ahead of print]. doi: 10.2215/CJN.0000000000000149

Introduction and methods


In an effort to optimize treatment for patients with both T2DM and CKD, several drugs are being investigated. However, treatment options are limited for T2DM patients with stage 4 CKD, a population that is also understudied. The FIDELIO-DKD trial recently demonstrated that the selective, nonsteroidal MRA finerenone reduced the risk of the primary composite renal outcome in T2DM patients with a mean eGFR of 44.3 mL/min per 1.73 m²2 and median urine albumin-to-creatinine ratio (UACR) of 852 mg/g [1], whereas the FIGARO-DKD trial showed finerenone reduced the risk of the primary composite CV outcome in patients with less advanced CKD [2]. The data of these 2 trials were pooled in the FIDELITY dataset.

Aim of the study

In an exploratory subgroup analysis of the FIDELITY dataset, the authors evaluated the efficacy and safety of finerenone versus placebo in patients with T2DM and stage 4 CKD.


This was a subgroup analysis of FIDELITY (Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD trial programme analysis), a prespecified, individual participant data pooled analysis of the FIDELIO-DKD and FIGARO-DKD trials (n=13,026) with a median follow-up duration of 3.0 years [3]. The FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) and FIGARO-DKD (Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease) trials were multicenter, double-blind, placebo-controlled, phase 3 RCTs in which patients with T2DM and CKD were randomized to finerenone (10 or 20 mg once daily based on eGFR at the screening visit) or placebo.

For this subgroup analysis, participants were categorized by CKD stage at baseline: stage 4 (eGFR <30 mL/min per 1.73 m²) (n=890; 7%) or stages 1–3 (eGFR ≥30 mL/min per 1.73 m²) (n=12,133; 93%).


To assess efficacy, CV and renal endpoints were employed. The CV endpoint was a composite outcome of time to CV death, nonfatal MI, nonfatal stroke, or hospitalization for HF. The renal endpoint was a composite outcome of time to kidney failure, sustained eGFR decrease ≥57% from baseline for ≥4 weeks, or kidney disease death. Kidney failure was defined as end-stage renal disease (i.e., initiation of long-term dialysis (for ≥90 days) or kidney transplantation) or sustained eGFR decrease <15 mL/min per 1.73 m² for ≥4 weeks. Other efficacy endpoints were the individual components of the composite CV and renal endpoints and changes in eGFR and UACR over time.

Safety outcomes included investigator-reported adverse events and changes in systolic blood pressure and serum potassium over time.

Main results

CV outcomes

Renal outcomes

Safety outcomes


In this exploratory subgroup analysis of the FIDELITY dataset, the CV benefits and safety profile of finerenone versus placebo in patients with T2DM and stage 4 CKD were similar to those seen in the overall FIDELITY population. The effects of finerenone on the composite renal endpoint were inconsistent over time, with a slower accumulation of first renal events with finerenone compared with placebo only observed in the first 2 years. However, finerenone did improve markers of kidney injury (as shown by a reduction in UACR) and function (better preservation of eGFR in the chronic phase) in stage 4 CKD patients over time.


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Find this article online at Clin J Am Soc Nephrol.

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