Finerenone in Persons with Chronic Kidney Disease without Diabetes

Authors, Journal, Affiliations, Type, DOI

• Authors: Hiddo J.L. Heerspink, Brendon L. Neuen, Rajiv Agarwal, David Z.I. Cherney, Carolyn S.P. Lam, Katherine R. Tuttle, Christoph Wanner, Pantelis Sarafidis, Niels Jongs, J. David Smeijer, Meike Brinker, Nicole Rethemeier, Patrick Schloemer, Paula Vesterinen, David Goldsbury, Sara Dizayee, Jon W. Mares, Vlado Perkovic, for the FIND-CKD Investigators
• Journal: New England Journal of Medicine (NEJM) 2026;395:533-545
• Affiliations: George Institute for Global Health (Sydney), University Medical Center Groningen, Indiana University, University of Toronto, National Heart Centre Singapore, University of Washington, University of Würzburg, Aristotle University of Thessaloniki, Bayer, University of New South Wales
• Type: Phase 3, international, double-blind, randomized, placebo-controlled trial
• DOI: 10.1056/NEJMoa2604625
• ClinicalTrials.gov: NCT05047263

Overview

FIND-CKD is a landmark Phase 3 RCT (n=1,584) that examined whether finerenone — a nonsteroidal mineralocorticoid receptor antagonist (MRA) previously shown to improve kidney and cardiovascular outcomes in CKD with type 2 diabetes — provides similar benefits in adults with CKD without diabetes. Participants with eGFR 25 to <90 ml/min/1.73m² and albuminuria (UACR 200–3500 mg/g) on background RAS inhibitor therapy were randomized to finerenone (10 or 20 mg daily, eGFR-adjusted) or placebo. Finerenone significantly slowed the annual rate of eGFR decline (−3.3 vs −4.0 ml/min/1.73m²/year; difference 0.7; P<0.001) and reduced the composite of kidney or cardiovascular events (HR 0.77; P=0.04). This is the first trial to establish finerenone's kidney-protective efficacy in non-diabetic CKD, extending the drug's indication beyond the diabetic CKD population.

Keywords

Finerenone, nonsteroidal mineralocorticoid receptor antagonist, chronic kidney disease, non-diabetic CKD, eGFR slope, albuminuria, FIND-CKD, randomized controlled trial

Key Takeaways

BACKGROUND

• Finerenone improved kidney and cardiovascular outcomes in patients with type 2 diabetes and CKD in prior randomized trials (FIDELIO-DKD, FIGARO-DKD).
• Whether finerenone has similar effects in patients without diabetes who have CKD was unknown.
• Overactivation of the mineralocorticoid receptor is implicated in CKD pathophysiology through increased sodium/fluid retention and activation of proinflammatory and profibrotic processes.
• More than half of CKD cases globally are in persons without diabetes. Despite RAS inhibitors and SGLT2 inhibitors, progressive kidney function loss and adverse cardiovascular outcomes still occur.

METHODS — Trial Design

• Design: Phase 3, international, prospective, double-blind, randomized, placebo-controlled trial.
• Sponsor: Bayer; designed by steering committee and sponsor.
• Independent oversight: Data and safety monitoring committee; independent data confirmation at University Medical Center Groningen.
• Population: Adults without diabetes (no type 1/type 2 diabetes diagnosis; HbA1c <6.5%) with CKD.
• Key inclusion: eGFR ≥25 to <60 + UACR 200–500 mg/g, or eGFR ≥25 to <90 + UACR 500–3500 mg/g; serum K⁺ ≤4.8 mmol/L; stable ACEi/ARB dose ≥4 weeks.
• Key exclusion: Polycystic kidney disease, lupus nephritis, ANCA-associated vasculitis; immunosuppressive therapy within 6 months; indication for steroidal MRA.
• Randomization: 1:1 to oral finerenone or placebo; stratified by baseline SGLT2i use (yes/no) and screening UACR (≤1000 vs >1000).
• Dosing: Finerenone initiated at 20 mg/day (if screening eGFR ≥60) or 10 mg/day (if eGFR 25 to <60); dose uptitration from 10→20 mg permitted from month 1 if K⁺ ≤4.8 and eGFR not decreased >30%; dose reduction or temporary withholding for K⁺ >5.5 mmol/L.
• Visits: Screening, baseline, months 1/3/6/9/12, then every 4 months; minimum treatment 32 months.

Outcomes

• Primary efficacy: Total eGFR slope (mean annual rate of change in eGFR from baseline to month 32), analyzed by two-slope linear spline mixed-effects model with fixed change point at month 3.
• Secondary (hierarchical testing): (1) Composite of kidney or CV events (sustained ≥57% eGFR decline, kidney failure, HF hospitalization, or CV death); (2) Composite kidney outcome (sustained ≥57% eGFR decline or kidney failure); (3) Composite CV outcome (HF hospitalization or CV death).
• Exploratory: Chronic eGFR slope (month 3 to treatment discontinuation); eGFR change 4 weeks post-treatment; UACR change at month 6; composite of sustained ≥40% eGFR decline or kidney failure.
• Safety: Adverse events, hyperkalemia (K⁺ >5.5 and >6.0 mmol/L), hospitalization for hyperkalemia, permanent discontinuation due to hyperkalemia.

Statistical Analysis

• Sample size: 1,500 participants → >90% power to detect 0.7 ml/min/1.73m²/year slower eGFR decline (two-sided α=0.05).
• Primary analysis: Two-slope linear spline mixed-effects model (change point at month 3 to separate acute from chronic eGFR effects).
• Intercurrent events (dialysis, transplant, death) handled by composite strategy with multiple imputation using unfavorable eGFR values.
• Sensitivity analyses: multiple imputation with discontinuation indicators, tipping-point analysis, shared-parameter model.

RESULTS

Participants

• Between September 2021 and May 2023: 3,231 assessed → 1,584 randomized (793 finerenone, 791 placebo).
• Median treatment period: 36.6 months.
• Discontinued trial: 0.5% finerenone vs 0.3% placebo.
• Discontinued trial regimen: 19.8% vs 22.4%.
• Baseline characteristics (balanced): Mean age 54.7 years; 33.8% women; median UACR 818.9 mg/g; 99.7% on RAS inhibitor; 17.0% on SGLT2 inhibitor.

Primary Outcome — Total eGFR Slope

• Mean baseline eGFR: 46.8±16.2 (finerenone) vs 46.6±16.0 (placebo) ml/min/1.73m².
• Acute eGFR effect (baseline to month 3): eGFR increased 1.2 ml/min/1.73m² more with finerenone than placebo (hemodynamic response opposite to SGLT2i).
• Total eGFR slope (baseline to month 32): −3.3 (95% CI −3.6 to −3.1) vs −4.0 (95% CI −4.3 to −3.8) ml/min/1.73m²/year.
• Between-group difference: 0.7 ml/min/1.73m²/year (95% CI 0.3 to 1.1; P<0.001).
• At month 32: mean eGFR 39.4±18.2 vs 38.1±18.4 ml/min/1.73m².
• Effect consistent across all prespecified subgroups (SGLT2i use, UACR strata, eGFR).
• Results confirmed by cystatin C-based eGFR, shared-parameter model, and all sensitivity analyses.

Secondary Outcomes

• Composite kidney/CV events: 13.9% vs 16.9%; HR 0.77 (95% CI 0.60–0.99; P=0.04); 4.7 vs 5.8 events/100 person-years.
• Composite kidney outcome: HR 0.78 (95% CI 0.60–1.01; P=0.06 — not significant).
• Composite CV outcome: HR 0.60 (95% CI 0.27–1.33) — not significant; underpowered for CV endpoints.
• Proportional-hazards assumption not violated.

Exploratory Outcomes

• eGFR change 4 weeks post-treatment: −8.8 vs −11.2 ml/min/1.73m² (difference 2.4; 95% CI 1.3–3.5).
• UACR change at month 6: −41.3% vs −9.1% (relative difference 35.4%; 95% CI 30.9–39.6); sustained over time.
• UACR reduction ≥30% at month 6: 56.0% vs 24.4% (OR 3.99; 95% CI 3.22–4.95).
• Composite ≥40% eGFR decline or kidney failure: 21.2% vs 26.0%; HR 0.76 (95% CI 0.62–0.93).
• Systolic BP change at month 3: −5.1 mmHg vs −0.1 mmHg.
• Diastolic BP change at month 3: −3.1 mmHg vs <−0.1 mmHg.

Safety

• Any adverse event: 68.3% finerenone vs 65.4% placebo.
• Serious adverse events: 20.9% vs 21.2%.
• Discontinuation due to AE: 2.1% vs 2.9%.
• Death (any cause): 2.4% vs 3.5%.
• Hyperkalemia (any): 17.0% vs 13.3% (135 vs 105 participants).
• K⁺ >5.5 mmol/L: 18.8% vs 12.2%.
• K⁺ >6.0 mmol/L: 4.3% vs 2.3%.
• Hyperkalemia → hospitalization: 0.9% vs 0.6%.
• Hyperkalemia → permanent discontinuation: 1.5% vs 0.1% (12 vs 1 participant).
• No fatal hyperkalemia events.
• Acute kidney injury: Similar between groups; <0.5% led to permanent discontinuation.
• Symptomatic hypotension: Low and similar between groups.

Limitations

• Predominantly male population with advanced CKD and severe albuminuria; few Black participants.
• Excluded polycystic kidney disease, lupus nephritis, ANCA-associated vasculitis, and patients with very low eGFR or low-level albuminuria — findings cannot be generalized to all CKD etiologies.
• Not powered for clinical outcomes (CV composite HR 0.60 but wide CI 0.27–1.33; kidney composite HR 0.78 narrowly missed significance P=0.06).
• eGFR slope as surrogate: While increasingly accepted as a CKD trial endpoint (validated by Inker meta-analysis), clinical outcome confirmation requires larger/longer trials.
• SGLT2i use only 17% at baseline; while efficacy appeared consistent, the trial was not designed to test additive benefit.
• Single-drug comparison against placebo on RAS inhibitor background; no comparison with steroidal MRAs (spironolactone/eplerenone).
• Short-term follow-up (32 months) for a chronic progressive disease; long-term safety and durability of benefit unknown.

Key Concepts Mentioned

• entities/Finerenone — nonsteroidal MRA; FIND-CKD extends kidney protection evidence to non-diabetic CKD
• concepts/Mineralocorticoid-Receptor-Antagonists-Post-MI — broader MRA evidence framework; FIND-CKD adds non-diabetic CKD nephroprotection
• concepts/Chronic-Kidney-Disease — non-diabetic CKD epidemiology, pathophysiology, and now three-pillar pharmacotherapy (RASi + SGLT2i + MRA)
• concepts/SGLT2-Inhibitors-in-CKD — complementary mechanism; 17% of FIND-CKD participants on SGLT2i at baseline
• concepts/Aldosterone-Synthase-Inhibitors — related aldosterone pathway inhibition strategy (upstream enzyme inhibition)

Key Entities Mentioned

• entities/Finerenone — Kerendia (Bayer); now with evidence spanning diabetic and non-diabetic CKD plus HFpEF/HFmrEF

Wiki Pages Updated

• wiki/sources/Finerenone-FIND-CKD-NEJM-2026.md — created (this page)
• wiki/entities/Finerenone.md — FIND-CKD trial data added; CKD non-diabetic indication; source_count updated
• wiki/concepts/Mineralocorticoid-Receptor-Antagonists-Post-MI.md — Connections updated
• wiki/concepts/Chronic-Kidney-Disease.md — created; comprehensive CKD concept
• wiki/sourceindex.md — source entry added
• wiki/wikiindex.md — concept entry added
• log.md — ingest entry appended