Abstract and Introduction
Abstract
Background: In FIGARO-DKD, finerenone reduced the risk of cardiovascular events in patients with type 2 diabetes (T2D) and stage 1–4 chronic kidney disease (CKD). In FIDELIO-DKD, finerenone improved kidney and cardiovascular outcomes in patients with advanced CKD. This analysis further explores kidney outcomes in FIGARO-DKD.
Methods: FIGARO-DKD (NCT02545049) included patients with urine albumin-to-creatinine ratio (UACR) 30–<300 mg/g and estimated glomerular filtration rate (eGFR) 25–90 mL/min/1.73 m2 or UACR 300–5000 mg/g and eGFR ≥60 mL/min/1.73 m2. Outcomes included two composite kidney endpoints, a composite of ≥40% decrease in eGFR from baseline sustained over ≥4 weeks, kidney failure or renal death, and a composite of ≥57% decrease in eGFR from baseline sustained over ≥4 weeks, kidney failure or renal death. Changes in albuminuria and eGFR slope were also analyzed. Kidney and CV outcomes were evaluated by baseline UACR.
Results: A lower incidence rate for the eGFR ≥40% kidney composite endpoint was observed with finerenone compared with placebo, but the between-group difference was not significant [hazard ratio (HR) = 0.87; 95% confidence interval (CI): 0.76–1.01; P = .069]. A greater treatment effect was observed on the eGFR ≥57% kidney composite endpoint (HR = 0.77; 95% CI: 0.60–0.99; P = 0.041) with a 36% relative risk reduction for end-stage kidney disease. A larger magnitude of effect on kidney outcomes was observed with finerenone versus placebo for patients with severely increased albuminuria than with moderately increased albuminuria. Improvements in UACR, eGFR slope and cardiovascular risk were evident in both subgroups with finerenone.
Conclusions: The present analyses suggest that finerenone protects against kidney disease progression and cardiovascular events in patients with T2D and early- or late-stage CKD.
Graphical Abstract
Introduction
Diabetes is one of the main causes of kidney failure,[1] and approximately 40% of patients with type 2 diabetes (T2D) globally are estimated to be affected by chronic kidney disease (CKD).[2] Patients with CKD and T2D are also at increased risk of cardiovascular (CV) morbidity and mortality; compared with T2D alone, and comorbid CKD increases the risk of all-cause and CV mortality approximately threefold.[3] Albuminuria is an independent and robust prognostic marker of progression to kidney failure as well as CV disease. The risk of CV mortality and heart failure (HF) in patients with diabetes increases as albuminuria progresses beyond a urine albumin-to-creatinine ratio (UACR) of 10 mg/g and as estimated glomerular filtration rate (eGFR) falls below 75 mL/min/1.73 m2.[4] Standard-of-care in CKD and T2D includes control of blood glucose and blood pressure, and guidelines recommend treatment with a renin–angiotensin system (RAS) inhibitor and a sodium-glucose co-transporter-2 inhibitor (SGLT-2i) in most patients.[5,6] However, patients with CKD and T2D remain at high risk of CV events and kidney disease progression despite best-recommended therapy, particularly for patients in whom albuminuria persists.[7,8] Therefore, there remains a high therapeutic unmet need in these patients and an opportunity for drugs with mechanisms of action that extend beyond glomerular hemodynamics.[7]
Finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist (MRA) that slowed CKD progression and improved CV outcomes versus placebo in patients with predominantly stage 3–4 CKD with severely increased albuminuria in the Phase 3 FIDELIO-DKD trial.[9] FIGARO-DKD was a parallel study investigating the effect of finerenone in patients with earlier stages of CKD and included more patients with moderately increased albuminuria (UACR 30–<300 mg/g), a population under-represented in other studies in CKD. FIGARO-DKD showed a statistically significant benefit favoring finerenone versus placebo for the primary CV composite endpoint (time to CV death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for HF).[10] However, although there was a trend favoring finerenone for the first secondary kidney composite endpoint in the testing hierarchy (time to kidney failure, sustained ≥40% decrease in eGFR or renal death), this difference was not statistically significant.[10]
The purpose of this exploratory analysis was to further evaluate the effects of finerenone on cardiorenal outcomes in patients with CKD and T2D beyond the results of the primary analysis. This investigation included prespecified subgroup analyses by baseline albuminuria to evaluate for treatment-effect heterogeneity.
Nephrol Dial Transplant. 2023;38(2):372-383. © 2023 Oxford University Press
