Finerenone in CKD

I read with great enthusiasm the comprehensive pooled analysis by Ostrominski et al.,1 published in JASN, examining the effects of finerenone on morbidity and mortality across the spectrum of CKD in patients with type 2 diabetes. The Finerenone in heart failure and chronic kidney disease with type 2 diabetes (FINEHEART) analysis pooled 14,180 participants from three major trials and demonstrated that finerenone reduced cardiovascular death or heart failure hospitalization by 17% and improved composite kidney outcomes by 21%. This study has several notable strengths. First, the inclusion of FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure (FINEARTS-HF) participants substantially enhanced generalizability by capturing older adults, women, and individuals with established cardiovascular disease, populations historically underrepresented in diabetic kidney disease trials. The consistency of cardiovascular benefits across a broad range of eGFR, urine albumin-creatinine ratio, and glycated hemoglobin levels supports finerenone's use earlier in the disease trajectory, aligning with contemporary cardiorenal-metabolic treatment paradigms.2 In addition, the number needed to treat of 60 for preventing cardiovascular death or heart failure hospitalization demonstrates clinically meaningful absolute risk reduction, building upon findings from the FIDELITY analysis.2 However, this study has several limitations. The exploratory analyses in populations with urine albumin-creatinine ratio <30 mg/g (n=737) or without diabetes remain underpowered, limiting definitive conclusions for these expanding CKD phenotypes. While the Family Investigation of Nephropathy and Diabetes-CKD (FIND-CKD) trial (NCT05047263) will address nondiabetic CKD,3 additional studies on normoalbuminuric populations are needed. The observed heterogeneity in kidney outcomes across trials may reflect differences in baseline kidney risk and warrants further investigation into which CKD subpopulations derive maximal renal protection, as suggested by the differential effects observed in FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease FIDELIO-DKD and FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease FIGARO-DKD.4 Although the safety profile is acceptable, it requires clinical vigilance. Although hyperkalemia-related hospitalizations were rare (1% versus 0.2%), real-world monitoring, adherence patterns, and long-term safety beyond the median follow-up of 3 years remain unexplored areas and require constant surveillance. The consistency of the safety findings across the various component trials is reassuring. Finally, the lack of multiplicity adjustment and the narrowly missed cardiovascular death end point in the overall FINE-HEART analysis necessitate cautious interpretation of the secondary outcomes. The authors have appropriately acknowledged these limitations. Notwithstanding these considerations, this comprehensive analysis substantially advances the evidence supporting finerenone as a cornerstone therapy for patients with CKD and type 2 diabetes mellitus. The consistent cardiorenal benefits (Figure 1) across diverse populations support guideline recommendations for the early initiation of mineralocorticoid receptor antagonists in this high-risk population.Figure 1: Treatment effects of finerenone across key cardiorenal outcomes. 1 , 2 , 4 CI, confidence interval; CV, cardiovascular; HF, heart failure.