Nephrology · Medical Literature
Finerenone in Patients With Chronic Kidney Disease Due to Glomerular Diseases: A Randomized Clinical Trial.
Abstract
Glomerular diseases are a leading cause of chronic kidney disease (CKD) and kidney failure. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces the risk of kidney function loss in CKD, but its effects in individuals with CKD due to glomerular diseases are uncertain. To evaluate the efficacy and safety of finerenone in patients with glomerular diseases. Prespecified exploratory subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled trial conducted across 24 countries and regions, focusing on participants with an investigator-reported glomerular disease diagnosis. The overall trial enrolled adults with nondiabetic CKD and an estimated glomerular filtration rate (eGFR) of either (1) at least 25 to less than 60 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 200 mg/g to less than 500 mg/g or (2) an eGFR of at least 25 to less than 90 mL/min/1.73 m2 and urinary albumin to creatinine ratio of at least 500 mg/g to less than 3500 mg/g. Finerenone 10 mg or 20 mg taken orally once daily (n = 446) vs matching placebo (n = 457). Annualized rate of eGFR decline (total eGFR slope) from baseline to month 32 (primary outcome of the main trial); percent change in albuminuria to 12 months; and a composite outcome of kidney failure or sustained 40% or more decline in eGFR (prespecified exploratory outcomes). Of 1584 participants, 903 (57.0%) had investigator-reported glomerular disease, including 416 (46.1%) with immunoglobulin A nephropathy, 215 (23.8%) with focal segmental glomerulosclerosis, and 90 (10.0%) with membranous nephropathy. Participants with glomerular disease (mean [SD] age, 51.1 [13.6] years; 362 female [40.1%]; 558 Asian [61.9%]) had a mean eGFR of 48.8 mL/min/1.73 m2 and median urinary albumin to creatinine ratio of 839.6 mg/g. The total eGFR slope up to 32 months was -3.50 mL/min/1.73 m2 per year with finerenone and -4.23 mL/min/1.73 m2 per year with placebo (0.73 mL/min/1.73 m2 per year difference; 95% CI, 0.22-1.24). Finerenone reduced albuminuria at month 12 by 42% (95% CI, 35%-48%) and lowered the risk of kidney failure or 40% or more eGFR decline (7.42 vs 9.60 events per 100 patient-years; hazard ratio, 0.74; 95% CI, 0.57-0.97). In this exploratory analysis, treatment with finerenone slowed kidney function decline, reduced albuminuria, and lowered the risk of kidney failure or substantial loss of kidney function in patients with glomerular diseases. These findings suggest an important role for finerenone in preserving kidney function in this population. ClinicalTrials.gov Identifier: NCT05047263.
Clinical relevance
In adults with non-diabetic chronic kidney disease attributed to glomerular diseases, does finerenone (a nonsteroidal mineralocorticoid receptor antagonist) slow the rate of eGFR decline and reduce the risk of kidney failure or substantial eGFR loss compared with placebo when added to background RAS inhibition? __SNAPSHOT__ {"studyDesign":"Prespecified exploratory subgroup analysis of a phase 3, randomized, double-blind, placebo-controlled trial (FIND-CKD; NCT05047263)","setting":"24 countries and regions; multinational academic and clinical nephrology centers","sampleSize":"n=903 with investigator-reported glomerular disease (finerenone: n=446, placebo: n=457) drawn from the overall FIND-CKD trial (N=1,584)","population":"Adults with non-diabetic CKD attributable to glomerular disease (46.1% IgA nephropathy, 23.8% focal segmental glomerulosclerosis, 10.0% membranous nephropathy, 2.9% membranoproliferative GN, 17.3% other); mean age 51.1 years, 40.1% female, 61.9% Asian; mean eGFR 48.8 mL/min/1.73 m², median UACR 839.6 mg/g; all receiving maximum-tolerated RAS inhibition (ACEi or ARB). Excluded: ADPKD, lupus nephritis, ANCA-associated vasculitis.","intervention":"Finerenone 10 mg or 20 mg orally once daily (dose based on eGFR and serum potassium at baseline)","comparator":"Matching placebo once daily","primaryOutcome":"Annualized rate of eGFR decline (total eGFR slope) from baseline to month 32, assessed via a two-slope linear spline mixed-effects model (same primary outcome as the parent FIND-CKD trial)","followUp":"32 months (trial completion rate 99.1%)","fundingSource":"Industry (Bayer)"}
Key findings
PRIMARY OUTCOME — eGFR SLOPE: The total eGFR slope over 32 months was −3.50 mL/min/1.73 m²/year with finerenone versus −4.23 mL/min/1.73 m²/year with placebo, yielding a between-group difference of 0.73 mL/min/1.73 m²/year (95% CI, 0.22–1.24). A p-value for this subgroup analysis was not separately reported; the CI excludes the null. The eGFR slope benefit was particularly pronounced in the FSGS subgroup (difference = 1.34 mL/min/1.73 m²/year; 95% CI, 0.29–2.39). A two-phase slope pattern was observed: an early acute eGFR dip of −1.01 mL/min/1.73 m²/year (95% CI, −1.80 to −0.22) within the first 3 months, followed by attenuation of chronic eGFR loss of 1.22 mL/min/1.73 m²/year (95% CI, 0.72–1.73) thereafter. ALBUMINURIA: Finerenone reduced UACR by 42% at 12 months (95% CI, 35%–48%). In the IgAN subgroup specifically, UACR reduction was 47% and urinary protein-to-creatinine ratio was reduced by 58%. A concomitant 52% reduction in UPCR was also reported. COMPOSITE KIDNEY OUTCOME: Kidney failure or sustained ≥40% eGFR decline occurred at 7.42 versus 9.60 events per 100 patient-years (finerenone vs. placebo; HR 0.74; 95% CI, 0.57–0.97). The absolute rate difference is 2.18 events per 100 patient-years (calculated). NNT over the study period was not reported. No evidence of treatment effect heterogeneity across glomerular disease subtypes or by baseline SGLT2 inhibitor use was observed for the eGFR slope. SAFETY: Hyperkalemia occurred in 14.3% of the finerenone group versus 7.6% in the placebo group. Serious investigator-reported hyperkalemia was <1% in both groups. Adverse events leading to permanent discontinuation were 3% (finerenone) versus 4% (placebo). Serious adverse event rates were 19.5% (finerenone) versus 21.4% (placebo).
Practice implications
This analysis establishes that finerenone significantly attenuated eGFR decline, reduced albuminuria, and lowered the composite risk of kidney failure or substantial eGFR loss in adults with non-diabetic CKD due to heterogeneous glomerular diseases. The findings apply to patients with moderate-to-severe albuminuria (UACR 200–3,500 mg/g) already receiving maximally tolerated RAS blockade, predominantly those with IgAN, FSGS, and membranous nephropathy. The notably large representation of Asian patients (61.9%) warrants caution when extrapolating to other racial/ethnic groups. Critically, this is a prespecified EXPLORATORY SUBGROUP ANALYSIS — not an independently powered confirmatory trial. As such, formal hypothesis testing with adjusted significance thresholds was not performed for most endpoints, and results must be interpreted as hypothesis-generating. The study does NOT establish whether finerenone provides additive benefit over and above SGLT2 inhibitors or disease-specific agents (e.g., sparsentan, budesonide for IgAN) in clinical practice, as direct head-to-head comparisons were not performed. The acute eGFR dip at treatment initiation (analogous to RAS inhibitors and SGLT2 inhibitors) should be anticipated but does not appear to negate long-term benefit. Disease subtype diagnoses were investigator-reported without mandatory biopsy confirmation, introducing potential misclassification. The promising FSGS signal — in the context of the failed DUPLEX trial with sparsentan — is biologically plausible given mineralocorticoid receptor expression on podocytes, but requires dedicated trial confirmation. Practice change should await either regulatory approval for this indication or prospectively powered glomerular disease-specific trials; however, given the strength of the parent FIND-CKD trial and the consistency of effect across subtypes, incorporation into supportive care protocols may be considered alongside existing guideline-directed therapies. Only abstract-level and conference presentation data supplemented by secondary press sources were available for full numerical verification; clinicians should consult the full peer-reviewed JAMA publication (doi:10.1001/jama.2026.9923) for complete data tables, pre-specified statistical analysis plans, and safety summaries. __LIMITATIONS__ Exploratory prespecified subgroup analysis of a larger trial — not independently powered; formal alpha-controlled hypothesis testing for the glomerular subgroup was not performed, so all p-values and CIs should be interpreted as exploratory rather than confirmatory.,Glomerular disease etiologies were investigator-reported without mandatory kidney biopsy confirmation, risking disease misclassification across subtypes.,Marked demographic imbalance: 61.9% Asian, ~60% male, and only 2–3% Black participants, limiting generalizability to diverse real-world populations.,Absence of direct comparison with or on top of SGLT2 inhibitors (as protocolized add-on), disease-specific agents (sparsentan, budesonide, calcineurin inhibitors), or immunosuppressive therapy; additive or synergistic effects cannot be assessed.,Industry-sponsored (Bayer) trial with multiple investigator financial conflicts of interest disclosed; potential for selective reporting or optimistic framing of subgroup results.,The primary endpoint (eGFR slope) is a validated surrogate — not a patient-level clinical event endpoint such as ESKD or mortality — and the translation of a 0.73 mL/min/1.73 m²/year slope improvement to long-term clinical benefit has inherent uncertainty.,Trial excluded patients with ADPKD, lupus nephritis, and ANCA-associated vasculitis — common causes of glomerular disease — reducing generalizability.,Although treatment effect appeared consistent across subtypes, subgroup-by-subgroup analyses (e.g., FSGS) were based on small numbers (n=215) and the wide CIs preclude definitive conclusions for individual disease entities.,The 32-month follow-up may be insufficient to capture divergence in hard clinical outcomes (dialysis initiation, mortality) between arms. __BOTTOM_LINE_CATEGORY__ potentially_practice_informing __BOTTOM_LINE__ In this prespecified exploratory analysis of the FIND-CKD trial, finerenone added to maximum-tolerated RAS inhibition attenuated eGFR decline by 0.73 mL/min/1.73 m²/year, reduced albuminuria by 42% at 12 months, and lowered the hazard of kidney failure or ≥40% eGFR decline by 26% (HR 0.74; 95% CI, 0.57–0.97) across heterogeneous non-diabetic glomerular diseases including IgAN, FSGS, and membranous nephropathy. Because these are exploratory subgroup findings from an industry-sponsored trial, without mandatory biopsy confirmation and with significant Asian over-representation, they are best regarded as strongly hypothesis-generating rather than definitively practice-changing. Pending regulatory label expansion and dedicated confirmatory trials, nephrology clinicians may reasonably consider finerenone as a component of supportive care in this population — particularly given a manageable safety profile — but should weigh these results alongside disease-specific approved therapies and individual patient risk profiles.