Brendon L. Neuen, V Perkovic, Rajiv Agarwal, D Cherney, C S P Lam, Christoph Wanner, K R Tuttle, Pantelis Sarafidis, Jonathan Barratt, Anna Burgner, Xiangmei Chen, Alfredo Chew‐Wong, Vladimir A. Dobronravov, Jürgen Floege, Kieran McCafferty, Masaomi Nangaku, David Packham, Evangelos Papachristou, Pablo E. Pérgola, Marijn M. Speeckaert, Arunkumar Subbiah, Sydney CW Tang, Shuifu Tang, See Cheng Yeo, Niels Jongs, J David Smeijer, Mario Berger, Meike Brinker, Rania Dayoub, Jay Elliott, Na Li, Katharina Mueller, Nicole Rethemeier, Marina Yael Finkelsztein, Hiddo J. L. Heerspink, FIND-CKD Investigators, Glenn M. Chertow, Tim Friede, Adeera Levin, Johannes F.E. Mann, Rafaël Maldonado, Paola Aguerre, Paula Arenas, M. Arriola, Claudia Emilce Baccaro, Maria Bevilacqua, Julio Bittar, Dafne Brodschi, Julia Cáceres, Gina Campestri, Maria Cecilia Cantero, Santiago Cardona, Florencia Casan, Evelin Cassini, Gustavo Catalano, Mariano Chahin, Natalia Cluigt, Ana Florencia Comes, Pamela Delgado, Maria Paula Dionisi, Silvina Dominguez, Rocio Fernandez, Elizabeth Gelersztein, Sandra Giacometti, Diego Andres Mohr Gosparini, Fernando Pedro Guerlloy, Fernando Halac, Miguel Hominal, Cecilia Igarzabal, Veronica Lacoste, Micaela Leis, Pablo Martinez, Virginia Rama, Lucia Rodriguez, Silvia Rodriguez, Luciana Rovegno, Benjamin Saenz, Maria Victoria Sobredo, Matias Suarez, Patricia Varela, Guido Villalobo, Sernia Virginia, Diego Waserman, Daniela Magali Zaccaro, Javier Zaidman, S Badve, Melissa Cheetham, Jenny Chen, Kathryn Ducharlet, Dov Degen, Yusuf Eqbal, Adam Flavell, Celine Foote, Nicholas Gray, Carmel Hawley, Peter Hollett, Jane Holt, Louis Huang, Nicole Isbel, Dev Jegatheesan
Importance: 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. Objectives: To evaluate the efficacy and safety of finerenone in patients with glomerular diseases. Design, Setting, and Participants: 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. Intervention: Finerenone 10 mg or 20 mg taken orally once daily (n = 446) vs matching placebo (n = 457). Main Outcomes and Measures: 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). Results: 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). Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT05047263.