A prespecified analysis explored renal outcomes in a group of 903 patients with glomerular disease diagnoses who received either finerenone or placebo.
In an analysis, researchers recruited participants with investigator-reported glomerular diseases from the phase 3 randomized, double-blind, placebo-controlled FIND-CKD clinical trial. The parent trial enrolled 1,584 adult patients with nondiabetic chronic kidney disease across 24 countries and regions. The participants received finerenone 10 mg or 20 mg once daily (n = 446) or placebo (n = 457) in addition to stable, maximum-tolerated dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.
Among the participants with glomerular diseases, the total estimated glomerular filtration rate (eGFR) slope through 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, for a between-group difference of 0.73 mL/min/1.73 m² per year. Kidney failure or sustained eGFR decline of 40% or more occurred at rates of 7.42 vs 9.60 events per 100 patient-years with finerenone and placebo, respectively.
Among the 903 participants with glomerular diseases, 46.1% (n = 416) of them had immunoglobulin A nephropathy, 23.8% (n = 215) had focal segmental glomerulosclerosis, 10% (n = 90) had membranous nephropathy, 2.9% (n = 26) had membranoproliferative glomerulonephritis, and 17.3% (n = 156) had other glomerular diseases. Overall, 78.8% (n = 712) of the participants had undergone kidney prior to before enrollment.
Finerenone was associated with a reduction in eGFR from randomization to 3 months compared with placebo. After 3 months, finerenone attenuated chronic eGFR decline by 1.22 mL/min/1.73 m² per year. The researchers reported no evidence that the treatment effects differed by glomerular disease subtype or baseline sodium-glucose cotransporter 2 inhibitor use for total eGFR slope analyses.
In the immunoglobulin A nephropathy subgroup, finerenone reduced urinary albumin-to-creatinine ratio by 47% compared with placebo.
“The observed 47% reduction in the urinary albumin-to-creatinine ratio at 12 months (and 58% reduction in urinary protein-to-creatinine ratio) in the [immunoglobulin A nephropathy] cohort compares favorably with recently approved therapies,” wrote lead study author Brendon L. Neuen, MBBS, PhD, of The George Institute for Global Health at the University of New South Wales in Australia, and colleagues.
Subgroup analyses of total eGFR slope yielded a treatment effect of 1.34 mL/min/1.73 m² per year among the participants with focal segmental glomerulosclerosis and 0.61 mL/min/1.73 m² per year among those with immunoglobulin A nephropathy. The estimates were less precise for membranous nephropathy, membranoproliferative glomerulonephritis, and other glomerular diseases.
Eligible participants had an eGFR of 25 to less than 60 mL/min/1.73 m² and a urinary albumin-to-creatinine ratio of at least 200 mg/g to less than 500 mg/g or an eGFR of 25 to less than 90 mL/min/1.73 m² and a urinary albumin-to-creatinine ratio of at least 500 mg/g to less than 3,500 mg/g. The participants were required to have a serum potassium level of 4.8 mmol/L or less and be receiving stable angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy. Those with type 1 or type 2 diabetes, lupus nephritis, antineutrophil cytoplasmic antibody-associated vasculitis, polycystic kidney disease, and symptomatic heart failure with reduced ejection fraction were excluded, as were patients receiving systemic immunosuppressive therapy for kidney disease within 6 months prior to screening.
The safety findings were consistent with those of the overall FIND-CKD population. Serious adverse events occurred in 20% of participants receiving finerenone and 21% of those receiving placebo. Serious investigator-reported hyperkalemia occurred in less than 1% of participants in both groups, and adverse events leading to permanent discontinuation of study treatment occurred in 3% and 4%, respectively.
The researchers noted several limitations. The analysis was exploratory, kidney disease etiology was based on investigator-reported diagnoses, and approximately one-fifth of the participants did not have biopsy confirmation. When available, biopsy specimens were historical rather than obtained at study entry. In addition, patients receiving immunosuppressive therapy for kidney disease were excluded. The study was not powered to assess time-to-event kidney outcomes or to detect differences in eGFR slope across glomerular disease subgroups.
The FIND-CKD trial was funded by Bayer AG. Full disclosures of the study authors can be found in the published study.
Source: JAMA
