Impact of Finerenone-Induced Albuminuria Reduction on Chronic Kidney Disease Outcomes in Type 2 Diabetes : A Mediation Analysis.
Publication Title
Annals of internal medicine
Document Type
Article
Publication Date
12-1-2023
Keywords
washington; spokane; Humans; Diabetes Mellitus, Type 2; Mediation Analysis; Diabetic Nephropathies; Albuminuria; Renal Insufficiency, Chronic; Renal Insufficiency; Glomerular Filtration Rate
Abstract
BACKGROUND: In patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), finerenone, a nonsteroidal mineralocorticoid receptor antagonist, reduces cardiovascular and kidney failure outcomes. Finerenone also lowers the urine albumin-to-creatinine ratio (UACR). Whether finerenone-induced change in UACR mediates cardiovascular and kidney failure outcomes is unknown.
OBJECTIVE: To quantify the proportion of kidney and cardiovascular risk reductions seen over a 4-year period mediated by a change in kidney injury, as measured by the change in log UACR between baseline and month 4.
DESIGN: Post hoc mediation analysis using pooled data from 2 phase 3, double-blind trials of finerenone. (ClinicalTrials.gov: NCT02540993 and NCT02545049).
SETTING: Several clinical sites in 48 countries.
PATIENTS: 12 512 patients with CKD and T2D.
INTERVENTION: Finerenone and placebo (1:1).
MEASUREMENTS: Separate mediation analyses were done for the composite kidney (kidney failure, sustained =57% decrease in estimated glomerular filtration rate from baseline [approximately a doubling of serum creatinine], or kidney disease death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) outcomes.
RESULTS: At baseline, median UACR was 514 mg/g. A 30% or greater reduction in UACR was seen in 3338 (53.2%) patients in the finerenone group and 1684 (27.0%) patients in the placebo group. Reduction in UACR (analyzed as a continuous variable) mediated 84% and 37% of the treatment effect on the kidney and cardiovascular outcomes, respectively. When change in UACR was analyzed as a binary variable (that is, whether the guideline-recommended 30% reduction threshold was met), the proportions mediated for each outcome were 64% and 26%, respectively.
LIMITATION: The current findings are not readily extendable to other drugs.
CONCLUSION: In patients with CKD and T2D, early albuminuria reduction accounted for a large proportion of the treatment effect against CKD progression and a modest proportion of the effect against cardiovascular outcomes.
PRIMARY FUNDING SOURCE: Bayer AG.
Clinical Institute
Kidney & Diabetes
Specialty/Research Institute
Endocrinology
Specialty/Research Institute
Nephrology
DOI
10.7326/M23-1023
