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SHR Neuro Cancer Cardio Lipid Metab Microb

Agarwal, R; Tu, W; Farjat, AE; Farag, YMK; Toto, R; Kaul, S; Lawatscheck, R; Rohwedder, K; Ruilope, LM; Rossing, P; Pitt, B; Filippatos, G; Anker, SD; Bakris, GL, , FIDELIO-DKD, and, FIGARO-DKD, Investigators.
Impact of Finerenone-Induced Albuminuria Reduction on Chronic Kidney Disease Outcomes in Type 2 Diabetes : A Mediation Analysis.
Ann Intern Med. 2023; 176(12): 1606-1616. Doi: 10.7326/M23-1023
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Sourij Harald

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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.

Find related publications in this database (using NLM MeSH Indexing)

Humans - administration & dosage

Diabetes Mellitus, Type 2 - complications, drug therapy

Mediation Analysis - administration & dosage

Diabetic Nephropathies - administration & dosage

Albuminuria - urine

Renal Insufficiency, Chronic - complications, drug therapy

Renal Insufficiency - administration & dosage

Glomerular Filtration Rate - administration & dosage

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