TY - JOUR
T1 - Impact of Finerenone-Induced Albuminuria Reduction on Chronic Kidney Disease Outcomes in Type 2 Diabetes
AU - FIDELIO-DKD and FIGARO-DKD Investigators
AU - Agarwal, Rajiv
AU - Tu, Wanzhu
AU - Farjat, Alfredo E.
AU - Farag, Youssef M.K.
AU - Toto, Robert
AU - Kaul, Sanjay
AU - Lawatscheck, Robert
AU - Rohwedder, Katja
AU - Ruilope, Luis M.
AU - Rossing, Peter
AU - Pitt, Bertram
AU - Filippatos, Gerasimos
AU - Anker, Stefan D.
AU - Bakris, George L.
N1 - Publisher Copyright:
© 2023 American College of Physicians.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - 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.
AB - 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.
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U2 - 10.7326/M23-1023
DO - 10.7326/M23-1023
M3 - Article
C2 - 38048573
AN - SCOPUS:85180405726
SN - 0003-4819
VL - 176
SP - 1606
EP - 1616
JO - Annals of internal medicine
JF - Annals of internal medicine
IS - 12
ER -