June 27, 2026Open Access
View Full PaperSystolic blood pressure and albuminuria reduction mediate cardiovascular benefits of finerenone in T2 diabetes and CKD
Key Result
Early reductions in UACR and SBP jointly mediated 50% (95% CI 21-100) of the long-term cardiovascular benefit of finerenone in patients with type 2 diabetes and chronic kidney disease.
Key Points
- This research aims to quantify the pathways through which finerenone reduces cardiovascular events in patients with type 2 diabetes and chronic kidney disease.
- Causal mediation analysis was performed using individual patient data from FIDELITY with 12,143 participants.
- Mediators included changes in urine albumin-to-creatinine ratio (UACR), systolic blood pressure (SBP), body weight, and serum potassium over 4 months.
- Outcome models employed parametric accelerated failure time regression with Weibull distribution.
- Finerenone reduced UACR by 32.2% (95% CI 30.3 to 34.2) and SBP by 3.6 mmHg (95% CI 3.1 to 4.1).
- UACR mediated 39% (95% CI 7 to 71) and SBP mediated 21% (95% CI 3 to 40) of cardiovascular outcomes.
- Together, UACR and SBP accounted for 50% (95% CI 21 to 100) of the cardiovascular benefit from finerenone.
Structured PICO
Do early reductions in UACR and SBP mediate the cardiovascular benefits of finerenone in patients with type 2 diabetes and chronic kidney disease?
P
Population
12,143 patients with type 2 diabetes and chronic kidney disease from the pooled FIDELITY analysis.
I
Intervention
Finerenone
O
Outcome
Time from month 4 to first cardiovascular event (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization)composite
Early reductions in UACR and SBP jointly account for half of finerenone's long-term cardiovascular benefit in patients with T2D and CKD, supporting their use as complementary indicators of cardiovascular efficacy.
Main Result
Effect estimate: 50% mediation (95% CI 21-100)
Abstract
Abstract Background and Hypothesis Finerenone reduces cardiovascular events in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The cardiovascular benefit emerges within months, before measurable kidney protection, but the early pathways carrying it are not comprehensively quantified. We hypothesized that early reductions in urine albumin-to-creatinine ratio (UACR) and systolic blood pressure (SBP) jointly mediate a substantial proportion of finerenone’s long-term cardiovascular benefit, whereas changes in body weight and serum potassium do not. Methods We performed causal mediation analysis using individual patient data from FIDELITY (pooled FIDELIO-DKD and FIGARO-DKD; n = 12,143). Mediators were change from baseline to month 4 in log urine albumin-to-creatinine ratio (UACR), systolic blood pressure (SBP), body weight, and serum potassium. The outcome was time from month 4 to first cardiovascular event (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization). Outcome models used parametric accelerated failure time regression with Weibull distribution. Joint mediation by UACR and SBP was estimated by bootstrapping. Results At month 4, finerenone reduced UACR by 32.2% (95% CI 30.3 to 34.2), SBP by 3.6 mmHg (3.1 to 4.1), and body weight by 0.23 kg (0.13 to 0.32), and increased serum potassium by 0.19 mEq/L (0.17 to 0.20). Although all four biomarkers changed significantly, only UACR and SBP mediated cardiovascular outcomes: UACR mediated 39% (95% CI 7 to 71) and SBP mediated 21% (3 to 40); body weight and potassium did not. Jointly, UACR and SBP mediated 50% (95% CI 21 to 100) of the cardiovascular benefit. Conclusions In T2D and CKD, early reductions in UACR and SBP jointly account for half of finerenone’s long-term cardiovascular benefit. Body weight and potassium changes do not mediate the benefit, supporting UACR and SBP as complementary indicators of cardiovascular efficacy.