Investigating new treatment opportunities for patients with chronic kidney disease in type 2 diabetes: the role of finerenone

Abstract

Despite the standard of care, patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) progress to dialysis, are hospitalized for heart failure and die prematurely. Overactivation of the mineralocorticoid receptor (MR) causes inflammation and fibrosis that damages the kidney and heart. Finerenone, a nonsteroidal, selective MR antagonist, confers kidney and heart protection in both animal models and Phase II clinical studies; the effects on serum potassium and kidney function are minimal. Comprising the largest CKD outcomes program to date, FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) and FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease) are Phase III trials investigating the efficacy and safety of finerenone on kidney failure and cardiovascular outcomes from early to advanced CKD in T2D. By including echocardiograms and biomarkers, they extend our understanding of pathophysiology; by including quality of life measurements, they provide patient-centered outcomes; and by including understudied yet high-risk cardiorenal subpopulations, they have the potential to widen the scope of therapy in T2D with CKD. Trial registration number: FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049).

Keywords: CKD; albuminuria; clinical trial; diabetic kidney disease; mineralocorticoid receptor antagonist.

FIGURE 1

Schematic representation of the pathophysiological effects of MR overactivation and the subsequent impact of MRA intervention using finerenone or spironolactone. K⁺, potassium; Na⁺, sodium

FIGURE 2

Percentage of patients with a treatment-emergent adverse event of hyperkalemia defined as serum potassium ≥5.6 mEq/L in Phase II finerenone trials. Data are point estimates ± 95% CIs. eple: eplerenone; F: finerenone; HFrEF: heart failure with reserved ejection fraction; spiro: spironolactone.

FIGURE 3

FIDELIO-DKD and FIGARO-DKD endpoints. ^aKidney failure defined as occurrence of ESKD (initiation of chronic dialysis for ≥90 days or renal transplantation) or sustained eGFR <15 mL/min/1.73 m². HF: heart failure; HRQoL: health-related quality of life; MI: myocardial infarction.

FIGURE 4

(A) Overlap of patient populations according to inclusion values for UACR and eGFR in the FIDELIO-DKD and the FIGARO-DKD trials. (B) Pooled data showing the baseline KDIGO risk categories of patients included in the FIDELIO-DKD and FIGARO-DKD trials (KDIGO score risk category data were missing for 4 patients in the FIDELIO-DKD trial and 10 patients in the FIGARO-DKD trial). Values are presented as n (%).

FIGURE 5.

Comparison of baseline median UACR (mg/g) and mean eGFR (mL/min/1.73 m²) of patients enrolled in recent trials investigating cardiovascular and/or renal outcomes in patients with CKD in T2D (circle sizes are proportional to the population sizes of the trials.) [12, 14, 43–49].