Kidney Week

Abstract: PO2528

Association of Urine Albumin-to-Creatinine Ratio and Its Early Change with Cardiorenal Outcomes in FIDELIO-DKD: A Mediation Analysis

Session Information

• Late-Breaking Clinical Trials Posters
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Agarwal, Rajiv, Richard L Roudebush VA Medical Center, Indianapolis, Indiana, United States

Rajiv Agarwal,

• Anker, Stefan D., Berlin Institute of Health Center for Regenerative Therapies, Berlin, Berlin, Germany

Stefan D. Anker,

• Pitt, Bertram, University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States

Bertram Pitt,

• Ruilope, Luis M., Institute of Research imas12, Madrid, Spain

Luis M. Ruilope,

• Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark

Peter Rossing,

• Brinker, Meike Daniela, Bayer AG, Berlin, Nordrhein-Westfalen, Germany

Meike Daniela Brinker,

• Joseph, Amer, Bayer AG, Berlin, Nordrhein-Westfalen, Germany

Amer Joseph,

• Lawatscheck, Robert, Bayer AG, Berlin, Nordrhein-Westfalen, Germany

Robert Lawatscheck,

• Scott, Charlie, Bayer plc, Reading, Berkshire, United Kingdom

Charlie Scott,

• Filippatos, Gerasimos, Attikon University Hospital, Athens, Athens, Greece

Gerasimos Filippatos,

• Bakris, George L., The University of Chicago Medicine, Chicago, Illinois, United States

George L. Bakris,

Background

The selective, nonsteroidal mineralocorticoid receptor antagonist finerenone slowed chronic kidney disease (CKD) progression and improved cardiovascular (CV) outcomes in patients with CKD and type 2 diabetes (T2D) in FIDELIO-DKD (NCT02540993). Previous studies have shown that treatment-induced urine albumin-to-creatinine ratio (UACR) reduction correlates with kidney and CV benefits. Here, we investigate the association of UACR and its early change with the magnitude of cardiorenal protection.

Methods

Patients (N=5674) with T2D, UACR ≥30–≤5000 mg/g and estimated glomerular filtration rate (eGFR) 25–<75 mL/min/1.73 m² receiving optimized renin–angiotensin system blockade were randomized 1:1 to finerenone or placebo. Key outcomes included a kidney composite of time to kidney failure, sustained ≥40% or ≥57% eGFR decline from baseline, or renal death, and a CV composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Outcomes were assessed using cubic-basis splines including UACR at baseline and change in UACR from baseline to month 4 as continuous variables. Mediation analyses were performed to determine the proportion of change in UACR to month 4 contributing to the kidney and CV benefits of finerenone.

Results

Finerenone was associated with a 31% greater reduction in the UACR from baseline to month 4 than placebo (ratio of least-squares mean change from baseline, 0.69; 95% confidence interval 0.66–0.71). Overall, the risk of adverse kidney and CV outcomes increased as UACR at baseline increased. Reduction in UACR from baseline to month 4 was also associated with a reduction in risk for kidney outcomes. Mediation analyses indicated a variable proportion of the kidney and CV benefits observed with finerenone could be explained by early change in UACR.

Conclusion

Finerenone resulted in early reductions in UACR in patients with T2D and CKD that are associated with its beneficial effects on kidney and CV outcomes. We will discuss early changes in UACR as a biomarker of subsequent finerenone-associated cardiorenal benefit.

Funding

• Commercial Support – Bayer AG