FIDELITY Analysis Details Benefits of Early Albuminuria Reduction in CKD

Data from a study presented at the American Society of Nephrology Kidney Week 2023 emphasize the importance of addressing albuminuria as part of early management strategies in chronic kidney disease (CKD).

An analysis of data from FIDELITY, results of the analysis suggest the change in UACR from baseline to month 4 mediates a considerable proportion of the treatment effect against CKD progression and a modest proportion of the effect against cardiovascular outcomes during the 4-year study period.

“We found that, if you use the drug and you had a reduction in albuminuria of 30% or more, there was an 84% mediation by albuminuria on the kidney outcomes. In other words, most of the effect of the drug was traveling through albuminuria reduction,” said study presenter Rajiv Agarwal, MD, professor of medicine at the Indiana University School of Medicine and co-chair of the FIDELIO-DKD and FIGARO-DKD Steering Committee, in an interview with HCPLIve Nephrology.

The basis of the US Food and Drug Administration’s approval of finerenone in people with type 2 diabetes and CKD, the FIDELIO-DKD and FIGARO-DKD trials contained 13,026 patients, including 12,512 with UACR data available at baseline and/or month 4, which became the study population for the Kidney Week 2023. Among this cohort, 6273 received finerenone and 6239 received placebo therapy.^1,2,3

Results of the investigators’ analysis suggested those receiving finerenone experienced a 31% greater reduction in UACR at 4 months than their counterparts receiving placebo (33.6 [-0.9 to 5.7]vs 2.6 [-38.2 to 32.3]). Investigators pointed out 73% of the placebo arm experienced a reduction in UACR of less than 30% while 53% of patients receiving finerenone experienced a UACR of 30% or greater.¹

When examining the effect of UACR reduction and mediation on composite kidney outcomes, results indicated experiencing an early reduction in UACR of 30% or greater was associated with a lower relative risk of adverse kidney outcomes compared with their counterparts with a reduction of less than 30%, regardless of treatment arm.¹

Investigators highlighted UACR reduction, when assessed as a continuous variable mediated 84% (0.49 to 1.00) and 37% (0.08 to 0.65) of the treatment effect of finerenone on the kidney and cardiovascular outcomes, respectively. Further analysis using UACR as a dichotomous variable indicated the proportions of kidney and cardiovascular outcomes mediated were 64% and 26%, respectively.¹

To learn more about this study and how it emphasizes the role of addressing albuminuria early in the management of CKD, HCPLive Nephrology sat down Agarwal for further perspective.

Agarwal’s disclosures of note include Bayer, Boehringer Ingelheim, Chinook, CSL Vifor, Diamedica, Eli Lilly and Company, and others.

References:

1. Agarwal R, Tu W, Farjat AE, et al. Impact of Finerenone-induced albuminuria reduction on chronic kidney disease outcomes in type 2 diabetes: A causal mediation analysis. Paper Presented at: American Society of Nephrology Kidney Week 2023. November 1-5, 2023.
2. FDA updates Finerenone label to reflect Cardiovascular Outcomes Data. HCP Live. September 8, 2022. Accessed November 2, 2023. https://www.hcplive.com/view/fda-updates-finerenone-label-to-reflect-cardiovascular-outcomes-data.
3. Campbell P. Finerenone (Kerendia) approved for chronic kidney disease associated with type 2 diabetes. HCP Live. July 9, 2021. Accessed November 2, 2023. https://www.hcplive.com/view/finerenone-kerendia-approved-chronic-kidney-disease-associated-with-type-2-diabetes.