Hyperkalemia Risk And The Effect Of Finerenone In Patients With Diabetes And Chronic Kidney Disease: An Analysis From Fidelity

Introduction

Finerenone (FIN) reduced CV and kidney events in patients (pts) with chronic kidney disease (CKD) and type 2 diabetes (T2D) in FIDELITY, a pooled analysis of the FIDELIO-DKD and FIGARO-DKD trials. Clinically relevant hyperkalemia- (HK-) related AEs were infrequent but the perceived risk may limit FIN use in pts with high risk of increased serum K+. Currently, no incident HK risk models exist in pts with CKD and T2D to identify those at high risk. Using FIDELITY data, we developed a risk prediction model and analyzed FIN efficacy in reducing the incidence of cardiorenal outcomes across pts with different HK risk levels.

Methods

Adults with CKD and T2D receiving RASi were randomized to FIN or placebo (PBO). New-onset HK was defined by serum K+ >5.5 mmol/l. Variables independently associated with HK were identified with Cox models with stepwise selection using PBO data and validated with FIN data. An integer risk score was built based on β-coefficients of variables retained in the final model; the score was divided into low, intermediate, and high HK risk categories. FIN efficacy was assessed across HK risk categories tertiles.

Results

7 baseline variables were independently associated with incident treatment-emergent serum K+ >5.5 mmol/l (Table). Model C-index (SE) was 0.732 (0.012); the model was well-calibrated across HK risk deciles at 2 years. Pts were divided into HK risk categories based on derived integer risk score tertiles: low (0-3 points), intermediate (4-6 points), and high-risk (7-12 points; Table). The score ranged from 0-12 points, with a mean (SD) of 4.7 (2.1) points. Treatment-emergent serum K+ >5.5 mmol/l was increased in pts with a higher HK risk category; 2.7%, 7.0%, and 16.7% of pts assigned PBO reported an event in the low-, intermediate- and high-risk group. In the FIN risk groups, this finding was confirmed (Fig). FIN reduced major CV and kidney event incidence vs PBO irrespective of HK risk category.

Conclusions

Based on FIDELITY data, we developed and validated an easy-to-use integer risk score model for new-onset HK in patients with CKD and T2D. The risk score enables HK risk identification of individual patients, irrespective of FIN treatment. As FIN benefited pts across all HK risk categories, the developed risk score could facilitate tailored follow-up and therapeutic strategies aimed to mitigate HK in high-risk patients with indication for FIN.