Undiagnosed chronic kidney disease, outcomes, and finerenone in heart failure with preserved ejection fraction
J Ostrominski, B Claggett, A Desai, P Jhund, C Lam, M Senni, A Voors, F Zannad, F Amarante, M Brinker, P Schloemer, K Rohwedder, J Mcmurray, S Solomon, M VaduganathanAbstract
Background
Chronic kidney disease (CKD) is an important driver of disease progression and mortality in heart failure (HF) but remains underdiagnosed.
Purpose
To ascertain the prevalence of undiagnosed CKD in persons with HF and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) in a clinical trial setting, and its association with adverse cardiovascular outcomes.
Methods
In this secondary analysis of the FINEARTS-HF trial, clinical outcomes and treatment effects of finerenone versus placebo were evaluated according to baseline CKD status: no CKD, undiagnosed CKD, and diagnosed CKD (investigator-reported history of CKD, chronic glomerulonephritis, or any nephropathy). Undiagnosed CKD was defined as either estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio (UACR) ≥30 mg/g in the absence of an investigator-reported history of CKD.
Results
Among 5,797 (97%) participants with available eGFR and UACR, 1,863 (32%) had no CKD, 1,389 (24%) had diagnosed CKD, and 2,545 (44%) had undiagnosed CKD at baseline (Figure 1A). A similar prevalence of undiagnosed CKD (41%) was observed in a sensitivity analysis requiring UACR ≥30 mg/g or screening and randomization eGFR <60 mL/min/1.73 m2. Among those with undiagnosed CKD at baseline, 42% were classified as having CKD through UACR values. Participants with undiagnosed CKD had a higher mean eGFR vs. diagnosed CKD (58 vs. 48 mL/min/1.73 m2), but similar median UACR (40 vs. 37 mg/g). Compared with participants without CKD, those with undiagnosed (adjusted rate ratio [aRR], 1.45; 95% CI, 1.20-1.75) and diagnosed (aRR, 1.76; 95% CI, 1.45-2.15) CKD experienced a substantially higher rate of cardiovascular death and total HF events, with undiagnosed CKD exhibiting an intermediate risk phenotype (aRR for diagnosed vs. undiagnosed CKD, 1.21; 95% CI, 1.05-1.41; P=0.010) (Figure 1B-C). Finerenone consistently reduced cardiovascular death and total HF events in persons with and without CKD (P for interaction=0.69) (Figure 1D).
Conclusion
Undiagnosed CKD was observed in nearly half of FINEARTS-HF participants at baseline and was associated with increased risks of adverse cardiovascular outcomes. These findings amplify support for systematic CKD screening efforts inclusive of eGFR and UACR in HFmrEF/HFpEF.For image description, please refer to the figure legend and surrounding text.