Outcomes of KDIGO-Defined CKD in U.S. Veterans With HFpEF, HFmrEF, and HFrEF

Abstract

Background

Chronic kidney disease (CKD) is defined by the KDIGO (Kidney Disease: Improving Global Outcomes) guideline as abnormal kidney structure or function, present for >3 months, with implications for health. KDIGO-defined CKD is associated with poor outcomes in patients with heart failure (HF). Less is known about whether these associations vary by left ventricular ejection fraction.

Objectives

This study aims to determine the prevalence and outcomes of KDIGO-defined CKD in heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF), and heart failure with reduced ejection fraction (HFrEF).

Methods

Of the 1,446,053 veterans with an HF diagnosis (1991-2017) in the national Veterans Affairs electronic health record data, 365,000 with data on EF had KDIGO-defined CKD or normal kidney function (NKF). CKD was defined as 2 values measured 90 days apart of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² (categorized into 4 eGFR stages based on the last eGFR: 45-59 mL/min/1.73 m², 30-44 mL/min/1.73 m², 15-29 mL/min/1.73 m², and <15 mL/min/1.73 m²) or urinary albumin-to-creatinine ratio (uACR) >30 mg/g (albuminuria). NKF was defined as 2 values measured >90 days apart of eGFR ≥60 mL/min/1.73 m², without eGFR <60 mL/min/1.73 m² or albuminuria for 3 years before HF diagnosis. Patients were categorized into HFpEF (EF ≥50%, n = 85,855), HFmrEF (EF 41%-49%, n = 39,397), and HFrEF (EF ≤40%, n = 139,748). HRs and 95% CIs for 5-year all-cause mortality and HF hospitalization through December 31, 2022, associated with the 5 CKD groups (vs NKF) were estimated using Cox regression.

Results

Among patients with HF and NKF, mortality occurred in 39%, 37%. and 41%, and HF hospitalization occurred in 12%, 15%, and 21% of those with HFpEF, HFmrEF. and HFrEF, respectively. Compared with NKF, CKD was associated with 16%, 19%, and 26% higher multivariable-adjusted risks for death in patients with HFpEF, HFmrEF, and HFrEF, respectively. Respective risks for HF hospitalization were 31%, 33%, and 32% higher. The eGFR-associated risks were incrementally higher with decreasing eGFR, except for eGFR <15 mL/min/1.73 m², likely because of the initiation of dialysis during follow-up. Albuminuria was associated with 16%, 10%, and 12% higher multivariable-adjusted risks for death and 29, 30%, and 24% for HF hospitalization in HFpEF, HFmrEF, and HFrEF, respectively. All associations were statistically significant.

Conclusions

These findings based on KDIGO-defined CKD and NKF provide new information about the best estimates of true prevalence and outcomes of CKD in HFpEF, HFmrEF, and HFrEF.