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

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.

Objective: 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.