Kidney Failure Risk Equation and Risk of Kidney and Cardiovascular Outcomes in Patients with Heart Failure with Reduced Ejection Fraction: Insights from PARADIGM-HF

Abstract Background and Aims The use of the Kidney Failure Risk Equation (KFRE) is guideline recommended in patients with chronic kidney disease (CKD) to predict risk of kidney failure, however, this has not been well studied in patients with heart failure (HF). Methods The KFRE score incorporates baseline urine albumin-creatinine ratio (UACR), age, sex, and estimated glomerular filtration rate (eGFR). Among patients with HF and reduced EF (HFrEF) and CKD in PARADIGM-HF, we explored the association of the 2- and 5-year KFRE score continuously, risk-based categories, and in quartiles with subsequent cardiovascular and kidney outcomes. Results Among 794 patients with HFrEF and eGFR60 ml/min/1.73m2 with all KFRE variables available, median 5-year KFRE score was 0.63% 0.28%-1.67%. Patients with higher KFRE baseline score had higher systolic blood pressure and NT-proBNP levels and were more likely to have a history of diabetes or atrial fibrillation, or to be treated with diuretics at baseline. The KFRE 5-year score was not significantly associated with the composite of ESKD or 50% decline in eGFR (HR 1.45; 95% CI 0.93-2.25; P=0.10), although confidence limits were wide in light of few events. Continuous KFRE 5-year score was associated with cardiovascular death or HF hospitalization (HR 1.22; 95% 1.09-1.36; P0.001) and all-cause mortality (HR 1.24; 95% CI 1.10-1.39; P0.001). Conclusions These data suggest that the KFRE is associated with risk of cardiovascular events in patients with HFrEF. However, as the median KFRE was low in PARADIGM-HF, these data require validation in HF populations with more advanced CKD.