부산대학교 도서관

Introduction: Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for both acute and progressive kidney disease. Elevated levels of the circulating soluble urokinase plasminogen activator receptor (suPAR), Galectin-3, and soluble suppression of tumorigenicity 2 (ST2) have been associated with kidney disease progression in those with CKD. However, there is little known about their predictive value for glomerular filtration rate (GFR) decline in populations with HFrEF.Methods: We aimed to determine whether these biomarkers were associated with decline in GFR and death in patients with HFrEF. We included 310 participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life in whom baseline suPAR, Galectin-3, and ST2 and repeated measures of GFR were obtained. The primary outcome was change in 2021 CKD-EPI creatinine-based GFR over 2 years. Secondary outcome was mortality. A joint cox regression model for mortality controlled for age, sex, race, NYHA class, and change in GFR and accounted for competing risks of ventricular assist device (VAD) implantation and heart transplantation.Results: Participants were followed for 2 years or until VAD, transplant, or death. Mean age was 59 years (standard error of mean 0.7) and 36% had diabetes mellitus. Median GFR was 60 ml/min/1.73m with 58% NYHA Class III. Of these, 45 died, 33 received LVAD, and 25 were transplanted. Higher baseline suPAR (β coefficient -0.22 √(ml/min/1.73m); 95%CI -0.29, -0.15; P<0.001), Galectin-3 (β coefficient -0.02 √(ml/min/1.73m); 95%CI -0.04, -0.01; P=0.012), and ST2 (β coefficient -0.01 √(ml/min/1.73m); 95%CI -0.02, -0.01, -0.19; P<0.001) plasma concentrations were associated with a decline in eGFR over time in multivariable models. Only ST2 (HR 1.02 per ng/mL increase; 95%CI 1.01, 1.03; P<0.001) was associated with mortality, after controlling for longitudinal change in GFR.Conclusions: Higher baseline suPAR, Galectin-3, and ST2 were associated with GFR decline over 2 years in patients with HFrEF. ST2 was associated with a greater risk of mortality, while suPAR and Galectin-3 were not. These biomarkers may be incremental tools used to predict GFR decline in patients with advanced heart failure.