Galectin-3 as a prognostic biomarker in hemodialysis patients with preserved or mildly reduced ejection fraction

Abstract Background Risk prediction for heart failure (HF) and mortality in hemodialysis (HD) patients with preserved or mildly reduced left ventricular ejection fraction (LVEF) is challenging, as conventional markers often underperform. Galectin-3, a biomarker of fibrosis and inflammation, may offer prognostic value, but its utility in this population remains unclear. Method We prospectively enrolled 244 incident HD patients with LVEF ≥ 40%. The primary outcome was a composite of cardiovascular (CV) death or acute HF hospitalization. Secondary outcomes included all-cause mortality and individual primary outcome components. Predictive performance was assessed by comparing a baseline clinical model with models incorporating brain natriuretic peptide (BNP) and/or galectin-3, using area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results Mean baseline LVEF was 59.5%, and median BNP and galectin-3 levels were 357.5 pg/mL and 34.3 ng/mL, respectively. Over a median follow-up of 37 months, high galectin-3 levels (≥34.3 ng/mL) were associated with higher incidence rates of the primary outcome (14.09 vs. 5.87 per 100 person-years PYs) and all-cause mortality (14.09 vs. 6.33 per 100 PYs). In multivariate analysis, elevated galectin-3 independently predicted the composite outcome (HR 2.16; 95% CI 1.17–4.00; P = 0.014), acute HF (HR 2.11; 95% CI 1.07–4.14, P = 0.033), and all-cause mortality (HR 1.90; 95% CI 1.04–3.55, P = 0.043). Adding galectin-3 to the clinical model significantly improved discrimination (AUC 0.735 vs. 0.678; ΔAUC = 0.057; P = 0.025) and reclassification metrics (NRI = 0.565; IDI = 0.058; both P 0.001). In contrast, BNP addition did not significantly enhance prediction. Conclusion In incident HD patients with LVEF ≥ 40%, elevated galectin-3 was an independent predictor of CV death or acute HF events, and provided incremental prognostic value beyond conventional clinical parameters and BNP. These findings support galectin-3 as a complementary biomarker for enhanced risk stratification in this population.