Renal function largely influences Galectin-3 prognostic value in heart failure

•Gal-3 has been considered a cardiac fibrosis and remodeling marker.•Gal-3 correlates highly with renal function.•Gal-3 correlates highly with Cystatin C.•The prognostic value of Gal-3 in HF declines when adjusted by renal function.•Gal-3 might possibly be considered a cardio-renal biomarker.

BackgroundGalectin-3 (Gal-3) has been associated with cardiac remodeling and heart failure (HF) prognosis. Renal function is also a well known HF prognostic indicator. The link between renal insufficiency, HF, and Gal-3 is not completely elucidated.Methods and resultsWe explored the association between Gal-3 and renal function in a cohort of 876 consecutive ambulatory patients with HF (mean age: 68 years; mean left ventricular ejection fraction [LVEF]: 36%), 52.2% had HF etiology of ischemic heart disease. Circulating Gal-3 was highly correlated with estimated glomerular filtration rate (eGFR), calculated with either the chronic kidney disease-epidemiology (CKD-EPI) equation (r = − 0.64) or the CKD-EPI-cystatin-C equation (r = − 0.59) and with Cystatin-C levels (r = 0.70), after adjusting for age, sex, New York Heart Association (NYHA) functional class, LVEF, and HF etiology (all p < 0.001). Patients were stratified by CKD-EPI-eGFR (ml/min/1.73 m2), as follows: ≥ 60 (n = 218), 30 to 59 (n = 434), and < 30 (n = 224). In these strata, Gal-3 significantly increased (median [IQR]: 12.3 [10.4-15.6]; 16.1 [13-19.8]; and 24.5 [20-33.8] ng/ml, respectively; trend p < 0.001). This was independent of NYHA functional class (I-II and III-IV) and LVEF (< 45% and ≥ 45%). Gal-3 was associated with mortality in univariate analyses, but after adjusting for CKD-EPI-eGFR, the hazard ratios were 1.10 (95% CI: 0.89-1.34, p = 0.39) for all cause death, and 0.90 (95% CI: 0.68-1.21, p = 0.50) for cardiovascular death. Similar results were obtained with eGFRs calculated with the CKD-EPI-cystatin-C equation.ConclusionCirculating Gal-3 was highly associated with renal function in outpatients with HF. The value of Gal-3 for HF prognosis declined after adjusting for renal function.