Galectin-3, renal function, and clinical outcomes: Results from the luric and 4D studies

Abstract

Galectin-3 has been linked to incident renal disease, experimental renal fibrosis, and nephropathy. However, the association among galectin-3, renal function, and adverse outcomes has not been described. We studied this association in two large cohorts of patients over a broad range of renal function. We measured galectin-3 concentrations in baseline samples from the German Diabetes mellitus Dialysis (4D) study (1168 dialysis patients with type 2 diabetes mellitus) and the Ludwigshafen Risk and Cardiovascular Health (LURIC) study (2579 patients with coronary angiograms). Patients were stratified into three groups: eGFR of ≥90 ml/min per 1.73 m2, 60-89 ml/min per 1.73 m2, and <60 ml/min per 1.73 m2.We correlated galectin-3 concentrationswith demographic, clinical, and biochemical parameters. The association ofgalectin-3 with clinical end pointswas assessed by Cox proportional hazards regressionwithin 10 years (LURIC) or 4 years (4D) of follow-up. Mean±SD galectin-3 concentrations were 12.8±4.0 ng/ml (eGFR≥90 ml/min per 1.73 m2), 15.6±5.4 ng/ml (eGFR 60-89 ml/min per 1.73 m2), 23.1±9.9 ng/ml (eGFR<60 ml/min per 1.73 m2), and 54.1±19.6 ng/ml (dialysis patients of the 4D study). Galectin-3 concentration was significantly associated with clinical end points in participants with impaired kidney function, but not in participants with normal kidney function. Per SD increase in log-transformed galectin-3 concentration, the risks of all-cause mortality, cardiovascularmortality, and fatal infection increasedsignificantly. Indialysispatients, galectin-3was associatedwith the combined end point of cardiovascular events. In conclusion, galectin-3 concentrations increased with progressive renal impairment and independently associated with cardiovascular end points, infections, and all-cause death in patients with impaired renal function.