Galectin-3 is linked to peripheral artery disease severity, and urinary excretion is associated with long-term mortality

BACKGROUND AND AIMS: Galectin-3 (Gal-3) is a biomarker involved in fibrosis and vascular inflammation. Gal-3 has been linked to chronic kidney disease (CKD) and patients with peripheral artery disease (PAD). Conflicting reports exist about the relevance of Gal-3 in PAD. The study aims to elucidate a possible link between serum and urinary Gal-3 and long-term survival in PAD patients without critical limb ischemia and mild to moderate CKD.

METHODS: Galectin-3 (Gal-3) was measured in serum (n = 311) and urine (n = 266) of PAD patients (age 69 (62-77) years) by bead-based multiplex assay. Urinary Gal-3 concentration was normalized to urine creatinine (cr) levels. Mortality data were retrieved from the Austrian central death registry after a median observation period of 9.2 years. Survival analyses were performed by the Kaplan-Meier method and Cox-regression.

RESULTS: Serum Gal-3 was higher in patients with claudication symptoms (p = 0.001) and correlated inversely with the patients' ankle-brachial index (R = -0.168, p = 0.009). Serum Gal-3 and urinary Gal-3 (uGal-3/cr) were associated with the estimated glomerular filtration rate (R = -0.359, p < 0.001; R = -0.285, p < 0.001). Serum Gal-3 was not linked to all-cause mortality [HR 1.17 (CI 0.96-1.42)] over 9.2 years. However, uGal-3/cr was associated with all-cause mortality [HR 1.60 (CI 1.31-1.95)]. This association sustained multivariable adjustment for cardiovascular risk factors and renal function [HR 1.71 (CI 1.35-2.17)].

CONCLUSIONS: This study is the first to show an association of uGal-3/cr and long-term mortality in patients with PAD. Gal-3 was not predictive of long-term mortality but seems to be a marker of PAD severity in patients without critical limb ischemia.