GALECTIN-3, A BIOMARKER OF CARDIOVASCULAR RISK, INVERSELY CORRELATES WITH eGFR George Tidmarsh1, Pablo E. Pergola2, Bhupinder Singh3, George Fadda4, James Rolke1, Stacey Ruiz1, Gerard Smits5, Geoffrey Block6 1La Jolla Pharmaceutical Company, Inc, San Diego, CA, 2Clinical Advancement Center, San Antonio, TX, 3Southwest Kidney Institute, Tempe, AZ, 4Balboa Nephrology Medical Group, La Mesa, CA, 5CSC, Inc, Santa Barbara, CA, 6Denver Nephrology, Denver, CO Background Galectin-3: • Important mediator of fibrosis and clinically regarded as a marker of cardiovascular risk1 • Correlates with kidney function in patients with cardiovascular disease2,3 • Predicts CKD risk in the general population4 Purpose: Changes in circulating levels of Galectin-3 in patients with CKD (not ascertained based on preexisting CVD) have not been studied. We evaluated the relationship between galectin-3 levels and kidney function, as determined by eGFR, in two studies • Serum levels of galectin-3 were measured 1) retrospectively in 99 patients with an eGFR of <20 to >90 mL/min/1.73m2 and 2) cross-sectionally in 28 patients with an eGFR of 15 to 50 mL/min/1.73m2 • Galectin-3 was analyzed using an ELISA kit by BG Medicine (Waltham, MA) Methods Correlation between Galectin-3 Levels and eGFR Galectin-3 Levels and High Cardiovascular Risk in CKD Conclusions • Galectin-3 is substantially elevated in the setting of even mildly reduced eGFR • Mean levels of galectin-3 were markedly elevated at levels that correlate with CV risk in individuals with eGFR <50 mL/min/1.73m2 • Galectin-3 likely mediates both progressive CKD and CV disease • Clinical trials aimed at investigating the effect of pharmacological reductions in galectin-3 levels in CKD patients is warranted • Mean galectin-3 levels in subjects with eGFR >90 mL/min/1.73m2 were 15±3.8 ng/mL • To define high CV risk, we identified a galectin-3 threshold of >25 ng/mL (>2 SD above the mean for the >90 eGFR group) • Galectin-3 levels >25 ng/mL (High CV Risk) were found in: • >40% of subjects with eGFR of <50 mL/min/1.73m2 • >90% of subjects with eGFR of <20 mL/min/1.73m2 Retrospective Study References: 1de Boer et al, 2010 Curr Heart Fail Rep 2Tang et al, 2011 Am J Cardiol 3de Boer et al, 2012 J Intern Med 4O’Seaghdha et al, 2013 J Am Soc Nephrol Signal Transduction to Modulate Cellular Functions Receptor-Receptor Interaction Cell-Cell, Cell-Matrix, Cell-Pathogen Communication Galectin-3 Cell Membrane Retrospective Study Cross-Sectional Study • A significant inverse, log-linear correlation was observed between galectin-3 levels and eGFR in the retrospective study of subjects with eGFR levels ranging from 20 - 100 mL/min/1.73m2; eGFR <20 or >100 mL/min/1.73m2 did not appear to be associated with galectin-3, due either to lack of data or to a leveling off of the relationship • The correlation was upheld and maintained significance in the cross-sectional study of patients with Stage 3/4 CKD