title: Elevated galectin-3 precedes the development of CKD.
abstract: Galectin-3, a profibrotic mediator, is linked to the development of renal fibrosis in animal models and inversely correlates with GFR in humans, but whether galectin-3 predicts incident kidney disease is unknown. Here, we assessed renal outcomes for 2450 Framingham Offspring participants who attended examination 6 (1995-1998) and had follow-up data at examination 8 (2005-2008). Renal outcomes of interest included rapid decline in renal function (≥3 ml/min per 1.73 m(2) per year decline in estimated GFR [eGFR]), CKD (eGFR < 60 ml/min per 1.73 m(2)), and albuminuria (albumin-to-creatinine ratio ≥17 mg/g in men or ≥25 mg/g in women). We used multivariable logistic regression models to evaluate associations between galectin-3 with incident renal outcomes at examination 8. During a mean follow-up of 10.1 years, GFR declined rapidly in 241 (9.2%) participants, incident CKD developed in 277 (11.3%), and albuminuria developed in 194 (10.1%). Higher plasma levels of galectin-3 were associated with rapid decline in eGFR (per 1-SD log-galectin-3; adjusted odds ratio [OR], 1.49; 95% confidence interval [CI], 1.28 to 1.73]) and a higher risk of incident CKD (OR, 1.47; 95% CI, 1.27 to 1.71), but not with the risk of incident albuminuria. The addition of galectin-3 to clinical predictors improved the C-statistic (0.837-0.845; P=0.02) but did not reach predefined thresholds for clinically significant improvements to risk prediction based on reclassification indices. In conclusion, elevated levels of plasma galectin-3 are associated with increased risks of rapid GFR decline and of incident CKD in the community, which calls for further study in higher-risk groups.
authors.affiliation: National Heart, Lung, and Blood Institute's Intramural Research Program, Framingham Heart Study, Massachusetts, USA.
authors.forename: Conall M
authors.initials: CM
authors.lastname: O'Seaghdha
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Ho
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000175:diagnosis / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D037502:Galectin 3 / Q000097:blood*; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D015994:Incidence; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis* / Q000453:epidemiology* / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D037502:Galectin 3