Abstract
Introduction: Galectin-3 is a 35 kDa β-galactoside-binding lectin which has been proposed as a novel biomarker of heart failure primarily due to its involvement in myocardial fibrosis. Elevated levels of galectin-3 may be associated with fibrosis of other organs, such as the kidney, and increase the risk of developing kidney disease. Methods: Using Cox proportional hazards regression, we prospectively analyzed Atherosclerosis Risk in Communities (ARIC) study participants with measurements of plasma galectin-3 levels at baseline (visit 4, 1996-98) and without prevalent kidney disease or heart failure (N=9,647). Incident chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 accompanied by 25% eGFR decline, chronic kidney disease-related hospitalization or death, or end-stage renal disease between baseline and December 31, 2013. Results: 2,105 participants (22%) developed incident chronic kidney disease over a median follow-up of 16 years. The mean (standard deviation) plasma level of galectin-3 was 14.7 (4.4) ng/mL. At baseline, galectin-3 was cross-sectionally associated with eGFR (r = -0.31) and urine albumin-to-creatinine ratio (UACR) (r = 0.19). After adjusting for demographics and kidney disease risk factors, there was a significant, graded, and positive association between galectin-3 and incident chronic kidney disease (quartile 4 vs. 1 HR: 1.84, 95% CI: 1.62, 2.09, p for trend <0.001). The association between galectin-3 and incident chronic kidney disease was attenuated but remained significant after accounting for eGFR and UACR (quartile 4 vs. 1 HR: 1.58, 95% CI: 1.39, 1.80, p for trend <0.001). The association was similar by diabetes status (p for interaction = 0.33) and stronger among those with hypertension (p for interaction = 0.004). Conclusion: In this community-based population, higher plasma galectin-3 levels were associated with elevated risk of developing incident chronic kidney disease, particularly among those with hypertension.
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