Plasma galectin-3 levels are associated with the risk of incident chronic kidney disease

Abstract

Galectin-3 has been proposed as a novel biomarker of heart failure and cardiac fibrosis, and may also be associated with fibrosis of other organs such as the kidney. To determine this, we prospectively analyzed data from 9,148 Atherosclerosis Risk in Communities (ARIC) Study participants with measured plasma galectin-3 levels (baseline, visit 4, 1996-98) and without prevalent chronic kidney disease (CKD) or heart failure. We identified 1,983 incident CKD cases through December 31, 2013 over a median follow-up of 16 years. At baseline, galectin-3 was cross-sectionally associated with estimated glomerular filtration rate and urine albumin-to-creatinine ratio; both significant. The results were adjusted for age, sex, race-center, education, physical activity, smoking status, body mass index, systolic blood pressure, anti-hypertensive medication use, history of cardiovascular disease, diabetes, fasting blood glucose, and rs4644 (a single nucleotide polymorphism of galactin-3). There was a significant, graded, and positive association between galectin-3 and incident CKD (quartile 4 vs. 1 hazard ratio: 2.22 [95% confidence interval: 1.89, 2.60]). The association was attenuated but remained significant after adjustment for estimated glomerular filtration rate, urine albumin-to-creatinine ratio, troponin T, and N-terminal pro-brain natriuretic peptide (quartile 4 vs. 1 hazard ratio: 1.75 [95% confidence interval: 1.49, 2.06]), and was stronger among those with hypertension at baseline (significant interaction). Thus, in this community-based population, higher plasma galectin-3 levels were associated with an elevated risk of developing incident CKD, particularly among those with hypertension.

Keywords: chronic kidney disease; fibrosis; galectin-3; hypertension.

Figure 1. Spline of Adjusted* Hazard Ratios (95% CI) for Incident Chronic Kidney Disease According to Baseline Plasma Level of Galectin-3

*Adjusted for age, sex, race-center, body mass index, smoking, education, physical activity, systolic blood pressure, anti-hypertensive medication use, history of cardiovascular disease, diabetes, fasting glucose, rs4644, estimated glomerular filtration rate-creatinine, and urine albumin-to-creatinine ratio, troponin T, and N-terminal pro B-type natriuretic peptide Histogram of baseline plasma level galectin-3 are shown in grey. The solid lines represent the restricted cubic spline with knots at the 5^th, 27.5^th, 50^th, 72.5^th, and 95^th percentiles for galectin-3. Galectin-3 levels were truncated at the 99^th percentile. The 10^th percentile of galectin-3 (10.2 ng/mL) was used as the reference point. Dashed lines represent the 95% confidence intervals.