Abstract P350: Association of Plasma Levels of Soluble Receptor for Advanced Glycation End Products and Risk of Kidney Disease is Explained by Baseline Kidney Function
Introduction: Advanced glycation end products and their cell-bound receptors (RAGE) are thought to mediate the adverse effects of dysglycemia and vascular disease through oxidative stress, inflammation, and endothelial dysfunction. The soluble form of RAGE (sRAGE) is a 48-kDa, positively-charged cleavage product of RAGE. There is limited evidence on the role of sRAGE in the pathogenesis of kidney disease.
Methods: We conducted cross-sectional and prospective analyses of a case-cohort study nested within the ARIC Study. Plasma sRAGE was measured at baseline (1990-92) in a cohort random sample (n=1,218) and three case groups of participants with incident chronic kidney disease [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and ≥25% eGFR decline; n=151], incident end-stage renal disease [U.S. Renal Data System registry; n=152], and incident kidney failure (eGFR <15 mL/min/1.73 m2, U.S. Renal Data System registry, or kidney failure-related hospitalization or death; n=266).
Results: Baseline sRAGE levels were inversely related to baseline eGFR (r = -0.13). After adjusting for age, sex, and race, one interquartile range increase in log10-transformed sRAGE was associated with development of end-stage renal disease [hazard ratio: 1.97; 95% confidence interval (CI): 1.47, 2.64; p<0.001], kidney failure (hazard ratio: 1.59; 95% CI: 1.27, 2.00; p<0.001), and chronic kidney disease (odds ratio: 1.39; 95% CI: 1.06, 1.83; p=0.02). However, none of these associations were significant after additional adjustment for eGFR (all p>0.10; Figure).
Conclusions: High sRAGE levels are associated with decreased kidney function. The association of sRAGE with kidney disease risk may be explained by its partial clearance by the kidney.
Author Disclosures: C.M. Rebholz: None. B.C. Astor: None. M.E. Grams: None. M.K. Halushka: None. M. Lazo: None. R.C. Hoogeveen: None. C.M. Ballantyne: None. J. Coresh: None. E. Selvin: None.
This research has received full or partial funding support from the American Heart Association, Mid-Atlantic Affiliate (Maryland, North Carolina, South Carolina, Virginia & Washington, DC).
- © 2014 by American Heart Association, Inc.