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 m
2
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 m
2
, 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 log
10
-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.
Possible Significance of Advanced Glycation End Products in Serum in End-Stage Renal Disease and in Late Complications of Diabetes
