Elevated levels of serum endogenous secretory RAGE are associated with decreased glomerular filtration rate in healthy adults

Abstract

Objectives: Binding of advanced glycation end products (AGE) to the receptor for AGE (RAGE) contributes to the development and progression of vascular diseases, including diabetic complications and chronic kidney disease. The endogenous secretory RAGE (esRAGE), which is a spliced variant of RAGE, is known to prevent the toxic effect of AGE by acting as a decoy. However the relations between kidney function and esRAGE have not been characterized. Design: A population based cross-sectional study. Material and Methods: A cross-sectional study was carried out in a Korean population of 531 adults. But we excluded 107 subjects who had insufficient blood samples, incomplete data or diabetic condition, so total 424 subjects were available for analysis (mean age of 60.1 years). As an index of renal function, we determined estimated glomerular filtration rate (eGFR) using MDRD study equation. The fasting glucose, carboxymethyllysine (CML) and esRAGE levels of all subjects were measured. Results: The eGFR was inversely correlated with esRAGE (r = -0.116, p = 0.017), but not correlated with CML levels. Furthermore, a stepwise multivariate regression analysis revealed that esRAGE (p = 0.003), but not CML, was associated with eGFR. Conclusions: We conclude that the serum CML levels are not associated with the eGFR in a non-diabetic healthy population. In contrast, increased esRAGE levels are associated with a decreased eGFR, and this is independent of age, BMI, CML and other possible confounding variables. In conclusion, elevated circulating serum esRAGE levels can be used as a predictive marker for decreased renal function in a non-diabetic healthy population.