Advanced glycation end products (AGEs) and the receptor for AGE (RAGE) are implicated in the pathogenesis of renal disease but their relation with level of kidney function has not been well characterized.
Cross-sectional and prospective.
Setting and Participants
548 moderately to severely disabled community-dwelling women in the Women's Health and Aging Study I in Baltimore, Maryland.
Serum L-carboxymethyl-lysine (CML), a dominant AGE, total RAGE (sRAGE), and endogenous secretory RAGE (esRAGE).
Outcomes & Measurements
Glomerular filtration rate (GFR), prevalent and incident reduced GFR (GFR <60 mL/min/1.73 m2). Serum CML, sRAGE, and esRAGE.
Of 548 women, 283 (51.6%) had reduced GFR at baseline. Serum CML was associated with reduced GFR (Odds Ratios [O.R.; all expressed per 1 Standard Deviation], 1.98, 95% Confidence Interval [C.I.] 1.41-2.76, P <0.001) in a multivariate logistic regression model adjusting for age, race, hemoglobin A1c, and chronic diseases. Serum sRAGE (ng/mL) and esRAGE (ng/mL), respectively, were associated with reduced GFR (O.R. 1.42, 95% C.I. 1.12-1.79, P = 0.003; O.R. 1.42, 95% C.I. 1.14-1.77, P = 0.001) in separate multivariate logistic regression models, adjusting for potential confounders. Of 230 women without reduced GFR at baseline, 32 (13.9%) developed reduced GFR by the follow-up visit 12 months later. Serum CML (μg/mL), sRAGE (ng/mL), and esRAGE (ng/mL), respectively, at baseline was associated with the prevalence of reduced GFR 12 months later (O.R. 1.80, 95% C.I. 1.19-2.71, P = 0.005; O.R. 1.32, 95% C.I. 1.01-1.74, P = 0.05; O.R. 1.33, 95% C.I. 1.01-1.77, P = 0.05) in separate multivariate logistic regression models adjusting for potential confounders.
Small number of incident cases, limited follow-up interval, creatinine not standardized.
AGEs and circulating RAGE are independently associated with reduced GFR and seem to predict reduced GFR. AGEs are amenable to interventions, as serum AGEs can be lowered by change in dietary pattern and pharmacological treatment.