Advanced Glycation End Products and Their Circulating Receptors and Level of Kidney Function in Older Community-Dwelling Women
Received 18 February 2008; accepted 18 June 2008. published online 16 September 2008.
Background
Advanced glycation end products (AGEs) and the receptor for AGE (RAGE) are implicated in the pathogenesis of kidney disease; however, their relation with level of kidney function has not been well characterized.
Study Design
Cross-sectional and prospective.
Setting & Participants
548 moderately to severely disabled community-dwelling women in the Women's Health and Aging Study I in Baltimore, MD.
Predictor
Serum carboxymethyl-lysine (CML), a dominant AGE; total soluble RAGE (sRAGE); and endogenous secretory RAGE (esRAGE).
Outcomes & Measurements
Glomerular filtration rate (GFR), prevalent and incident decreased GFR (GFR < 60 mL/min/1.73 m2). Serum CML, sRAGE, and esRAGE.
Results
Of 548 women, 283 (51.6%) had decreased GFR at baseline. Serum CML level was associated with decreased GFR (OR [all expressed per 1 SD], 1.98; 95% CI, 1.41 to 2.76; P < 0.001) in a multivariate logistic regression model adjusting for age, race, hemoglobin A1c level, and chronic diseases. Serum sRAGE and esRAGE levels (both in nanograms per milliliter) were associated with decreased GFR (OR, 1.42; 95% CI, 1.12 to 1.79; P = 0.003; OR, 1.42; 95% CI, 1.14 to 1.77; P = 0.001, respectively) in separate multivariate logistic regression models adjusting for potential confounders. Of 230 women without decreased GFR at baseline, 32 (13.9%) developed decreased GFR by the follow-up visit 12 months later. Serum CML (in micrograms per milliliter), sRAGE, and esRAGE levels at baseline were associated with the prevalence of decreased GFR 12 months later (OR, 1.80; 95% CI, 1.19 to 2.71; P = 0.005; OR, 1.32; 95% CI, 1.01 to 1.74; P = 0.05; and OR, 1.33; 95% CI, 1.01 to 1.77; P = 0.05, respectively) in separate multivariate logistic regression models adjusting for potential confounders.
Limitations
Small number of incident cases, limited follow-up, creatinine values not standardized.
Conclusions
AGE and circulating RAGE levels are independently associated with decreased GFR and seem to predict decreased GFR. AGEs are amenable to interventions because serum AGE levels can be decreased by change in dietary pattern and pharmacological treatment.
ABSTRACT