Advanced Glycation End Products and Their Circulating Receptors and Level of Kidney Function in Older Community-Dwelling Women

Semba, Richard D.; Ferrucci, Luigi; Fink, Jeffrey C.; Sun, Kai; Beck, Justine; Dalal, Mansi; Guralnik, Jack M.; Fried, Linda P.

doi:10.1053/j.ajkd.2008.06.018

« Previous Next »American Journal of Kidney Diseases
Volume 53, Issue 1 , Pages 51-58, January 2009

Advanced Glycation End Products and Their Circulating Receptors and Level of Kidney Function in Older Community-Dwelling Women

Richard D. Semba, MD, MPH
- Johns Hopkins Medical Institutions, Bethesda, MD
- Address correspondence to Richard Semba, MD, MPH, 550 N Broadway, Ste 700, Baltimore, MD 21205
Luigi Ferrucci, MD, PhD
- Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Bethesda, MD
Jeffrey C. Fink, MD, MS
- Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Bethesda, MD
Kai Sun, MS
- Johns Hopkins Medical Institutions, Bethesda, MD
Justine Beck, BS
- Johns Hopkins Medical Institutions, Bethesda, MD
Mansi Dalal, BS
- Johns Hopkins Medical Institutions, Bethesda, MD
Jack M. Guralnik, MD, PhD
- Epidemiology and Demography Section, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD
Linda P. Fried, MD, MPH
- Johns Hopkins Medical Institutions, Bethesda, MD

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 A_1c 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.

Index Words: Advanced glycation end products, reduced glomerular filtration rate