TY - JOUR
T1 - Advanced Glycation End Products and Their Circulating Receptors and Level of Kidney Function in Older Community-Dwelling Women
AU - Semba, Richard D.
AU - Ferrucci, Luigi
AU - Fink, Jeffrey C.
AU - Sun, Kai
AU - Beck, Justine
AU - Dalal, Mansi
AU - Guralnik, Jack M.
AU - Fried, Linda P.
N1 - Funding Information:
Support: This work was supported by the National Institutes of Health (NIH) National Institute on Aging through Grants R01 AG027012 and AG11703-01A1, Contract N01-AG12112, and the Intramural Research Program. Additional support was received in the form of Grant RR00722 from the NIH National Center for Research Resources and Out Patient Department-General Clinical Research Center.
PY - 2009/1
Y1 - 2009/1
N2 - 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.
AB - 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.
KW - Advanced glycation end products
KW - reduced glomerular filtration rate
UR - http://www.scopus.com/inward/record.url?scp=57749206655&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57749206655&partnerID=8YFLogxK
U2 - 10.1053/j.ajkd.2008.06.018
DO - 10.1053/j.ajkd.2008.06.018
M3 - Article
C2 - 18789567
AN - SCOPUS:57749206655
SN - 0272-6386
VL - 53
SP - 51
EP - 58
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 1
ER -