Carboxymethyl-lysine, an advanced glycation end product, and decline of renal function in older community-dwelling adults

Advanced glycation end products (AGEs) are bioactive molecules found in greater concentrations in foods that have been processed at high temperatures. AGEs have been associated with impaired renal function in diabetes and in uremia. The relationship between AGEs and renal function in community-dwelling adults has not been well characterized. The objective was to determine whether plasma AGEs are independently associated with chronic kidney disease (CKD) and predictive of renal function in older adults. The relationship between plasma carboxymethyl-lysine (CML), an AGE, and CKD (= stage 3 of National Kidney Foundation classification; estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m²) and eGFR at 3- and 6-years follow-up was examined in a population-based study of aging, the InCHIANTI study, in Tuscany, Italy. Of 1,008 adults, aged =65 years, 153 (15.2%) had CKD at enrollment. Mean (standard deviation [S.D.]) plasma CML was 365 (110) ng/ml. Plasma CML was associated with CKD (odds ratio [O.R.] expressed per 1 S.D., 1.53, 95% confidence interval [C.I.] 1.27-1.84, P < 0.0001) in a multivariate logistic regression model, adjusting for potential confounders. Plasma CML was associated with eGFR (β = -2.77, standard error [S.E.] = 0.51, P < 0.0001) at baseline, 3-year (β = -2.54, S.E. = 0.61, P < 0.0001) and 6-year follow-up visits (β = -1.21, S.E. = 0.70, P = 0.08) in multivariate linear regression models, adjusting for potential confounders. The associations between plasma CML and prevalent CKD, eGFR, and eGFR at 3- and 6-year follow-up were significant and nearly unchanged after exclusion of adults with diabetes. Plasma CML is independently associated with CKD and is an independent predictor of decline in renal function in older community-dwelling adults.