Is the serum concentration of pentosidine a predictor of cardiovascular events in patients with type 2 diabetes and kidney disease

BACKGROUND AND OBJECTIVE: Advanced glycation end-products (AGEs) are implicated in the pathogenesis of vascular damage of atherosclerosis, especially in diabetes and renal failure. Pentosidine, an AGE, is generated by glycation and oxidation reactions (glycoxidation product). METHODS: 218 patients at high risk of cardiovascular events (from the "Irbesartan in Diabetic Nephropathy Trial” [IDNT] cohort) with type 2 diabetes and nephropathy (mean age 61 ± 6,4 years, 68 female, 150male) were followed for a mean of 2.2 years. The mean GFR at baseline was 47,9 ± 16,0 ml/min (MDRD formula). Serum levels of pentosidine were measured by high-performance liquid chromatography. The relationship between pentosidine, traditional risk factors and cardiovascular events (CVE) was tested in Cox proportional hazards models. Results: The mean serum level of pentosidine at baseline was 148 ± 113 pmol/ml, that of hemoglobin A 1c (HbA 1c) 8.6 ± 1.7 %. During follow-up, 93 CVE occurred; a total of 50 patients died, 39 of cardiovascular causes. Final multivariate analysis showed low density lipoprotein (LDL) and duration of diabetes to be independent risk factors for a first cardiovascular event (including death from cardiovascular causes) (relative risk [RR] for the highest quartile compared with the lowest: LDL 3,041, confidence interval 1.616 - 5.724, P = 0.001; duration of diabetes: RR 2.629, CI 1.279 - 6.151, P = 0.011). CONCLUSION: The serum level of pentosidine was not an independent risk factor for cardiovascular outcomes in the selected cohort. This suggests that traditional risk factors may play a more important role in causing cardiovascular events and that serum levels of AGEs are of low predictive value. Further investigations are necessary to assess whether tissue levels of AGEs are of greater relevance.