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Advanced Glycation Endproducts in Various Stages of Proteinuria

Nonenzymatic glycation leading to advanced glycation endproduct (AGE) formation is one of the important biochemical pathways involved in the development of long-term complications of diabetes, with a potential role also in diabetic nephropathy. The objective of the present study was to evaluate the relationship between advanced glycation-derived proteins in urine and progression of diabetic nephropathy. AGE-immunoreactivity was measured in 24-h urine collection of diabetic patients with normoalbuminuria (N), microalbuminuria (Mi), macroalbuminuria (Ma), and persistent proteinuria with elevated serum creatinine level (PC). A competitive immunoassay (solid-phase bound AGE-human serum albumin) and polyclonal anti-AGE antibodies were used to monitor AGE excretion. Comparison of urine AGE content among various stages of proteinuria showed significant between-group differences: Mi vs N (p<0.003) and Ma vs Mi (p<0.001). In the group of normoalbuminuric patients, AGE-immunoreactivity was not detected in 50% of samples, whereas in the group of patients with microalbuminuria only 15% of samples were AGE negative. However, there was no statistically significant difference in AGE excretion between the patients with persistent proteinuria and elevated serum creatinine, and those with macroalbuminuria (PC vs Ma, p<0.36). In these two groups of patients in whom highest AGE content in 24-h urine collection was measured, no negative AGE-immunoreactivity was recorded. Multiple regression analysis emphasized significant correlation (r=0.72, p<0.022) between urinary AGE-immunoreactivity and urinary albumin excretion. The results suggested that urinary AGE-immunoreactivity is mainly associated with albumin molecules or minor protein fragments. Since an increased urinary albumin excretion predicts clinical diabetic nephropathy, we consider that determination of AGE-linked albuminuria may be used as a predictive marker for early detection of not only diabetic nephropathy but also of other diabetic complications.

Advanced glycation; Proteinuria; Diabetic nephropathy

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