Increased collagen-linked pentosidine levels and advanced glycosylation end products in early diabetic nephropathy.

Abstract

Rationale: Advanced glycosylation end products (AGEs) may play an important role in the development of diabetic vascular sequelae. An AGE cross-link, pentosidine, is a sensitive and specific marker for tissue levels of AGEs.Objectives: To evaluate the role of AGEs in the development of diabetic nephropathy and retinopathy, we studied pentosidine levels and the clinical characteristics of 48 subjects with insulin-dependent diabetes mellitus. Diabetic nephropathy was classified as normal, microalbuminuria, or gross proteinuria, and retinopathy was graded as none, background, or proliferative.Newly observed findings: Significant elevation of pentosidine (P = 0.025) was found in subjects with microalbuminuria or gross proteinuria (73.03±9.47 vs 76.46±6.37 pmol/mg col) when compared with normal (56.96±3.26 pmol/mg col). Multivariate analysis to correct for age, duration of diabetes, and gender did not modify the results. Elevated pentosidine levels were also found in those with proliferative when compared with those with background retinopathy (75.86±5.66 vs 60.42 ± 5.98 pmol/mg col) (P < 0.05).Conclusions: Microalbuminuria is associated with elevated levels of pentosidine similar to those found in overt diabetic nephropathy suggesting that elevated AGE levels are already present during the earliest detectable phase ofdiabetic nephropathy. (J. Clin. Invest. 1993.92:212-217.)

Relationship between glyco-oxidation, antioxidant status and microalbuminuria in type 2 diabetic patients

“…In this setting, several studies have examined the possible relationship between microalbuminuria and AGE in type 1 diabetic patients [12][13][14]; a few have focused on type 2 diabetic patients [15][16][17]. In type 1 diabetes, serum AGE levels correlate with the stage of nephropathy [14], even suggesting a pathogenic role for them in the progression of early diabetic nephropathy [13].…”

“…In type 1 diabetes, serum AGE levels correlate with the stage of nephropathy [14], even suggesting a pathogenic role for them in the progression of early diabetic nephropathy [13]. Increases in skin collagen-linked pentosidine levels and AGE have also been correlated with AER [12]. In type 2 diabetes, renal function and various stages of proteinuria affect the urinary concentrations of pentosidine [15] and AGE [16].…”

Advanced glycation end products regulate extracellular matrix protein and protease expression by human glomerular mesangial cells

“…AGEs accumulate during diabetes (8), but also during chronic renal failure and ageing. They may therefore be involved in the non-specific progression of chronic nephropathies, and in the progressive sclerosis of the kidney that occurs with age (37).…”

“…AGEs, such as Nε-carboxymethyl lysine (CML) and pentosidine, which derive from the non-enzymatic coupling between amino-acid residues and oxidative derivatives of glucose or pentose, have been shown to accumulate during chronic hyperglycaemia and diabetes (7), and to either activate certain cell types, or to modify extracellular matrix proteins, which may become more resistant to degradation (8).…”

Autofluorescence characterization of advanced glycation end products of hemoglobin

“…They have reported a very good exponential correlation (r = 0.993). Inspite of many earlier reports on correlation between collagen post-translational modifications and presence of diabetic complications [18][19][20], these suffered the drawbacks of tedious extraction procedures in addition to the accumulation of collagen-AGEs due to aging. A variety of experimental studies suggest that AGEs play several critical roles in the structural and functional alterations which result from their accumulation in tissues and on serum proteins during normal aging and at an accelerated rate in diabetes [21].…”