Increased plasma levels of sRAGE in patients with diabetic nephropathy
| Authors | |
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| Year of publication | 2006 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Background and Aims: Advanced Glycation End products (AGEs) accumulate in diabetic patients in a greater rate than in age-matched non-diabetic subjects and exert various adverse effects via the Receptor of AGE (RAGE). Soluble RAGE (sRAGE) is a 50kDa naturally occurring C-terminally truncated form of RAGE that functions as an inhibitor of AGE-mediated signalling events. Decreased levels of supposedly protective sRAGE were ascertained in patients with macrovascular disease and hypertension. Data about the role of sRAGE in diabetic nephropathy are so far lacking. The aim of the study was to analyse the relationship between sRAGE and renal functions in subjects with diabetic nephropathy and, hereby, implicit protective capacity against AGE-mediated toxicity. Material and Methods: Study was designed as a cross-sectional analysis of a cohort of 255 diabetic patients with variable extent of diabetic nephropathy. Total number of subjects consisted if 36 diabetics with T1DM, 219 with T2DM (approx. 1:1 male-to-female ratio). Mean duration of diabetes was 12.2 +/- 9.4 yrs, mean age was 61.3 +/- 14.5 yrs. Among all study subjects, 82 subjects had normoalbuminuria, 50 had persistent microalbuminuria, 112 had persistent proteinuria and 10 subjects had ESRD. Plasma concentration of sRAGE was assessed immunochemically (ELISA) using standard kits (Quantikine, RD Systems). Routine biochemical parameters were measured by certified methods using automated analysers. Relationship between circulating levels of sRAGE and the grade of diabetic nephropathy, renal function parameters and diabetes duration and compensation was analysed by means of non-parametric correlation, difference between groups were tested by Mann-Whitney test. Results: sRAGE was significantly higher in nephropathy subjects (any degree of DN) than normoalbuminuric patients (P=0.0015), 2154.4 +/- 2612 pg/ml vs. 1622.7 +/- 1981.4 pg/ml, respectively. In patients with nephropathy, sRAGE positively correlated with severity of nephropathy (P=0.0028). Further, sRAGE positively correlated with patient age, duration of diabetes, serum urea, serum creatinine and albumin excretion rate and negatively with glomerular filtration rate (all P<0.05). No significant correlation was ascertained with fasting plasma glucose or HbA1c. Conclusions: Contrary to our anticipations, serum sRAGE levels are in fact (i) increased in diabetics with diabetic nephropathy compared to normoalbuminuric subjects and (ii) further rise with decreasing renal function. It remains to be elucidated whether the increase merely reflects decreased renal clearance of sRAGE or up-regulation of sRAGE in order to protect cells against AGE-mediated effects. |
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