Soluble RAGE, diabetic nephropathy and genetic variability in the AGER gene

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Authors

KAŇKOVÁ Kateřina KALOUSOVA Marta HERTLOVÁ Miluše KRUSOVÁ Darja OLŠOVSKÝ Jindřich ZIMA Tomáš

Year of publication 2008
Type Article in Periodical
Magazine / Source Arch Physiol Biochem
MU Faculty or unit

Faculty of Medicine

Citation
Field Endocrinology, diabetology, metabolism, nutrition
Keywords diabetes mellitus; soluble RAGE; AGEs; diabetic nephropathy; glomerular filtration rate
Description Diabetes mellitus, especially when complicated with decline of renal function due to diabetic nephropathy (DN), is associated with accumulation of Advanced Glycation End products (AGEs) exerting their adverse effects via Receptor of AGE (RAGE). Soluble RAGE (sRAGE) is a truncated form of RAGE functioning as an inhibitor of AGE-mediated signalling. We studied relationships between sRAGE, renal function and genetic variability in the AGER gene in diabetic subjects. Study comprised a total of 265 diabetics (type 1 or 2 or LADA) with normoalbuminuria (n=94) or DN (n=171). sRAGE (assessed by ELISA) was significantly higher in DN than normoalbuminuria subjects (P=0.007) and positively correlated with age, S-urea, S-creatinine and albuminuria and AGEs (determined spectrofluorimetrically), negatively with GFR (all P<0.05); however, multivariate regression revealed that GFR was the only independent variable associated with sRAGE (P=0.047). sRAGE did not correspond with carrier state of risk-haplotype copies (RAGE2) (P>0.05). In conclusion, GFR is a principal determinant of sRAGE concentration and gradual sRAGE increase in subjects with advancing impairment of renal function is paralleled by AGEs
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