a 2006

Increased plasma levels of sRAGE in patients with diabetic nephropathy

KAŇKOVÁ, Kateřina, Marta KALOUSOVÁ, Miluše HERTLOVÁ, Darja KRUSOVÁ, Tomáš ZIMA et. al.

Basic information

Original name

Increased plasma levels of sRAGE in patients with diabetic nephropathy

Name in Czech

Zvýšené plazmatické hladiny sRAGE u pacientů s diabetickou nefropatií

Authors

KAŇKOVÁ, Kateřina (203 Czech Republic, guarantor), Marta KALOUSOVÁ (203 Czech Republic), Miluše HERTLOVÁ (203 Czech Republic), Darja KRUSOVÁ (203 Czech Republic) and Tomáš ZIMA (203 Czech Republic)

Edition

2006

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

30202 Endocrinology and metabolism

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

RIV identification code

RIV/00216224:14110/06:00015385

Organization unit

Faculty of Medicine

UT WoS

000240626201517

Keywords in English

diabetes mellitus; diabetic nephropathy; RAGE; AGEs; susceptibility
Změněno: 2/4/2010 15:15, prof. MUDr. Kateřina Kaňková, Ph.D.

Abstract

V originále

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.

In Czech

Práce popisuje nález zvýšdených hladin sRAGE u osob s diabetickou nefropatií a identifikuje pokles GFR jako hlavníi faktor determinující jeho plazmatické koncentrace.

Links

KJB501620601, research and development project
Name: Funkční analýza rizikového haplotypu RAGE genu a jeho role v patogenezi hyperglykemií indukovaných změn
Investor: Academy of Sciences of the Czech Republic, Functional analysis of the RAGE gene susceptibility haplotype and its role in the hyperglycemia-driven pathology