Receptor for advanced glycation end products--soluble form and gene polymorphisms in chronic haemodialysis patients.
BACKGROUND
The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of vascular and inflammatory diseases. The pathological effects mediated via RAGE are physiologically inhibited by soluble RAGE (sRAGE). Our aim was to study sRAGE and RAGE gene polymorphisms in haemodialysis (HD) patients.


METHODS
A total of 261 stable HD patients were enrolled in the study and prospectively followed up for 30 months. At the begining of the study, sRAGE inflammatory and nutritional parameters were determined. RAGE polymorphisms were determined in a subgroup of 214 HD patients. A group of 100 healthy controls was used for comparison.


RESULTS
In HD patients, sRAGE is elevated in comparison with healthy controls (3427+/-1508 vs 1758+/-637 pg/ml, P<0.001). It correlates negatively with residual diuresis (r=-0.193, P<0.05), with the acute phase reactants fibrinogen (r=-0.174, P<0.05) and orosomucoid (r=-0.135, P<0.05) and with the leucocyte count (r=-0.158, P<0.05). On the other hand, it is not related to the presence of diabetes mellitus, cardiovascular disease, nutritional status and mortality. The highest sRAGE levels are found in -429 CC and 2184 GG polymorphisms of the RAGE gene. The same results as for sRAGE were obtained for endogenous secretory RAGE (esRAGE), which correlated significantly with sRAGE (r=0.88, P<0.001).


CONCLUSIONS
We conclude that in HD patients, sRAGE is increased due to decreased renal function, which is a very strong determinant of sRAGE levels, and is inversely related to inflammation. The highest sRAGE levels are influenced genetically. In our study, sRAGE levels were not related to mortality of HD patients.
Kalousová
Marta
M
Institute of Clinical Chemistry and Laboratory Diagnostics, Department of Nephrology, 1st Faculty of Medicine and General University Hospital, Charles University, Karlovo nám. 32, 121 11 Prague 2, Czech Republic. marta.kalousova@seznam.cz
Jáchymová
Marie
M
Mestek
Oto
O
Hodková
Magdaléna
M
Kazderová
Markéta
M
Tesar
Vladimír
V
Zima
Tomás
T
D000209:Acute-Phase Proteins / Q000378:metabolism; D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications; D048909:Diabetes Complications; D004231:Diuresis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications; D007249:Inflammation / Q000150:complications; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000150:complications / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D006435:Renal Dialysis; D012995:Solubility
D000209:Acute-Phase Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic