Positive association of serum levels of advanced glycation end products and high mobility group box-1 with asymmetric dimethylarginine in nondiabetic chronic kidney disease patients.
There is accumulating evidence that engagement of the receptor for advanced glycation end products (RAGE) with ligands such as advanced glycation end products (AGEs) and high mobility group box-1 (HMGB-1) elicits vascular inflammation, thus contributing to the increased risk for cardiovascular disease. Furthermore, enhanced accumulation of asymmetric dimethylarginine (ADMA) plays a role in cardiovascular disease in chronic kidney disease (CKD) patients. However, the relationships among serum levels of AGEs, HMGB-1, soluble form of RAGE (sRAGE), and ADMA are largely unknown. The aim of the present study is to determine their relationships in CKD patients. Twenty nondiabetic normotensive CKD patients with dyslipidemia and 20 age- and sex-matched healthy controls were enrolled. All subjects underwent determination of blood chemistries; urinary proteinuria; and serum levels of AGEs, HMGB-1, sRAGE, and ADMA. Serum AGE, HMGB-1, sRAGE, and ADMA levels in CKD patients were significantly higher than those in control subjects. Circulating levels of AGEs in CKD patients were positively associated with sRAGE and ADMA, and HMGB-1 with ADMA, but not sRAGE. There were no significant associations among these markers and serum creatinine, estimated glomerular filtration rate, proteinuria, and lipid levels. In multiple regression analyses, AGEs and HMGB-1 were independently correlated with ADMA. The present study demonstrated that AGE and sRAGE levels were correlated with each other and that AGEs and HMGB-1 were independently associated with ADMA in nondiabetic CKD patients. Elevation of the RAGE ligands may enhance ADMA levels, suggesting the active involvement of AGE/HMGB-1-RAGE-ADMA axis in CKD patients.
Nakamura
Tsukasa
T
Division of Nephrology, Department of Internal Medicine, Shinmatsudo Central General Hospital, Chiba 270-0034, Japan.
Sato
Eiichi
E
Fujiwara
Nobuharu
N
Kawagoe
Yasuhiro
Y
Ueda
Yoshihiko
Y
Suzuki
Tsukasa
T
Yamada
Shingo
S
Takeuchi
Masayoshi
M
Fukami
Kei
K
Ueda
Seiji
S
Adachi
Hisashi
H
Matsui
Takanori
T
Okuda
Seiya
S
Yamagishi
Sho-ichi
S
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D003430:Cross-Sectional Studies; D050171:Dyslipidemias / Q000097:blood / Q000150:complications; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D024243:HMGB1 Protein / Q000097:blood*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood; D012044:Regression Analysis
D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C018524:N,N-dimethylarginine; D001120:Arginine