title: High serum level of methylglyoxal-derived AGE, Nδ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine, independently relates to renal dysfunction.
abstract: BACKGROUND
  The dicarbonyl methylglyoxal reacts primarily with arginine residues to form advanced glycation end products, including Nδ-(5-hydro-5-methyl-4 -imidazolone-2-yl)-ornithine (MG-H1), which are risk factors for not only diabetic complications but also lifestyle-related disease including renal dysfunction. However, the data on serum level and clinical significance of this substance in chronic kidney disease are limited.
  
  
  METHODS
  Serum levels of MG-H1 and Nε-(carboxymethyl) lysine (CML) in 50 patients with renal dysfunction were measured by liquid chromatography/triple-quadruple mass spectrometry.
  
  
  RESULTS
  The median serum MG-H1 levels in patients with estimated glomerular filtration rate (eGFR) of ≥30, 15-30, and <15 ml/min/1.73 m2was 4.16, 12.58, and 14.66 mmol/mol Lys, respectively (p > 0.05). On the other hand, MG-H1 levels in patients with HbA1c of <6 and ≥6 % was 12.85 and 10.45 mmol/mol Lys, respectively, the difference between which is not significant. In logistic regression analysis, decreased renal function (eGFR <15 ml/min/1.73 m2) significantly associated with high serum levels of MG-H1 [odds ratio: 9.39 (95 % confidence interval 1.528-57.76), p = 0.015; Spearman rank correlation: MG-H1 vs. eGFR, r = -0.691, p < 0.01]. In contrast, the serum level of CML did not correlate with eGFR, but correlated with systolic blood pressure [odds ratio 16.17 (95 % confidence interval 1.973-132.5), p = 0.010; Spearman rank correlation coefficient: CML vs. eGFR, r = 0.454, p < 0.01].
  
  
  CONCLUSIONS
  These results showed that the serum concentration of MG-H1 was strongly related to renal function rather than to DM.
authors.affiliation: Division of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. kito@fukuoka-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ito
authors.affiliation: Division of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sakata
authors.affiliation: Laboratory of Food and Regulation Biology Department of Bioscience, School of Agriculture, Tokai University, Kumamoto, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nagai
authors.affiliation: Laboratory of Food and Regulation Biology Department of Bioscience, School of Agriculture, Tokai University, Kumamoto, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Shirakawa
authors.affiliation: Division of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Maho
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Division of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Mimata
authors.affiliation: Division of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Division of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Yasuno
authors.affiliation: Division of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Sasatomi
authors.affiliation: Division of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Miyake
authors.affiliation: Division of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ueki
authors.affiliation: Division of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Hamauchi
authors.affiliation: Division of Nephrology and Rheumatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakashima
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002853:Chromatography, Liquid; D003430:Cross-Sectional Studies; D005260:Female; D005919:Glomerular Filtration Rate; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007093:Imidazoles / Q000097:blood*; D007668:Kidney / Q000503:physiopathology*; D016015:Logistic Models; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009952:Ornithine / Q000031:analogs & derivatives* / Q000097:blood; D011237:Predictive Value of Tests; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D007093:Imidazoles; C000620571:Ndelta-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine; C048496:N(6)-carboxymethyllysine; D009952:Ornithine; D008239:Lysine
keywords: Advanced glycation end-products; CML; Chronic kidney disease; Liquid chromatography/triple-quadruple mass spectrometry; MG-H1; Nδ-(5-Hydro-5-methyl-4-imidazolone-2-yl)-ornithine); Nε-Carboxymethyl lysine