title: Low Serum Neutrophil Gelatinase-associated Lipocalin Level as a Marker of Malnutrition in Maintenance Hemodialysis Patients.
abstract: BACKGROUND
  Neutrophil gelatinase-associated lipocalin (NGAL or LCN2) is an iron-transporting factor which possesses various activities such as amelioration of kidney injury and host defense against pathogens. Its circulating concentrations are elevated in acute and chronic kidney diseases and show a positive correlation with poor renal outcome and mortality, but its clinical significance in maintenance hemodialysis (HD) patients remains elusive.
  
  
  METHODS
  Serum NGAL levels were determined by enzyme-linked immunosorbent assay in out-patient, Japanese HD subjects. Their correlation to laboratory findings and morbidity (as development of severe infection or serum albumin reduction) was investigated using linear regression analysis and χ2 test.
  
  
  RESULTS
  Pre-dialysis serum NGAL levels in HD patients were elevated by 13-fold compared to healthy subjects (n=8, P<0.001). In a cross-sectional study of 139 cases, serum NGAL concentrations were determined independently by % creatinine generation rate (an indicator of muscle mass, standardized coefficient β=0.40, P<0.001), peripheral blood neutrophil count (β=0.38, P<0.001) and anion gap (which likely reflects dietary protein intake, β=0.16, P<0.05). Iron administration to anemic HD patients caused marked elevation of peripheral blood hemoglobin, serum ferritin and iron-regulatory hormone hepcidin-25 levels, but NGAL levels were not affected. In a prospective study of 87 cases, increase in serum albumin levels a year later was positively associated to baseline NGAL levels by univariate analysis (r=0.36, P<0.01). Furthermore, within a year, patients with the lowest NGAL tertile showed significantly increased risk for marked decline in serum albumin levels (≥0.4 g/dl; odds ratio 5.5, 95% confidence interval 1.5-20.3, P<0.05) and tendency of increased occurrence of severe infection requiring admission (odds ratio 3.1, not significant) compared to the middle and highest tertiles.
  
  
  CONCLUSIONS
  Low serum NGAL levels appear to be associated with current malnutrition and also its progressive worsening in maintenance HD patients.
authors.affiliation: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Imamaki
authors.affiliation: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ishii
authors.affiliation: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yokoi
authors.affiliation: Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kasahara
authors.affiliation: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Takashige
authors.initials: T
authors.lastname: Kuwabara
authors.affiliation: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Keita P
authors.initials: KP
authors.lastname: Mori
authors.affiliation: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Nephrology, Saiseikai Ibaraki Hospital, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuwahara
authors.affiliation: Misugikai Satou Hospital, Osaka, Japan.
authors.forename: Masugi
authors.initials: M
authors.lastname: Satoh
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Nara, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Nakatani
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Nara, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Division of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kanazawa, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Tomosugi
authors.affiliation: Department of Nephrology, Osaka Red Cross Hospital, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sugawara
authors.affiliation: TK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
authors.affiliation: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mukoyama
authors.affiliation: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan; TMK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Yanagita
authors.affiliation: TMK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Mori
mesh_terms: D000209:Acute-Phase Proteins; D000367:Age Factors; D000368:Aged; D001011:Aorta / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007501:Iron / Q000008:administration & dosage / Q000494:pharmacology; D016014:Linear Models; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D044342:Malnutrition / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D011518:Proto-Oncogene Proteins / Q000097:blood*; D006435:Renal Dialysis; D012082:Renal Veins / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012709:Serum Albumin; D007501:Iron