Low Serum Neutrophil Gelatinase-associated Lipocalin Level as a Marker of Malnutrition in Maintenance Hemodialysis Patients

PLoS One. 2015 Jul 10;10(7):e0132539. doi: 10.1371/journal.pone.0132539. eCollection 2015.

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.

Conclusion: Low serum NGAL levels appear to be associated with current malnutrition and also its progressive worsening in maintenance HD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins
  • Age Factors
  • Aged
  • Aorta / metabolism
  • Biomarkers / blood
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation / pathology
  • Iron / administration & dosage
  • Iron / pharmacology
  • Linear Models
  • Lipocalin-2
  • Lipocalins / blood*
  • Male
  • Malnutrition / blood*
  • Middle Aged
  • Multivariate Analysis
  • Proto-Oncogene Proteins / blood*
  • Renal Dialysis*
  • Renal Veins / metabolism
  • Serum Albumin / metabolism

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • Serum Albumin
  • Iron

Grant support

This work was supported in part by JSPS KAKENHI Grant Numbers 23390225 and 26461224 (KM and HI), Grant-in-Aid for Diabetic Nephropathy and Nephrosclerosis Research from the Ministry of Health, Labour and Welfare of Japan (KM), the Japan Kidney Foundation (KM), and research fund from Mitsubishi Tanabe Pharma Corporation (KM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.