title: Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as prognostic markers in idiopathic membranous nephropathy.
abstract: BACKGROUND
  Urinary excretion of alpha-1-microglobulin and beta-2-microglobulin reflects tubular damage and predicts outcome in patients with idiopathic membranous nephropathy with reasonable accuracy. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are novel biomarkers of tubular damage. We investigated if these markers could improve prediction of outcome in idiopathic membranous nephropathy.
  
  
  METHODS
  We measured kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in urine samples from patients with idiopathic membranous nephropathy, who had nephrotic proteinuria and normal renal function. Excretion of alpha-1-microglobulin and beta-2-microglobulin had been measured previously. Progression was defined as a serum creatinine rise >30%, a rise in serum creatinine to an absolute value of ≥135 µmol/L, or a clinical decision to start immunosuppressive therapy. Remission was defined as proteinuria <3.5 g/day and >50% reduction from baseline.
  
  
  RESULTS
  Sixty-nine patients were included. Median follow-up was 35 months (interquartile range 18-63 months). Progression occurred in 30 patients (44%), and spontaneous remission in 36 (52%). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates were significantly correlated with each other, and with alpha-1-microglobulin and beta-2-microglobulin. The areas under the receiver operating characteristic curves for progression were 0.75 (0.62-0.87) for kidney injury molecule-1 and 0.74 (0.62-0.87) for neutrophil gelatinase-associated lipocalin. In multivariate analysis with either alpha-1-microglobulin and beta-2-microglobulin, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin did not independently predict outcome.
  
  
  CONCLUSIONS
  Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates correlated with excretion rates of other tubular damage markers and predicted outcome in patients with idiopathic membranous nephropathy. They did not add prognostic value compared to measurement of either alpha-1-microglobulin or beta-2-microglobulin.
authors.affiliation: Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands Rutger.Maas@radboudumc.nl.
authors.forename: Rutger Jh
authors.initials: RJ
authors.lastname: Maas
authors.affiliation: Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jan Ajg
authors.initials: JA
authors.lastname: van den Brand
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Waanders
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Meijer
authors.affiliation: Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Goor van
authors.affiliation: Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Hilde P
authors.initials: HP
authors.lastname: Peters
authors.affiliation: Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Hofstra
authors.affiliation: Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Jack Fm
authors.initials: JF
authors.lastname: Wetzels
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine*; D000328:Adult; D015415:Biomarkers / Q000652:urine; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000175:diagnosis* / Q000652:urine*; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine*; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000652:urine*; D011991:Receptors, Virus
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus
keywords: Membranous nephropathy; biomarkers; kidney injury molecule-1; nephrotic syndrome; neutrophil gelatinase-associated lipocalin; prognosis