title: High urinary excretion of kidney injury molecule-1 is an independent predictor of end-stage renal disease in patients with IgA nephropathy.
abstract: BACKGROUND
  The variable course of immunoglobulin A nephropathy (IgAN) warrants accurate tools for the prediction of progression. Urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are markers for the detection of early tubular damage caused by various renal conditions. We evaluated the prognostic value of these markers in patients with IgAN.
  
  
  METHODS
  We included patients (n = 65, 72% male, age 43 ± 13 years) with biopsy-proven IgAN, who were evaluated for proteinuria. Urinary KIM-1 and NGAL were measured by enzyme-linked immunosorbent assay. We analysed data using Cox regression for the outcome end-stage renal disease (ESRD).
  
  
  RESULTS
  Median serum creatinine was 142 μmol/L and proteinuria 2.2 g/day. During follow-up (median 75 months), 23 patients (35%) developed ESRD. In patients with IgAN median urinary KIM-1 excretion was 1.7 ng/min and NGAL excretion was 47 ng/min, both significantly higher than in healthy controls. KIM-1 and NGAL were correlated with proteinuria (r = 0.40 and 0.34, respectively, P < 0.01) and each other (r = 0.53, P < 0.01) but not with estimated glomerular filtration rate (eGFR). Interestingly, KIM-1 was not significantly correlated with the excretion of α(1)-microglobulin (α(1)m) and β(2)-microglobulin (β(2)m), known markers of tubular injury. Univariate analysis showed that baseline serum creatinine and urinary excretion of total protein, α(1)m, β(2)m, immunoglobulin G, KIM-1 and NGAL were significantly associated with ESRD. By multivariate analysis, serum creatinine and KIM-1 excretion proved to be significant independent predictors of ESRD.
  
  
  CONCLUSIONS
  KIM-1 and NGAL excretion are increased in patients with IgAN and correlate with proteinuria but not with eGFR. Baseline serum creatinine and urinary KIM-1, but not proteinuria, are independent predictors of ESRD.
authors.affiliation: Department of Nephrology, Radboud University Nijmegen Medical Centre Nijmegen, Nijmegen, The Netherlands. h.peters@aig.umcn.nl
authors.forename: Hilde P E
authors.initials: HP
authors.lastname: Peters
authors.forename: Femke
authors.initials: F
authors.lastname: Waanders
authors.forename: Esther
authors.initials: E
authors.lastname: Meijer
authors.forename: Jan
authors.initials: J
authors.lastname: van den Brand
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Steenbergen
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000150:complications*; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000209:etiology* / Q000652:urine; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D008562:Membrane Glycoproteins / Q000652:urine*; D011379:Prognosis; D011507:Proteinuria / Q000175:diagnosis / Q000209:etiology; D011518:Proto-Oncogene Proteins / Q000652:urine; D011991:Receptors, Virus; D006435:Renal Dialysis
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; D003404:Creatinine