title: Identification of β2-microglobulin as a urinary biomarker for chronic allograft nephropathy using proteomic methods.
abstract: OBJECTIVE
  Chronic allograft nephropathy (CAN) remains the leading cause of renal graft loss after the first year following renal transplantation. This study aimed to identify novel urinary proteomic profiles, which could distinguish and predict CAN in susceptible individuals.
  
  
  METHODS
  The study included 34 renal transplant patients with histologically proven CAN and 36 patients with normal renal transplant function. High-throughput proteomic profiles were generated from urine samples with three different ProteinChip arrays by surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Following SELDI, a biomarker pattern software analysis was performed which led to the identification of a novel biomarker pattern that could distinguish patients with CAN from those with normal renal function.
  
  
  RESULTS
  An 11.7 kDa protein identified as β2 microglobulin was the primary protein of this biomarker pattern, distinguishing CAN from control patients (receiver operator characteristic [ROC]=0.996). SELDI-TOF-MS comparison of purified β2 microglobulin protein and CAN urine demonstrated identical 11.7 kDa protein peaks. Significantly, higher concentrations of 2 microglobulin were found in the urine of patients with CAN compared with the urine of normal renal function transplant recipients (p<0.001).
  
  
  CONCLUSIONS
  Although further validation in a larger more diverse patient population is required to determine if this β2 microglobulin protein biomarker will provide a potential means of diagnosing CAN by noninvasive methods in a clinical setting, this study clearly shows a capability to stratify control and disease patients.
authors.affiliation: School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Olwyn
authors.initials: O
authors.lastname: Johnston
authors.forename: Hilary
authors.initials: H
authors.lastname: Cassidy
authors.forename: Séin
authors.initials: S
authors.lastname: O'Connell
authors.forename: Aisling
authors.initials: A
authors.lastname: O'Riordan
authors.forename: William
authors.initials: W
authors.lastname: Gallagher
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Maguire
authors.forename: Kieran
authors.initials: K
authors.lastname: Wynne
authors.forename: Gerard
authors.initials: G
authors.lastname: Cagney
authors.forename: Michael P
authors.initials: MP
authors.lastname: Ryan
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Conlon
authors.forename: Tara
authors.initials: T
authors.lastname: McMorrow
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology / Q000652:urine; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology / Q000652:urine; D006801:Humans; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D040081:Protein Array Analysis / Q000379:methods; D040901:Proteomics / Q000379:methods*; D012984:Software; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D014184:Transplantation, Homologous; D001613:beta 2-Microglobulin / Q000032:analysis*
chemical_list: D015415:Biomarkers; D001613:beta 2-Microglobulin