title: Proteomic-based identification of cleaved urinary beta2-microglobulin as a potential marker for acute tubular injury in renal allografts.
abstract: Our aim is to develop noninvasive tests to monitor the renal allograft posttransplant. Previously, we have reported that an unbiased proteomic-based approach can detect urine protein peaks associated with acute tubulointerstitial renal allograft rejection. Identification of these proteins peaks by mass spectrometry demonstrated that they all derive from nontryptic cleaved forms of beta2-microglobulin. In vitro experiments showed that cleavage of intact beta2-microglobulin requires a urine pH < 6 and the presence of aspartic proteases. Patients with acute tubulointerstitial rejection had lower urine pH than stable transplants and healthy individuals. In addition, they had higher amounts of aspartic proteases and intact beta2-microglobulin in urine. These factors ultimately lead to increased amounts of cleaved urinary beta2-microglobulin. Cleaved beta2-microglobulin as an indicator of acute tubular injury may become a useful tool for noninvasive monitoring of renal allografts.
authors.affiliation: Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schaub
authors.forename: John A
authors.initials: JA
authors.lastname: Wilkins
authors.forename: Mihaela
authors.initials: M
authors.lastname: Antonovici
authors.forename: Oleg
authors.initials: O
authors.lastname: Krokhin
authors.forename: Tracey
authors.initials: T
authors.lastname: Weiler
authors.forename: David
authors.initials: D
authors.lastname: Rush
authors.forename: Peter
authors.initials: P
authors.lastname: Nickerson
mesh_terms: D000595:Amino Acid Sequence; D015415:Biomarkers; D006801:Humans; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000293:injuries* / Q000378:metabolism; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000652:urine; D040901:Proteomics; D014184:Transplantation, Homologous; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000652:urine*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D001613:beta 2-Microglobulin