title: Mining the human urine proteome for monitoring renal transplant injury.
abstract: The human urinary proteome provides an assessment of kidney injury with specific biomarkers for different kidney injury phenotypes. In an effort to fully map and decipher changes in the urine proteome and peptidome after kidney transplantation, renal allograft biopsy matched urine samples were collected from 396 kidney transplant recipients. Centralized and blinded histology data from paired graft biopsies was used to classify urine samples into diagnostic categories of acute rejection, chronic allograft nephropathy, BK virus nephritis, and stable graft. A total of 245 urine samples were analyzed by liquid chromatography-mass spectrometry using isobaric Tags for Relative and Absolute Quantitation (iTRAQ) reagents. From a group of over 900 proteins identified in transplant injury, a set of 131 peptides were assessed by selected reaction monitoring for their significance in accurately segregating organ injury causation and pathology in an independent cohort of 151 urine samples. Ultimately, a minimal set of 35 proteins were identified for their ability to segregate the 3 major transplant injury clinical groups, comprising the final panel of 11 urinary peptides for acute rejection (93% area under the curve [AUC]), 12 urinary peptides for chronic allograft nephropathy (99% AUC), and 12 urinary peptides for BK virus nephritis (83% AUC). Thus, urinary proteome discovery and targeted validation can identify urine protein panels for rapid and noninvasive differentiation of different causes of kidney transplant injury, without the requirement of an invasive biopsy.
authors.affiliation: The Department of Surgery, University of California San Francisco, San Francisco, California, USA.
authors.forename: Tara K
authors.initials: TK
authors.lastname: Sigdel
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
authors.forename: Jintang
authors.initials: J
authors.lastname: He
authors.affiliation: The Department of Surgery, University of California San Francisco, San Francisco, California, USA.
authors.forename: Anyou
authors.initials: A
authors.lastname: Wang
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
authors.forename: Carrie D
authors.initials: CD
authors.lastname: Nicora
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Fillmore
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
authors.forename: Tujin
authors.initials: T
authors.lastname: Shi
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
authors.forename: Bobbie-Jo
authors.initials: BJ
authors.lastname: Webb-Robertson
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Qian
authors.affiliation: Department of Surgery, Stanford University, Palo Alto, California, USA.
authors.forename: Oscar
authors.initials: O
authors.lastname: Salvatierra
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Camp
authors.affiliation: The Department of Surgery, University of California San Francisco, San Francisco, California, USA. Electronic address: minnie.sarwal@ucsf.edu.
authors.forename: Minnie M
authors.initials: MM
authors.lastname: Sarwal
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts / Q000473:pathology*; D001739:BK Virus / Q000302:isolation & purification; D015415:Biomarkers / Q000652:urine; D001706:Biopsy; D002648:Child; D002853:Chromatography, Liquid; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000473:pathology / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation; D008297:Male; D013058:Mass Spectrometry; D009393:Nephritis / Q000175:diagnosis / Q000473:pathology / Q000652:urine* / Q000821:virology; D040901:Proteomics; D016482:Urinalysis / Q000379:methods; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: acute rejection; kidney transplantation injury; noninvasive biomarkers; protein biomarkers; urine proteomics