title: Biomarkers for early and late stage chronic allograft nephropathy by proteogenomic profiling of peripheral blood.
abstract: BACKGROUND
  Despite significant improvements in life expectancy of kidney transplant patients due to advances in surgery and immunosuppression, Chronic Allograft Nephropathy (CAN) remains a daunting problem. A complex network of cellular mechanisms in both graft and peripheral immune compartments complicates the non-invasive diagnosis of CAN, which still requires biopsy histology. This is compounded by non-immunological factors contributing to graft injury. There is a pressing need to identify and validate minimally invasive biomarkers for CAN to serve as early predictors of graft loss and as metrics for managing long-term immunosuppression.
  
  
  METHODS
  We used DNA microarrays, tandem mass spectroscopy proteomics and bioinformatics to identify genomic and proteomic markers of mild and moderate/severe CAN in peripheral blood of two distinct cohorts (n = 77 total) of kidney transplant patients with biopsy-documented histology.
  
  
  RESULTS
  Gene expression profiles reveal over 2400 genes for mild CAN, and over 700 for moderate/severe CAN. A consensus analysis reveals 393 (mild) and 63 (moderate/severe) final candidates as CAN markers with predictive accuracy of 80% (mild) and 92% (moderate/severe). Proteomic profiles show over 500 candidates each, for both stages of CAN including 302 proteins unique to mild and 509 unique to moderate/severe CAN.
  
  
  CONCLUSIONS
  This study identifies several unique signatures of transcript and protein biomarkers with high predictive accuracies for mild and moderate/severe CAN, the most common cause of late allograft failure. These biomarkers are the necessary first step to a proteogenomic classification of CAN based on peripheral blood profiling and will be the targets of a prospective clinical validation study.
authors: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA.
authors: Sunil M
authors: SM
authors: Kurian
authors: Raymond
authors: R
authors: Heilman
authors: Tony S
authors: TS
authors: Mondala
authors: Aleksey
authors: A
authors: Nakorchevsky
authors: Johannes A
authors: JA
authors: Hewel
authors: Daniel
authors: D
authors: Campbell
authors: Elizabeth H
authors: EH
authors: Robison
authors: Lin
authors: L
authors: Wang
authors: Wen
authors: W
authors: Lin
authors: Lillian
authors: L
authors: Gaber
authors: Kim
authors: K
authors: Solez
authors: Hamid
authors: H
authors: Shidban
authors: Robert
authors: R
authors: Mendez
authors: Randolph L
authors: RL
authors: Schaffer
authors: Jonathan S
authors: JS
authors: Fisher
authors: Stuart M
authors: SM
authors: Flechner
authors: Steve R
authors: SR
authors: Head
authors: Steve
authors: S
authors: Horvath
authors: John R
authors: JR
authors: Yates
authors: Christopher L
authors: CL
authors: Marsh
authors: Daniel R
authors: DR
authors: Salomon
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002853:Chromatography, Liquid; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D007674:Kidney Diseases / Q000097:blood*; D016030:Kidney Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers