title: Molecular assessment of disease states in kidney transplant biopsy samples.
abstract: Progress in renal transplantation requires improved understanding and assessment of rejection and injury. Study of the relationship between gene expression and clinical phenotypes in kidney transplant biopsy samples has led to the development of a system that enables diagnoses of specific disease states on the basis of messenger RNA levels in the biopsy sample. Using this system we have defined the molecular landscape of T cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), acute kidney injury (AKI), and tubular atrophy and interstitial fibrosis. TCMR and ABMR share IFNγ-mediated effects and TCMR has emerged as a cognate T cell-antigen presenting cell process in the interstitium, whereas ABMR is a natural-killer-cell-mediated process that occurs in the microcirculation. The specific features of these different processes have led to the creation of classifiers to test for TCMR and ABMR, and revealed that ABMR is the principal cause of kidney transplant deterioration. The molecular changes associated with renal injury are often more extensive than suggested by histology and indicate that the progression to graft failure is caused by continuing nephron injury, rather than fibrogenesis. In summary, advances in the molecular assessment of disease states in biopsy samples has improved understanding of specific processes involved in kidney graft outcomes.
authors.affiliation: Alberta Transplant Applied Genomics Centre, University of Alberta.|Department of Medicine, Division of Nephrology and Transplant Immunology, 250 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
authors.forename: Philip F
authors.initials: PF
authors.lastname: Halloran
authors.affiliation: Alberta Transplant Applied Genomics Centre, University of Alberta.|Department of Laboratory Medicine &Pathology, 4B1.21 Walter Mackenzie Centre, University of Alberta, Edmonton, Alberta T6G 2B7, Canada.
authors.forename: Konrad S
authors.initials: KS
authors.lastname: Famulski
authors.affiliation: Alberta Transplant Applied Genomics Centre, University of Alberta.|Department of Laboratory Medicine &Pathology, 4B1.21 Walter Mackenzie Centre, University of Alberta, Edmonton, Alberta T6G 2B7, Canada.
authors.forename: Jeff
authors.initials: J
authors.lastname: Reeve
mesh_terms: D006084:Graft Rejection / Q000175:diagnosis / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D016030:Kidney Transplantation; D046228:Microarray Analysis; D025202:Molecular Diagnostic Techniques; D011183:Postoperative Complications / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000473:pathology*