Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 13, Issue 3, Pages 634-644Publisher
WILEY
DOI: 10.1111/ajt.12080
Keywords
Fibrosis; gene expression; graft failure; inflammation; renal injury
Categories
Funding
- Canada Foundation for Innovation
- Genome Canada
- University of Alberta
- University of Alberta Hospital Foundation
- Alberta Advanced Education and Technology
- Roche Molecular Systems
- Hoffmann-La Roche Canada Ltd.
- Alberta Ministry of Advanced Education and Technology
- Kidney Foundation of Canada
- Stromedix Inc.
- Astellas Canada
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We previously reported that kidney transplants with early acute injury express transcripts indicating injury repairthe acute kidney injury signal. This study investigated the significance of this signal in transplants with other conditions, including rejection and recurrent disease. The injury signal was elevated in biopsies in many different conditions, including T cell-mediated rejection and potentially progressive diseases such as antibody-mediated rejection and glomerulonephritis. A high injury signal correlated with poor function and with inflammation in areas of fibrosis, but not with fibrosis without inflammation. In multivariate survival analysis, the injury signal in late kidney transplant biopsies strongly predicted future graft loss, similar to a published molecular risk score derived in late kidneys. Indeed, the injury signal shared many individual transcripts with the risk score, e.g. ITGB6, VCAN, NNMT. The injury signal was a better predictor of future graft loss than fibrosis, inflammation or expression of collagen genes. Thus the acute injury signal, first defined in early reversible injury, is present in many diseases as a reflection of parenchymal distress, where its significance is dictated by the inducing insult, i.e. treatable/self-limited versus untreatable and sustained. Progression in troubled transplants is primarily a function of ongoing parenchymal injury by disease, not fibrogenesis.
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