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Updated: May 14, 2026
Mouse Kidney Transplantation: Models of Allograft Rejection
Published on: October 11, 2014
Kidney transplants with progressing chronic diseases express high levels of acute kidney injury transcripts
K S Famulski1, J Reeve, D G de Freitas
1Department of Laboratory Medicine and Pathology, Manchester, UK.
Abstract:
We previously reported that kidney transplants with early acute injury express transcripts indicating injury repair--the 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.
Insights
The acute kidney injury signal in kidney transplants indicates ongoing parenchymal distress. This signal predicts future graft loss better than fibrosis or inflammation, highlighting its importance in managing transplant outcomes.
Area of Science:
- Nephrology
- Transplant Immunology
- Molecular Biology
Background:
- The acute kidney injury signal, identified by specific transcripts, was previously linked to early kidney transplant injury.
- Its presence and significance in various post-transplant conditions remained to be fully elucidated.
Purpose of the Study:
- To investigate the role and predictive value of the acute kidney injury signal in kidney transplants experiencing diverse pathologies beyond initial injury.
- To determine if this signal correlates with graft function, inflammation, fibrosis, and predicts long-term graft survival.
Main Methods:
- Analysis of kidney transplant biopsies across various conditions, including T cell-mediated rejection, antibody-mediated rejection, and glomerulonephritis.
- Correlation of the injury signal's expression levels with clinical parameters like graft function, histological findings (inflammation, fibrosis), and patient survival data.
- Multivariate survival analysis to assess the predictive power of the injury signal for graft loss.
Main Results:
- The acute kidney injury signal was elevated in multiple conditions, including T cell-mediated and antibody-mediated rejection, and glomerulonephritis.
- A higher injury signal correlated with poorer graft function and inflammation within fibrotic areas, but not with fibrosis alone.
- The injury signal proved to be a stronger predictor of future graft loss than traditional markers like fibrosis or inflammation, and shared transcripts with a known molecular risk score.
Conclusions:
- The acute kidney injury signal reflects ongoing parenchymal distress in kidney transplants across various diseases.
- This molecular signal is a potent predictor of long-term graft loss, outperforming histological assessments of fibrosis and inflammation.
- Transplant outcomes are primarily driven by the nature and persistence of the underlying injury, rather than solely by fibrotic changes.
Related Concept Videos
01:28Kidney Transplant I: Introduction
01:26Kidney Transplant II: Surgical Procedure
01:16Kidney Transplant III: Nursing Management
01:29Acute Kidney Injury III: Clinical Manifestations
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:22Acute Kidney Injury I: Introduction