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Updated: Aug 9, 2026
In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Therapeutic targets in the treatment of allograft fibrosis
1Transplantation Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. rozm@mail.nih.gov
Abstract:
The dramatic improvements in short-term graft survival and acute rejection rates could only have been dreamed of 20 years ago. Late graft loss following kidney transplantation is now the critical issue of this decade. Frequently, graft loss is associated with the development of tubular atrophy and interstitial fibrosis within the kidney (i.e. chronic allograft nephropathy; CAN). Major treatment strategies in this disorder are non-specific and the focus of intervention has been on limiting injurious events. Following graft injury is a fibrogenesis phase featuring both proliferative and infiltrative responses mediated by chemokines, cytokines and growth factors. In particular, TGFbeta has been strongly implicated in the pathogenesis of chronic injury and epithelial-mesenchymal transformation (EMT) may be part of this process. The cascade of events results in matrix accumulation, due to either increased production and/or reduced degradation of matrix. Recent investigations into the pathogenesis of tissue fibrosis have suggested a number of new strategies to ameliorate matrix synthesis. While the majority of therapies have focused on TGFbeta, this may not be an ideal maneuver in transplant settings and alternative targets identified in other fibrotic diseases will be discussed. Attacking graft fibrosis should be a new focus in organ transplantation.
Insights
Late kidney transplant loss is a major challenge. Targeting graft fibrosis, not just TGF-beta, offers new hope for improving long-term transplant survival and preventing chronic allograft nephropathy.
Area of Science:
- Nephrology
- Transplantation Immunology
- Fibrosis Research
Background:
- Significant advancements in short-term kidney graft survival and acute rejection rates contrast with the persistent challenge of late graft loss.
- Chronic allograft nephropathy (CAN), characterized by tubular atrophy and interstitial fibrosis, is a primary cause of late graft failure.
- Current treatments for CAN are largely non-specific, focusing on mitigating injurious events rather than directly addressing fibrosis.
Purpose of the Study:
- To highlight late graft loss as the critical issue in kidney transplantation.
- To discuss the pathogenesis of chronic allograft nephropathy, including the role of fibrogenesis and TGF-beta.
- To explore novel therapeutic strategies targeting matrix synthesis and fibrosis, potentially beyond TGF-beta inhibition.
Main Methods:
- Review of current literature on kidney transplant outcomes and chronic allograft nephropathy.
- Analysis of the fibrogenesis cascade involving chemokines, cytokines, growth factors, and epithelial-mesenchymal transformation (EMT).
- Discussion of emerging strategies for ameliorating matrix synthesis based on recent investigations into tissue fibrosis.
Main Results:
- Late graft loss due to chronic allograft nephropathy remains a significant problem despite improved short-term outcomes.
- TGF-beta is strongly implicated in the pathogenesis of chronic kidney injury and fibrosis.
- Alternative targets for antifibrotic therapies, beyond TGF-beta, are being identified in other fibrotic diseases.
Conclusions:
- Addressing graft fibrosis is crucial for improving long-term kidney transplant success.
- Therapeutic strategies should consider targeting matrix synthesis and degradation pathways.
- Exploring novel antifibrotic targets beyond TGF-beta may offer more effective interventions for chronic allograft nephropathy.
