Chronic rejection.
The pathogenesis of chronic rejection is a complex network of immunological, metabolic and haemodynamic events leading to a cascade of cellular and molecular events with a subsequent remodelling of the graft. Evidence suggests that the frequency and intensity of acute rejection episodes strongly correlate with graft loss as a result of chronic rejection. The most characteristic feature of chronic rejection, shared by all organs, is concentric generalized arteriosclerosis with low-grade perivasculitis affecting all intragraft arteries of the transplant. In-vitro studies have demonstrated that a variety of cells and molecules may regulate smooth muscle cell replication in the vascular wall, the migration of smooth muscle cells from the media into the intima, and the development of arteriosclerotic lesions throughout the entire length of the vessel wall. These molecules include peptide growth factors, cytokines, vasoactive hormones, and lipid mediators of inflammation (eicosanoids), and they are secreted in situ by inflammatory, endothelial and smooth muscle cells in the vascular wall. In order to prevent chronic rejection it is necessary to optimize immunosuppression, possibly by the use of new immunosuppressive drugs that also seem to have direct inhibitory effect on smooth muscle cells and on transplant arteriosclerosis. The scope of this review is to highlight our current understanding of the risk factors, pathogenesis and prevention of chronic renal allograft rejection. This review will also briefly discuss present animal models used to investigate chronic rejection at the cellular and molecular level.
Koskinen
P
P
Transplantation Laboratory, University of Helsinki, Finland.
Lemström
K
K
Häyry
P
P
D000818:Animals; D001011:Aorta / Q000637:transplantation; D002339:Carotid Arteries / Q000502:physiology; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000502:physiology; D005544:Forecasting; D006084:Graft Rejection; D006652:Histological Techniques; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D016030:Kidney Transplantation; D012307:Risk Factors
D007166:Immunosuppressive Agents