title: Molecular mechanisms of chronic renal allograft rejection.
abstract: The etiology of chronic rejection is most likely multifactorial. Taking into account the two major histological manifestations of chronic rejection--inflammation and arteriosclerosis--we have formulated the following working hypothesis: the immune response characterized by the perivascular inflammation induces a persistent low-grade damage to vascular endothelium, which in turn begins to secrete growth factors to repair the damage. This results in smooth muscle cell replication in the vascular wall and the influx of myocytes from the media into the intima and generation of an arteriosclerotic lesion, and in glomeruli mesangial cell proliferation and glomerular sclerosis. Both nonimmunological and immunological factors contribute to the development of chronic rejection. It seems that acute inflammation (acute rejection) is on most occasions a prerequisite for chronic changes. In addition, increased glomerular capillary pressure may have an additional role in chronic rejection of kidney transplants. Several different molecular cascades seem to participate in the generation of allograft arteriosclerosis. Most likely the final effector molecules may be growth factors that are synthesized, in response to injury, by the parenchymal and endothelial cells of the transplant. If this hypothetical sequence of events is true, there will be no single therapy or treatment of this disorder. Thus, prophylaxis may be more applicable than therapy to a pre-existing lesion. Most likely several different parameters have to be encountered simultaneously in order to counteract these alterations. However, if the current half-life of the renal transplants, seven to eight years, could be doubled, chronic rejection would be overcome.
authors.affiliation: Transplantation Laboratory, University of Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Lemström
authors.forename: P
authors.initials: P
authors.lastname: Koskinen
authors.forename: P
authors.initials: P
authors.lastname: Häyry
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology