Lemström K, Koskinen P, Häyry P
Transplantation Laboratory, University of Helsinki, Finland.
Kidney Int Suppl. 1995 Dec;52:S2-10.
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.
慢性排斥反应的病因很可能是多因素的。考虑到慢性排斥反应的两个主要组织学表现——炎症和动脉硬化，我们提出了以下工作假说：以血管周围炎症为特征的免疫反应会对血管内皮造成持续性的轻度损伤，进而内皮细胞开始分泌生长因子来修复损伤。这会导致血管壁平滑肌细胞增殖，肌细胞从血管中膜流入内膜，并形成动脉硬化病变，同时肾小球系膜细胞增殖，导致肾小球硬化。非免疫因素和免疫因素都对慢性排斥反应的发展起作用。似乎急性炎症（急性排斥反应）在大多数情况下是慢性改变的先决条件。此外，肾小球毛细血管压力升高可能在肾移植的慢性排斥反应中起额外作用。几种不同的分子级联反应似乎参与了同种异体移植动脉硬化的发生。最有可能的是，最终的效应分子可能是移植的实质细胞和内皮细胞在受到损伤时合成的生长因子。如果这个假设的事件序列是真的，那么针对这种疾病将没有单一的治疗方法。因此，对于已存在的病变，预防可能比治疗更适用。很可能必须同时应对几个不同的参数才能抵消这些改变。然而，如果目前肾移植的半衰期（7至8年）能够翻倍，慢性排斥反应将被克服。
