Gray J R, Kasiske B L
Department of Medicine, Hennepin County Medical Center, University of Minnesota College of Medicine, Minneapolis 55415.
Semin Nephrol. 1992 Jul;12(4):343-52.
Finding the proper balance between too much and not enough immunosuppression is just as important in the late posttransplant period as it is during the first year after transplantation. In general, too much immunosuppression leads to an increase in patient mortality, whereas inadequate immunosuppression can lead to an inordinately high rate of allograft failure (Fig 5). In the late posttransplant period, patient and allograft survival are both critically dependent on the degree of immunosuppression and on the long-term side effects of the agents used to achieve this immunosuppression. Adequate immunosuppression is important in treating and preventing the acute allograft rejection episodes that are common during the first year after transplantation (Fig 6). Some data suggest that the severity of early acute rejection episodes may influence the development of chronic rejection, the most common cause of graft failure in the late posttransplant period. Otherwise, the role of immunosuppression in treating and preventing chronic rejection is unclear. The discontinuation of immunosuppression by noncompliant patients is a major cause of late graft failure. Whether the nephrotoxicity of CsA will also result in graft failure in the very late posttransplant period is still unknown. The agents used to achieve immunosuppression, along with decreased graft function and proteinuria, contribute to hypercholesterolemia, hypertension, and hyperglycemia. These and other risk factors have a negative impact on both graft and patient survival. Thus, immunosuppression is directly, or indirectly linked to most of the common causes of death and graft failure after renal transplantation. Although potent new immunosuppression protocols have increased the rate of short-term patient and allograft survival after renal transplantation, future advances in long-term survival after renal transplantation will depend on improvements that are effective in the late posttransplant period. Currently, the best approach to preventing complications in the late posttransplant period is to maintain a vigilant, comprehensive program of on-going medical care. The minimal amount of immunosuppression required to prevent allograft rejection should be used, while adhering to the principle that it is better to lose the graft than to lose the patient.
在移植后期找到免疫抑制过度与不足之间的恰当平衡，与移植后第一年同样重要。一般而言，免疫抑制过度会导致患者死亡率增加，而免疫抑制不足则可能导致移植失败率过高（图5）。在移植后期，患者和移植器官的存活都严重依赖于免疫抑制的程度以及用于实现这种免疫抑制的药物的长期副作用。充分的免疫抑制对于治疗和预防移植后第一年常见的急性移植排斥反应至关重要（图6）。一些数据表明，早期急性排斥反应的严重程度可能会影响慢性排斥反应的发生，而慢性排斥反应是移植后期移植失败的最常见原因。否则，免疫抑制在治疗和预防慢性排斥反应中的作用尚不清楚。不依从患者停用免疫抑制药物是移植后期移植失败的主要原因。环孢素A的肾毒性在移植极后期是否也会导致移植失败仍不清楚。用于实现免疫抑制的药物，连同移植功能下降和蛋白尿，会导致高胆固醇血症、高血压和高血糖。这些及其他危险因素对移植器官和患者的存活都有负面影响。因此，免疫抑制与肾移植后大多数常见的死亡和移植失败原因直接或间接相关。尽管强效的新免疫抑制方案提高了肾移植后患者和移植器官的短期存活率，但肾移植后长期存活的未来进展将取决于在移植后期有效的改进措施。目前，预防移植后期并发症的最佳方法是维持一个警惕、全面的持续医疗护理计划。应使用预防移植排斥所需的最低剂量免疫抑制药物，同时坚持宁可失去移植器官也不可失去患者的原则。
