Srinivas Titte R, Meier-Kriesche Herwig-Ulf
Division of Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, Florida, USA.
Clin J Am Soc Nephrol. 2008 Mar;3 Suppl 2(Suppl 2):S101-16. doi: 10.2215/CJN.03510807.
Exceptionally low acute rejection rates and excellent graft survival can be achieved with cyclosporine and tacrolimus (CNI)-based immunosuppressive protocols that incorporate antiproliferative immunosuppressants and corticosteroids. However, despite short-term success, long-term attrition of graft function and side effects of immunosuppressive agents continue to be significant problems, leaving clinicians looking for possible interventions. CNI nephrotoxicity is but one of numerous factors that may contribute to long-term damage in transplant kidneys. Metabolic, cosmetic, and neuropsychiatric complications of steroids affect quality of life after transplantation. Newer immunosuppressive agents such as mycophenolate mofetil and sirolimus (Rapa) have raised the possibility of withdrawing or avoiding CNIs or steroids altogether. In this report we review studies that address either CNI or steroid minimization strategies and discuss their risks versus benefits. Given the accumulated experience to date, in our opinion the use of CNIs and steroids as part of immunosuppressive regimens remains the proven standard of care for renal transplant patients. The long-term safety and efficacy of CNI and steroid minimization strategies needs to be further validated in controlled clinical trials with adequate long-term follow-up.
采用包含抗增殖免疫抑制剂和皮质类固醇的基于环孢素和他克莫司(CNI)的免疫抑制方案,可实现极低的急性排斥率和出色的移植物存活率。然而,尽管短期取得了成功,但移植物功能的长期衰退和免疫抑制剂的副作用仍然是重大问题,这使得临床医生一直在寻找可能的干预措施。CNI肾毒性只是可能导致移植肾长期损害的众多因素之一。类固醇的代谢、外观和神经精神并发症会影响移植后的生活质量。新型免疫抑制剂,如霉酚酸酯和西罗莫司(雷帕霉素),增加了完全停用或避免使用CNI或类固醇的可能性。在本报告中,我们回顾了涉及CNI或类固醇最小化策略的研究,并讨论了它们的风险与益处。鉴于迄今为止积累的经验,我们认为,将CNI和类固醇用作免疫抑制方案的一部分,仍然是肾移植患者已被证实的标准治疗方法。CNI和类固醇最小化策略的长期安全性和有效性需要在有足够长期随访的对照临床试验中进一步验证。