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[不同器官(肾脏、心脏和肝脏)移植中钙调神经磷酸酶抑制剂(CNIs)的最小化和中断以及无CNIs方案的临床试验综述]

[Review of clinical trials on minimization and interruption of calcineurin inhibitors (CNIs) and protocols without CNIs in the transplantation of different organs (kidney, heart, and liver)].

作者信息

Albano L

机构信息

Unité de Transplantation Rénale, CHU de Nice, Hôpital Pasteur, 30 avenue de la Voie Romaine, Nice, France.

出版信息

Nephrol Ther. 2009 Dec;5 Suppl 6:S371-8. doi: 10.1016/S1769-7255(09)73428-5.

Abstract

Immunosuppressive therapy with calcineurin inhibitors (CNI) must be continued during the weeks following transplant to avoid acute rejection. Over the long-term, however, nephrotoxicity and morbidity induced by CNIs have a negative impact on patient and transplant survival. Therefore, for any organ, it is crucial to free patients from the nephrotoxicity associated with CNIs without risking under-immunosuppression and while maintaining good overall tolerance. For kidney transplants, minimization of CNI use in association with mycophenolate seems to be relatively safe and allows for improved kidney function without an added risk of rejection. The strategy of making a complete switch from CNIs to proliferation signal inhibitors (PSI) also seems to be promising. In patients with chronic allotransplant dysfunction, reduction of CNI doses by 30 to 50% in association with MPA seems to be safe and effective and replacement of CNIs with PSIs is pertinent, though limited by their effect on proteinuria. For liver transplants, late and minimal introduction of CNIs under induction seems to be safe and effective for the preservation of kidney function, especially when precarious. For heart transplants, preliminary studies conducted on a small number of patients suggest that delayed introduction of CNIs at minimal doses and late elimination of the therapy are safe after transplant.

摘要

移植后的数周内必须持续使用钙调神经磷酸酶抑制剂(CNI)进行免疫抑制治疗,以避免急性排斥反应。然而,从长期来看,CNI诱导的肾毒性和发病率会对患者和移植器官的存活产生负面影响。因此,对于任何器官移植而言,使患者摆脱与CNI相关的肾毒性,同时又不冒免疫抑制不足的风险,并维持良好的整体耐受性,这一点至关重要。对于肾移植,将CNI与霉酚酸酯联合使用并尽量减少CNI用量似乎相对安全,且能改善肾功能,同时不会增加排斥反应的风险。从CNI完全转换为增殖信号抑制剂(PSI)的策略似乎也很有前景。对于慢性同种异体移植功能障碍患者,将CNI剂量降低30%至50%并联合霉酚酸(MPA)似乎是安全有效的,用PSI替代CNI也是合理的,尽管其对蛋白尿的影响会对此有所限制。对于肝移植,在诱导期晚期且少量引入CNI似乎对肾功能的保护是安全有效的,尤其是在肾功能不稳定时。对于心脏移植,对少数患者进行的初步研究表明,移植后以最小剂量延迟引入CNI并在后期停用该治疗是安全的。

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