Augustine Joshua J, Hricik Donald E
Department of Medicine, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, Ohio 44106, USA.
Curr Opin Nephrol Hypertens. 2007 Nov;16(6):535-41. doi: 10.1097/MNH.0b013e3282f0b319.
In an effort to reduce the long-term toxicities of immunosuppressant drugs, corticosteroid and calcineurin inhibitor-sparing immunosuppression protocols have become increasingly popular in managing kidney transplant recipients. This article focuses on outcomes of these strategies described in recently published trials.
The use of induction antibody therapy and potent residual immunosuppressants has increased the safety of steroid-free regimens, resulting in a paradigm shift towards earlier elimination of steroids after kidney transplantation. Even in the modern era, results of randomized trials generally indicate that steroid elimination increases the risk of rejection compared with maintenance steroid therapy. Among calcineurin inhibitor-sparing strategies, withdrawal of these agents after their initial use in stable patients, or conversion to either mycophenolate mofetil or sirolimus in patients with early renal dysfunction appears to yield the greatest benefit in preserving renal function. The outcomes of calcineurin inhibitor avoidance protocols have been mixed and have fallen into disfavor.
The benefits of minimizing immunosuppression in kidney transplant recipients must be weighed against the risks of precipitating acute rejection or chronic allograft dysfunction. Additional research is needed to identify clinical and immune parameters that will enable selection of patients for whom the benefits outweigh the risks.
为了降低免疫抑制药物的长期毒性,在肾移植受者管理中,减少皮质类固醇和钙调神经磷酸酶抑制剂的免疫抑制方案越来越受欢迎。本文重点关注最近发表的试验中描述的这些策略的结果。
诱导抗体治疗和强效残留免疫抑制剂的使用提高了无类固醇方案的安全性,导致肾移植后更早停用类固醇的模式转变。即使在现代,随机试验结果通常表明,与维持类固醇治疗相比,停用类固醇会增加排斥反应的风险。在保留钙调神经磷酸酶抑制剂的策略中,在稳定患者初次使用这些药物后停药,或在早期肾功能不全患者中转换为霉酚酸酯或西罗莫司,似乎在保护肾功能方面获益最大。避免使用钙调神经磷酸酶抑制剂方案的结果不一,且已不受青睐。
必须权衡肾移植受者免疫抑制最小化的益处与引发急性排斥或慢性移植物功能障碍的风险。需要进一步研究以确定临床和免疫参数,从而能够选择受益大于风险的患者。