a Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation , Centre Hospitalier Universitaire (CHU) Grenoble-Alpes , Grenoble , France.
b Health Department , Grenoble Alpes University , Grenoble , France.
Expert Rev Clin Pharmacol. 2018 Jun;11(6):581-588. doi: 10.1080/17512433.2018.1479638. Epub 2018 May 25.
The prevalence of end-stage renal disease is increasing worldwide. The best treatment is kidney transplantation, although life-long immunosuppressive therapy is then mandatory. Currently, the cornerstone immunosuppressive therapy relies on tacrolimus (Tac), a calcineurin inhibitor that is nephrotoxic but whose exposition can be minimized in a delicate balance. Area covered: We addressed whether, in the setting of kidney transplantation, Tac-based therapy can be tailored to medical needs: to achieve this, we searched for suitable articles in PubMed. Expert commentary: Too over-minimization of Tac, when associated with mycophenolic acid (MPA), may cause the development of de novo donor-specific alloantibodies (DSA). However, Tac minimization, in the context of everolimus-associated therapy instead of MPA, does not increase DSA formation as demonstrated in the TRANSFORM study and, in addition, can prevent cytomegalovirus (CMV) infection/reactivation. Nonetheless, Tac therapy, regardless of its formulation (immediate or extended release) compared to cyclosporine A, increases the risk of posttransplant diabetes mellitus; this increase is not affected by steroid therapy. Tac-based immunosuppression remains the best immunosuppressive therapy in kidney-transplant recipients and can be tailored according to patients' need.
终末期肾病的患病率在全球范围内呈上升趋势。最佳治疗方法是肾移植,但随后必须进行终身免疫抑制治疗。目前,基石免疫抑制疗法依赖于他克莫司(Tac),一种肾毒性的钙调磷酸酶抑制剂,但可以通过微妙的平衡将其暴露最小化。
我们探讨了在肾移植中,Tac 为基础的治疗是否可以根据医疗需求进行调整:为此,我们在 PubMed 中搜索了相关文章。
当 Tac 与霉酚酸(MPA)联合使用时,如果过度最小化,可能会导致新的供体特异性同种抗体(DSA)的产生。然而,正如 TRANSFORM 研究所示,在 everolimus 相关治疗而非 MPA 的情况下,Tac 的最小化并不会增加 DSA 的形成,此外,还可以预防巨细胞病毒(CMV)感染/再激活。尽管如此,与环孢素 A 相比,无论其制剂(速释或缓释)如何,Tac 治疗都会增加移植后糖尿病的风险;这种增加不受类固醇治疗的影响。Tac 为基础的免疫抑制仍然是肾移植受者的最佳免疫抑制治疗方法,可以根据患者的需求进行调整。