Malvezzi Paolo, Jouve Thomas, Rostaing Lionel
Clinique de Néphrologie, University Hospital, Grenoble, France.
Department of Nephrology, Dialysis, and Organ Transplantation, CHU Rangueil, Toulouse University Hospital, Toulouse, France ; INSERM U563, IFR-BMT, CHU Purpan, Toulouse, France ; Université Paul Sabatier, Toulouse, France.
J Nephropathol. 2015 Oct;4(4):110-5. doi: 10.12860/jnp.2015.21. Epub 2015 Oct 1.
Preventing acute rejection (AR) after kidney transplantation is of utmost importance because an AR can have a negative impact on long-term allograft survival.
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At the moment this can be done by using rabbit anti-thymocyte globulins (rATGs) as an induction therapy. However, because rATGs are associated with some deleterious side-effects, such as the opportunistic infections cytomegalovirus (CMV) and de novo post-transplant cancer, it is very important they are used optimally, i.e., at minimal doses that avoid many side-effects but still retain optimal treatment efficacy. Recent data show that the risk of CMV infection can be minimized using tacrolimus plus everolimus, and not tacrolimus plus mycophenolic acid, as the maintenance immunosuppression. The use of rATG is particularly valuable in; (a) sensitized patients; (b) in recipients from an expanded-criteria donor, thus enabling the introduction of calcineurin inhibitors at reduced doses; and (c) for patients where steroid avoidance is contemplated. However, we also need to consider that rATG may increase the risk of de novo cancer, even though recent data indicate this is unlikely and that any risk can be reduced by using mammalian target of rapamycin (mTOR) inhibitors instead of mycophenolic acid combined with low-dose calcineurin inhibitors.
Even though rATGs do not improve long-term kidney-allograft survival, they may help reduce calcineurin-inhibitor dosage during the early post-transplant period and minimize the risk of AR.
预防肾移植后的急性排斥反应(AR)至关重要,因为急性排斥反应会对长期移植肾存活产生负面影响。
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目前可以通过使用兔抗胸腺细胞球蛋白(rATG)进行诱导治疗来实现这一点。然而,由于rATG会引发一些有害的副作用,如机会性感染巨细胞病毒(CMV)和移植后新发癌症,因此以最佳方式使用它们非常重要,即使用最小剂量,既能避免许多副作用,又能保持最佳治疗效果。最新数据表明,使用他克莫司加依维莫司作为维持免疫抑制,而非他克莫司加霉酚酸,可将CMV感染风险降至最低。rATG的使用在以下情况中尤其有价值:(a)致敏患者;(b)接受扩大标准供体器官的受者,从而能够降低钙调神经磷酸酶抑制剂的使用剂量;(c)考虑避免使用类固醇的患者。然而,我们还需要考虑到rATG可能会增加新发癌症的风险,尽管最新数据表明这种可能性不大,并且通过使用雷帕霉素靶蛋白(mTOR)抑制剂而非霉酚酸联合低剂量钙调神经磷酸酶抑制剂,可以降低任何风险。
尽管rATG不能提高移植肾的长期存活,但它们可能有助于在移植后早期减少钙调神经磷酸酶抑制剂的用量,并将急性排斥反应的风险降至最低。