Martins L, Fonseca I, Sousa S, Matos C, Santos J, Dias L, Henriques A C, Sarmento A M, Cabrita A
Nephrology Department, Renal Transplant Unit, Hospital Geral de Santo António, Largo Professor Abel Salazar, 4050-011 Porto, Portugal.
Transplant Proc. 2007 Oct;39(8):2489-93. doi: 10.1016/j.transproceed.2007.07.033.
New immunosuppressive drugs used in kidney transplantation decreased the incidence of acute rejection. It was hypothesized that, with their power, the importance of HLA matching was decreased. To evaluate the influence of HLA matching, immunosuppression, and other possible risk factors, we analyzed data of 1314 consecutive deceased donor kidney transplantation. We divided the patient population into 4 cohorts, according to the era of transplantation: era 1, before 1990, azathioprine (Aza) and cyclosporine (Csa) no microemulsion; era 2, between 1990 and 1995, Csa microemulsion; era 3, between 1996 and 2000, wide use of mycophenolate mofetil (MMF) and anti-thymocyte globulin (ATG); and era 4, after 2000, marked by sirolimus and tacrolimus (TAC) use. Multivariate analysis compared death-censored graft survival. Using as reference the results obtained with 0 HLA mismatches, we verified, during era 1 and era 2, an increased risk of graft loss for all of the subgroups with HLA mismatch >0. However, during era 3 and era 4, the number of HLA mismatches did not influence graft survival. Although acute rejection and delayed graft function, which decreased in the later periods, remained as prognostic factors for graft loss. Considering the immunosuppressive protocol with Csa+Aza+Pred as reference, protocols used after 1995 with Pred+Csa+ATG, with Pred+Csa+MMF, and with Pred+Tac+MMF presented better survival results. Results showed that the significance of HLA matching decreased while the results improved with the new immunosuppressant drugs. These observations support the hypothesis that the weakened importance of HLA matching may be a consequence of the increasing efficacy of the immunosuppression.
肾移植中使用的新型免疫抑制药物降低了急性排斥反应的发生率。据推测，鉴于其强大作用，HLA配型的重要性有所降低。为评估HLA配型、免疫抑制及其他可能的风险因素的影响，我们分析了1314例连续的尸体供肾移植数据。根据移植时代，我们将患者群体分为4个队列：队列1，1990年以前，使用硫唑嘌呤（Aza）和非微乳环孢素（Csa）；队列2，1990年至1995年，使用微乳环孢素（Csa）；队列3，1996年至2000年，广泛使用霉酚酸酯（MMF）和抗胸腺细胞球蛋白（ATG）；队列4，2000年以后，以使用西罗莫司和他克莫司（TAC）为标志。多变量分析比较了校正死亡后的移植物存活率。以0个HLA错配所获结果为参照，我们证实，在队列1和队列2中，所有HLA错配>0的亚组移植物丢失风险均增加。然而，在队列3和队列4中，HLA错配数量并未影响移植物存活。尽管后期急性排斥反应和移植肾功能延迟恢复有所减少，但它们仍是移植物丢失的预后因素。以Csa+Aza+Pred免疫抑制方案为参照，1995年后使用的Pred+Csa+ATG、Pred+Csa+MMF以及Pred+Tac+MMF方案显示出更好的存活结果。结果表明，HLA配型的重要性降低，而新型免疫抑制药物使结果得到改善。这些观察结果支持了以下假设，即HLA配型重要性减弱可能是免疫抑制效果增强的结果。
