Kumar Dhiren, Fattah Hasan, Kimball Pamela M, LeCorchick Spencer, McDougan Felecia A, King Anne L, Gupta Gaurav
Division of Nephrology, Department of Surgery, Virginia Commonwealth University, Richmond, VA.
Division of Transplant Surgery, Department of Surgery, Virginia Commonwealth University, Richmond, VA.
Clin Transpl. 2016;32:143-151.
The highly-sensitized kidney transplant candidate with no available living donors remains at a major disadvantage with decreased access and worse outcomes post-transplant. We have previously reported our initial data on both pre-transplant and post-transplant desensitization. We observed only a modest decline in unacceptable antigens with pretransplant intravenous immunoglobin (IVIG) and rituximab. Due to these observations, we have focused on a peri-operative post-transplant desensitization protocol in our program. Beginning in 2006, we implemented a simple point-based algorithm [variables included: panel reactive antibody (PRA) status; flow cytometric crossmatch (FCXM); and delayed graft function] to identify kidney transplant recipients who would undergo peri-operative plasmapheresis/IVIG to abrogate preformed antibody-mediated allograft rejection (AMR). Our previous results suggested acceptable 5-year outcomes. Here, in an expanded population (N=66), we report an overall death-censored graft survival of 73% at a mean follow-up of 8.5 years post-transplant. Our patients were largely African American (85%) and regrafts (39%), with a median PRA of 88%, and a mean T- and B-FCXM of 97 mean channel shifts (MCS) and 117 MCS, respectively. Although acute AMR rates were acceptable (12%), 22% of patients developed chronic AMR. A pre-transplant T-cell FCXM of > 200 MCS (p=0.02) or presence of donor specific antibodies (DSA) at most recent follow-up (p=0.02) were associated with graft loss. Current studies with revised protocols utilizing additional DSA information, surveillance biopsies, and proteasome inhibition are ongoing.
对于没有合适活体供体的高敏肾移植候选者而言,他们在获取移植机会方面处于极大劣势,且移植后的预后较差。我们之前曾报告过关于移植前和移植后脱敏治疗的初步数据。我们观察到,移植前静脉注射免疫球蛋白(IVIG)和利妥昔单抗治疗后,不可接受抗原仅有适度下降。基于这些观察结果,我们在项目中重点关注了移植后围手术期脱敏方案。从2006年开始,我们实施了一种简单的积分算法[变量包括:群体反应性抗体(PRA)状态;流式细胞术交叉配型(FCXM);以及移植肾功能延迟],以确定哪些肾移植受者将接受围手术期血浆置换/IVIG治疗,以消除预先形成的抗体介导的同种异体移植排斥反应(AMR)。我们之前的结果显示5年预后良好。在此,在一个扩大的队列(N = 66)中,我们报告移植后平均随访8.5年时,总体死亡截尾移植物存活率为73%。我们的患者大多为非裔美国人(85%)且为再次移植者(39%),PRA中位数为88%,T细胞和B细胞FCXM平均值分别为97平均通道位移(MCS)和117 MCS。虽然急性AMR发生率可以接受(12%),但2%的患者发生了慢性AMR。移植前T细胞FCXM > 200 MCS(p = 0.02)或在最近一次随访时存在供体特异性抗体(DSA)(p = 0.02)与移植物丢失相关。目前正在进行利用额外DSA信息、监测活检和蛋白酶体抑制的修订方案的研究。