Kälble Florian, Süsal Caner, Pego da Silva Luiza, Speer Claudius, Benning Louise, Nusshag Christian, Pham Lien, Tran Hien, Schaier Matthias, Sommerer Claudia, Beimler Jörg, Mehrabi Arianeb, Zeier Martin, Morath Christian
Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany.
Transplant Immunology Research Center of Excellence, Koç University Hospital, Istanbul, Turkey.
Front Med (Lausanne). 2021 Dec 17;8:781491. doi: 10.3389/fmed.2021.781491. eCollection 2021.
Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From March 2007 to December 2016, 58 sensitized living donor kidney transplant candidates were identified and 38 patients eventually included in the study: 36 patients (95%) had pre-transplant and pre-desensitization Luminex-detected donor-specific HLA antibodies (DSA), and 17/36 patients (47%) in addition had a positive crossmatch result. Two patients had no detectable DSA but a positive CDC B-cell crossmatch result. Patients were treated with pre- and post-transplant apheresis and powerful immunosuppression including the anti-CD20 antibody rituximab ( = 36) in combination with thymoglobulin ( = 20) or anti-IL2 receptor antibody ( = 18). The results of the 38 successfully desensitized and transplanted patients were retrospectively compared to the results of 76 matched standard-risk recipients. Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients ( = 0.55 and = 0.16, respectively). There was a trend toward reduced death-censored graft survival in desensitized patients ( = 0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed ( = 0.43). The incidence of rejection episodes without borderline changes were in desensitized patients with 21% similar to the 18% in standard-risk patients ( = 0.74). Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85 and 81%, respectively, during pre-transplant desensitization ( < 0.001 for both). On day 360 after transplantation, 20 of 36 (56%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent and DSA during year 1; 2 (40%) of whom lost their graft due to AMR. Eleven (31%) patients with persistent DSA but without DSA had an AMR rate of 18% without graft loss while one patient lost her graft without signs of AMR. Our desensitization protocol for pre-sensitized living donor kidney transplant recipients with DSA resulted in good graft outcomes with side effects and rejection rates similar to that of standard-risk recipients. Adequate patient selection prior to transplantation and frequent immunological monitoring thereafter is critical to minimize rejection episodes and subsequent graft loss.
由于目前器官短缺,活体供肾移植越来越多地跨越人类白细胞抗原(HLA)或ABO抗体屏障进行。抗体介导的排斥反应(AMR)发作的风险仍不确定,这可能会限制移植物的长期存活。2007年3月至2016年12月,确定了58例致敏的活体供肾移植候选者,最终38例患者纳入研究:36例患者(95%)在移植前和脱敏前通过Luminex检测出供者特异性HLA抗体(DSA),其中17/36例患者(47%)交叉配型结果为阳性。2例患者未检测到DSA,但补体依赖细胞毒试验(CDC)B细胞交叉配型结果为阳性。患者在移植前后接受了血液成分单采术,并接受了强效免疫抑制治疗,包括抗CD20抗体利妥昔单抗(n = 36)联合抗胸腺细胞球蛋白(n = 20)或抗白细胞介素2受体抗体(n = 18)。将38例成功脱敏并移植的患者的结果与76例匹配的标准风险受者的结果进行回顾性比较。脱敏患者的患者和移植物存活率与标准风险受者相似(分别为P = 0.55和P = 0.16)。脱敏患者的死亡删失移植物存活率有降低趋势(P = 0.053),然而,在分析引入敏感Luminex检测后移植的34例患者时,这种趋势消失了(P = 0.43)。无临界变化的排斥反应发作发生率在脱敏患者中为21%,与标准风险患者中的18%相似(P = 0.74)。36例患者在移植前有HLAⅠ类和/或Ⅱ类DSA,在移植前脱敏期间分别降低了85%和81%(两者P均<0.001)。移植后360天,36例患者中有20例(56%)失去了DSA。这些患者的总体AMR率为6%,但在第1年中,5例(14%)持续存在高水平DSA的患者中高达60%;其中2例(40%)因AMR失去了移植物。11例(31%)持续存在DSA但无高水平DSA的患者AMR率为18%,未发生移植物丢失,而1例患者在无AMR迹象的情况下失去了移植物。我们针对有DSA的致敏活体供肾移植受者的脱敏方案产生了良好的移植物结果,副作用和排斥率与标准风险受者相似。移植前进行充分的患者选择以及此后频繁的免疫监测对于尽量减少排斥反应发作和随后的移植物丢失至关重要。