Division of Nephrology, Department of Medicine, Ramathibodi Hospital, Phyathai, Bangkok Thailand.
Division of Nephrology, Department of Medicine, Ramathibodi Hospital, Phyathai, Bangkok Thailand; Section for Clinical Epidemiology and Biostatistics, Ramathibodi Hospital, Phyathai, Bangkok, Thailand.
Transplant Proc. 2021 Apr;53(3):995-1000. doi: 10.1016/j.transproceed.2020.08.019. Epub 2020 Sep 15.
Pretransplant desensitization protocols, including plasmapheresis, intravenous immunoglobulin, induction antibody therapy, and intensive maintenance immunosuppression, are generally employed in kidney transplant recipients who have positive status for donor-specific anti-HLA antibody (DSA). To avoid serious infectious complications, the authors designed a novel low-dose protocol in Thai patients undergoing DSA+ living-related kidney transplantation (LRKT).
A retrospective cohort study of the patients who underwent DSA+ LRKT was conducted. The novel protocol consisted of 3 to 5 sessions of pretransplant double-filtration plasmapheresis (DFPP) with or without low-dose intravenous immunoglobulin together with low-dose anti-thymocyte globulin (ATG) induction (1-1.5 mg/kg/d for 3-4 days) and low-dose tacrolimus (Tac) (trough level 5-10 ng/mL), mycophenolate, and prednisolone.
The study included 17 patients. The lymphocyte crossmatch via complement-dependent cytotoxicity was negative in 12 patients and positive for B cell immunoglobulin M in 5 patients. The novel desensitization protocol resulted in a decrease of at least 50% of DSA mean fluorescence intensity from baseline (from 4320 ± 549 before DFPP to 1601 ± 350 before transplantation, P < .005) and successful kidney transplantation with good allograft function in all cases. Early DSA rebound was observed in 3 patients after transplantation, and kidney biopsy revealed subclinical antibody-mediated rejection in 1 patient and diffuse C4d staining without cell infiltration in 2 patients. There were good long-term outcomes in patient and graft survival (100% and 94.1%, respectively). Only 1 allograft loss occurred because of nonadherence. The majority of patients have stable allograft function with serum creatinine less than 1.5 mg/dL. However, infections, including CMV and other organisms, were commonly observed.
Desensitization protocol with DFPP, low-dose ATG, and Tac provides excellent outcomes in living donor kidney transplantation in highly sensitized Asian populations.
在移植前，包括血浆置换、静脉注射免疫球蛋白、诱导抗体治疗和强化维持免疫抑制在内的脱敏方案通常应用于有供体特异性抗 HLA 抗体（DSA）阳性的肾移植受者。为了避免严重的感染并发症，作者设计了一种新型的低剂量方案，用于泰国接受 DSA+活体相关肾移植（LRKT）的患者。
对接受 DSA+LRKT 的患者进行了回顾性队列研究。该新型方案包括 3-5 次移植前双重滤过血浆置换（DFPP），可伴有或不伴有低剂量静脉注射免疫球蛋白，同时联合低剂量抗胸腺细胞球蛋白（ATG）诱导（1-1.5mg/kg/d，3-4 天）和低剂量他克莫司（Tac）（谷浓度 5-10ng/mL）、霉酚酸酯和泼尼松龙。
该研究共纳入 17 例患者。12 例患者淋巴细胞交叉配合通过补体依赖性细胞毒性试验呈阴性，5 例患者 B 细胞免疫球蛋白 M 阳性。新型脱敏方案使 DSA 平均荧光强度至少降低 50%（从 DFPP 前的 4320±549 降至移植前的 1601±350，P<.005），所有患者均成功进行了肾移植，移植物功能良好。3 例患者在移植后早期出现 DSA 反弹，肾活检显示 1 例存在亚临床抗体介导的排斥反应，2 例存在弥漫性 C4d 染色而无细胞浸润。患者和移植物的存活率均良好（分别为 100%和 94.1%）。仅 1 例移植物丢失是由于不遵医嘱。大多数患者的移植肾功能稳定，血清肌酐小于 1.5mg/dL。然而，感染（包括 CMV 和其他病原体）很常见。
DFPP、低剂量 ATG 和 Tac 的脱敏方案在高度致敏的亚洲人群中为活体供肾移植提供了极好的结果。
