RPA Transplantation Services, Royal Prince Alfred, Sydney, Australia.
Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, Australia.
BMC Nephrol. 2020 Feb 12;21(1):47. doi: 10.1186/s12882-020-01714-y.
Kidney transplantation performed in the presence of high-titre donor-specific antibodies (DSA) may result in hyper-acute or accelerated antibody-mediated rejection and rapid allograft loss. Previous studies have shown that this risk may be mitigated with simultaneous liver-kidney transplantation (SLKT); however, the mechanisms are not well defined. Here we report the evolution of pre-formed, high-level DSAs in two highly sensitised SLKT recipients peri-operatively and describe a profound sustained depletion of all DSAs from the time of liver anastomosis with no extra desensitisation therapy required.
Two patients underwent SLKT and received our centre's standard renal transplant immunosuppression with basiliximab and methylprednisolone for induction therapy and prednisolone, mycophenolate and tacrolimus for maintenance therapy. HLA antibody samples were collected pre-operatively, and immediately post-liver and post-kidney revascularisation, and then regularly in the post-transplant period. Complement Dependant Cytotoxicity (CDC) crossmatches were also performed. Both patients were highly sensitised with a PRA over 97%. One patient had a positive B- and T-cell crossmatch pre-transplant. These positive CDC crossmatches became negative and the level of pre-formed DSAs reduced profoundly and rapidly, within 3 h post-liver revascularisation. The reduction in pre-formed DSAs, regardless of subclass, was seen immediately post-liver revascularisation, before implantation of the renal allografts. No significant reduction in non-donor specific HLA-antibodies was observed. Both patients maintained good graft function with no rejection on kidney allograft protocol biopsies performed at 10-weeks post-transplant.
These cases support the protective immunoregulatory role of the liver in the setting of SLKT, with no extra desensitisation treatment given pre-operatively for these highly sensitised patients.
在存在高滴度供体特异性抗体（DSA）的情况下进行肾移植可能导致超急性或加速的抗体介导的排斥反应和快速移植物丢失。先前的研究表明，这种风险可以通过同时进行肝肾移植（SLKT）来减轻；然而，其机制尚未明确。在这里，我们报告了两名高度致敏的 SLKT 受者围手术期预先形成的高水平 DSA 的演变，并描述了从肝吻合术开始，所有 DSA 被深度持续耗竭，而无需额外的脱敏治疗。
两名患者接受了 SLKT，并接受了我们中心标准的肾移植免疫抑制治疗，包括巴利昔单抗和甲基强的松龙进行诱导治疗，以及泼尼松、霉酚酸酯和他克莫司进行维持治疗。HLA 抗体样本在术前、肝和肾再灌注后即刻以及移植后定期采集。还进行了补体依赖性细胞毒性（CDC）交叉匹配。两名患者均高度致敏，PRA 超过 97%。一名患者在移植前有 B 细胞和 T 细胞交叉匹配阳性。这些阳性的 CDC 交叉匹配在肝再灌注后 3 小时内迅速变为阴性，预先形成的 DSA 水平也显著且快速降低。无论亚类如何，在肾移植前，在肝再灌注后立即观察到预先形成的 DSA 减少。未观察到非供体特异性 HLA 抗体的显著减少。两名患者在移植后 10 周进行的肾移植协议活检中均未出现排斥反应，保持了良好的移植物功能。
这些病例支持 SLKT 中肝脏的保护性免疫调节作用，对于这些高度致敏的患者，术前未给予额外的脱敏治疗。
