高致敏二次肾移植患者术前应用硼替佐米行脱敏治疗1例报告及文献复习

目的  总结硼替佐米术前脱敏治疗用于1例高致敏二次肾移植患者的临床经验。方法  1例移植前供体特异性抗体（DSA）阳性的二次肾移植患者，术前应用硼替佐米（1.3 mg/m²，分别于移植术前13、10、6 d，皮下注射）加低剂量免疫球蛋白。术后采用他克莫司（FK506）+麦考酚钠+甲泼尼龙三联免疫抑制方案，观察患者血清肌酐（Scr）和血尿素氮（BUN）水平、FK506血药浓度、DSA滴度、C3d结合性DSA（C3d-DSA）滴度及移植肾病理活组织检查（活检）等变化，以及不良反应。结果  硼替佐米应用后随访12个月，Scr下降并稳定在130 μmol/L，BUN维持在3.9 mmol/L，DSA水平明显下降，C3d-DSA阴性。术后4个月和9个月移植肾病理穿刺检测均为C4d阳性，提示慢性活动性抗体介导的排斥反应（AMR）。患者出现3级周围神经病变。结论  术前使用硼替佐米脱敏方案可有效降低肾移植受者体内DSA水平，避免高致敏二次肾移植患者发生急性排斥反应。高致敏移植患者术前脱敏治疗可选择硼替佐米在内的综合治疗。

Desensitization treatment with bortezomib in a highly-sensitized patient before secondary renal transplantation:report of one case and literature review

Objective To summarize the clinical experience of the application of bortezomib desensitization regime prior to secondary renal transplantation in a highly-sensitized recipient. Methods At 13, 10 and 6 d prior to secondary renal transplantation, one patient positive for donor specific antibody (DSA) was subcutaneously administered with bortezomib at a dose of 1.3 mg/m2 combined with a low dose of immunoglobulin. Postoperatively, immunosuppressive regime of tacrolimus (FK506), mycophenolat sodium and methylprednisolone was adopted. The serum creatinine (Scr), blood urea nitrogen (BUN) levels, FK506 concentration, DSA titre, C3d binding DSA (C3d-DSA) titre, pathological biopsy of the renal graft and adverse reactions were observed. Results During 12-month follow-up after administration of bortezomib, the Scr level was declined and maintained at 130 μmol/L, and the BUN level was remained at 3.9 mmol/L. The DSA level was significantly decreased and the C3d-DSA was negative. At postoperative 4 and 9 months, pathological biopsy of the renal graft revealed that the patient was positive for C4d, prompting the chronic active antibody mediated rejection (AMR). The patient presented with grade Ⅲ peripheral neuropathy. Conclusions Application of preoperative bortezomib desensitization regime can effectively down-regulate the DSA level in the recipient and avert the incidence of acute rejection in highly-sensitized patients undergoing secondary renal transplantation. Comprehensive treatment using bortezomib is recommended for preoperative desensitization in the highly-sensitized transplant recipients.