供者特异性抗体对难治性移植肾功能恢复延迟的影响二例报道

Role of early de novo donor specific antibody in prolonged delayed graft function after kidney transplantation： A report of 2 cases

目的探讨肾移植术后新生供者特异性抗体（DSA）对难治性移植肾功能恢复延迟（EGF）的影响。方法病例1为42岁女性，接受丈夫供肾的活体供肾移植，受者术前群体反应性抗体（PRA）曾轻度升高，但术前DSA和淋巴细胞毒交叉配合试验（cDC）阴性；病例2为49岁女性，接受公民逝世后器官捐献（D（、D）供者供肾移植，术前PRA和CDC均为阴性。2例受者术后均出现难治性DGF，且DGF超过1个月未逆转。病例1术后10dPRA轻度升高（PRAI类为28％），流式CDC（Flow-CDC）检测显示为低水平DSA（13．9%）；病例2在术后17d通过Luminex单抗原微珠法检测II类DSA阳性（抗DR9，平均荧光度MFI2500）。2例受者经移植肾穿刺活检均未发现急性抗体介导排斥反应的典型病理表现。结果病例1未经特殊处理，于术后6周恢复尿量，术后第62天血肌酐降至96μmol／L。病例2经血浆置换＋静脉注射用免疫球蛋白（WIG）处理后DSA转阴，术后7周恢复尿量，第56天血肌酐降至95μmol／L。结论早期新生DSA在水平较低和细胞毒作用较弱时可能不足以引起急性抗体介导的排斥反应，而主要表现为移植肾。肾小管损伤，导致DGF的恢复时间显著延长。及时发现和有效清除DSA能促进延期恢复的DGF早日逆转。

Objective To study the potential role of early generated de novo donor specific antibodies （DSA） in the occurrence of prolonged delayed graft function （DGF）. Method Patient 1 was a 42-year-old female who received a living kidney donation from her husband. She had a historic positive PRA but none DSA was detected before kidney transplantation. Patient 2 was a 49-year-old female who received a DCD kidney transplant with negative PRA and CDC. Both patients had prolonged DGF that lasted for more than 1 month. In patient 1, the retrospective measurement of PRA using serum collected on day 10 showed that PRA-I increased to 28%, meanwhile, the flow-CDC showed a clear shift from 2. 3% at the baseline to 13.9 %, indicating that a relative low level of cytotoxic DSA had been generated. In patient 2, single antigen bead test by Luminex demonstrated the existence of anti-DR9 DSA with a MFI value of 2500 at day 17. Biopsies did not show any typical features of AAMR in both patients. Result In patient 1, without any special treatment of the DSA, the graft function began to recover at 8th week. At day 62 after transplantation, the serum creatinine level decreased to 96 mol/L. In patient 2, with the treatments of plasmapheresis （PP） and intravenous immunoglobulin （IVIG）, DSA turned to negative and the urine output began to increase at 7th week after transplantation, followed by a serum creatinine level of 95 mol/L at day 56 post-transplant. Conclusion When the early produced de novo DSA is not potent enough to mediate acute humoral rejection, it may cause renal tubular injury, which can have significant impact on the degree of DGF and its recovery time. Early detection and treatment of DSA seems to be beneficial for the recovery of patients from prolonged DGF.