Böhmig Georg A, Regele Heinz, Exner Markus, Derhartunian Victor, Kletzmayr Josef, Säemann Marcus D, Hörl Walter H, Druml Wilfred, Watschinger Bruno
Department of Internal Medicine III, University of Vienna, Vienna, Austria.
Institute of Clinical Pathology, University of Vienna, Vienna, Austria.
J Am Soc Nephrol. 2001 Nov;12(11):2482-2489. doi: 10.1681/ASN.V12112482.
There is increasing evidence for an important pathogenetic role of alloantibodies in acute renal allograft rejection. Acute humoral rejection (AHR) has been reported to be associated with a poor transplant survival. Although treatment modalities for cellular rejection are fairly well established, the optimal treatment for AHR remains undefined. Ten of 352 kidney allograft recipients transplanted at the authors' institution between November 1998 and September 2000 were diagnosed as having AHR, supported by severe graft dysfunction, C4d deposits in peritubular capillaries (PTC), and accumulation of granulocytes in PTC. AHR was diagnosed 18.9 +/- 17.5 d posttransplantation. All patients were subjected to immunoadsorption (IA) with protein A (median number of treatment sessions, 9; range, 3 to 17). Seven recipients with additional signs of cellular rejection (according to the Banff classification) received also antithymocyte globulin. In nine of ten patients, AHR was associated with an increase in panel reactive antibody reactivity. A pathogenetic role of alloantibodies was further supported by a positive posttransplant cytotoxic crossmatch in all tested recipients (n = 4). In nine of ten recipients, renal function recovered after initiation of anti-humoral therapy. One patient lost his graft shortly after initiation of specific therapy. Another recipient with partial reversal of AHR returned to dialysis 8 mo after transplantation. Mean serum creatinine in functioning grafts was 2.2 +/- 1.2 mg/dl after the last IA session (n = 9) and 1.5 +/- 0.5 mg/dl after a follow-up of 14.2 +/- 7.1 mo (n = 8). In conclusion, this study suggests that AHR, characterized by severe graft dysfunction, C4d staining, and peritubular granulocytes, can be effectively treated by timely IA. In the majority of patients, IA treatment can restore excellent graft function over a prolonged time period.
越来越多的证据表明同种异体抗体在急性肾移植排斥反应中具有重要的致病作用。据报道，急性体液排斥反应（AHR）与移植肾存活率低有关。虽然细胞排斥反应的治疗方法已相当成熟，但AHR的最佳治疗方法仍不明确。1998年11月至2000年9月在作者所在机构接受移植的352例肾移植受者中，有10例被诊断为AHR，其依据是严重的移植肾功能障碍、肾小管周围毛细血管（PTC）中C4d沉积以及PTC中粒细胞聚集。AHR在移植后18.9±17.5天被诊断出来。所有患者均接受了蛋白A免疫吸附（IA）治疗（治疗次数中位数为9次；范围为3至17次）。7例有细胞排斥反应其他迹象（根据班夫分类法）的受者还接受了抗胸腺细胞球蛋白治疗。10例患者中有9例，AHR与群体反应性抗体反应性增加有关。所有接受检测的受者（n = 4）移植后细胞毒性交叉配型呈阳性，进一步支持了同种异体抗体的致病作用。10例受者中有9例在开始抗体液治疗后肾功能恢复。1例患者在开始特异性治疗后不久移植肾失功。另1例AHR部分逆转的受者在移植后8个月重新开始透析。最后一次IA治疗后，功能良好的移植肾平均血清肌酐为（n = 9）2.2±1.2mg/dl，随访14.2±7.1个月后为（n = 8）1.5±0.5mg/dl。总之，本研究表明，以严重的移植肾功能障碍、C4d染色和肾小管周围粒细胞为特征的AHR，可通过及时的IA有效治疗。在大多数患者中，IA治疗可在较长时间内恢复良好的移植肾功能。
