Section of Nephrology, University of Chicago Medicine, Chicago, Illinois.
Clin J Am Soc Nephrol. 2014 Mar;9(3):590-7. doi: 10.2215/CJN.07390713. Epub 2013 Dec 26.
Late kidney transplant dysfunction may be a harbinger of graft failure. For many years, calcineurin inhibitor toxicity was felt to be the main cause for graft dysfunction with fibrosis and transplant loss. Recently this idea has come into question. With the observation that peritubular capillary C4d staining in kidney allografts may indicate antibody-mediated injury in conjunction with biopsy study findings, an appreciation for antibody-mediated rejection as a major cause of late graft dysfunction and loss has emerged. Twenty percent to 30% of patients develop de novo donor-specific antibodies after kidney transplantation. There are no US Food and Drug Administration-approved treatments for antibody-mediated rejection, nor have any randomized controlled trials assessed efficacy. Off-label treatment strategies include some combination of plasma exchange, intravenous immunoglobulin, and rituximab. Other approaches, including splenectomy, bortezomib, and eculizumab, have also been tried.
晚期肾移植功能障碍可能是移植物衰竭的先兆。多年来,钙调磷酸酶抑制剂毒性被认为是导致移植物纤维化和功能丧失的主要原因。最近,这种观点受到了质疑。随着观察到肾移植中肾小管周围毛细血管 C4d 染色可能表明抗体介导的损伤与活检研究结果相结合,抗体介导的排斥反应作为晚期移植物功能障碍和丧失的主要原因已被人们所认识。20%至 30%的肾移植患者在移植后会产生新的供体特异性抗体。目前尚无美国食品和药物管理局批准的治疗抗体介导排斥反应的药物,也没有任何随机对照试验评估其疗效。非适应证治疗策略包括血浆置换、静脉注射免疫球蛋白和利妥昔单抗的一些组合。其他方法,包括脾切除术、硼替佐米和依库珠单抗,也已被尝试。