Antibody-Mediated Microcirculation Injury Is the Major Cause of Late Kidney Transplant Failure
Antibody-Mediated Microcirculation Injury Is the Major Cause of Late Kidney Transplant Failure
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DOI：
10.1111/j.1600-6143.2009.02799.x
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发表时间：
2009-11-01
影响因子：
8.8
通讯作者：
Halloran, P. F.
中科院分区：
文献类型：
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作者：
Einecke, G.;Sis, B.;Halloran, P. F.
我们在一项前瞻性研究中研究了晚期肾移植失败的表型，这项研究是对临床适应症的非选择性肾移植活检进行的。我们分析了移植后6天至31年173例患者的234例连续活检的组织病理学、人类白细胞抗原抗体和死亡审查移植物存活率。晚期活检(>；1年)的患者经常出现供者特异性的人类白细胞抗原抗体(特别是II类)和微循环改变，包括肾小球炎、肾小球病变、毛细血管炎症、毛细血管多层和C4D染色。早期活检的移植物很少失败(1/68)，而晚期活检的移植物通常在3年内进展到失败(27/105)。T细胞介导的排斥反应及其损害与活检后失败风险的增加无关。在多变量分析中，移植失败与微循环炎症和瘢痕形成相关，但C4D染色并不显著。以微循环改变和人类白细胞抗原抗体来定义抗体介导的排斥反应时，17/27(63%)的晚期肾功能衰竭可归因于抗体介导的排斥反应，但许多C4D阴性的患者被现行诊断标准遗漏。肾小球肾炎占晚期丢失的6/27，而T细胞介导的排斥反应、药物毒性和原因不明的瘢痕形成并不常见。晚期肾移植失败的主要原因是抗体介导的微循环损伤，但这种表型的检测需要新的诊断标准。
We studied the phenotype of late kidney graft failure in a prospective study of unselected kidney transplant biopsies taken for clinical indications. We analyzed histopathology, HLA antibodies and death-censored graft survival in 234 consecutive biopsies from 173 patients, taken 6 days to 31 years posttransplant. Patients with late biopsies (> 1 year) frequently displayed donor-specific HLA antibody (particularly class II) and microcirculation changes, including glomerulitis, glomerulopathy, capillaritis, capillary multilayering and C4d staining. Grafts biopsied early rarely failed (1/68), whereas grafts biopsied late often progressed to failure (27/105) within 3 years. T-cell-mediated rejection and its lesions were not associated with an increased risk of failure after biopsy. In multivariable analysis, graft failure correlated with microcirculation inflammation and scarring, but C4d staining was not significant. When microcirculation changes and HLA antibody were used to define antibody-mediated rejection, 17/27 (63%) of late kidney failures after biopsy were attributable to antibody-mediated rejection, but many were C4d negative and missed by current diagnostic criteria. Glomerulonephritis accounted for 6/27 late losses, whereas T-cell-mediated rejection, drug toxicity and unexplained scarring were uncommon. The major cause of late kidney transplant failure is antibody-mediated microcirculation injury, but detection of this phenotype requires new diagnostic criteria.