1 Renal Institute of Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom. 2 Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD. 3 Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD. 4 Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD. 5 Address correspondence to: Robert Montgomery, Ph.D., Department of Surgery, Johns Hopkins Medical Institutions, 720 Rutland Avenue, Ross Research 765, Baltimore, MD 21205.
Transplantation. 2014 Mar 15;97(5):541-7. doi: 10.1097/01.TP.0000442513.27641.7e.
The correlation between histopathologic phenotypes and allograft outcomes among patients desensitized for donor-specific antibody (HLA-incompatible) is unknown.
We analyzed 1-year biopsies from desensitized recipients transplanted between 1999 and 2010 and estimated graft survival for each histologic phenotype identified. Median time posttransplant for the 1-year biopsy was 367 days (interquartile range 357-388 days) and median follow-up of all patients post-1-year biopsy was 42 months (interquartile range 19.5-65 months).
Transplant glomerulopathy was present in 25.0% of biopsies and resulted in worse graft survival (66.7% vs. 96.7%, P<0.001). C4d positivity and transplant glomerulopathy together portended exceptionally poor graft survival (33.3% vs. 97.2%, P<0.001). Microcirculation inflammation was prevalent, with glomerulitis and peritubular capillaritis found in 60.0% and 47.6% of 1-year biopsies, respectively. Glomerulitis was associated with worse graft survival (82.1% vs. 98.1%, P=0.004), whereas capillaritis was not (88.1% vs. 97.7% respectively, P=0.091). Among C4d-negative HLA-incompatible recipients (82.6% of biopsies), no difference in graft survival was observed between patients with or without microcirculation inflammation in contrast to previous reports by other investigators. Patients who had no C4d deposition, transplant glomerulopathy, or microcirculation inflammation had a 100.0% graft survival. On Cox regression analysis, no independent histopathological parameter was associated with graft survival.
We have identified several histopathologic phenotypes in HLA-incompatible kidney recipients that correlate with allograft outcomes. Characterization of these phenotypes is the first step towards better understanding the pathophysiologic basis of chronic antibody-mediated allograft injury and individualizing therapeutic intervention.
在经过供体特异性抗体（HLA 不相容）脱敏治疗的患者中，组织病理学表型与移植物结局之间的相关性尚不清楚。
我们分析了 1999 年至 2010 年间接受脱敏治疗的患者的 1 年活检标本，并对每种组织病理学表型进行了移植物存活率的评估。1 年活检的中位移植后时间为 367 天（四分位距 357-388 天），所有患者 1 年活检后的中位随访时间为 42 个月（四分位距 19.5-65 个月）。
25.0%的活检标本存在移植肾小球病，导致移植物存活率更差（66.7%比 96.7%，P<0.001）。C4d 阳性和移植肾小球病共同预示着极差的移植物存活率（33.3%比 97.2%，P<0.001）。微循环炎症很常见，60.0%和 47.6%的 1 年活检标本分别发现肾小球肾炎和肾小管周围毛细血管炎。肾小球肾炎与移植物存活率较差相关（82.1%比 98.1%，P=0.004），而毛细血管炎则不然（分别为 88.1%比 97.7%，P=0.091）。在 C4d 阴性 HLA 不相容的受者中（82.6%的活检标本），与其他研究者的先前报告相反，在有或无微循环炎症的患者之间，移植物存活率没有差异。没有 C4d 沉积、移植肾小球病或微循环炎症的患者移植物存活率为 100.0%。在 Cox 回归分析中，没有独立的组织病理学参数与移植物存活率相关。
我们在 HLA 不相容的肾移植受者中发现了几种与移植物结局相关的组织病理学表型。这些表型的特征描述是更好地理解慢性抗体介导的移植物损伤的病理生理基础并实现个体化治疗干预的第一步。
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