Renal transplant patients with preformed anti-HLA antibodies: early biopsy findings and clinical outcomes

Abstract Introduction: Renal fibrosis is the end point of a process that begins at transplant, with ischemia reperfusion and early inflammation, and progresses over time with immunological and non-immunological phenomena. Early identification of morphological markers and intervention could improve graft function and survival. Objective: to evaluate the correlation between intensity and specificity of pre-transplant anti-HLA antibodies and kidney allograft pathology in order to identify early risk factors or markers of allograft dysfunction. Methods: A retrospective cohort of kidney transplant recipients with pre-transplant anti-HLA antibodies who underwent graft biopsy within the first two years post-transplant was divided into two groups according to the specificity of anti-HLA antibodies: nonspecific (non-DSA, n = 29) and specific (DSA+, n = 16). Kidney graft pathology, renal function, and proteinuria were analyzed. Results: general characteristics were similar in both groups, except for the higher dose of thymoglobulin in DSA+ group (p < 0.05). The non-DSA group had higher scores for glomerulosclerosis, interstitial inflammation (i) and interstitial fibrosis (ci) (p < 0.05) and higher incidence of cell-mediated acute rejection. No statistical difference in incidence of antibody-mediated rejection, renal function, and proteinuria was observed during follow up. Discussion and conclusions: the difference in inflammation scores and interstitial fibrosis may be associated to the higher incidence of acute cell-mediated rejection and polyomavirus nephropathy in the Non-DSA group. We also should take into account the protective effect of higher doses of thymoglobulin, reducing ischemia reperfusion injury in the DSA+ group. The short follow-up might have been insufficient to detect long-term changes in allograft tissue, renal function, and proteinuria.

摘要
引言：肾纤维化是始于移植过程的终末期病理改变，其起始环节为缺血再灌注与早期炎症，并随病程进展伴随免疫性与非免疫性病理过程。早期识别形态学标志物并实施干预，可改善移植物功能与患者存活时间。
研究目的：评估移植前抗人类白细胞抗原（HLA）抗体的强度与特异性和肾移植移植物病理之间的相关性，以明确移植物功能障碍的早期危险因素或标志物。
研究方法：纳入移植前存在抗HLA抗体且于移植后2年内接受移植物活检的肾移植受者作为回顾性队列，根据抗HLA抗体特异性分为两组：非特异性组（非供体特异性抗体，non-DSA，n=29）与特异性组（供体特异性抗体阳性，DSA+，n=16）。对两组的肾移植物病理、肾功能及蛋白尿水平进行分析。
研究结果：两组一般临床特征无显著差异，仅特异性组（DSA+）所使用的胸腺球蛋白剂量更高（p<0.05）。非特异性组（non-DSA）的肾小球硬化评分、间质炎症（i）评分与间质纤维化（ci）评分更高（p<0.05），且细胞介导的急性排斥反应发生率更高。随访期间，两组在抗体介导的排斥反应发生率、肾功能及蛋白尿水平方面均无统计学差异。
讨论与结论：非特异性组（non-DSA）的炎症评分与间质纤维化差异，可能与其细胞介导的急性排斥反应及多瘤病毒肾病发生率更高相关。同时需考虑到，特异性组（DSA+）所使用的更高剂量胸腺球蛋白可减轻缺血再灌注损伤，发挥保护作用。本研究随访周期较短，可能不足以检测移植物组织、肾功能及蛋白尿的长期变化。