Division of Pediatric Nephrology, UCLA Mattel Children's Hospital, University of California, Los Angeles, Los Angeles, California, USA.
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Kidney Int. 2018 Jan;93(1):260-269. doi: 10.1016/j.kint.2017.06.034. Epub 2017 Sep 18.
Angiotensin II type 1 receptor (AT1R) antibody has been linked to poor allograft outcomes in adult kidney transplantation. However, its clinical consequences in children are unknown. To study this, we examined the relationship of AT1R antibody with clinical outcomes, biopsy findings, inflammatory cytokines, and HLA donor-specific antibodies (DSA) in a cohort of pediatric renal transplant recipients. Sixty-five patients were longitudinally monitored for AT1R antibody, HLA DSA, IL-8, TNF-α, IL-1β, IFN-γ, IL-17, and IL-6, renal dysfunction, hypertension, rejection, and allograft loss during the first two years post transplantation. AT1R antibody was positive in 38 of the 65 of children but was not associated with HLA DSA. AT1R antibody was associated with renal allograft loss (odds ratio of 13.1 [95% confidence interval 1.48-1728]), the presence of glomerulitis or arteritis, and significantly higher TNF-α, IL-1β, and IL-8 levels, but not rejection or hypertension. AT1R antibody was associated with significantly greater declines in eGFR in patients both with and without rejection. Furthermore, in patients without rejection, AT1R antibody was a significant risk factor for worsening eGFR over the two-year follow-up period. Thus, AT1R antibody is associated with vascular inflammation in the allograft, progressive decline in eGFR, and allograft loss. AT1R antibody and inflammatory cytokines may identify those at risk for renal vascular inflammation and lead to early biopsy and intervention in pediatric kidney transplantation.
血管紧张素 II 型 1 型受体（AT1R）抗体与成人肾移植中移植物不良结局有关。然而，其在儿童中的临床后果尚不清楚。为了研究这一点，我们检查了血管紧张素 II 型 1 型受体（AT1R）抗体与临床结果、活检结果、炎症细胞因子和 HLA 供体特异性抗体（DSA）在儿科肾移植受者队列中的关系。在移植后两年内，对 65 例儿童进行了 AT1R 抗体、HLA DSA、IL-8、TNF-α、IL-1β、IFN-γ、IL-17 和 IL-6、肾功能障碍、高血压、排斥反应和移植物丢失的纵向监测。在 65 例儿童中有 38 例 AT1R 抗体呈阳性，但与 HLA DSA 无关。AT1R 抗体与肾移植丢失相关（比值比为 13.1[95%置信区间 1.48-1728]），存在肾小球炎或血管炎，并且 TNF-α、IL-1β 和 IL-8 水平显著升高，但与排斥反应或高血压无关。AT1R 抗体与有或没有排斥反应的患者的 eGFR 下降显著相关。此外，在没有排斥反应的患者中，AT1R 抗体是两年随访期间 eGFR 恶化的显著危险因素。因此，AT1R 抗体与移植物中的血管炎症、eGFR 的进行性下降和移植物丢失有关。AT1R 抗体和炎症细胞因子可能识别出那些有肾血管炎症风险的患者，并导致在儿科肾移植中进行早期活检和干预。
