Pretransplant angiotensin II type 1-receptor antibodies are a risk factor for earlier detection of de novo HLA donor-specific antibodies
Pretransplant angiotensin II type 1-receptor antibodies are a risk factor for earlier detection of de novo HLA donor-specific antibodies
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DOI：
10.1093/ndt/gfw204
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发表时间：
2016-10-01
影响因子：
6.1
通讯作者：
Alberu, Josefina
中科院分区：
文献类型：
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作者：
Cuevas, Eric;Arreola-Guerra, Jose M.;Alberu, Josefina
血管紧张素 II 1 型受体抗体 (AT1Rabs) 与移植物存活率显着降低有关。在移植前具有 AT1Rabs 和移植后供体特异性抗体 (DSA) 的患者中观察到早期移植物丢失。这项回顾性队列研究的主要目的是检查活体肾移植受者 (KTR) 移植后 AT1Rabs 与检测新人类白细胞抗原 (HLA-DSA) 的时间段之间的关联。该分析包括 141 个 KTR。在 KT 前后时间点，通过 ELISA 检测移植前冷冻血清样本中的 AT1Rab，并通过 SAB (Luminex) 检测 HLA-DSA。AT1Rab 中位水平为 9.13 U（四分位距 5.22-14.33）。经过平均 3.55 年的随访，48 名患者被发现携带新的 HLA-DSA。 AT1Rabs的存在[风险比（HR）1.009，95%置信区间（CI）1.002-1.01，P = 0.010]，男性间移植（HR 2.57，95% CI 1.42-4.67，P = 0.002）以及先前的边界变化或急性细胞排斥（ACR）（HR 2.47， 95% CI (1.29-4.75, P = 0.006) 与 de novo DSA 检测显着相关。观察到 AT1Rab 水平（< 10 U、10.1-16.9 U、17-29.9 U 和 > 30 U）与从头 DSA 检测之间存在剂量依赖性关联（对数秩 P = 0.0031）。对 AT1Rab 水平（连续变量）进行多变量分析后，AT1Rab > 30 U、男性对男性移植、供体年龄、较高的 I 类面板反应性抗体百分比以及先前的边界变化或 ACR 仍然是检测从头 DSA 的独立重要危险因素。研究结果表明，肾移植受者中较高水平的移植前抗 AT1R 循环抗体（> 30 U）构成早期从头 DSA 的独立危险因素。移植后期间的HLA-DSA检测。
Angiotensin II type 1 receptor antibodies (AT1Rabs) have been associated with significantly reduced graft survival. Earlier graft loss has been observed in patients who had pretransplant AT1Rabs and posttransplant donor-specific antibodies (DSA).The main goal of this retrospective cohort study was to examine the association between AT1Rabs and the time period to detection of de novo human leukocyte antigen (HLA-DSA) posttransplantation in living donor kidney transplant recipients (KTR). The analysis included 141 KTRs. Pretransplant frozen serum samples were tested for AT1Rabs by ELISA and HLA-DSA by SAB (Luminex) at both the pre- and post-KT time points.The median AT1Rab level was 9.13 U (interquartile range 5.22-14.33). After a mean follow-up period of 3.55 years, 48 patients were found to harbour de novo HLA-DSAs. The presence of AT1Rabs [hazard ratio (HR) 1.009, 95% confidence interval (CI) 1.002-1.01, P = 0.010], male-to-male transplantation (HR 2.57, 95% CI 1.42-4.67, P = 0.002) and antecedent borderline changes or acute cellular rejection (ACR) (HR 2.47, 95% CI 1.29-4.75, P = 0.006) were significantly associated with de novo DSA detection. A dose-dependent association between AT1Rab levels (< 10 U, 10.1-16.9 U, 17-29.9 U and > 30 U) and de novo DSA detection was observed (log-rank P = 0.0031). After multivariate analysis of AT1Rab levels (continuous variable), AT1Rabs > 30 U, male-to-male transplantation, donor age, higher class I percentage of Panel Reactive Antibody and antecedent borderline changes or ACR remained as independent significant risk factors for the detection of de novo DSAs.The findings suggest that higher levels of pretransplant circulating antibodies against AT1R (> 30 U) in kidney graft recipients constitute an independent risk factor for earlier de novo HLA-DSA detection during the posttransplant period.