移植后同种异体抗体出现后早期肾小球滤过率下降的趋势和特征。

Trends and characteristics in early glomerular filtration rate decline after posttransplantation alloantibody appearance.

机构信息

1 Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China. 2 Terasaki Foundation Laboratory, Los Angeles, CA. 3 Department of Pathology, Brody School of Medicine at East Carolina University, Greenville, NC. 4 Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC. 5 Department of Medicine, Brody School of Medicine at East Carolina University, Greenville, NC. 6 Eastern Nephrology and Associates, Greenville, NC. 7 Address correspondence to: Matthew J. Everly, Pharm.D. Terasaki Foundation Laboratory, 11570 West Olympic Boulevard, Los Angeles, CA 90064.

出版信息

Transplantation. 2013 Nov 27;96(10):919-25. doi: 10.1097/TP.0b013e3182a289ac.

DOI:10.1097/TP.0b013e3182a289ac

PMID:23912173

Abstract

BACKGROUND

Approximately 7% to 9% of patients with donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) fail within 1 year post-DSA onset. However, little is known as to how this DSA-associated failure temporally progresses. This longitudinal study investigates DSA's temporal relationship to allograft dysfunction and identifies predictors of allograft function's progressive deterioration post-DSA.

METHODS

A cohort of 175 non-HLA identical patients receiving their first transplant between March 1999 and March 2006 were analyzed. Protocol testing for DSA via single antigen beads was done before transplantation and at 1, 3, 6, 9, and 12 months after transplantation then annually. Estimated glomerular filtration rate (eGFR) was analyzed before and after DSA onset.

RESULTS

Forty-two patients developed DSA and had adequate eGFR information for analysis. Before DSA onset, the 42 patients had stable eGFR. By 1 year post-DSA, the cohort's eGFR was significantly lower (P<0.001); however, 30 of 42 had stable function. Twelve patients had failure or early allograft dysfunction (eGFR decline >25% from DSA onset). Those who failed early (by 1 year post-DSA) had more antibody-mediated rejection than stable patients (P=0.03). Late failures (after 1 year post-DSA) were predictable with evidence of early allograft dysfunction (eGFR decline >25% by 1 year post-DSA; P<0.001). Early allograft dysfunction preceded late failure by nearly 1 year.

CONCLUSIONS

DSA is temporally related to allograft function deterioration. However, in many cases, late allograft failures are preceded by early allograft dysfunction. Therefore, monitoring for early allograft dysfunction provides treating physicians with a window of opportunity for treatment or continued monitoring.

摘要

背景

大约有 7%至 9%的出现供者特异性抗人类白细胞抗原（HLA）抗体（DSA）的患者在 DSA 出现后 1 年内失败。然而，对于 DSA 相关的失败如何随时间进展，人们知之甚少。本纵向研究调查了 DSA 与移植物功能障碍的时间关系，并确定了 DSA 后移植物功能进行性恶化的预测因素。

方法

分析了 1999 年 3 月至 2006 年 3 月期间接受首次移植的 175 名非 HLA 相同患者的队列。在移植前和移植后 1、3、6、9 和 12 个月以及每年进行通过单抗原珠检测 DSA 的方案检测。分析了 DSA 出现前后的估算肾小球滤过率（eGFR）。

结果

42 名患者出现 DSA 并具有足够的 eGFR 信息进行分析。在 DSA 出现之前，42 名患者的 eGFR 稳定。在 DSA 出现后 1 年，该队列的 eGFR 显著降低（P<0.001）；然而，42 名中有 30 名患者的功能稳定。12 名患者出现失败或早期移植物功能障碍（从 DSA 出现到 eGFR 下降>25%）。早期失败（DSA 出现后 1 年内）的患者比稳定患者更易发生抗体介导的排斥反应（P=0.03）。用早期移植物功能障碍（DSA 出现后 1 年内 eGFR 下降>25%；P<0.001）的证据可以预测晚期失败。早期移植物功能障碍比晚期失败早近 1 年。