Acute Kidney Injury in Children after Hematopoietic Cell Transplantation Is Associated with Elevated Urine CXCL10 and CXCL9
Acute Kidney Injury in Children after Hematopoietic Cell Transplantation Is Associated with Elevated Urine CXCL10 and CXCL9
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DOI：
10.1016/j.bbmt.2020.02.024
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发表时间：
2020-07-01
影响因子：
4.3
通讯作者：
Sullivan, Kathleen E.
中科院分区：
文献类型：
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作者：
Erez, Daniella Levy;Denburg, Michelle R.;Sullivan, Kathleen E.
急性肾损伤 (AKI) 几乎普遍与较差的预后相关，尤其是在造血干细胞移植 (HCT) 后的儿童中。我们的目标是检查 HCT 后 AKI 的尿液免疫生物标志物，以深入了解该人群肾损伤的新机制。研究接受同种异体 HCT 的患者为检查 AKI 的免疫标志物提供了独特的机会，因为 AKI 的风险很高，而且移植后免疫系统会重新发育。接受第一次同种异体 HCT 并在 2 家大型儿童医院参加前瞻性观察队列研究的儿童（> 2 岁）和年轻人在 HCT 前和 HCT 后前 4 个月每月收集尿液。对每个月时间点的尿液样本进行 8 种免疫相关生物标志物检测。 AKI 定义为与 HCT 前基线相比，每月血清肌酐值增加 1.5 倍，该值是在获得研究尿液样本后 +/-1 天后记录的。广义估计方程回归分析评估了每月重复测量（尿液生物标志物和 AKI）之间的关联。共有来自 2 个儿科中心的 176 名患者被纳入。来自 1 个中心的 36 名患者作为发现队列进行分析，来自第二个中心的其余 140 名患者作为验证队列进行分析。 AKI 发生率为 18% 至 35%，具体取决于 HCT 后的每月时间点。在两个队列中，与未发生 AKI 的儿童相比，发生 AKI 的儿童的尿液 CXCL10 和 CXCL9 浓度显着较高 (P < .01)。为了更好地了解尿液中这些生物标志物的细胞来源，我们还分析了干扰素-γ和干扰素-α刺激后肾细胞系中 CXCL10 和 CXCL9 的体外表达。 HEK293 上皮肾细胞表现出干扰素诱导的 CXCL10 和 CXCL9 表达，表明推动这一关键发现的潜在机制。 CXCL10 和 CXCL9 与 HCT 后的 AKI 相关，因此是有前途的生物标志物，可指导改进这一高危人群中 AKI 的诊断和治疗策略。 (C) 2020 年美国移植和细胞治疗学会。由爱思唯尔公司出版
Acute kidney injury (AKI) is nearly universally associated with worse outcomes, especially among children after hematopoietic stem cell transplant (HCT). Our objective was to examine urinary immune biomarkers of AKI after HCT to provide insights into novel mechanisms of kidney injury in this population. Studying patients undergoing allogeneic HCT provides a unique opportunity to examine immune markers of AKI because the risk of AKI is high and the immune system newly develops after transplant. Children (>2 years old) and young adults undergoing their first allogeneic HCT and enrolled in a prospective, observational cohort study at 2 large children's hospitals had urine collected pre-HCT and monthly for the first 4 months after HCT. Urine samples at each monthly time point were assayed for 8 immune-related biomarkers. AKI was defined as a 1.5-fold increase in the monthly serum creatinine value, which was recorded +/- 1 day from when the research urine sample was obtained, as compared with the pre-HCT baseline. Generalized estimating equation regression analysis evaluated the association between the monthly repeated measures (urinary biomarkers and AKI). A total of 176 patients were included from 2 pediatric centers. Thirty-six patients from 1 center were analyzed as a discovery cohort and the remaining 140 patients from the second center were analyzed as a validation cohort. AKI rates were 18% to 35% depending on the monthly time point after HCT. Urine CXCL10 and CXCL9 concentrations were significantly higher among children who developed AKI compared with children who did not (P < .01) in both cohorts. In order to gain a better understanding of the cellular source for these biomarkers in the urine, we also analyzed in vitro expression of CXCL10 and CXCL9 in kidney cell lines after stimulation with interferon-gamma and interferon-alpha. HEK293-epithelial kidney cells demonstrated interferon-induced expression of CXCL10 and CXCL9, suggesting a potential mechanism driving the key finding. CXCL10 and CXCL9 are associated with AKI after HCT and are therefore promising biomarkers to guide improved diagnostic and treatment strategies for AKI in this high-risk population. (C) 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.