Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, USA.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
Pediatr Nephrol. 2024 Feb;39(2):589-595. doi: 10.1007/s00467-023-06051-4. Epub 2023 Aug 19.
Acute kidney injury (AKI) occurs frequently after infant cardiac surgery and is associated with poor outcomes, including mortality and prolonged length of stay. AKI mechanisms are poorly understood, limiting therapeutic targets. Emerging data implicates dysregulated immune activation in post-cardiac surgery AKI development. We sought to identify immune-mediated AKI biomarkers after infant cardiopulmonary bypass (CPB)-assisted cardiac surgery.
A single-center prospective study of 126 infants less than 1 year old undergoing CPB-assisted surgery enrolled between 10/2017 and 6/2019. Urine samples were collected before CPB and at 6, 24, 48, and 72 h after surgery. Immune-mediated biomarkers were measured using commercial ELISA and Luminex™ multiplex kits. Based on subject age, neonatal KDIGO (< 1 month) or KDIGO criteria defined AKI. The Kruskal-Wallis rank test determined the relationship between urinary biomarker measurements and AKI.
A total of 35 infants (27%) developed AKI. AKI subjects were younger, underwent more complex surgery, and had longer CPB time. Subjects with AKI vs. those without AKI had higher median urinary chemokine 10 (C-X-C motif) ligand levels at 24, 48, and 72 h, respectively: 14.3 pg/ml vs. 5.3 pg/ml, 3.4 pg/ml vs. 0.8 pg/ml, and 1.15 pg/ml vs. 0.22 pg/ml (p < 0.05) post-CPB. At 6 h post-CPB, median vascular cell adhesion protein 1 (VCAM) levels (pg/mL) were higher among AKI subjects (491 pg/ml vs. 0 pg/ml, p = 0.04).
Urinary CXCL10 and VCAM are promising pro-inflammatory biomarkers for early AKI detection and may indicate eventual AKI therapeutic targets. A higher resolution version of the Graphical abstract is available as Supplementary information.
急性肾损伤（AKI）在婴儿心脏手术后经常发生，与不良预后相关，包括死亡率和住院时间延长。AKI 发病机制尚不清楚，限制了治疗靶点的选择。新出现的数据表明，心脏手术后 AKI 发病中存在免疫激活失调。我们试图确定婴儿体外循环（CPB）辅助心脏手术后与免疫相关的 AKI 生物标志物。
这是一项单中心前瞻性研究，纳入了 2017 年 10 月至 2019 年 6 月期间 126 名接受 CPB 辅助手术的年龄小于 1 岁的婴儿。在 CPB 前和手术后 6、24、48 和 72 小时收集尿液样本。使用商业 ELISA 和 Luminex™ 多重试剂盒测量免疫介导的生物标志物。根据患儿年龄，新生儿 KDIGO（<1 个月）或 KDIGO 标准定义 AKI。Kruskal-Wallis 秩检验确定尿生物标志物测量值与 AKI 之间的关系。
共有 35 名婴儿（27%）发生 AKI。AKI 患儿年龄更小，手术更复杂，CPB 时间更长。与无 AKI 患儿相比，AKI 患儿术后 24、48 和 72 小时尿液趋化因子 10（C-X-C 基序）配体水平中位数更高，分别为：14.3pg/ml 比 5.3pg/ml，3.4pg/ml 比 0.8pg/ml，1.15pg/ml 比 0.22pg/ml（p<0.05）。CPB 后 6 小时，AKI 患儿血管细胞黏附蛋白 1（VCAM）水平（pg/ml）中位数更高（491pg/ml 比 0pg/ml，p=0.04）。
尿液 CXCL10 和 VCAM 是早期 AKI 检测有前途的促炎生物标志物，可能表明最终的 AKI 治疗靶点。图摘要的高分辨率版本可在补充资料中查看。
