Center for Pediatric Precision Medicine, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Am Heart J. 2022 Dec;254:57-65. doi: 10.1016/j.ahj.2022.08.003. Epub 2022 Aug 19.
Acute kidney injury (AKI) complicates 30% to 50% of cardiac surgeries in pediatric patients. Genetic variants that affect renal blood flow and inflammation have been associated with AKI after cardiac surgery in diverse populations of adults but have not been studied in children. The objective of this study is to test the hypothesis that common candidate genetic variants are associated with AKI following pediatric cardiac surgery.
This is a retrospective cohort study at a single tertiary referral children's hospital of 2,062 individual patients undergoing surgery for congenital heart disease from September 2007 to July 2020. Pre-specified variants in candidate genes (AGTR1, APOE, IL6, NOS3, and TNF) were chosen. AKI was defined using Kidney Disease: Improving Global Outcomes serum creatinine criteria in the first week following surgery. Outcomes were analyzed by univariate and multivariable analysis of demographic, clinical, and genetic factors.
The study population had median age of 6 (interquartile range [IQR], 1-53) months, 759 (37%) of whom met criteria for postoperative AKI. In unadjusted analyses of each genetic variant, only NOS3 (rs2070744) was associated with lower risk for AKI (OR 0.75, 95% CI 0.62-0.9, P = .002). In logistic regression analyses adjusting for body surface area, previously identified genetic syndrome, Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) score, cardiopulmonary bypass time, and nephrotoxic medication exposure, the NOS3 variant remained protective against AKI (OR 0.7, 95% CI 0.58-0.85, P<.001).
A common variant in NOS3 is associated with decreased incidence of AKI in children undergoing cardiac surgery. Further analysis of the genetic contributions to postoperative AKI may help identify individual risk in the pediatric population.
急性肾损伤（AKI）在儿科患者心脏手术中发病率为 30%至 50%。影响肾血流量和炎症的遗传变异与成人心脏手术后 AKI 相关，但在儿童中尚未进行研究。本研究旨在检验假设，即常见候选遗传变异与儿科心脏手术后 AKI 相关。
这是一项回顾性队列研究，在一家单一体检转诊儿童医院对 2062 名接受先天性心脏病手术的个体患者进行研究，时间为 2007 年 9 月至 2020 年 7 月。选择候选基因（AGTR1、APOE、IL6、NOS3 和 TNF）的预定义变异。术后第一周使用肾脏病：改善全球结局（KDIGO）血清肌酐标准定义 AKI。通过单变量和多变量分析人口统计学、临床和遗传因素分析结果。
研究人群的中位年龄为 6 个月（四分位距 [IQR]，1-53），759 人（37%）符合术后 AKI 标准。在每个遗传变异的未调整分析中，只有 NOS3（rs2070744）与 AKI 风险降低相关（OR 0.75，95%CI 0.62-0.9，P =.002）。在调整体表面积、先前确定的遗传综合征、胸外科医师协会-欧洲心血管外科学会（STAT）评分、体外循环时间和肾毒性药物暴露的逻辑回归分析中，NOS3 变异仍对 AKI 具有保护作用（OR 0.7，95%CI 0.58-0.85，P<.001）。
NOS3 中的常见变异与儿童心脏手术后 AKI 发生率降低相关。对术后 AKI 的遗传贡献的进一步分析可能有助于确定儿科人群的个体风险。
