Odum James D, Wong Hector R, Stanski Natalja L
Division of Critical Care, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
Front Pediatr. 2021 Apr 14;9:632248. doi: 10.3389/fped.2021.632248. eCollection 2021.
Sepsis is a leading cause of morbidity and mortality in critically ill children, and acute kidney injury (AKI) is a frequent complication that confers an increased risk for poor outcomes. Despite the documented consequences of sepsis-associated AKI (SA-AKI), no effective disease-modifying therapies have been identified to date. As such, the only treatment options for these patients remain prevention and supportive care, both of which rely on the ability to promptly and accurately identify at risk and affected individuals. To achieve these goals, a variety of biomarkers have been investigated to help augment our currently limited predictive and diagnostic strategies for SA-AKI, however, these have had variable success in pediatric sepsis. In this mini-review, we will briefly outline the current use of biomarkers for SA-AKI, and propose a new framework for biomarker discovery and utilization that considers the individual patient's sepsis inflammatory response. Now recognized to be a key driver in the complex pathophysiology of SA-AKI, understanding the dysregulated host immune response to sepsis is a growing area of research that can and should be leveraged to improve the prediction and diagnosis of SA-AKI, while also potentially identifying novel therapeutic targets. Reframing SA-AKI in this manner - as a direct consequence of the individual patient's sepsis inflammatory response - will facilitate a precision medicine approach to its management, something that is required to move the care of this consequential disorder forward.
脓毒症是危重症儿童发病和死亡的主要原因，急性肾损伤（AKI）是常见并发症，会增加不良预后风险。尽管已有脓毒症相关急性肾损伤（SA-AKI）后果的记录，但迄今为止尚未确定有效的疾病改善疗法。因此，这些患者唯一的治疗选择仍然是预防和支持性护理，二者都依赖于及时、准确识别有风险和受影响个体的能力。为实现这些目标，人们研究了多种生物标志物，以帮助完善我们目前对SA-AKI有限的预测和诊断策略，然而，这些生物标志物在儿童脓毒症中的成效不一。在本综述中，我们将简要概述SA-AKI生物标志物的当前应用情况，并提出一个生物标志物发现和利用的新框架，该框架考虑了个体患者的脓毒症炎症反应。现在人们认识到，宿主对脓毒症的免疫反应失调是SA-AKI复杂病理生理学的关键驱动因素，了解这一点是一个不断发展的研究领域，可用于并应利用其来改善SA-AKI的预测和诊断，同时还可能确定新的治疗靶点。以这种方式将SA-AKI重新定义为个体患者脓毒症炎症反应的直接后果，将有助于采用精准医学方法对其进行管理，这是推动对这种严重疾病的治疗取得进展所必需的。
