Department of Pediatrics, Section of Nephrology, Yale University School of Medicine.
Yale Program of Applied Translational Research, Yale University School of Medicine, New Haven, Connecticut, USA.
Curr Opin Pediatr. 2020 Jun;32(3):354-359. doi: 10.1097/MOP.0000000000000891.
The clinical diagnosis of acute kidney injury (AKI) relies largely on changes in serum creatinine; a delayed biomarker. Research in children has been focused on developing novel AKI biomarkers, which can improve the prediction, early detection and diagnosis of kidney injury, as well as our understanding of AKI pathophysiology. In this review, we describe recently published studies on urine or blood biomarkers of AKI. The mechanistic relevance of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, interleukin (IL)-18, liver-type fatty acid binding protein, tissue inhibitor of metalloproteinase (TIMP)-2/insulin-like growth factor-binding protein (IGFBP)-7, uromodulin, as well as other inflammatory biomarkers are discussed in the context of AKI pathophysiology, as well as their performance predicting or diagnosing AKI.
Biomarkers of tubular injury, cell cycle arrest and inflammation are presented in this review. NGAL continues to be the most frequently studied biomarker and continues to have good performance in a variety of clinical settings, most notably after cardiopulmonary bypass. We also found promising results with less studied biomarkers for the prediction of AKI in children, including TIMP2, IGFBP7, uromodulin, tumor necrosis factor-α and IL-8.
Identifying new AKI biomarkers is a priority in pediatric nephrology research because of the morbidity associated with AKI, as well as the lack of therapies for AKI. Recent research suggests that novel AKI biomarkers have the potential to predict the development of AKI and diagnose AKI earlier than changes in serum creatinine. The diverse causes of AKI, the different settings where patients develop AKI and the changing biomarker reference ranges throughout childhood remain challenges in biomarker development.
急性肾损伤（AKI）的临床诊断主要依赖于血清肌酐的变化，而后者是一种延迟的生物标志物。儿童研究的重点是开发新的 AKI 生物标志物，以改善对肾损伤的预测、早期检测和诊断，并加深对 AKI 病理生理学的认识。在本综述中，我们描述了最近发表的关于 AKI 的尿液或血液生物标志物的研究。中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、肾损伤分子-1、白细胞介素（IL）-18、肝型脂肪酸结合蛋白、金属蛋白酶组织抑制剂（TIMP）-2/胰岛素样生长因子结合蛋白（IGFBP）-7、尿调蛋白以及其他炎症生物标志物在 AKI 病理生理学中的机制相关性，以及它们在预测或诊断 AKI 方面的性能。
本综述介绍了肾小管损伤、细胞周期停滞和炎症的生物标志物。NGAL 仍然是研究最多的生物标志物，并且在各种临床环境中（尤其是体外循环后）表现出良好的性能。我们还发现了一些研究较少的生物标志物在预测儿童 AKI 方面有很有前景的结果，包括 TIMP2、IGFBP7、尿调蛋白、肿瘤坏死因子-α和 IL-8。
由于 AKI 相关的发病率以及缺乏 AKI 的治疗方法，确定新的 AKI 生物标志物是儿科肾脏病学研究的重点。最近的研究表明，新型 AKI 生物标志物有可能预测 AKI 的发生，并比血清肌酐的变化更早地诊断 AKI。AKI 的病因多种多样，患者发生 AKI 的环境也不同，儿童时期的生物标志物参考范围也在不断变化，这些都是生物标志物开发面临的挑战。
