Abstract

Despite advancements in standardizing the criteria for acute kidney injury (AKI), its definition remains based on changes in serum creatinine and urinary output that do not specifically represent tubular function or injury and that have significant limitations in the acute hospital setting. Much effort in nephrology has centered on identifying biomarkers of AKI to address these limitations. This review summarizes recent advances in our knowledge of biomarkers involved in pathophysiological processes during AKI and describes their potential clinical implications. Blood and urine biomarkers are released via various mechanisms during renal tubular injury. Urinary kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), insulin-like growth factor-binding protein-7 (IGFBP-7), and tissue inhibitor of metalloprotease-2 (TIMP-2) are released from the proximal tubule while uromodulin (UMOD) is secreted from the loop of Henle and neutrophil gelatinase-associated lipocalin (NGAL) is released from the distal tubule. These biomarkers could therefore be used to localize specific segments of injured tubules. Biomarkers also have diverse roles in pathophysiological processes in AKI, including inflammation, repair, and fibrosis. Current evidence suggests that these biomarkers could be used to predict the transition to chronic kidney disease (CKD), decrease discard of AKI kidneys, differentiate between kidney dysfunction and injury, guide AKI management, and improve diagnosis of diseases such as acute interstitial nephritis (AIN). They could differentiate between disease phenotypes, facilitate the inclusion of a homogenous patient population in future trials of AKI, and shed light on therapeutic pathways to prevent the transition from AKI to CKD. However, a major limitation of current biomarker research in AKI is the lack of tissue correlation. The Kidney Precision Medicine Project, a large-scale national effort, is currently underway to construct a kidney tissue atlas and expand the use of biomarkers to assess nephron health. Numerous biomarkers are involved in distinct pathophysiological processes after kidney injury and have demonstrated potential to improve diagnosis and risk stratification as well as provide a prognosis for patients with AKI. Some biomarkers are ready for use in clinical trials of AKI and could guide management in various clinical settings. Further investigation of these biomarkers will provide insight that can be applied to develop novel therapeutic agents for AKI.

摘要

尽管在标准化急性肾损伤 (AKI) 标准方面取得了进展，但其定义仍然基于血清肌酐和尿量的变化，这些变化并不具体代表肾小管功能或损伤，并且在急性医院环境中具有显着局限性。肾脏病学的许多努力都集中在识别 AKI 的生物标志物以解决这些限制。这篇综述总结了我们在 AKI 期间参与病理生理过程的生物标志物知识方面的最新进展，并描述了它们潜在的临床意义。血液和尿液生物标志物通过以下途径释放肾小管损伤过程中的各种机制。尿肾损伤分子-1 (KIM-1)、肝型脂肪酸结合蛋白 (L-FABP)、胰岛素样生长因子结合蛋白-7 (IGFBP-7) 和金属蛋白酶组织抑制剂-2 (TIMP) -2) 从近端小管释放，而尿调节素 (UMOD) 从 Henle 环分泌，中性粒细胞明胶酶相关载脂蛋白 (NGAL) 从远端小管释放。因此，这些生物标志物可用于定位受损肾小管的特定部分。生物标志物在 AKI 的病理生理过程中也有不同的作用，包括炎症、修复和纤维化。目前的证据表明，这些生物标志物可用于预测向慢性肾病 (CKD) 的转变，减少 AKI 肾脏的丢弃，区分肾功能不全和损伤，指导 AKI 管理，提高急性间质性肾炎（AIN）等疾病的诊断水平。它们可以区分疾病表型，促进在未来的 AKI 试验中纳入同质患者群体，并阐明防止从 AKI 转变为 CKD 的治疗途径。然而，目前 AKI 生物标志物研究的一个主要限制是缺乏组织相关性。肾脏精准医学项目是一项大规模的全国性工作，目前正在构建肾脏组织图谱并扩大生物标志物的使用以评估肾单位健康。许多生物标志物参与了肾损伤后不同的病理生理过程，并已证明具有改善诊断和风险分层以及为 AKI 患者提供预后的潜力。一些生物标志物已准备好用于 AKI 的临床试验，并可以指导各种临床环境中的管理。对这些生物标志物的进一步研究将提供可用于开发新的 AKI 治疗剂的见解。