Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio 45229-3039, USA.
Nephrology (Carlton). 2010 Jun;15(4):419-28. doi: 10.1111/j.1440-1797.2010.01317.x.
Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which currently depends on functional markers such as serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers of structural kidney injury (akin to troponin in acute myocardial injury) has hampered our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The discovery, translation and validation of neutrophil gelatinase-associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed. NGAL is emerging as an excellent stand-alone troponin-like structural biomarker in the plasma and urine for the early diagnosis of AKI, and for the prediction of clinical outcomes such as dialysis requirement and mortality in several common clinical scenarios. The approach of using NGAL as a trigger to initiate and monitor therapies for AKI, and as a safety biomarker when using potentially nephrotoxic agents, is also promising. In addition, it is hoped that the use of sensitive and specific biomarkers such as NGAL as endpoints in clinical trials will result in a reduction in required sample sizes, and hence the cost incurred. Furthermore, predictive biomarkers like NGAL may play a critical role in expediting the drug development process. However, given the complexity of AKI, additional biomarkers (perhaps a panel of plasma and urinary biomarkers) may eventually need to be developed and validated for optimal progress to occur.
急性肾损伤（AKI）是一种常见且严重的病症，其诊断目前依赖于血清肌酐测量等功能标志物。不幸的是，肌酐是 AKI 的一种延迟且不可靠的指标。缺乏结构性肾损伤的早期生物标志物（类似于急性心肌损伤中的肌钙蛋白）阻碍了我们将有前途的实验疗法转化为人类 AKI 的能力。幸运的是，对肾脏急性损伤早期应激反应的理解揭示了许多潜在的生物标志物。本文回顾了中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的发现、转化和验证，NGAL 可能是最有前途的新型 AKI 生物标志物之一。NGAL 作为一种独立的肌钙蛋白样结构性生物标志物，在血浆和尿液中用于 AKI 的早期诊断，并可预测几种常见临床情况下的临床结局，如透析需求和死亡率。使用 NGAL 作为启动和监测 AKI 治疗的触发因素，并在使用潜在肾毒性药物时作为安全生物标志物的方法也很有前途。此外，希望使用 NGAL 等敏感和特异性生物标志物作为临床试验的终点，将减少所需样本量，从而降低成本。此外，预测生物标志物如 NGAL 可能在加速药物开发过程中发挥关键作用。然而，鉴于 AKI 的复杂性，可能最终需要开发和验证额外的生物标志物（也许是一组血浆和尿液生物标志物），以实现最佳进展。
