Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, 1161 21 Avenue South, Medical Center North S-3223, Nashville, TN 37232, USA.
J Am Soc Nephrol. 2011 May;22(5):810-20. doi: 10.1681/ASN.2010080796. Epub 2011 Apr 14.
An abrupt change in serum creatinine, the most common indicator of acute kidney injury (AKI), is strongly linked to poor outcomes across multiple clinical settings. Despite endless attempts to distill the magnitude and timing of a changing serum creatinine into a standardized metric, singular focus on this traditional functional marker obligates the characterization of AKI to remain, at best, retrospective and causally noninformative. The resultant inability to meaningfully segregate critical aspects of injury such as type, onset, propagation, and recovery from ongoing decrements in renal function has hindered successful translation of promising therapeutics. Over the past decade, however, the emerging field of clinical proteomics reinvigorates hope of identifying novel plasma and urine biomarkers to characterize cause and course of kidney injury. Efforts to validate these markers for use in clinical studies now show early promise but face important obstacles including interpretive difficulties inherent in using serum creatinine as a sole comparator for diagnostic performance, a need to better evaluate the incremental performance of new markers above established clinical and biochemical predictors, a relative lack of power to sufficiently examine hard clinical end points, and a potential over-reliance on use alone of receiver operating curves for assessing biomarker utility. Here, we discuss efforts to address these barriers and further ascertain the clinical value of new markers.
血清肌酐的急剧变化是急性肾损伤（AKI）的最常见指标，与多个临床环境中的不良结局密切相关。尽管人们不断尝试将血清肌酐变化的幅度和时间提炼成标准化指标，但对这种传统功能标志物的单一关注迫使 AKI 的特征描述最多只能是回顾性的，而且没有因果关系。这种无法将损伤的关键方面（如损伤类型、起始、传播和恢复）与肾功能的持续下降区分开来的情况，阻碍了有前途的治疗方法的成功转化。然而，在过去的十年中，临床蛋白质组学这一新兴领域重新燃起了希望，即发现新的血浆和尿液生物标志物，以描述肾损伤的原因和过程。目前，为验证这些标志物在临床研究中的应用而进行的努力显示出了早期的希望，但仍面临着重要的障碍，包括将血清肌酐作为唯一比较物用于诊断性能时存在的解释困难，需要更好地评估新标志物在既定临床和生化预测因素之上的增量性能，相对缺乏足够检查硬临床终点的能力，以及可能过度依赖使用接收者操作曲线来评估生物标志物的效用。在这里，我们讨论了为解决这些障碍以及进一步确定新标志物的临床价值所做的努力。
