Comparative Evaluation of Urinary Biological Markers for the Prognostic Stratific

描述（由申请人提供）： 急性肾衰竭（ARF）是住院患者的严重并发症，通常与不良临床结局相关。然而，ARF也可能与更良性、自限性的临床病程相关。有不良结局风险的患者往往不易与那些病程较良性的患者区分开来，这使得适当和及时地应用治疗策略成为一项艰巨的任务。因此，迫切需要能够改善ARF患者风险分层的新型预后工具。近年来，越来越多的急性肾损伤的尿液生物标志物被描述。其中，临床上最相关的尿液标志物包括肾损伤分子-1（KIM-1）（肾小管去分化标志物），神经胶质酶相关脂质运载蛋白（NGAL）（肾小管增殖标志物）、白细胞介素-18（IL-18）（肾小管缺血性损伤的介质），N-乙酰基-β-D-氨基葡萄糖苷酶（NAG）（一种肾小管刷状缘酶）、半胱氨酸蛋白酶抑制剂C和β-1微球蛋白（肾小管蛋白吸收受损的两种标志物）。虽然主要研究用于ARF的早期检测，但这些标志物中的一些也可能预测已确诊ARF患者的不良临床结局，因此可能对风险分层有用。 迄今为止，尚无研究以综合和比较的方式评价上述尿液生物标志物预测已确诊ARF患者不良结局的性能特征。待研究的假设是尿KIM-1、NGAL、IL-18、NAG、半胱氨酸蛋白酶抑制剂C和β-1微球蛋白，单独或联合使用，在预测确诊ARF患者的不良结局（包括透析需求和住院死亡率）方面上级临床预后评分。我们将在300例ARF住院患者的大队列中检验这些假设，其中200多例已经累积。我们还将结合联合收割机尿液生物学标记物与或不与临床预后评分，并比较这些组合的性能特征与单一的预后测试。我们希望证明单个标志物与已确诊的ARF患者的不良结局相关，并且可能上级临床预后评分。我们进一步假设，两种或多种标志物的组合将增加预测不良结局的预后准确性。 该研究项目是可以实现的，因为三分之二的队列已经入组，并提供了重要的新见解，尿液生物标志物的预后价值，用于预测ARF患者的不良结局。这项研究可能为开发一种更可靠的ARF预后风险分层工具提供基础，该工具将在其他ARF队列中进行外部验证，并有助于为ARF患者提供更具指导性的治疗干预。

DESCRIPTION (provided by applicant): Acute renal failure (ARF) is a serious complication in hospitalized patients and is frequently associated with adverse clinical outcomes. However, ARF can also be associated with a more benign, self-limited clinical course. Patients at risk for adverse outcomes are often not easily distinguished from those with a more benign course, making the appropriate and timely application of treatment strategies a difficult task. Novel, prognostic tools that can improve risk stratification among patients with ARF are therefore urgently needed. In recent years, an increasing number of urinary biological markers of acute kidney injury have been described. Among these, the most clinically relevant urinary markers include Kidney Injury Molecule-1 (KIM-1) (a tubular dedifferentiation marker), Neutrophil Gelatinase-Associated Lipocalin (NGAL) (a tubular proliferation marker), interleukin-18 (IL-18) (a mediator of tubular ischemic injury), N-acetyl-(-D-glucosaminidase (NAG) (a tubular brush border enzyme), cystatin C and (-1 microglobulin (two markers of impaired tubular protein absorption). Although predominantly studied for the early detection of ARF, some of these markers might also predict adverse clinical outcomes among patients with established ARF, and therefore, might be useful for risk stratification. To date, no studies have evaluated the performance characteristics of the above-mentioned urinary biological markers for the prediction of adverse outcomes in patients with established ARF in a comprehensive and comparative fashion. The hypotheses to be investigated are that urinary KIM-1, NGAL, IL-18, NAG, cystatin C, and (-1 microglobulin, individually or in combination, are superior to clinical prognostic scores in predicting adverse outcomes in patients with established ARF, including dialysis requirement and hospital mortality. We will test these hypotheses in a large cohort of 300 hospitalized patients with ARF, of which over 200 have already been accrued. We will also combine urinary biological markers with or without the addition of a clinical prognostic score, and compare the performance characteristics of these combinations with that of single prognostic tests. We expect to demonstrate that individual markers are associated with adverse outcomes in patients with established ARF, and might be superior to clinical prognostic scores. We further hypothesize that a combination of two or more markers will increase prognostic accuracy for predicting adverse outcomes. The research project is achievable as two thirds of the cohort has already been enrolled, and offers important new insights into the prognostic value of urinary biomarkers for the prediction of adverse outcomes in patients with ARF. This study might provide a foundation for the development of a more reliable prognostic risk stratification tool in ARF, which will be validated externally in other ARF cohorts, and help provide a more guided therapeutic intervention for patients with ARF.