Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh, UK.
Academy of Primary Care, Hull York Medical School, Hull, UK.
Health Technol Assess. 2018 May;22(32):1-274. doi: 10.3310/hta22320.
Acute kidney injury (AKI) is highly prevalent in hospital inpatient populations, leading to significant mortality and morbidity, reduced quality of life and high short- and long-term health-care costs for the NHS. New diagnostic tests may offer an earlier diagnosis or improved care, but evidence of benefit to patients and of value to the NHS is required before national adoption.
To evaluate the potential for AKI in vitro diagnostic tests to enhance the NHS care of patients admitted to the intensive care unit (ICU) and identify an efficient supporting research strategy.
We searched ClinicalTrials.gov, The Cochrane Library databases, Embase, Health Management Information Consortium, International Clinical Trials Registry Platform, MEDLINE, Register of Current Controlled Trials, PubMed and Web of Science databases from their inception dates until September 2014 (review 1), November 2015 (review 2) and July 2015 (economic model). Details of databases used for each review and coverage dates are listed in the main report.
The AKI-Diagnostics project included horizon scanning, systematic reviewing, meta-analysis of sensitivity and specificity, appraisal of analytical validity, care pathway analysis, model-based lifetime economic evaluation from a UK NHS perspective and value of information (VOI) analysis.
The horizon-scanning search identified 152 potential tests and biomarkers. Three tests, Nephrocheck (Astute Medical, Inc., San Diego, CA, USA), NGAL and cystatin C, were subjected to detailed review. The meta-analysis was limited by variable reporting standards, study quality and heterogeneity, but sensitivity was between 0.54 and 0.92 and specificity was between 0.49 and 0.95 depending on the test. A bespoke critical appraisal framework demonstrated that analytical validity was also poorly reported in many instances. In the economic model the incremental cost-effectiveness ratios ranged from £11,476 to £19,324 per quality-adjusted life-year (QALY), with a probability of cost-effectiveness between 48% and 54% when tests were compared with current standard care.
The major limitation in the evidence on tests was the heterogeneity between studies in the definitions of AKI and the timing of testing.
Diagnostic tests for AKI in the ICU offer the potential to improve patient care and add value to the NHS, but cost-effectiveness remains highly uncertain. Further research should focus on the mechanisms by which a new test might change current care processes in the ICU and the subsequent cost and QALY implications. The VOI analysis suggested that further observational research to better define the prevalence of AKI developing in the ICU would be worthwhile. A formal randomised controlled trial of biomarker use linked to a standardised AKI care pathway is necessary to provide definitive evidence on whether or not adoption of tests by the NHS would be of value.
The systematic review within this study is registered as PROSPERO CRD42014013919.
The National Institute for Health Research Health Technology Assessment programme.
急性肾损伤（AKI）在医院住院患者中普遍存在，导致显著的死亡率和发病率，降低了生活质量，增加了 NHS 的短期和长期医疗保健费用。新的诊断测试可能提供更早的诊断或更好的护理，但需要在全国范围内采用之前，证明对患者有益，对 NHS 有价值。
评估 AKI 体外诊断测试在改善 ICU 住院患者护理方面的潜力，并确定一种有效的支持研究策略。
我们在临床试验.gov、Cochrane 图书馆数据库、Embase、健康管理信息联盟、国际临床试验注册平台、MEDLINE、当前对照试验登记册、PubMed 和 Web of Science 数据库中进行了检索，这些数据库的检索时间均从成立日期开始，一直检索到 2014 年 9 月（综述 1）、2015 年 11 月（综述 2）和 2015 年 7 月（经济模型）。每个综述中使用的数据库的详细信息和涵盖日期均列在主要报告中。
AKI-Diagnostics 项目包括前瞻性扫描、系统评价、灵敏度和特异性的荟萃分析、分析有效性评估、护理路径分析、基于模型的英国 NHS 视角下的终生经济评估和价值信息（VOI）分析。
前瞻性扫描搜索确定了 152 种潜在的测试和生物标志物。对三种测试，即 Nephrocheck（Astute Medical，Inc.，圣地亚哥，CA，美国）、NGAL 和胱抑素 C 进行了详细审查。荟萃分析受到报告标准、研究质量和异质性的限制，但灵敏度在 0.54 到 0.92 之间，特异性在 0.49 到 0.95 之间，具体取决于测试。一个定制的专门评估框架表明，在许多情况下，分析有效性也没有得到很好的报告。在经济模型中，增量成本效益比范围为每质量调整生命年（QALY）11476 到 19324 英镑，当与当前标准护理相比时，成本效益的概率在 48%到 54%之间。
关于测试的证据的主要限制是研究之间在 AKI 的定义和测试时间方面存在异质性。
重症监护室 AKI 的诊断测试有可能改善患者护理并为 NHS 增加价值，但成本效益仍然高度不确定。进一步的研究应集中在新测试可能改变重症监护室中当前护理流程的机制以及随后的成本和 QALY 影响上。价值信息分析表明，进一步观察性研究以更好地定义 ICU 中 AKI 的发展情况将是值得的。需要进行一项关于生物标志物使用与标准化 AKI 护理路径相关的随机对照试验，以提供关于 NHS 是否采用这些测试是否有价值的明确证据。
本研究中的系统评价在 PROSPERO CRD42014013919 中进行了注册。
英国国家卫生研究院健康技术评估计划。
