Background:

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.

Objectives:

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.

Data sources:

We searched ClinicalTrials.gov, The Cochrane Library databases, Embase, Health Management Information Consortium, International Clinical Trials Registry Platform, MEDLINE, metaRegister 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.

Review methods:

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.

Results:

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.

Limitations:

The major limitation in the evidence on tests was the heterogeneity between studies in the definitions of AKI and the timing of testing.

Conclusions:

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.

Study registration:

The systematic review within this study is registered as PROSPERO CRD42014013919.

Funding:

The National Institute for Health Research Health Technology Assessment programme.

Article history

The research reported in this issue of the journal was funded by the HTA programme as project number 13/116/13. The contractual start date was in October 2014. The draft report began editorial review in October 2016 and was accepted for publication in August 2017. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

Andrew Lewington has received honoraria from Alere, Inc. David Meads is a member of the Health Technology Assessment programme Emergency and Hospital Care panel. Patrick Hamilton has received funding from ChemoCentryx, Inc., outside this work.