Biomarkers for assessing acute kidney injury for people who are being considered for admission to critical care: a systematic review and cost-effectiveness analysis

Abstract

Background Acute kidney injury is a serious complication that occurs in the context of an acute critical illness or during a postoperative period. Earlier detection of acute kidney injury may facilitate strategies to preserve renal function, prevent further disease progression and reduce mortality. Acute kidney injury diagnosis relies on a rise in serum creatinine levels and/or fall in urine output; however, creatinine is an imperfect marker of kidney function. There is interest in the performance of novel biomarkers used in conjunction with existing clinical assessment, such as NephroCheck® (Astute Medical, Inc., San Diego, CA, USA), ARCHITECT® urine neutrophil gelatinase-associated lipocalin (NGAL) (Abbott Laboratories, Abbott Park, IL, USA), and urine and plasma BioPorto NGAL (BioPorto Diagnostics A/S, Hellerup, Denmark) immunoassays. If reliable, these biomarkers may enable earlier identification of acute kidney injury and enhance management of those with a modifiable disease course. Objective The objective was to evaluate the role of biomarkers for assessing acute kidney injury in critically ill patients who are considered for admission to critical care. Data sources Major electronic databases, conference abstracts and ongoing studies were searched up to June 2019, with no date restrictions. MEDLINE, EMBASE, Health Technology Assessment Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Web of Science, World Health Organization Global Index Medicus, EU Clinical Trials Register, International Clinical Trials Registry Platform and ClinicalTrials.gov were searched. Review methods A systematic review and meta-analysis were conducted to evaluate the performance of novel biomarkers for the detection of acute kidney injury and prediction of other relevant clinical outcomes. Random-effects models were adopted to combine evidence. A decision tree was developed to evaluate costs and quality-adjusted life-years accrued as a result of changes in short-term outcomes (up to 90 days), and a Markov model was used to extrapolate results over a lifetime time horizon. Results A total of 56 studies (17,967 participants), mainly prospective cohort studies, were selected for inclusion. No studies addressing the clinical impact of the use of biomarkers on patient outcomes, compared with standard care, were identified. The main sources of bias across studies were a lack of information on blinding and the optimal threshold for NGAL. For prediction studies, the reporting of statistical details was limited. Although the meta-analyses results showed the potential ability of these biomarkers to detect and predict acute kidney injury, there were limited data to establish any causal link with longer-term health outcomes and there were considerable clinical differences across studies. Cost-effectiveness results were highly uncertain, largely speculative and should be interpreted with caution in the light of the limited evidence base. To illustrate the current uncertainty, 15 scenario analyses were undertaken. Incremental quality-adjusted life-years were very low across all scenarios, ranging from positive to negative increments. Incremental costs were also small, in general, with some scenarios generating cost savings with tests dominant over standard care (cost savings with quality-adjusted life-year gains). However, other scenarios generated results whereby the candidate tests were more costly with fewer quality-adjusted life-years, and were thus dominated by standard care. Therefore, it was not possible to determine a plausible base-case incremental cost-effectiveness ratio for the tests, compared with standard care. Limitations Clinical effectiveness and cost-effectiveness results were hampered by the considerable heterogeneity across identified studies. Economic model predictions should also be interpreted cautiously because of the unknown impact of NGAL-guided treatment, and uncertain causal links between changes in acute kidney injury status and changes in health outcomes. Conclusions Current evidence is insufficient to make a full appraisal of the role and economic value of these biomarkers and to determine whether or not they provide cost-effective improvements in the clinical outcomes of acute kidney injury patients. Future work Future studies should evaluate the targeted use of biomarkers among specific patient populations and the clinical impact of their routine use on patient outcomes and management. Study registration This study is registered as PROSPERO CRD42019147039. Funding This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 26, No. 7. See the NIHR Journals Library website for further project information.

Alerting to acute kidney injury - Challenges, benefits, and strategies

“…While clinical laboratories are not typically involved in monitoring or measuring UO, the reduction in UO is an important criterion for diagnosis of AKI, and neglecting this marker could potentially delay AKI diagnosis or, even worse, miss it [ 50 ]. When there is UO, subsequent biochemical [ [53] , [54] , [55] ] or microscopic analysis [ 56 , 57 ] can be performed. However, non-oliguric AKI does not necessarily correlate with renal dysfunction as factors such as diuretics, vasodilators, or aggressive fluid resuscitation can contribute to urine flow [ 54 , 58 ].…”

“…What has been lacking is adoption and universal acceptance of new markers of kidney stress or injury and how such markers would fit into current definitions. Some examples of markers that have gained popularity in North America include NephroCheck (makes use of two markers: tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7), urinary neutrophil gelatinase-associated lipocalin (uNGAL) and cystatin C [ 55 , 64 ]. Consequently, the consensus meeting outlined an expanded criteria for staging AKI, based on the notion that novel biomarkers could be incorporated into the KDIGO 2012 AKI guidelines ( Table 1 ).…”

Prognostic Biomarkers and AKI: Potential to Enhance the Identification of Post-Operative Patients at Risk of Loss of Renal Function

“… 71 Several studies have shown that IL-18 levels are raised 4–6 hours following cardiac surgery and that it may also predict the severity of AKI. 68 , 69 , 75 A meta-analysis of 11 papers demonstrated an AUC of 0.77. Of those, 4 assessed cardiac surgery and 1 liver transplantation.…”

Exploring the Cost-Utility of a Biomarker Predicting Persistent Severe Acute Kidney Injury: The Case of C-C Motif Chemokine Ligand 14 (CCL14)

“…Two UK health technology appraisals 19 , 20 conducted original analyses to inform the biomarker decision space and concluded that determining the cost-effectiveness of biomarkers is currently limited by the lack of evidence on efficacious interventions addressing AKI progression. The controversy resides specifically in clinically defining these interventions given the multiplicity of AKI etiologies.…”