The primary objective was to develop systematic evidence maps of novel kidney biomarkers from a mapping review to inform future implementation in patient care for acute kidney injury (AKI) in critically ill populations. The maps were intended to summarize where clinical evidence exists and to identify gaps that must be addressed before routine clinical adoption.
Searches were conducted in PubMed/MEDLINE and Embase. The review included clinical trials and observational studies that investigated novel kidney biomarkers in critically ill patients and related to AKI. Studies focusing on prediction, prognosis, diagnosis of etiology, trial enrichment, and management of AKI were captured for mapping.
A total of 6,805 records were screened. From that screening, 1,116 studies were included that related to one or more novel biomarkers and AKI. The included body of evidence formed the basis for the systematic evidence maps organized by intended clinical use.
Most included studies evaluated adult populations, comprising 78.6% of the dataset. The predominant study design was cohort studies, accounting for 93.3% of included reports. These characteristics indicate that existing evidence heavily favors observational assessments of biomarker associations with AKI rather than randomized interventional designs.
Mixed critically ill populations, cardiac surgery, and sepsis were the most frequently studied clinical contexts, together representing 69.5% of the studies. This concentration suggests that biomarker research has focused on generalized ICU cohorts and high-risk surgical and septic patients, where AKI risk and monitoring needs are pronounced.
The authors synthesized evidence into distinct maps according to the intended application of biomarkers in clinical care:
Predict AKI: n = 944 studies. These assessed biomarkers for their ability to forecast development of AKI before conventional diagnostic criteria are met.
Prognosticate clinical outcomes: n = 647 studies. These evaluated associations between biomarker levels and outcomes such as mortality, need for renal replacement therapy, or other clinical endpoints.
Diagnose AKI etiology: n = 109 studies. These investigated the utility of biomarkers to distinguish causes of AKI or to aid diagnostic classification.
Enrich clinical trials: n = 6 studies. These explored biomarker-based strategies to select or stratify patients for interventional trials.
Manage AKI: n = 12 studies. These reports considered biomarker use to guide therapeutic or monitoring decisions in clinical care.
The distribution shows a strong emphasis on predictive and prognostic evaluation and far fewer studies addressing enrichment or management applications that directly inform clinical actions.
Based on the mapped evidence, the authors describe potential implementation strategies where biomarker data could be applied in practice. Key suggested uses include targeted surveillance of patients at elevated risk for AKI—examples being patients undergoing surgery and patients exposed to multiple nephrotoxic medications. The review indicates that in these contexts, available evidence may support use of biomarkers to enhance monitoring or to trigger preventive measures.
However, the review also notes that while there is substantial evidence comparing biomarker accuracy to AKI diagnosis, there are relatively few practical trials that demonstrate improved clinical outcomes when biomarkers are used to guide decision-making. This limits definitive implementation recommendations and highlights the need for trials that test biomarker-informed management strategies.
The evidence map demonstrates substantial clinical literature assessing the accuracy of novel biomarkers relative to AKI diagnosis, but fewer interventional or implementation studies showing clinical utility. The authors emphasize that insights for implementation can be gleaned from existing evaluations—particularly in perioperative and nephrotoxin-exposed populations where biomarker evidence is more developed.
The review identifies priorities for future research: specifically, management and enrichment trials designed to bridge the gap from biomarker predictive accuracy to actionable clinical decision-making. These trials are needed to determine whether biomarker-guided strategies improve patient-centered outcomes in critically ill populations and to define practical implementation approaches in intensive care settings.
The full review was published online ahead of print with DOI 10.1097/CCM.0000000000007362 and carries keywords including acute kidney injury, biomarkers, critical illness, intensive care unit, prediction, and prognosis. Conflict-of-interest disclosures and a list of references accompany the article in the original publication.