Impact of Using Biomarkers in Eligibility Criteria in Acute Kidney Injury Randomized Controlled Trials: A Systematic Review and Methodological Meta-Analysis

Why clinicians should know about it

• Picked for Biochemistry (medical) (paper of the day, 26 July 2026): SR/MA of RCTs, biomarker eligibility impact on AKI trials
• Picked for Internal Medicine (paper of the day, 26 July 2026): AKI biomarker eligibility methodology review
• Picked for Nephrology (paper of the day, 26 July 2026).
• Picked for Epidemiology (top studies of the week, 26 July 2026).

Abstract

RATIONALE & OBJECTIVE: Many recent randomized controlled trials (RCTs) for acute kidney injury have incorporated biomarkers as part of their eligibility criteria. The sample size calculation of these trials is often based on prior studies that did not include such criteria. This meta-analysis evaluates the impact of a biomarker-based enrichment strategy on the rate of anticipated versus observed primary events and explores the effect of integrating such biomarkers on statistical power. STUDY DESIGN: We performed a PRISMA-guided systematic review and methodological meta-analysis of RCTs extracted from 6 databases. SETTING & STUDY POPULATION: The RCTs included patients at risk for or diagnosed with acute kidney injury. SELECTION CRITERIA FOR STUDIES: Clinical trials with a biomarker-based eligibility criterion and either a renal or mortality primary outcome, published between 2010 and 2023. DATA EXTRACTION: Data were extracted independently by 2 reviewers. ANALYTICAL APPROACH: The absolute risk difference between anticipated and observed event rates was measured for all patients and stratified for control and intervention groups. RESULTS: Fourteen RCTs involving 3,817 patients were included. Biomarkers of interest were neutrophil gelatinase-associated lipocalin, TIMP-2∗IGFBP7, proteinuria, serum albumin, NT-pro-BNP, homocysteine, and uric acid. The pooled absolute risk difference between anticipated and observed event rates was 0.12 (95% CI; 0.06-0.17). In the control and interventional groups, the absolute risk differences were 0.10 (95% CI, 0.01-0.19) and 0.12 (95% CI, 0.06-0.18), respectively. For kidney damage biomarkers, the risk difference was 0.13 (95% CI, 0.06-0.20). The mean preplanned and achieved statistical powers were 0.84 ± 0.07 and 0.43 ± 0.28, respectively, with no improvement when extrapolating the preplanned sample size. LIMITATIONS: Most RCTs were underpowered for their primary outcome. There was a high level of heterogeneity. CONCLUSIONS: There is a difference between expected and observed incidence rates that may be partly attributed to biomarker-based enrichment methods. These findings highlight the need for rigorous validation of biomarkers before their incorporation into the eligibility criteria of RCTs.

Abstract as published, via PubMed.