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Abstract: FR-PO103

Impact of Biomarkers in the Eligibility Criteria of AKI Randomized Controlled Trials: A Systematic Review with Meta-Analysis

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Chennou, Fella, Universite de Montreal, Montreal, Quebec, Canada
  • Strader, Michael, University College Dublin, Dublin, Ireland
  • Beaubien-Souligny, William, Universite de Montreal, Montreal, Quebec, Canada
  • Cote, Jean Maxime, Universite de Montreal, Montreal, Quebec, Canada
Background

There is a growing interest around novel approaches for assessing acute kidney injury (AKI). Some clinical trials have used kidney biomarkers as part of their eligibility criteria to better select participants. This might cause a selection bias, as the expected event rate used to measure the sample size is based on prior studies without such criteria.

Methods

We searched for studies published after 2010 in MEDLINE, EMBASE, GOOGLE Scholar, EBM Reviews, MedRxiv and PROSPERO. We included RCTs with biomarkers as eligibility criteria that assess kidney outcomes, defined as the incidence or composite of acute kidney injury, major adverse renal or cardiac events, initiation of dialysis or death. The main aim of this review was to quantify the discrepancy between the anticipated (used in sample size estimation) and the observed event rates for control and intervention groups.

Results

A total of 14 RCTs involving 3817 patients were included. Biomarkers of interest were NGAL (4 studies), TIMP-2*IGFBP7 (3 studies), proteinuria (3 studies), albumin, NT-pro-BNP, homocysteine and uric acid. The mean risk difference between the anticipated and observed event rates was 0.098 (SD±0.115, p=0.58) for control groups and 0.116 (SD±0.106, p<0.01) for intervention groups. For RCTs with tubular damage biomarkers (NGAL, TIMP-2*IGFBP7 and proteinuria), the mean risk differences were 0.118 (SD±0.130, p=0.46) and 0.154 (SD±0.103, p=0.008) for the control and intervention groups respectively.

Conclusion

The use of biomarkers as an enrichment method for selecting participants in AKI RCTs is associated with a difference between expected and observed incidence rates. Investigators must consider the implications of integrating such criteria on the event rate of RCTs.

Funding

  • Clinical Revenue Support