Application of new acute kidney injury biomarkers in human randomized controlled trials

Abstract

The use of novel biomarkers of acute kidney injury (AKI) inclinical trials may help evaluate treatments for AKI. Herewe explore potential applications of biomarkers in simulated clinical trials of AKI using data from the TRIBE-AKI multicenter, prospective cohort study of patients undergoing cardiac surgery. First, in a hypothetical trial ofan effective therapy at the time of acute tubular necrosis to prevent kidney injury progression, use of an indirect kidney injury marker such as creatinine compared to a new direct biomarker of kidney injury reduces the proportion oftrueacute tubular necrosis cases enrolled. The result isalower observed relative risk reduction with the therapy, and lower statistical power to detect a therapy effect atagiven sample size. Second, the addition of AKI biomarkers (interleukin-18 and NGAL) to clinical risk factorsas eligibility criteria for trial enrollment in early AKIhas the potential to increase the proportion of patients who will experience AKI progression and reduce trial cost. Third, we examine AKI biomarkers as outcome measures for the purposes of identifying therapies that warrant further testing in larger, multicenter, multi-country trials. Inthe hypothetical trial of lower cardiopulmonary bypass time to reduce the risk of postoperative AKI, the sample size required to detect a reduction in AKI is lower if new biomarkers are used to define AKI rather than serum creatinine. Thus, incorporation of new biomarkers of AKI has the potential to increase statistical power, decrease thesample size, and lower the cost of AKI trials.