Biomarkers of Drug-Induced Kidney Injury: Use in Clinical Trials and Recent Examples of Impact on Drug Development.

This manuscript describes the scope of implementation and impact of a regulatory agency-qualified panel of six urine biomarkers on drug development, the process for which was conducted and funded by the Critical Path Institute, the Foundation for the National Institutes of Health, and the United States Food and Drug Administration. Since 2018, these qualified kidney injury urine biomarkers have been included in early clinical drug development programs. Drug-induced kidney injury has historically contributed to high drug candidate attrition rates, additional animal testing needed due to the limitations of standard clinical laboratory tests in timely nephrotoxicity detection, and unsustainable development program fiscal costs. By illustrating the practical application, case studies from pharmaceutical companies illustrate how FDA-qualified drug-induced kidney injury biomarkers can enhance early detection and enable more sensitive and/or specific monitoring of nephrotoxicity. Moreover, data from completed trials registered on ClinicalTrials.gov show that the use of these non-standard-of-care biomarkers as prespecified safety endpoints has increased since their qualification in 2018.