Clinical applications of biomarkers for acute kidney injury

Research into novel therapies for acute kidney injury (AKI) has been hampered by reliance on a diagnosis predicated on changes in serum creatinine level. As a marker for changing kidney function rather than frank kidney injury, creatinine level lacks sensitivity and specificity for the diagnosis of AKI and shows significant lag time before increasing after injury. It has been unclear whether the failure to translate promising results from animal studies in AKI into successful human trials has been caused by lack of therapeutic efficacy or inappropriately delayed application of the intervention. Multiple novel biomarkers with the potential to revolutionize the timing and accuracy of the diagnosis of AKI currently are under investigation. We have chosen to use one of these biomarkers, interleukin 18 (IL-18), to show the ways in which biomarkers at present can supplement the conventional management of AKI. IL-18 is well suited for this analysis because it is both a mediator of and marker for AKI. We describe 2 cases in which reliance on serum creatinine level for the diagnosis of AKI led to diagnostic and management uncertainty. In the context of these cases, we discuss how IL-18 and other biomarkers can facilitate earlier detection, enhance the differential diagnosis, and allow more prescient prognosis. Additionally, we describe the potential role for biomarkers in prospective trial design and discuss the utility of biomarkers in facilitating adequate powering of trials through more accurate characterization of cases and controls.