The Pharmacovigilance Symposium at the 39^th annual meeting of the Japanese Society of Toxicology (JSOT) in Sendai provided an opportunity for physicians and safety scientists to discuss a variety of new tools and techniques of evaluating mechanisms or risk factors for specific adverse reactions. Similar to pharmacovigilance symposia at other recent JSOT meetings this session came about thanks to the efforts of the Safety Evaluation Forum Pharmacovigilance Working Group (SEF-PV-WG), the Japanese Association of Pharmaceutical Medicine (JAPhMed) and the willingness of safety scientists working at a variety of agencies, institutes and companies both inside and outside Japan to share their data and expertise to help advance the science of drug safety for the benefit of patients and clinical trial subjects.

　Acute kidney injury (AKI) is the major dose-limiting side effect for administration of cisplatin, but current clinical tests for kidney function fail to predict patients that will proceed to AKI following cisplatin treatment, and they are not rapidly responsive in an acute injury situation. Here mass spectrometry-based global metabolic profiling of pre-treatment urine samples from 60 mesothelioma patients was used to identify small metabolite biomarkers predictive of an AKI following cisplatin treatment. Despite normal kidney function (eGFR > 60 mL/min) at baseline, 23 patients had an AKI following treatment, as defined by a 50% increase in SCr (AKI-50), and 7 of these patients had a more severe AKI defined by a 100% increase in SCr (AKI-100). Comparing the AKI-50 group to the control group identified a number of biochemicals that differed significantly (raw p-value < 0.05) at baseline between these groups. Biologically, these candidate biomarkers of susceptibility to nephrotoxicity may reflect activities of organic ion transporters in kidney proximal tubule endothelial cells that differed between patient groups prior to cisplatin administration. Differential activities in these transporters would be expected to affect renal accumulation of cisplatin, and thus nephrotoxicity, following cisplatin administration. The severe kidney injury group (AKI-100) was distinguished at baseline by a different set of biochemicals that report on oxidative stress and increased activity of enzymes known to convert cisplatin to a more nephrotoxic form. A selected panel of metabolites could be potentially used to predicate the risk of cisplatin induced AKI. Validation studies are required to determine robustness of these biomarkers in a new patient cohort.