Todd A. Miano, PharmD, PhD

Dr. Miano is a critical care pharmacist and epidemiologist whose work aims to reduce harm from adverse drug events in acutely ill patients. His research focuses on understanding the determinants and impacts of nephrotoxicity (the syndrome of rapid kidney function loss resulting from drug toxicity), and the health impacts of drug-drug interactions (DDI). Nephrotoxicity is a major, modifiable cause of acute kidney injury (AKI) in hospitalized patients, especially in the setting of polypharmacy, where numerous drug combinations can interact to increase toxicity risk. Nephrotoxic AKI accounts for nearly one third of AKI events in hospitalized patients, and has severe adverse consequences, including increased risk of death and a higher risk of chronic kidney disease onset and progression. To address these public health problems, he leads a translational, acute care pharmacoepidemiology research program that integrates information from observational causal inference studies, prospective molecular epidemiologic studies, and randomized clinical trials to examine the comparative safety of nephrotoxic drugs and to understand underlying molecular mechanisms of toxicity.

His work has advanced our understanding of the limitations of current phenotyping methods for nephrotoxic AKI. Serum creatinine, the standard biomarker of nephrotoxicity, is a kidney function biomarker that has poor sensitivity and specificity for kidney parenchymal injury. In a seminal paper, Dr. Miano found that commonly prescribed antibiotics, when used in combination, can lead to false elevations in creatinine, so called pseudo-nephrotoxicity. The study further found that cystatin C, a novel kidney function biomarker, can be used to accurately detect changes in kidney function during antibiotic treatment. This work questions the results of dozens of prior creatinine-based studies and stands to establish a new paradigm for evaluating drug-associated AKI. His lab was also the first to show that kidney disease strongly modifies the severity of drug-drug interactions that are mediated by inhibition of hepatic metabolism, a finding that has mechanistic implications for dozens of drug combinations commonly encountered in clinical practice.