Generation of a Drug-Induced Renal Injury List to Facilitate the Development of New Approach Methodologies for Nephrotoxicity

Drug -induced renal injury (DIRI) causes >1.5 million adverse events annually in the USA alone. Although standard biomarkers exist for DIRI, they lack the sensitivity or speci ficity to detect nephrotoxicity before the signi ficant loss of renal function. In this study, we describe the creation of DIRIL - a list of drugs associated with DIRI and nephrotoxicity - from two literature datasets with DIRI annotation, con firmed using FDA drug labeling. DIRIL comprises 317 orally administered drugs covering all 14 anatomical, therapeutic and chemical (ATC) classi fication categories. Of the 317 drugs, 171 were DIRI-positive and 146 were DIRI-negative. DIRIL will be a relevant and invaluable resource for discovery of new approach methods (NAMs) to predict the occurrence and possible severity of DIRI earlier in drug development.