ASK1 limits kidney glucose reabsorption, growth, and mid-late proximal tubule KIM-1 induction when diabetes and Western diet are combined with SGLT2 inhibition

Selonsertib is an apoptosis signal-regulating kinase 1 (ASK1) inhibitor that attenuated creatinine-based eGFR decline in humans with type 2 diabetes and kidney disease but increased acute kidney injury rates. Here, we report evidence in a murine model of early type 1 diabetes mellitus that housekeeping functions of ASK1 limit glucose reabsorption and the associated growth and cellular stress induced in the mid-to-late proximal tubule by combining hyperglycemia and Western diet with SGLT2 inhibition.