Understanding mitochondrial dysfunction in diabetic kidney disease: different cell perspectives
Diabetic kidney disease (DKD) is the leading cause of end stage renal disease globally, affecting between 30-40% of patients with diabetes, drastically increasing patients’ risk for cardiovascular mortality and death. Current treatment regimens slow but don’t prevent disease, as such, there is a clinical need for therapies that prevent or ameliorate DKD. Mitochondrial dysfunction has been identified as one of the main pathways contributing to the pathogenesis of DKD but different components of the kidney have very different metabolic preferences, different mitochondrial densities and respond differently to the change in metabolic fuels available in diabetes. We have been trialling a novel redox modulating agent that shows efficacy at improving diabetic kidney disease in animal models, but the mechanism of action is not yet understood. In this project we wish to examine the effects of diabetes and glucose modulation (mimicking the increased glucose variability experienced by patients with diabetes) on different renal cell populations in the context of other important factors present in the diabetic milieu (inflammatory cytokines, growth factors). Here, we wish to both further our understanding of the effects of diabetes on mitochondrial function in the different cell types that populate the kidney and to discover the mechanism of action of our redox therapy in diabetic kidney cells.