Inflammation and Diabetic Kidney Disease

Diabetes is the leading cause of end-stage kidney disease and significantly contributes to morbidity and mortality in people with diabetes. Despite significant advances in the last decade, including the development of novel therapies, the residual risk in diabetic kidney disease (DKD) remains high. One yet unaddressed factor in the pathogenesis of DKD is immune activation. Early in DKD, there is infiltration of macrophages, T-cells, B-cells, and dendritic cells in mouse models, while at later stages, neutrophils are also observed. This review will highlight novel insights into the contribution of immune cells to the development of DKD, with a particular focus on the innate immune system and the cellular crosstalk between immune cells and intrinsic kidney cells as contributors to DKD. One example of this bidirectional crosstalk is observed between macrophages and podocytes. While macrophages can directly mediate podocyte injury and apoptosis via TNF-α secretion, podocytes secrete cytokines that further recruit macrophages. Understanding the role of immune-mediated injury in kidney disease is critical in reducing the residual risk of DKD.