Various mechanisms related to the hyperglycemic state are involved in the development of DKD, which include metabolic disorders, hemodynamic alterations (e.g., hyperfiltration and hyperperfusion), podocyte injury caused by hyperglycemia-induced ROS generation, autophagy and apoptosis, activation of the renin-angiotensin system, accumulation of advanced glycation end products (AGEs), polyol pathway activation, and abnormal PKC activation [17,25]. Here, REN is linked to Hyperglycemia.