Twenty years after ACEIs and ARBs: Emerging Treatment Strategies

22 Diabetic nephropathy (DN) is a serious complication of both type 1 and type 2 diabetes mellitus. 23 The disease is now the most common cause of end-stage kidney disease (ESKD) in developed 24 countries, and both the incidence and prevalence of diabetes mellitus is increasing worldwide. 25 Current treatments are directed at controlling hyperglycemia and hypertension as well as 26 blockade of the renin angiotensin system (RAS) with angiotensin converting enzyme inhibitors 27 (ACEIs) and angiotensin receptor blockers (ARBs). Despite these therapies, DN progresses to 28 ESKD in many patients. As a result, much interest is focused on developing new therapies. It 29 has been over 2 decades since ACEIs were shown to have beneficial effects in DN independent 30 of their blood pressure (BP) lowering actions. Since that time, our understanding of disease 31 mechanisms in DN has evolved. In this review, we summarize major cell signaling pathways 32 implicated in the pathogenesis of diabetic kidney disease as well as emerging treatment 33 strategies. The goal is to identify promising targets that might be translated into therapies for 34 the treatment of patients with diabetic kidney disease. 35 36