Twenty years after ACEIs and ARBs: emerging treatment strategies for diabetic nephropathy

Am J Physiol Renal Physiol. 2015 Nov 15;309(10):F807-20. doi: 10.1152/ajprenal.00266.2015. Epub 2015 Sep 2.


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

Keywords: cell signaling; diabetes mellitus; diabetic nephropathy; oxidative stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiotensin Receptor Antagonists / pharmacology*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Nephropathies / drug therapy*
  • Humans
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / drug therapy*


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents