Kidney Res Clin Pract.  2022 Sep;41(Suppl 2):S74-S88. 10.23876/j.krcp.22.011.

Adenosine receptors as emerging therapeutic targets for diabetic kidney disease

• Pak ES
• Cha JJ
• Cha DR
• Kanasaki K
• Ha H

• KMID: 2535414
• DOI: http://doi.org/10.23876/j.krcp.22.011

Abstract

Diabetic kidney disease (DKD) is now a pandemic worldwide, and novel therapeutic options are urgently required. Adenosine, an adenosine triphosphate metabolite, plays a role in kidney homeostasis through interacting with four types of adenosine receptors (ARs): A1AR, A2AAR, A2BAR, and A3AR. Increasing evidence highlights the role of adenosine and ARs in the development and progression of DKD: 1) increased adenosine in the plasma and urine of diabetics with kidney injury, 2) increased expression of each of the ARs in diabetic kidneys, 3) the protective effect of coffee, a commonly ingested nonselective AR antagonist, on DKD, and 4) the protective effect of AR modulators in experimental DKD models. We propose AR modulators as a new therapeutic option to treat DKD. Detailed mechanistic studies on the pharmacology of AR modulators will help us to develop effective first-in-class AR modulators against DKD.

Keyword

Adenosine; Adenosine receptor; Agonist; Antagonist; Diabetic kidney disease; Fibrosis