ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO220

β2 Adrenergic Receptor Agonists as a Novel Treatment for CKD

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Arif, Ehtesham, Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States
  • Medunjanin, Danira, Medical University of South Carolina Department of Public Health Sciences, Charleston, South Carolina, United States
  • Solanki, Ashish K., Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States
  • Zuo, Xiaofeng, Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States
  • Su, Yanhui, Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States
  • Winkler, Brennan, Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States
  • Palygin, Oleg, Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States
  • Cornier, Marc-Andre, Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States
  • Wolf, Bethany, Department of Biostatistics, Medical University of South Carolina, Charleston, South Carolina, United States
  • Hunt, Kelly J., Department of Biostatistics, Medical University of South Carolina, Charleston, South Carolina, United States
  • Lipschutz, Joshua H., Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States
Background

We recently showed that formoterol, a long-acting beta 2 adrenergic receptor (β2-AR) agonist, induced recovery from kidney injury in mice.

Methods

To determine the effect of formoterol on renal function in humans, we performed a competing risk regression in Veterans, aged 65 and over, with incident chronic kidney disease (CKD) stage 4 to compare the rate of end stage kidney disease (ESKD) progression in Veterans without and with chronic obstructive pulmonary disease (COPD), who use β2-AR agonists. Additionally, we used a high fat diet (HFD), a murine model of type 2 diabetes, and streptozotocin, a murine model of type 1 diabetes, to examine the role of formoterol in diabetic nephropathy, the most common cause of ESKD.

Results

We found that COPD, by means of β2-AR agonist intake, was protective against progression to ESKD. A 39.4% [HR:0.61 (95% CI: 0.51-0.72)] reduction in the rate of ESKD in Veterans with COPD compared to those without was observed after adjusting for age, diabetes, sex, and race-ethnicity. Animal studies indicate that there was a marked recovery from and reversal of diabetic kidney disease in HFD mice treated with formoterol compared to those treated with vehicle alone at the ultrastructural, histological, and functional levels. Similar results were seen after formoterol treatment in mice receiving streptozotocin. The mechanism of action appeared to be improvement in mitochondrial function.

Conclusion

Together these data indicate that β2-AR agonists, especially formoterol, may be a novel treatment for diabetic nephropathy and perhaps other forms of CKD. If confirmed in a prospective randomized clinical trial this would be the first treatment able to reverse diabetic nephropathy.

Funding

  • NIDDK Support