Kidney Week

Abstract: TH-PO220

β2 Adrenergic Receptor Agonists as a Novel Treatment for CKD

Session Information

• Diabetic Kidney Disease: Basic - I
  November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

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

Ehtesham Arif,

• Medunjanin, Danira, Medical University of South Carolina Department of Public Health Sciences, Charleston, South Carolina, United States

Danira Medunjanin,

• Solanki, Ashish K., Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States

Ashish K. Solanki,

• Zuo, Xiaofeng, Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States

Xiaofeng Zuo,

• Su, Yanhui, Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States

Yanhui Su,

• Winkler, Brennan, Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States

Brennan Winkler,

• Palygin, Oleg, Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States

Oleg Palygin,

• Cornier, Marc-Andre, Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States

Marc-Andre Cornier,

• Wolf, Bethany, Department of Biostatistics, Medical University of South Carolina, Charleston, South Carolina, United States

Bethany Wolf,

• Hunt, Kelly J., Department of Biostatistics, Medical University of South Carolina, Charleston, South Carolina, United States

Kelly J. Hunt,

• Lipschutz, Joshua H., Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States

Joshua H. Lipschutz,

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