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Kidney Week

Abstract: PO0753

Role of β2-Adrenergic Receptor Agonists in the Treatment of Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Arif, Ehtesham, Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States
  • Solanki, Ashish K., Medical University of South Carolina Division of Nephrology, Charleston, South Carolina, United States
  • Wolf, Bethany, Medical University of South Carolina, Charleston, South Carolina, United States
  • Hunt, Kelly J., 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

Diabetes is the leading cause of end stage kidney disease (ESKD) and affects podocytes. We previously showed in cells and mice that pharmacological activation of mitochondrial biogenesis by the long-acting β2-AR agonist formoterol contributes to podocyte recovery from injury.

Methods

We examined the association between COPD, in which the vast majority of patients receive β2-AR agonists, and CKD progression in a national cohort created from patient records within the Veterans Health Administration (VHA). Cohort members were limited to age 65 to 85 years with stage 3 CKD defined based upon ICD-9 codes (ICD-9: 585.3, N18.3) or two eGFR values of 30-59 mL/min/1.73m2 at least 90 days apart. COPD was defined based upon ICD-9 codes (ICD-9: 416.8, 416.9, 490.x-505.x, 506.4, 508.1, 508.8). Veterans entered the cohort in 2010 and were followed through 2016. We are also currently testing the efficacy of formoterol in restoring glomerular function in type I (streptozotocin) and type 2 (high fat diet) diabetic murine models.

Results

Of 194,119 Veterans with stage 3 CKD in 2010, 4,727 progressed to stage 5 CKD by 2016. The age- and sex-adjusted odds ratio for the association between baseline COPD and progression to stage 5 CKD was 0.89 (95% CI: 0.83, 0.96), indicating that Veterans with COPD at baseline had lower odds of progression to stage 5 CKD than Veterans without COPD at baseline.

Conclusion

Our large retrospective cohort study suggests that β2-AR agonists slow the progression of CKD. Given that diabetes is the most common cause of ESKD, the effect of β2-AR agonists on progression of CKD is likely driven by the effect on diabetic nephropathy. Animal studies to directly test this hypothesis are underway.

Funding

  • NIDDK Support