Beta 2 adrenergic receptor agonists as a treatment for diabetic kidney disease

We previously showed that the long-acting β 2 -AR agonist formoterol induced recovery from AKI in mice. To determine if formoterol protected against diabetic nephropathy, the most common cause of ESKD, we used a high fat diet (HFD), a murine type 2 diabetes model, and streptozotocin, a murine type 1 diabetes model. Following formoterol treatment there was a marked recovery from and reversal of diabetic nephropathy in HFD mice 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. To investigate effects in humans we performed a competing risk regression analysis with death as a competing risk to examine the association between patients with COPD, who use β 2 -AR agonists, and patients without COPD and progression to ESKD in a large national cohort of Veterans with stage 4 CKD between 2011-2013. Veterans were followed until 2016 or death. ESKD was defined as initiation of dialysis and/or receipt of kidney transplant. We found that COPD was associated with a 25.6% reduction in progression from stage 4 CKD to ESKD compared to no COPD after adjusting for age, diabetes, sex, race-ethnicity, comorbidities, and medication use. Sensitivity analysis showed a 33.2% reduction in ESKD in Veterans with COPD taking long-acting formoterol and a 20.8% reduction in ESKD in Veterans taking other β 2 -AR agonists when compared to those with no COPD. These data indicate that β 2 -AR agonists, especially formoterol, may be a treatment for diabetic nephropathy and perhaps other forms of CKD.