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Abstract: SA-OR011

Alpha 2 Adrenergic Receptor Blockade Prevents AKI to CKD Transition

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Jang, Hee-Seong, University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Padanilam, Babu J., University of Nebraska Medical Center, Omaha, Nebraska, United States

Increased sympathetic nerve activity and norepinephrine (NE) levels are of importance in the onset and the early development of end stage renal disease. We reported that renal denervation (DNx) can prevent renal fibrosis and inflammation in renal fibrogenesis models. However, the underlying mechanism by which renal denervation prevents the long-term sequelae of acute kidney injury (AKI) remains to be elucidated.


Based on our data, we hypothesized that NE mediates its effect through activation of alpha 2 adrenergic receptors (α2ARs). In this study, we investigated whether genetic or pharmacological inhibition of α2ARs prevents ischemia/reperfusion injury (IRI)-induced CKD progression.


IRI resulted in severe kidney fibrosis in medullary region over 2 weeks with tubular cast and atrophy and massive macrophage infiltration. Renal DNx and pharmacological inhibition of α2AR did not affect renal functional and histological damage in the acute phase of the IRI. However, renal tubular damage, inflammation, and fibrosis progression was suppressed 2 weeks post-IRI by renal DNx and pharmacological inhibition of α2AR with downregulation of downstream targets of NE-α2AR axis, including angiotensinogen, fibrogenic factors and inflammatory cytokines. Similar with results in pharmacological inhibition of α2A-AR subtype, blockage of α2C-AR subtype by pharmacological or genetic manipulation prevented the long-term sequelae of IRI, including renal tubular atrophy, inflammation and fibrosis progression.


Collectively, inhibition of α2AR subtypes prevents IRI-induced AKI to CKD transition through inhibition of persistent renal tubular injury and inflammation, and fibrosis progression, suggesting that targeting α2ARs may be a potential therapeutic strategy to prevent long-term sequelae of ischemic AKI.


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