Abstract: SA-PO045

Renal Fibrosis and Tubular Transport Adaptation Caused by Cardiac Arrest and Cardiopulmonary Resuscitation (CA/CPR) in Mice

Session Information

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Hutchens, Michael, Oregon Health & Science, Portland, Oregon, United States
  • Wakasaki, Rumie, Oregon Health and Science University, Portland, Oregon, United States
  • Coe, Ian Patrick, Oregon Health and Science University, Portland, Oregon, United States
  • Ferdaus, Mohammed Zubaerul, Oregon Health & Science University, Portland, Oregon, United States
  • McCormick, James A., Oregon Health & Science University, Portland, Oregon, United States
  • Anderson, Sharon, Oregon Health and Science University, Portland, Oregon, United States
Background

Studies of of cardiorenal AKI-to-CKD transition report higher incidence of CKD than studies of all-cause AKI-to-CKD transition. The mechanism is unknown because animal models of AKI-CKD transition exclude cardiac disease. We have reported that murine cardiac arrest and cardiopulmonary resuscitation (CA/CPR) is an experimental model of acute cardiorenal syndrome (Ikeda, AJPR 2017). Here, we show that CA/CPR causes essential findings of CKD.

Methods

CA was induced in mice with potassium chloride and confirmed as described. Mice were resuscitated 8 min later with CPR and epinephrine. 28 days later GFR was measured and the right kidney stained for alpha-smooth muscle actin and picrosirius red, which were quantified in unbiased fashon. Immunoblotting was performed for the tubular transporters NKCC2, pNKCC2, NCC, and pNCC.

Results

28d after CA/CPR, mice demonstrate reduced GFR and elevated serum urea nitrogen (sham 33±4, CA/CPR 49±3 mg/dL, p=0.01). Tubulointerstitial collagen deposition is markedly increased 1 month after CA/CPR compared with sham. Quantification of αSMA revealed a CA/CPR-induced 20-fold increase in tubulointerstitial fibrosis compared with sham (figure 1). pNKCC2 was markedly reduced by CA/CPR compared with sham (49.7%,p=0.001,n=9).

Conclusion

Renal fibrosis and loss of renal function follows resolution of acute kidney injury in experimental acute cardiorenal syndrome. Because CKD damages tubular structure and leads to hypertension, we determined whether tubular sodium transporters critical to blood pressure regulation were altered by CA/CPR. Our findings are consistent with reduced tubular sodium reabsorption, which may reflect a compensatory response to sodium retention. Overall these findings suggest that experimental acute cardiorenal syndrome models AKI-CKD transition.

Funding

  • NIDDK Support