Normobanc hyperoxia ameliorates renal ischemia reperfusion injury in rats

Introduction Acute kidney injury (AKI) represents an ever‐increasing clinical problem with high morbidity and mortality. The kidney, due to its inhomogeneous blood flow, is particularly susceptible to changes in oxygen delivery. Renal hypoxia constitutes a common hallmark of AKI, and in the progression to chronic kidney disease (CKD). However, the role of hypoxia per se in the acute phase of renal injury remains largely unclear. The present study investigated 1) the role of systemic hypoxia in the acute progression and recovery of AKI, and 2) if normobaric global hyperoxia following AKI improves renal outcome. Methods Anaesthetized (thiobutabarbital 120mg/kg i.p.) adult male Sprague‐Dawley rats were subjected to unilateral complete warm renal ischemia for 45 minutes followed by 2 hours of reperfusion under normoxic (21% inspired oxygen, n=10), hypoxic (10% inspired oxygen, n=10), and hyperoxic (60% inspired oxygen n=10) conditions. Kidney function, renal hemodynamics, intrarenal tissue oxygen tension (PO 2 ), and renal oxygen consumption were estimated before and after the ischemic insult. Results All investigated parameters were similar between groups at baseline. Animals subjected to 10% inspired oxygen developed intrarenal tissue hypoxia, whereas animals subjected to 60% inspired oxygen presented with increased intrarenal PO 2 demonstrating that the approach to manipulate intrarenal tissue oxygen availability was successful. Furthermore, GFR at baseline were independent of renal tissue oxygenation. IR per se caused a steep decline in GFR in all groups (−97 ± 1, −87 ± 3, and −70 ± 11% for hypoxic, normoxic and hyperoxic animals, respectively), although renal blood flow and renal vascular resistance were similar before and after the ischemic insult. However, following IR there was a linear relationship between GFR and cortical PO 2 when analysing all animals in all groups (Fig 1, linear regression P<0.05). Conclusion This study demonstrates that renal function following IR is dependent on intrarenal oxygen availability. Furthermore, normobaric hyperoxia‐treatment initiated at the time of the ischemic insult has the potential to protect kidney function. Support or Funding Information This study was supported by the Swedish Research Council Medicine and Health. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .