Targeting renal hypoxia to avoid cardiac surgery associated acute kidney injury

  • Lankadeva, Yugeesh R. (Primary Chief Investigator (PCI))
  • May, Clive Newton (Chief Investigator (CI))
  • Evans, Roger (Chief Investigator (CI))
  • Cochrane, Andrew (Chief Investigator (CI))

Project: Research

Project Details

Project Description

More than 20,000 Australian’s undergo cardiac surgery requiring cardiopulmonary bypass (CPB) annually. Acute kidney injury (AKI) develops in ~30% of these patients. Even mild episodes of AKI pre-disposes patients to later develop chronic kidney disease (CKD). Renal tissue hypoxia has been implicated as a critical driver of AKI and in its progression to CKD. However, the absence of appropriate pre-clinical models has hindered our ability to definitively test this proposition and to develop effective therapies to prevent cardiac surgery associated AKI.
We have recently developed a clinically relevant ovine model of CPB, in which we can continuously monitor renal oxygenation and function across the entire course of cardiac surgery, from the conscious state prior to the operation to the four weeks of recovery after surgery. Our global hypothesis is that renal hypoxia is a major pathophysiological factor in both cardiac surgery associated AKI and progression from AKI to CKD. To test this hypothesis we will:
(1) Compare the natural history of renal oxygenation and function, before, during and after CPB in sheep with pre-existing heart failure and CKD, to that in
healthy sheep.
(2) Determine the effects of increased pump flow and arterial pressure during CPB on intra- and post-operative renal oxygenation and function.
(3) Determine the effects of peri-operative administration of the sympatholytic agent, dexmedetomidine.
In each aim, we will use cohorts of healthy sheep and sheep with heart failure and CKD to determine the effects on renal oxygenation and function of these
two major pre-operative risk factors for human cardiac-surgery associated AKI.
We are in an unprecedented position to improve our understanding of the pathophysiology of cardiac surgery associated AKI and provide the mechanistic
evidence-base for changing standard practice in clinical perfusion towards protecting the kidneys during CPB.
Short titleTargeting renal hypoxia to avoid cardiac surgery associated acute kidney injury
StatusActive
Effective start/end date1/10/2031/12/22