Intrarenal Oxygenation: An Early Marker for Risk of Developing AKI

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 DESCRIPTION (provided by applicant): Acute kidney injury (AKI) is a common hospital acquired condition in patients with compromised compensatory mechanisms such as endothelial function. Consequences of AKI are several including longer hospital stay to increased risk of mortality. While prevention is feasible, it has remained elusive primarily because of the lack of a suitable marker to indicate who is at risk of developing AKI. The current clinical marker has a slow response (above 48 hrs) and misses the window of opportunity to intervene. Novel markers that can indicate kidney injury are becoming available with faster response (4 to 8 hours after insult). It is believed that physiological markers such as blood flow and oxygenation may be sensitive to changes even earlier. We have a long standing interest in evaluating renal oxygenation and its consequences to different disease mechanisms, primarily using non-invasive magnetic resonance imaging (MRI). For AKI, we have demonstrated an animal model which is useful in studying the effects of iodinated contrast media, a well-known cause of renal injury in at-risk subjects. Our recent findings indicate that renal oxygenation changes happen almost in real time with the administration of iodinated contrast and these changes are indicative of renal injury as documented by one of the novel injury markers at 4 hours following contrast administration. This is the earliest known marker of risk of developing AKI. In the proposed study, we will validate a surrogate marker of renal medullary oxygenation that would allow for translating the findings to humans. This is based on measuring urine pO2. We will also extend our findings to- date to optimize the dose of preventive interventions and establish threshold values of hypoxia index that indicates risk of developing AKI, to generalize the findings to other animal models susceptible to iodinated contrast induced AKI. Ability to identify who is at higher risk of developing AKI following procedures such as coronary angiogram or computed tomography where iodinated contrast is used or in patients undergoing cardiac surgery will be of immense significance both in terms of improving outcomes, reducing costs and mortality.