Acute renal failure (ARF) is a syndrome that can be broadly defined as rapid deterioration of renal function resulting in the accumulation of nitrogenous wastes such as urea and creatinine. It is a major clinical problem and is a common hospital acquired syndrome with high mortality rates (approximately 50 percent). The pathophysiology of ischemic acute renal failure, the most common form of clinical ARF, is complex and not yet well understood. Based on previous studies on animal models, it is known that acute renal failure involves damage to the medulla which even under normal circumstances must function in an hypoxic environment. Hence an understanding of mechanisms that influence medullary hypoxia is important in the study of pathophysiology of ARF. To date, measurements of intrarenal oxygen tension have been made only with oxygen-sensitive microelectrodes implanted into the renal parenchyma of animals, a delicate and tedious procedure and impractical for human studies. BOLD (Blood Oxygenation Level Dependent) MRI has shown potential as a noninvasive method to assess on a regional basis the changes in the balance of oxygen supply and demand. We have previously demonstrated a strong correspondence between BOLD MRI measurements in vivo in human kidneys and earlier animal data using invasive microelectrodes. These studies provided evidence for the first time indicating a substantial degree of hypoxia in the human renal medulla. In this proposal, we will further evaluate this technique by comparing the BOLD MRI data obtained in an animal model with oxygenation measurements previously obtained with an invasive microelectrode technique. We will then apply the technique to both animal models and human subjects to derive new information about renal physiology/ pathophysiology especially related to ARF. The availability of a noninvasive method to evaluate regional oxygenation in kidneys in vivo should help to characterize therapeutic and protective mechanisms and thus lead to improved therapeutic and preventive measures for acute renal failure.
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