Intrarenal Oxygenation: An Early Marker for Risk of Developing AKI

 描述(由申请人提供)：急性肾损伤(AKI)是一种常见的医院获得性疾病，患者的代偿机制，如内皮功能受损。AKI的后果有几个，包括住院时间延长，死亡风险增加。虽然预防是可行的，但它仍然难以实现，主要是因为缺乏适当的标记来表明谁有患急性KI的风险。目前的临床标记物反应缓慢(超过48小时)，并错过了干预的机会之窗。可以指示肾脏损伤的新标记物正在变得可用，反应更快(受侮辱后4至8小时)。人们认为，血流和氧合等生理指标可能对变化敏感得更早。长期以来，我们一直有兴趣评估肾脏氧合及其对不同疾病机制的影响，主要是使用无创性磁共振成像(MRI)。对于AKI，我们已经证明了一个动物模型，该模型在研究碘化造影剂的效果方面很有用，碘化造影剂是高危受试者肾脏损伤的众所周知原因。我们最近的发现表明，在注射碘化造影剂后，肾脏氧合变化几乎是实时发生的，这些变化是肾脏损伤的迹象，在造影剂注射后4小时，一个新的损伤标志物证实了这一点。这是已知的最早的AKI风险标记物。在这项拟议的研究中，我们将验证肾脏髓质氧合的替代标记物，该标记物将允许将研究结果转化为人类。这是基于测量尿液中的PO2。我们还将扩展我们的最新发现，以优化预防性干预的剂量，并建立指示发生AKI风险的缺氧指数阈值，将这些发现推广到其他易受碘造影剂诱导的AKI的动物模型。在冠状动脉造影术或计算机断层扫描等使用碘造影剂的程序或接受心脏手术的患者之后，识别谁患AKI的风险更高，对于改善结果、降低成本和死亡率都具有巨大的意义。

 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.