Intrarenal Oxygenation: An Early Marker for Risk of Developing AKI

肾内氧合：发生 AKI 风险的早期标志

• 批准号: 9263691
• 负责人: POTTUMARTHI V PRASAD
• 金额: $ 23.4万
• 依托单位: NORTHSHORE UNIVERSITY HEALTHSYSTEM
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-15 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9263691
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Angiography; Animal Model; Biochemical Markers; Biological Markers; Bladder; Blood flow; Cardiac Surgery procedures; Cardiopulmonary Bypass; Cells; Clinic; Clinical; Clinical Markers; Contrast Media; Coronary; Coupled; Creatinine; Data; Development; Diabetes Mellitus; Disease; Dose; Environment; Epithelial Cells; Fiber Optics; Furosemide; Health care facility; Heart failure; Hospitals; Hour; Human; Hypoxia; Indomethacin; Injury; Ischemia; Kidney; LCN2 gene; Laboratories; Length of Stay; Magnetic Resonance Imaging; Measurement; Measures; Microcirculation; Mimosine; Modeling; Monitor; Morbidity - disease rate; NG-Nitroarginine Methyl Ester; Nitric Oxide; Osmolar Concentration; Outcome; Outcome Measure; Patients; Physiological; Physiology; Plasma; Postoperative Period; Predictive Value of Tests; Prevention; Preventive; Preventive Intervention; Preventive measure; Procedures; Prostaglandin Antagonists; Rattus; Renal pelvis; Risk; Risk Factors; Risk Marker; Serum; Surrogate Markers; Testing; Therapeutic Intervention; Time; Tissue Inhibitor of Metalloproteinases; Translating; Translations; Urine; Validation; X-Ray Computed Tomography; age effect; base; blood oxygen level dependent; cell injury; cost; diabetic rat; efficacy testing; endothelial dysfunction; falls; glomerular filtration; high risk; imaging modality; improved; improved outcome; indexing; insulin-like growth factor binding protein-related protein 1; interest; mortality; novel; novel marker; prevent; public health relevance; rat KIM-1 protein; response; tissue oxygenation; urinary

 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.

 描述（由申请方提供）：急性肾损伤（阿基）是代偿机制受损（如内皮功能）患者的常见医院获得性疾病。阿基的后果包括住院时间延长和死亡风险增加。虽然预防是可行的，但它仍然难以捉摸，主要是因为缺乏合适的标志物来指示谁有发生阿基的风险。目前的临床标志物反应缓慢（超过48小时），错过了干预的机会窗口。可以指示肾损伤的新标记物正在变得可用，并且具有更快的响应（损伤后4至8小时）。据信，生理标志物如血流和氧合可能对甚至更早的变化敏感。长期以来，我们主要使用非侵入性磁共振成像（MRI）来评估肾氧合及其对不同疾病机制的影响。对于阿基，我们已经证明了一种动物模型，该模型可用于研究碘化造影剂的作用，碘化造影剂是高危受试者肾损伤的众所周知的原因。我们最近的研究结果表明，肾氧合变化几乎发生在碘化造影剂给药的真实的时间，这些变化表明肾损伤，如造影剂给药后4小时的一种新损伤标志物所记录。这是已知的最早的阿基风险标志物。在拟议的研究中，我们将验证肾髓质氧合的替代标志物，这将允许将研究结果转化为人类。这是基于测量尿液pO2。我们还将扩展我们迄今为止的研究结果，以优化预防性干预措施的剂量，并建立指示发生阿基风险的缺氧指数阈值，以将研究结果推广到易受碘化造影剂诱导的阿基影响的其他动物模型。在使用碘化造影剂的冠状动脉血管造影或计算机断层扫描等手术后或接受心脏手术的患者中，识别谁患阿基的风险较高的能力对于改善结果、降低成本和死亡率都具有巨大意义。