The Intra-renal Oxygenation in CKD as evaluated by BOLD MRI

描述（由申请人提供）：慢性肾脏疾病（CKD）导致肾功能进行性丧失，对患者造成破坏性后果。虽然已经假设了CKD中氧合状态改变的作用，但没有与人类疾病相关的证据。这是由于缺乏非侵入性方法来评估人体内肾脏氧合。此外，晚期CKD通常与贫血有关，它被认为与促红细胞生成素（EPO）产生减少或缺乏增加有关。这反过来被认为是由于肾皮质氧水平的提高。血氧水平依赖（BOLD） MRI技术应用于肾内氧合已被证明是敏感的评估肾氧合在大鼠和人的肾脏。目前还没有其他已知的技术可以用来监测人体肾脏的氧合状态。基于这一背景，本提案扩展了目前在动物和人类健康和高血压肾脏中使用BOLD MRI评估CKD患者肾内氧合的研究结果。这项技术将首次扩展到处于疾病发展不同阶段的人类受试者。这一建议的成功结果将使我们第一次认识到与健康对照相比，CKD患者在疾病进展的各个阶段的肾氧合状态。这也将支持使用BOLD MRI测量作为一种有用的非侵入性工具来评估CKD患者。这些可能会激发对专门针对缺氧的新干预措施的评估，因此应该在CKD的临床管理中产生重大影响。公共卫生相关性：美国有超过700万人患有慢性肾脏疾病，约50万人将等待肾脏替代治疗。据信，肾脏内的氧气可用性可能是疾病进展的重要决定因素。本研究将采用非侵入性方法来研究疾病进展不同阶段人体肾脏内的氧气可用性。这将有助于更好地了解疾病过程，进而有助于制定预防措施。

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) leads to progressive loss of kidney function resulting in damaging consequences to the patient. While a role for altered oxygenation status in CKD has been postulated, there is no evidence relevant to human disease. This is due to the lack of non-invasive methods to assess renal oxygenation in vivo in humans. Also, advanced CKD is commonly associated with anemia and it is believed to be related to reduced or lack of increase in erythropoietin (EPO) production. This in turn is believed to be due to enhanced renal cortical oxygen levels. Blood oxygenation level dependent (BOLD) MRI technique as applied to intra-renal oxygenation has been shown to be sensitive in evaluating renal oxygenation both in rat and human kidneys. Currently there is no other known technique that can be used to monitor renal oxygenation status in human kidneys. Based on this background, this proposal extends the present findings in healthy and hypertensive kidneys in both animals and humans using BOLD MRI to evaluate intra-renal oxygenation in CKD patients. For the first time the technique will be extended to human subjects at different stages of disease progression. A successful outcome of this proposal would allow for the first time to appreciate that the renal oxygenation status in patients with CKD at various stages of disease progression compared to healthy controls. It would also support the use of BOLD MRI measurements as a useful non-invasive tool in the evaluation of patients with CKD. These may motivate evaluation of novel interventions specifically targeting hypoxia and hence should have significant consequences in the clinical management of CKD. PUBLIC HEALTH RELEVANCE: Over 7 million people in the US suffer from chronic kidney disease and about half a million will await kidney replacement therapy. It is believed that the oxygen availability within the kidney may be an important determinant of the progression of disease. This study will utilize a non-invasive method to study the oxygen availability within the human kidneys at various stages of disease progression. This would allow for better understanding of the disease process and in turn allow for developing preventive measures.