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

描述(申请人提供)：慢性肾脏疾病(CKD)会导致肾脏功能的进行性丧失，从而对患者造成破坏性后果。虽然氧合状态改变在慢性肾脏病中的作用已经被假设，但没有证据表明与人类疾病有关。这是由于缺乏非侵入性方法来评估人类体内的肾脏氧合作用。此外，晚期CKD通常与贫血有关，据信与促红细胞生成素(EPO)产生减少或缺乏增加有关。这反过来被认为是由于肾脏皮质氧气水平的增加。血液氧合水平依赖(BOLD)磁共振技术应用于肾内氧合已被证明是评估肾脏氧合的灵敏方法，在大鼠和人类肾脏中都是如此。目前还没有其他已知的技术可以用于监测人类肾脏的肾脏氧合状态。基于这一背景，这项建议扩展了目前在动物和人类健康和高血压肾脏中的发现，使用BOLD MRI来评估CKD患者的肾内氧合。这项技术将首次扩展到疾病发展的不同阶段的人类受试者。这一建议的成功结果将首次使人们能够认识到，与健康对照组相比，慢性肾脏病患者在疾病进展的不同阶段的肾脏氧合状态。它还将支持使用大胆的MRI测量作为一种有用的非侵入性工具来评估CKD患者。这可能会激发对专门针对低氧的新干预措施的评估，因此应该对慢性肾脏病的临床治疗产生重大影响。与公共健康相关：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疗法。人们认为肾脏内的氧气供应可能是疾病进展的一个重要决定因素。这项研究将利用一种非侵入性的方法来研究人类肾脏在疾病进展的不同阶段的氧气供应情况。这将使人们能够更好地了解疾病过程，进而制定预防措施。

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.