MR Angiography and Renography for Renovascular Disease

描述(由申请人提供)：在美国，肾血管疾病(RVD)是导致高血压和肾功能衰竭的最常见的潜在可逆原因。它的诊断是有问题的，因为仅有肾动脉狭窄(RAS)不足以诊断。高血压和RAS通常并存，因此，解剖研究，如X-射线血管造影术，不能准确预测血管重建术的反应。到目前为止，还没有一项测试能同时提供准确的解剖和功能评估来诊断RVD。RAS患者的管理也是一个两难选择。无法区分RVD和偶发RAS也是治疗方法普遍不确定的原因，缺乏检测个体肾脏反应的灵敏测试进一步限制了临床试验。在第一个资助期，我们建立了一种可靠和定量的低剂量Gd增强磁共振肾成像方法来测量单肾小球滤过率(GFR)，并实施了双注射血管紧张素转换酶抑制剂增强磁共振肾成像方法来诊断RVD。我们的功能研究可以结合肾脏MRA进行解剖学评估，早期结果令人振奋。我们还展示了将速尿增强的BOLD MR与ACE-I MR肾造影术相结合用于测量RAS患者肾脏缺血的可行性，并研究了非Gd增强MRA的新方法。在下一个资金阶段，我们建议测试一种全面的解剖和功能MR方案来诊断RVD，并纵向使用MR来测量单个肾脏的功能结果。广泛的长期目标：通过正确诊断疾病和确定哪些患者可能受益于血管重建治疗以及哪些患者应该单独使用药物治疗，来降低与RVD引起的高血压和肾功能衰竭相关的发病率和死亡率。具体目的/方法：(1)确定MRA、血管紧张素转换酶抑制剂MR肾成像和速尿-BOLD MRI联合应用诊断RVD的准确性。我们将在3年内对264名受试者进行前瞻性研究，并将我们的MR结果与MRA和X光血管造影术进行比较，以血压和肾功能对血管重建测量的反应作为参考标准。(2)应用MR肾成像和速尿-BOLD MRI进行纵向研究，研究接受血管重建术或内科治疗的RAS患者的自发性和对侧单肾GFR。我们将使用单肾GFR和氧合的测量来评估治疗的反应，假设我们的方法将检测到血管重建后肾功能的其他亚临床改善，以及医学管理的RVD患者的亚临床下降。在其结论中，我们的研究极有可能表明，通过在一次测试中独特地同时提供解剖和功能信息，全面的MR检查将准确地诊断RVD，并为评估治疗后的结果提供一个有价值的工具。 公共卫生相关性：拟议的项目将有助于提高对一种常见疾病--肾血管疾病--的诊断准确性，这种疾病会导致高血压和肾衰竭。利用新的MRI方法，我们可以检测肾动脉狭窄并评估其对肾脏功能的影响，以便预测谁应该接受介入治疗来开放动脉，谁应该只接受药物治疗。我们的解剖和功能磁共振技术也有可能为糖尿病和肾移植功能障碍等其他肾脏疾病的诊断和治疗提供新的见解。

DESCRIPTION (provided by applicant): Renovascular disease (RVD) is the most common potentially reversible cause of hypertension and renal failure in the US. Its diagnosis is problematic because renal artery stenosis (RAS) alone is insufficient for diagnosis. Essential hypertension and RAS often coexist, hence anatomic studies such as x-ray angiography do not accurately predict response to revascularization. To date, no test provides both accurate anatomic and functional assessment to diagnose RVD. Management of RAS patients is also a dilemma. The inability to differentiate RVD from incidental RAS has also contributed to the widespread uncertainty treatment, and lack of a sensitive test for detecting individual kidney response has further limited clinical trials. In the first funding period we developed a robust and quantitative low dose Gd-enhanced MR renography method for measuring single kidney glomerular filtration rate (GFR) and implemented a dual-injection method for ACE-inhibitor- enhanced MR renography to diagnose RVD. Our functional study can be performed in conjunction with renal MRA for anatomic evaluation with promising early results. We have also shown the feasibility of combining furosemide-enhanced BOLD MR with ACE-I MR renography for measuring renal ischemia in patients with RAS and have also investigated new non-Gd-enhanced MRA methods. In the next funding period, we propose to test a comprehensive-anatomic and functional-MR protocol to diagnose RVD and also to use MR longitudinally to measure single kidney functional outcomes. Broad, long-term objectives: To reduce the morbidity and mortality associated with hypertension and renal failure due to RVD by correctly diagnosing the disease and by determining which patients are likely to benefit from revascularization therapy and which patients should be treated with medication alone. Specific Aims/Methods: (1) To determine the accuracy of a single comprehensive exam that combines MRA with ACE-inhibitor MR renography and furosemide-BOLD MRI for the diagnosis of RVD. We will perform a prospective study in 264 subjects over 3 years and compare our MR results with MRA and x-ray angiography, using response to revascularization measures of blood pressure and renal function as the reference standard. (2) To perform a longitudinal study using MR renography and furosemide-BOLD MRI to study ipsi- and contralateral single kidney GFR in RAS patients who undergo revascularization or who are medically managed. We will use measurements of single kidney GFR and oxygenation to assess responses to therapies with the hypothesis that our methods will detect otherwise subclinical improvements in renal function after revascularization and otherwise subclinical declines in patients with RVD managed medically. At its conclusion, our study highly likely to show that a comprehensive MR exam, by uniquely providing both anatomic and functional information in a single test, will accurately diagnose RVD and provide a valuable tool for measuring outcomes following therapy. PUBLIC HEALTH RELEVANCE: The proposed project will be important for helping to improve the accuracy of diagnosis of a common disease, renovascular disease, which causes hypertension and kidney failure. With novel MRI methods, we can detect narrowings of the renal arteries and assess their impact on the functioning of kidneys in order to predict who should undergo an interventional treatment to open the arteries and who should be treated with medications only. Our anatomic and functional MRI techniques also have the potential to offer new insights into the diagnosis and treatment of other kidney diseases such as diabetes and kidney transplant dysfunction.