Exercise as an adjunct therapy to reduce blood pressure in Chronic Kidney Disease

描述（由申请人提供）：慢性肾脏疾病（CKD）影响超过2600万人（占美国人口的13%），预计到2015年将增加70%，超过4000万人。血压控制不当是CKD进展的主要因素。运动是降低CKD患者血压的潜在辅助疗法。然而，目前还没有专门设计的大型随机对照试验来调查运动训练对静息和24小时血压水平的影响，小型非随机研究的结果也好坏参半。PI （Bronas博士）目前对2-4期糖尿病CKD有氧运动的心脏保护作用的研究（K23）表明，运动诱导的平均静息血压水平降低了11.8 mm Hg收缩压和5.6 mm Hg舒张压（初步数据，n=31）。然而，非糖尿病性CKD患者是否会有类似的获益尚不清楚。拟议的研究将扩大PI当前研究项目的范围，并允许我们进行第一个专门设计的随机对照试验，研究定期有氧运动对3-4期CKD和高血压患者静息和24小时血压水平的影响。通过扩大当前研究的范围，我们将能够比较运动对两种主要CKD人群的降血压效果，这两种人群可能从运动疗法中获益最多。因此，提出的试点研究的目的是验证定期有氧运动可以降低3-4期非糖尿病性CKD合并高血压患者的静息和24小时动态血压水平的假设。我们将通过随机选择40例3-4期非糖尿病性CKD合并高血压患者进行12周的有氧运动训练（n=20）或常规医疗护理（n=20）来实现这一目标。此外，我们将确定12周运动训练对有效血管顺应性和与血压调节相关的生物标志物的影响，以及它们与运动引起的血压水平变化的关系。本研究将对运动疗法对ckd -高血压患者血压调节相关因素的影响产生新的假设，并为新的辅助治疗方案提供见解。这项工作的预期结果是进一步了解定期运动对CKD患者血压控制的益处，并为非糖尿病性CKD或糖尿病性CKD患者对运动的相对生理反应提供见解。此外，这项研究将直接提高Bronas博士的研究能力，因为他正在完成向完全独立研究者身份的过渡，并允许他迅速进入独立的R01资助。

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) affects more than 26 million individuals (13% of the U.S. population), and is projected to increase 70%, to over 40 million individuals by the year 2015. Inadequate blood pressure control is a major factor in the progression of CKD. Exercise is a potential adjunct therapy to reduce blood pressure in CKD patients. However, no large randomized, controlled trials specifically designed to investigate resting and 24-hr blood pressure levels in response to exercise training have been completed, and results of small, non- randomized studies have been mixed. The PI's (Dr. Bronas) current investigation (K23) on the cardioprotective effects of aerobic exercise in stage 2-4 diabetic CKD indicates significant exercise-induced reductions in mean resting blood pressure levels of 11.8 mm Hg systolic and 5.6 mm Hg diastolic (preliminary data, n=31). However, it is unknown if patients with non-diabetic CKD will experience a similar benefit. The proposed study will expand the scope of the PI's current research program and allow us to conduct the first randomized, controlled trial specifically designed to investigate the effect of regular aerobic exercise on resting and 24-hr blood pressure levels in patients with stage 3-4 CKD and hypertension. By expanding the scope of the current research we will be able to compare the blood-pressure reducing effect of exercise in the two major CKD populations that may benefit the most from exercise therapy. The objective of the proposed pilot study is therefore to test the hypothesis that regular aerobic exercise will lower resting and 24-hour ambulatory blood pressure levels in stage 3-4 non-diabetic CKD patients with hypertension. We will achieve this objective by randomizing 40 patients with stage 3-4 non-diabetic CKD with hypertension to either 12 weeks of aerobic exercise training (n=20) or usual medical care (n=20). In addition, we will determine the effect of 12 weeks of exercise training on effective vascular compliance and biomarkers associated with blood pressure regulation, and their association with exercise-induced changes in blood pressure levels. This study will generate new hypotheses regarding the impact of exercise therapy on factors associated with blood pressure regulation in patients with CKD-hypertension and provide insight into new and adjunctive treatment options. The expected outcomes of the work proposed is to further our understanding of the benefit of regular exercise on blood pressure control in patients with CKD and provide insight into the relative physiological responses to exercise in patients with non-diabetic CKD or diabetic CKD. Moreover, this study will directly enhance Dr. Bronas research capability as he is completing his transition to fully independent investigator status and allow him to quickly move into independent R01 funding.