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.
This study will be the first randomized, controlled trial that is 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. This study will, if successful, offer valuable insight into the efficacy of exercise training, which is not a routine prt of clinical practice, as an adjunctive therapeutic option for patients with CKD and hypertension. 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.
