Sympathetic nervous system overactivity in patients with chronic kidney disease : studies on the pathophysiology, clinical relevance and treatment

Abstract

The evidence summarized in Chapter 1, served as the rationale for the studies presented in this thesis. The questions addressed in this thesis are: - In chapter 3, we addressed the idea that sympathetic activity in CKD patients is related to cardiovascular organ damage. We hypothesized that patients with chronic kidney disease have agreater left ventricular mass than healthy volunteers independent of blood pressure and that MSNAis positively correlated to left ventricular mass; - In chapter 4, we studied the effect of the renin inhibitor aliskiren on MSNA. We hypothesized that aliskiren effectively lowers sympathetic activity in CKD patients. In addition, in this chapter we will look at the effect of 100% oxygen administration on sympathetic activity without and during chronic treatment with aliskiren; - The underlying mechanisms of antihypertensive effects of RAS inhibitors are difficult to study in humans. In chapter 5, we evaluate the changes in the blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) signal intensity induced by acute and chronic RAS inhibitors in CKD patients. We will compare these effects with BOLD signals in healthy volunteers after acute treatment with a RAS inhibitor. We hypothesized that a RAS inhibitor has an effect on the BOLD signal in CKD patients, whereas it has no effect in healthy controls; - There are some experimental studies that suggest that statins have a sympatholytic effect. However, this effect of statins is rarely studied in patients, and not yet in CKD patients. This is important because these agents are commonly prescribed in CKD patients. In chapter 6, the sympatholytic effect of statins will be tested in CKD patients, when added to RAS inhibitor; - In chapter 7, we briefly touch up on a novel application of an old concept: renal denervation as a new tool for treatment of hypertension; - Finally, I put the results presented in this thesis in perspective and speculate on the future