René van der Bel

| Appendices | 132 mon in cardio-metabolic disease and BRS has been shown to be a clinically relevant and independent prognostic factor in cardiovascular disease, hypertension, metabolic syndrome and obesity, amongst others. This wide range in applicability of BRS indicates a potential as an integrative risk factor for cardiovascular disease, that may be especially relevant to kidney disease patients. In Chapter 2 we therefore investigated the BRS in a large population study to evaluate and explore its associations between with cardiovascular risk factors and cardio-metabolic im- pairment. We found no particular increase in sympatho-vagal impairment with renal function decline compared to other cardio-metabolic risk factors among almost 6,000 participants of the HELIUS study. Whether sympathetic dysregulation in patients is cause or consequence of cardio-metabolic disease cannot yet be determined based on the studies so far, upcoming prospective data will provide the opportunity to make the distinction. The effect of hyperoxia on blood pressure in CKD patients All visceral organs contain peripheral chemoreceptors, which communicate their signal to the autonomic nervous system upon activation, whereby they can directly influence cardiac and respiratory function. Among these receptors there are those sensitive to hypoxia that induce sympathetic activity, once activated. Various groups have found altered renal chemo- receptor activation in CKD. The main proof of concept was provided by a study by Hering et al. who exposed CKD patients to 100% oxygen over a non-rebreathing mask for 15 minutes. This resulted in a 30% reduction in sympathetic nerve activity accompanied by a lower pulse pressure. This suggested an altered renal chemoreflex response in CKD patients during oxygen supple- mentation, attenuating sympathetic activity and blood pressure during systemic hyperoxia. However, these studies did not show the mechanism by which oxygen supplementation re- duced sympathetic nerve activity in CKD patients. Therefore we repeated these experiments in Chapter 3 , while including steps to measure the dose effect of the oxygen supplementa- tion and include measurements of systemic vascular resistance and baroreflex function. We were unable to repeat the results of these experiments in a group of 19 CKD patients. In our hands, oxygen supplementation caused a dose-dependent blood pressure increase in these patients. This was caused by an increase in systemic vascular resistance, likely as the result of hyperoxic vasoconstriction independent of baroreflex function in patients with in- sufficient nitric oxide reactivity. Although, oxygen supplementation may alleviate peripheral sympathetic activity, it presents a major cardiovascular stressor to CKD patients. The central hemodynamic effects overshadow any beneficial renal effect, if at all present.