Relation of pre-clinical arterial disease to blood pressure in children with chronic kidney disease

    Student thesis: Doctoral ThesisDoctor of Philosophy


    Childhood chronic kidney disease (CKD) is a devastating illness requiring life-long medical input, often progressing to end stage kidney disease (ESKD) requiring dialysis and renal transplantation. Despite an increasing number of children now surviving through childhood and early adulthood, heart disease remains one of the major causes of death in individuals with childhood-onset CKD as young adults and it is likely this relates to onset of pre-clinical cardiovascular disease developing during childhood.
    Arterial stiffening relates to the severity of CKD, being greatest in those with dialysis dependent CKD, and is thought to be driven, at least in part, by excess body weight, hypertension and metabolic changes associated with CKD but their contribution to arterial disease progression remains poorly understood.
    The relationship of blood pressure with arterial disease remains unclear in the paediatric literature. Previous studies performed in children pre-dialysis, those on dialysis and following kidney transplantation have measured pulse wave velocity (PWV) of the carotid-femoral pathway (i.e. mainly the aorta) and/or measures of carotid mechanics have been examined but these studies have been limited by lack of concurrent measures of carotid blood pressure (required to determine functional elasticity of the carotid artery). Furthermore, whilst the potential impact of age and blood pressure (BP) have been adjusted for, when comparing differences between children with and without CKD, this comparison has not been performed between age and blood pressure matched groups.
    The objectives of my thesis are to 1) to determine the use of an easy to perform, well tolerated technique to measure PWV in children. 2) to compare estimates of central aortic systolic pressure with that measured directly from catheter placed in the aortic root. 3) to determine typical estimates of systolic blood pressure amplification and 4) to determine the association of arterial function and structure with severity of childhood CKD and to examine the relation of these measures to blood pressure. 5) to design a controlled trial to evaluate effects of aggressive versus standard blood pressure control on cardiovascular target organ damage.
    My research findings report novel data relating to my project objectives. We compared two different techniques to measure PWV (volumetric and tonometric) and observed that the volumetric technique is easy to perform, well tolerated and reproducible when measurements are made by the same observer consecutively, but that the results are of the two techniques are not inter-changeable. My work for objective 2 and 3 measured central blood pressure at the aortic root at the time of arterial cannulation and confirmed that blood pressure measured in the arm differs from that close to the heart. We validated simple non-invasive methods to measure blood pressure in children and showed that peripheral systolic amplification is substantial, including those with and without hypertension and mild to advanced CKD, with a mean amplification of ~ 20 mmHg and thus may be relatively more important than in adults. In a cohort of children with and without CKD, we performed a comprehensive characterization of arterial biomechanics and observed that the changes in elastic properties of the carotid artery were related to increased blood pressure, and not to decreased glomerular filtration rate. Important limitations to this cross-sectional study include lack of knowledge of duration of both hypertension and CKD and lack of formal sample size calculation. Despite these limitations the results from my thesis suggest that blood pressure reduction may be an effective means to protect against arterial stiffening and needs to be evaluated using a controlled clinical trial. The design of such a trial is presented.
    Date of Award2016
    Original languageEnglish
    Awarding Institution
    • King's College London

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