Kari, Jameela Abdulaziz; (1999) Factors predisposing to arterial disease in children with chronic renal failure. Doctoral thesis (M.D), University of London, Institute of Child Health.

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Abstract

Premature atherosclerotic disease is a major cause of morbidity and mortality in chronic renal failure (CRF). Hypertension, hyperlipidaemia, abnormalities of nitric oxide (NO) biochemistry, drugs and the uraemic milieu are possible causes. Endothelial dysfunction is a key early event in atherogenesis. In this thesis, a non-invasive technique of high- resolution ultrasound has been used to assess the physiology of endothelial function in the brachial artery of children with stable CRF but without other risk factors of atherosclerosis. Lipid subfractions and nitric oxide (NO) biochemistry were also studied in the children. NO metabolites and endogenous NO synthetase (eNOS) inhibitors were measured as an assessment of endothelial NO metabolism. Brachial artery dilatation to flow (FMD) was reduced in CRF children when compared to matched controls for age and vessel diameter. In contrast, response to glyceryltrinitrate (GTN) was similar in both groups. Antibodies against oxidised LDL (ox-LDL) were high in CRF. Endogenous NOS inhibitors were high in CRF, and intermediate NO metabolites were low. This study shows that endothelium dependent dilatation of the brachial artery is impaired in children with CRF who do not have co-existing risk factors for atherosclerosis. This may represent early evidence of atherogenic vascular disease. In the second half of the thesis, the effect of enteral feeds on lipid levels in children with CRF were studied. This is important because the anorexia of CRF is frequently managed with high carbhydrate and high fat enternal feeds, which might predispose to atherogenic blood lipid profiles. Plasma lipid sub-fractions were, therefore, measured in children with CRF whose diet was either managed conservatively or by enteral feeding. Overall, TGs were high, TC was at the upper limit of normal, and LDL, HDL, apoprotein A1 (apo A1), A2 (apo A2) and B (apo B), and lipoprotein (a) (Lp (a)) were within the normal range. There was an inverse correlation between TGs and GFR. There were no differences in the levels of TC, TGs, LDL, HDL, apo A1, apo A2 or Lp (a) between tube fed and non-tube fed children. We conclude that enteral feeding does not enhance hyperlipidaemia.

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