PHYSIOLOGY AND BIOCHEMISTRY OF ENDOTHELIAL FUNCTION IN CHILDREN WITH CHRONIC-RENAL-FAILURE

Premature atherosclerosis is a major cause of morbidity and mortality in chronic renal failure (CRF). Endothelial dysfunction is a key early event in atherogenesis. The aim of this study was to assess the effec t of CRF on endothelial function using physiological and biochemical m easures. To focus on the effect of CRF itself. 23 children (matched wi th 23 controls for age and vessel diameter) were selected because they were normotensive had normal total cholesterol (TC) levels and were n ot on vasoactive drugs. Their mean (range) age was 12.0 (7.8 to 17.0) years GFR 17.5 (8.8 to 34.5) ml/min/1.73 m(2). The physiology of endot helial function in the brachial artery was assessed using high resolut ion ultrasound by measuring its diameter at rest, during reactive hype remia (endothelium dependent dilaton) and after sublingual glyceryl tr initrate (GTN; endothelium independent dilation). Nitric oxide (NO) me tabolites and endogenous NO synthetase (cNOS) inhibitors were measured as an assessment of endothelial metabolism. Brachial artery dilation to flow [FMD mean (SEM)%] was reduced in CRF to 4.9 (0.6) and controls 8.6 (0.6), P < 0.0001. In contrast, the response to GTN was similar i n both groups CRF 25.1 (1.6), controls 23.3 (1.2), P = 0.31. There was no difference in TC low density lipoprotein (LDL) or high density lip oprotein (HDL) between the patients and the controls. Triglycerides (T G) were higher in the patients but within the normal range. Antibodies against oxidized LDL (ox-LDL) were high in CRF. Endogenous NOS inhibi tors were high in CRF, and intermediate NO metabolites were low. There was no correlation between FMD of the brachial artery and lipid subfr actions, or with NO metabolites of eNOS inhibitors. Endothelium depend ent dilation of the brachial artery is impaired in children with CRF w ho do not have co-existing risk factors for atherosclerosis. This may represent early evidence of atherogenic vascular disease.