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Physiology and biochemistry of endothelial function in children with chronic renal failure
J A Kari1, A E Donald, D T Vallance
1Nephrourology Unit, Great Ormond St NHS Trust, England, United Kingdom.
Insights
Children with chronic renal failure (CRF) show impaired endothelial function, a key early sign of atherosclerosis. This study reveals early vascular disease in pediatric CRF patients without other risk factors.
Area of Science:
- Cardiovascular Research
- Pediatric Nephrology
- Vascular Biology
Background:
- Premature atherosclerosis is a significant cause of mortality in chronic renal failure (CRF).
- Endothelial dysfunction is a critical early event in the development of atherosclerosis.
- Assessing endothelial function in children with CRF is crucial for understanding early atherogenesis.
Purpose of the Study:
- To evaluate the impact of CRF on endothelial function in children.
- To differentiate the effects of CRF from other common atherosclerosis risk factors.
- To utilize physiological and biochemical markers to assess endothelial health.
Main Methods:
- Recruited 23 children with CRF and 23 matched controls, ensuring normotension and normal lipid profiles.
- Assessed brachial artery endothelial function using high-resolution ultrasound to measure flow-mediated dilation (FMD) and glyceryl trinitrate (GTN)-induced dilation.
- Measured nitric oxide (NO) metabolites and endogenous NO synthase (eNOS) inhibitors to assess endothelial metabolism.
Main Results:
- Children with CRF exhibited significantly reduced FMD (4.9%) compared to controls (8.6%), indicating impaired endothelium-dependent dilation.
- The response to GTN was similar between groups, suggesting preserved endothelium-independent vasodilation.
- Elevated antibodies against oxidized LDL (ox-LDL) and increased endogenous NOS inhibitors were observed in CRF patients, alongside lower NO metabolites.
Conclusions:
- Endothelium-dependent brachial artery dilation is impaired in children with CRF, even in the absence of traditional atherosclerosis risk factors.
- These findings suggest early atherogenic vascular disease in pediatric CRF patients.
- CRF itself appears to directly contribute to endothelial dysfunction and the initiation of vascular disease.
Abstract:
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 effect of CRF on endothelial function using physiological and biochemical measures. To focus on the effect of CRF itself, 23 children (matched with 23 controls for age and vessel diameter) were selected because they were normotensive, had normal total cholesterol (TC) levels, and were not 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 m2. The physiology of endothelial function in the brachial artery was assessed using high resolution ultrasound by measuring its diameter at rest, during reactive hyperemia (endothelium dependent dilation) and after sublingual glyceryl trinitrate (GTN; endothelium independent dilation). Nitric oxide (NO) metabolites and endogenous NO synthetase (eNOS) 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 in 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 lipoprotein (HDL) between the patients and the controls. Triglycerides (TG) were higher in the patients but within the normal range. Antibodies against oxidized LDL (ox-LDL) were high in CRF. Endogenous NOS inhibitors were high in CRF, and intermediate NO metabolites were low. There was no correlation between FMD of the brachial artery and lipid subfractions, or with NO metabolites or eNOS inhibitors. Endothelium dependent dilation 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.