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Published ahead of print on March 12, 2008
Journal of the American Society of Nephrology
© 2008 American Society of Nephrology
doi: 10.1681/ASN.2007090993
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Received September 10, 2007
Accepted on January 3, 2008

CLINICAL RESEARCH

A Bimodal Association of Vitamin D Levels and Vascular Disease in Children on Dialysis

Rukshana Shroff *{dagger}1, Martyn Egerton {ddagger}, Michala Bridel {ddagger}, Vanita Shah *, Ann E. Donald {dagger}, Tim J. Cole {sect}, Melanie P. Hiorns ||, John E. Deanfield {dagger}, and Lesley Rees *

Departments of *Nephrourology and ||Radiology, Great Ormond Street Hospital for Children, London and {dagger}Vascular Physiology Unit and {sect}Centre for Paediatric Epidemiology and Biostatistics, University College London Institute of Child Health, London, and {ddagger}Department of Chemical Pathology, West Park Hospital, Epsom, United Kingdom


1 To whom correspondence should be addressed. E-mail: shrofr{at}gosh.nhs.uk.


   Abstract

In addition to its classical role in calcium-phosphate homeostasis, vitamin D has anti-inflammatory effects that may influence vascular disease. This study examined the impact of vitamin D levels on the vascular phenotype in 61 children who had been on dialysis for ≥3 mo and in 40 age-matched control subjects. All dialysis patients were prescribed daily oral 1-{alpha} hydroxyvitamin D3. 92% of patients were deficient in 25-hydroxyvitamin D [25(OH)D]. 1,25-dihydroxyvitamin D [1,25(OH)2D] levels were low in 36% and high in 11% of patients. There was a weak correlation between 1{alpha}-hydroxyvitamin D3 dosage and 1,25(OH)2D levels. Both carotid intima-media thickness and calcification scores showed a U-shaped distribution across 1,25(OH)2D levels: patients with both low and high 1,25(OH)2D had significantly greater carotid intima-media thickness (P < 0.0001) and calcification (P = 0.0002) than those with normal levels. Low 1,25(OH)2D levels were associated with higher high-sensitivity C-reactive protein (P < 0.0001). Calcification was most frequently observed in patients with the lowest 1,25(OH)2D and the highest high-sensitivity C-reactive protein. In contrast, 25(OH)D levels did not correlate with any vascular measure. In conclusion, both low and high 1,25(OH)2D levels are associated with adverse morphologic changes in large arteries, and this may be mediated through the effects of 1,25(OH)2D on calcium-phosphate homeostasis and inflammation. For optimization of strategies to protect the vasculature of dialysis patients, careful monitoring of 1,25(OH)2D levels may be required.




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