Abstract
Arterial wall stiffness is a recognized complication in children with chronic kidney disease (CKD). Vascular abnormalities in these patients are shown to predate cardiac abnormalities such as left ventricular hypertrophy and diastolic dysfunction. The etiology of vascular abnormalities in these patients currently is not clear. This study explored the relationship between various parameters of calcium–phosphorus metabolism including 25-hydroxy vitamin D and arterial wall stiffness in pediatric patients with CKD. This study investigated a cohort of 43 children with CKD who had no history of underlying congenital or structural cardiac disease. The Augmentation Index (AI), a measure of peripheral arterial reflective properties using radial artery tonometry, was used as an indirect measure of central aortic stiffness. Serum biochemical markers of calcium–phosphorus metabolism were simultaneously measured. Univariate testing showed that AI correlated with worsening kidney function. Serum 25-hydroxy vitamin D levels were low and correlated negatively with AI (r = −0.39; p < 0.05). Multiple regression analysis showed that 25-hydroxy vitamin D was the only significant independent predictor of increased central arterial stiffness in the subgroup of children receiving hemodialysis. No association was observed between AI and any other measured biochemical parameter of calcium–phosphorus metabolism. This is the first study to investigate pediatric patients with CKD that suggests an association between nutritional vitamin D deficiency and increased arterial stiffness in children with CKD. The pathophysiologic mechanisms of vitamin D that regulate increased arterial stiffness need to be integrated further in pediatric CKD patients.
Similar content being viewed by others
References
Andrade J, Er L, Ignaszewski A, Levin A (2008) Exploration of association of 1,25-OH2D3 with Augmentation Index, a composite measure of arterial stiffness. J Am Soc Nephrol 3:1800–1806
Covic A et al (2006) Increased arterial stiffness in children on hemodialysis. Nephrol Dial Transplant 21:729–735
Goldstein SL, Currier H, Watters L, Hempe JM, Sheth RD, Silverstein D (2003) Acute and chronic inflammation in pediatric patients receiving hemodialysis. J Pediatr 143:653–657
Kerr PG, Guerin AP (2007) Arterial calcification and stiffness in chronic kidney disease. Clin Exp Pharmacol Physiol 34:683–687
Mardare NG, Goldsmith DJ, Gusbeth-Tatomir P, Covic A (2005) Intradialytic changes in reflective properties of the arterial system during a single hemodialysis session. Hemodial Int 9:376–382
Mascitelli L, Goldstein MR, Pezzetta F (2010) Vitamin D deficiency and cardiovascular diseases. Recenti Prog Med 101:202–211
Mitsnefes MM, Kimball TR, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2003) Left ventricular mass and systolic performance in pediatric patients with chronic renal failure. Circulation 107:864–868
Mitsnefes MM, Kimball TR, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2004) Abnormal carotid artery structure and function in children and adolescents with successful renal transplantation. Circulation 110:97–101
Mitsnefes MM, Kimball TR, Border WL, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2004) Impaired left ventricular diastolic function in children with chronic renal failure. Kidney Int 65:1461–1466
Mitsnefes MM, Kimball TR, Kartal J, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2005) Cardiac and vascular adaptation in pediatric patients with chronic kidney disease: role of calcium–phosphorus metabolism. J Am Soc Nephrol 16:2796–2803
Moe SM, O’Neill KD, Duan D, Ahmed S, Chen NX, Leapman SB, Fineberg N, Kopecky K (2002) Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. Kidney Int 61:638–647
Moe SM, Duan D, Doehle BP, O Neill KD, Chen NX (2003) Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels. Kidney Int 63:1003–1011
Nakae I, Matsuo S, Matsumoto T, Mitsunami K, Horie M (2008) Augmentation Index and pulse-wave velocity as indicators of cardiovascular stiffness. Angiology 59:421–426
Nayir A, Bilge I, Kilicaslan I, Ander H, Emre S, Sirin A (2001) Arterial changes in paediatric haemodialysis patients undergoing renal transplantation. Nephrol Dial Transplant 16:2041–2047
O’Connell TD, Berry JE, Jarvis AK, Somerman MJ, Simpson RU (1997) 1,25-Dihydroxyvitamin D3 regulation of cardiac myocyte proliferation and hypertrophy. Am J Physiol 272(4 Pt 2):H1751–H1758
Oh J, Wunsch R, Turzer M, Bahner M, Raggi P, Querfeld U, Mehls O, Schaefer F (2002) Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation 106:100–105
Parekh RS, Carroll CE, Wolfe RA, Port FK (2002) Cardiovascular mortality in children and young adults with end-stage kidney disease. J Pediatrics 141:191–197
Raymond MA, Désormeaux A, Labelle A, Soulez M, Soulez G, Langelier Y, Pshezhetsky AV, Hébert MJ (2005) Endothelial stress induces the release of vitamin D-binding protein, a novel growth factor. Biochem Biophys Res Commun 338:1374–1382
Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263
Zehnder D, Bland R, Chana RS, Wheeler DC, Howie AJ, Williams MC, Stewart PM, Hewison M (2002) Synthesis of 1,25-dihydroxyvitamin D(3) by human endothelial cells is regulated by inflammatory cytokines: a novel autocrine determinant of vascular cell adhesion. J Am Soc Nephrol 13:621–629
Zhao G, Simpson RU (2010) Interaction between vitamin D receptor with caveolin-3 and regulation by 1,25-dihydroxyvitamin D3 in adult rat cardiomyocytes. J Steroid Chem Mol Biol 121:159–163
Zhou C, Lu F, Cao K, Xu D, Goltzman D, Miao D (2008) Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1-alpha-hydroxylase knockout mice. Kidney Int 74:170–179
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Patange, A.R., Valentini, R.P., Du, W. et al. Vitamin D Deficiency and Arterial Wall Stiffness in Children With Chronic Kidney Disease. Pediatr Cardiol 33, 122–128 (2012). https://doi.org/10.1007/s00246-011-0101-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00246-011-0101-y