Skip to main content

Advertisement

SpringerLink
Log in

Vitamin D Deficiency Is Associated With Increased Left Ventricular Mass and Diastolic Dysfunction in Children With Chronic Kidney Disease

  • Original Article
  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

Abstract

Cardiovascular disease currently is the leading cause of morbidity and mortality among patients with chronic kidney disease (CKD). Abnormalities in arterial compliance, increased left ventricular mass, and diastolic dysfunction are some of the recognized cardiovascular complications observed in these patients. This study explored the relationship between various parameters of calcium-phosphorus metabolism including 25-hydroxy vitamin D and cardiovascular structure and function in pediatric patients with CKD. This cross-sectional study was conducted using a cohort of 34 children with CKD who had no history of underlying congenital or structural cardiac disease. Two-dimensional echocardiography was used to measure the left ventricular mass index (LVMI), E/A ratio, E′, E/E′ ratio, and myocardial performance index (MPI). The augmentation index (AI), derived via radial artery tonometry, was used as an indirect measure of central aortic stiffness. Serum biochemical markers of calcium-phosphorus metabolism were simultaneously measured. Univariate analysis showed that LVMI correlated with 25-hydroxy vitamin D (r = –0.54; p < 0.05), systolic blood pressure (SBP) (r = 0.36; p < 0.05), and AI (r = 0.26; p < 0.05). Serum-intact parathyroid hormone (PTH) levels correlated with the E/E′ ratio (r = 0.63; p < 0.05) and E′ (r = –0.61; p < 0.05). Multiple regression analysis showed that 25-hydroxy vitamin D and SBP were independent predictors of increased LVMI and that PTH was an independent predictor of diastolic dysfunction. This is the first study investigating pediatric patients with CKD that suggests an etiology of nutritional vitamin D deficiency associated with increased left ventricular mass and diastolic dysfunction. The cardiovascular changes observed are not easily reversible. Hence, early preventive therapy with vitamin D supplementation is advocated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Amann K, Ritz E, Wiest G, Klaus G, Mall G (1994) A role of parathyroid hormone for the activation of cardiac fibroblasts in uremia. J Am Soc Nephrol 4:1814–1819

    PubMed  CAS  Google Scholar 

  2. Artaza JN, Mehrotra R, Norris KC (2009) Vitamin D and the cardiovascular system. Clin J Am Soc Nephrol 4:1515–1522

    Article  PubMed  CAS  Google Scholar 

  3. Chinali M, de Simone G, Matteucci MC, Picca S, Mastrostefano A, Anarat A, Caliskan S, Jeck N, Neuhaus TJ, Peco-Antic A, Peruzzi L, Testa S, Mehls O, Wühl E, Schaefer F, ESCAPE Trial Group (2007) Reduced systolic myocardial function in children with chronic renal insufficiency. J Am Soc Nephrol 18:593–598

    Article  PubMed  Google Scholar 

  4. De Simone G, Daniels SR, Devreux RB et al (1992) Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. J Am Coll Cardiol 20:1251–1260

    Article  PubMed  Google Scholar 

  5. Devreux RB, Reichec N (1977) Echocardiographic determination of left ventricular mass in man: anatomic validation of the method. Circulation 55:613–618

    Article  Google Scholar 

  6. Haciomeroglu P, Ozkaya O, Gunal N, Baysal K (2008) An echocardiographic assessment of cardiac functions and structure in children on dialysis. Ren Fail 30:147–153

    Article  PubMed  Google Scholar 

  7. Issa LL, Leong GM, Sutherland RL et al (2002) Vitamin D analogue-specific recruitment of vitamin D receptor coactivators. J Bone Miner Res 17:879–890

    Article  PubMed  CAS  Google Scholar 

  8. Kong J, Kim GH, Wei M, Sun T, Li G, Liu SQ, Li X, Bhan I, Zhao Q, Thadhani R, Li YC (2010) Therapeutic effects of vitamin D analogs on cardiac hypertrophy in spontaneously hypertensive rats. Am J Pathol 177:622–631

    Article  PubMed  CAS  Google Scholar 

  9. Levin A, Bakris GL, Molitch M et al (2007) Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 71:31–38

    Article  PubMed  CAS  Google Scholar 

  10. Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP (2002) 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 110:229–238

    PubMed  CAS  Google Scholar 

  11. London GM, Pannier B, Guerin AP et al (2001) Alterations of left ventricular hypertrophy in and survival of patients receiving hemodialysis: follow-up of an interventional study. J Am Soc Nephrol 12:2759–2767

    PubMed  CAS  Google Scholar 

  12. Mancuso P, Rahman A, Hershey SD, Dandu L, Nibbelink KA, Simpson RU (2008) 1,25-Dihydroxyvitamin-D3 treatment reduces cardiac hypertrophy and left ventricular diameter in spontaneously hypertensive heart failure-prone (cp/+) rats independent of changes in serum leptin. J Cardiovasc Pharmacol 51:559–564

    Article  PubMed  CAS  Google Scholar 

  13. Massry SG (1984) Parathyroid hormone and uremic myocardiopathy. Contrib Nephrol 41:231–239

    PubMed  CAS  Google Scholar 

  14. Massry SG, Smogorzewski M (1995) The mechanisms responsible for the PTH-induced rise in cytosolic calcium in various cells are not uniform. Miner Electrolyte Metab 21:13–28

    PubMed  CAS  Google Scholar 

  15. Matias PJ, Jorge C, Ferreira C, Borges M, Aires I, Amaral T, Gil C, Cortez J, Ferreira A (2010) Cholecalciferol supplementation in hemodialysis patients: effects on mineral metabolism, inflammation, and cardiac dimension parameters. Clin J Am Soc Nephrol 5:905–911

    Article  PubMed  CAS  Google Scholar 

  16. 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

    Article  PubMed  Google Scholar 

  17. Mitsnefes MM, Kimball TR, Kartal J, Witt SA, Glascock BJ, Khoury PR, Daniels SRJ (2005) Cardiac and vascular adaptation in pediatric patients with chronic kidney disease: role of calcium-phosphorus metabolism. Am Soc Nephrol 16:2796–2803

    Article  CAS  Google Scholar 

  18. Mitsnefes MM, Kimball TR, Kartal J, Witt SA, Glascock BJ, Khoury PR, Daniels SR (2006) Progression of left ventricular hypertrophy in children with early chronic kidney disease: 2-year follow-up study. J Pediatr 149:671–675

    Article  PubMed  Google Scholar 

  19. Mitsnefes M, Flynn J, Cohn S, Samuels J, Blydt-Hansen T, Saland J, Kimball T, Furth S, Warady B, CKiD Study Group (2010) Masked hypertension associates with left ventricular hypertrophy in children with CKD. J Am Soc Nephrol 21:137–144

    Article  PubMed  CAS  Google Scholar 

  20. NAPRTCS (2005) The NAPRTCS 2005 annual report. Available at https://web.emmes.com/study/ped/annlrept/annlrept2005.pdf. Accessed 12 Mar 2012

  21. Nibbelink KA, Tishkoff DX, Hershey SD, Rahman A, Simpson RU (2007) 1,25(OH)2-vitamin D3 actions on cell proliferation, size, gene expression, and receptor localization in the HL-1 cardiac myocyte. J Steroid Biochem Mol Biol 103:533–537

    Article  PubMed  CAS  Google Scholar 

  22. 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

    Google Scholar 

  23. 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

    Article  CAS  Google Scholar 

  24. Patange AR, Valentini RP, Du W, Pettersen MD (2012) Vitamin D deficiency and arterial wall stiffness in children with chronic kidney disease. Pediatr Cardiol 33:122–128

    Article  PubMed  Google Scholar 

  25. Rinat C, Becker-Cohen R, Nir A, Feinstein S, Shemesh D, Algur N, Ben Shalom E, Farber B, Frishberg Y (2010) A comprehensive study of cardiovascular risk factors, cardiac function, and vascular disease in children with chronic renal failure. Nephrol Dial Transplant 25:785–793

    Article  PubMed  Google Scholar 

  26. Rostand SG, Drüeke TB (1999) Parathyroid hormone, vitamin D, and cardiovascular disease in chronic renal failure. Kidney Int 56:383–392

    Article  PubMed  CAS  Google Scholar 

  27. Rostand SG, Sanders C, Kirk KA, Rutsky EA, Fraser RG (1988) Myocardial calcification and cardiac dysfunction in chronic renal failure. Am J Med 85:651–657

    Article  PubMed  CAS  Google Scholar 

  28. 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

    PubMed  CAS  Google Scholar 

  29. Smogorzewski M (1995) Miner electrolyte: PTH, chronic renal failure, and myocardium. Metabolism 21:55–62

    CAS  Google Scholar 

  30. Takeyama K-I, Masuhiro Y, Fuse H et al (1999) Selective interaction of vitamin D receptor with transcriptional coactivators by a vitamin D analog. Mol Cell Biol 19:1049–1055

    PubMed  CAS  Google Scholar 

  31. Tan X, Li YC, Liu Y (2006) Paricalcitol and cardiac structure and function in animals and humans (abstract no. TH-FC155). J Am Soc Nephrol 17: 21A

  32. Tei C, Ling LH, Hodge DO (1995) New index combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function: a study in normal and dilated cardiomyopathy. J Cardiol 26:357–366

    PubMed  CAS  Google Scholar 

  33. Teng M, Wolf M, Ofsthun MN et al (2005) Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol 16:1115–1125

    Article  PubMed  CAS  Google Scholar 

  34. Terman DS, Alfrey AC, Hammond WS, Donndelinger T, Ogden DA, Holmes JH (1971) Cardiac calcification in uremia: a clinical, biochemical, and pathologic study. Am J Med 50:744–755

    Article  PubMed  CAS  Google Scholar 

  35. Weaver DJ Jr, Kimball T, Witt SA, Glascock BJ, Khoury PR, Kartal J, Mitsnefes MM (2008) Subclinical systolic dysfunction in pediatric patients with chronic kidney disease. J Pediatr 153:565–569

    Article  PubMed  Google Scholar 

  36. Weaver DJ Jr, Kimball TR, Knilans T, Mays W, Knecht SK, Gerdes YM, Witt S, Glascock BJ, Kartal J, Khoury P, Mitsnefes MM (2008) Decreased maximal aerobic capacity in pediatric chronic kidney disease. J Am Soc Nephrol 19:624–630

    Article  PubMed  Google Scholar 

  37. Wilson AC, Mitsnefes MM (2009) Cardiovascular disease in CKD in children: update on risk factors, risk assessment, and management. Am J Kidney Dis 54:345–360

    Article  PubMed  Google Scholar 

  38. Wu J, Garami M, Cheng T, Gardner DG (1996) 1,25(OH)2-vitamin D3 and retinoic acid antagonize endothelin-stimulated hypertrophy of neonatal rat cardiac myocytes. J Clin Invest 97:1577–1588

    Article  PubMed  CAS  Google Scholar 

  39. Wu-Wong JR, Nakane M, Traylor L et al (2005) Cardiovascular disease in chronic kidney failure: is there a role for vitamin D analogs. Curr Opin Invest Drug 6:245–254

    CAS  Google Scholar 

  40. Wu-Wong JR, Nakane M, Ma J et al (2006) Effects of vitamin D analogs on gene expression profiling in human coronary artery smooth muscle cells. Atherosclerosis 186:20–28

    Article  PubMed  CAS  Google Scholar 

  41. 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

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Carmen and Ann Adams Department of Pediatrics, Children’s Hospital of Michigan, Wayne State University, Detroit, MI, USA

    Amit R. Patange, Rudolph P. Valentini, Mayuri P. Gothe, Wei Du & Michael D. Pettersen

Authors
  1. Amit R. Patange
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rudolph P. Valentini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mayuri P. Gothe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael D. Pettersen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amit R. Patange.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Patange, A.R., Valentini, R.P., Gothe, M.P. et al. Vitamin D Deficiency Is Associated With Increased Left Ventricular Mass and Diastolic Dysfunction in Children With Chronic Kidney Disease. Pediatr Cardiol 34, 536–542 (2013). https://doi.org/10.1007/s00246-012-0489-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-012-0489-z

Keywords

Search

Navigation