Skip to main content

Advertisement

SpringerLink
Log in

Vitamin D and cardiovascular disease in chronic kidney disease

  • Educational Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Chronic kidney disease (CKD) is considered an independent risk factor for cardiovascular disease, with increased cardiovascular morbidity and mortality seen even in the early stages of CKD. Several studies have shown a high prevalence of vitamin D deficiency in individuals with CKD. Low vitamin D levels upregulate the renin-angiotensin-aldosterone system (RAAS), cause endothelial dysfunction, and increase inflammation. Epidemiological studies show an association between vitamin D deficiency and risk factors for cardiovascular disease, but a causal relationship has not been established. The high cardiovascular morbidity and mortality associated with CKD in adults requires therapies to decrease this elevated risk. However, results from several meta-analyses and randomized clinical trials in adults have not shown convincing evidence for the use of vitamin D therapy in improving cardiovascular outcomes. Lack of high-quality evidence from randomized clinical trials in children regarding the effectiveness and long-term safety of vitamin D treatment precludes any recommendations on its use to mitigate the cardiovascular burden of CKD.

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

Similar content being viewed by others

References

  1. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281

    CAS  PubMed  Google Scholar 

  2. Dusso AS, Brown AJ, Slatopolsky E (2005) Vitamin D. Am J Physiol Ren Physiol 289:F8–F28

    CAS  Google Scholar 

  3. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA (2011) The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 96:53–58

    CAS  PubMed  Google Scholar 

  4. Hajhosseiny R, Khavandi K, Goldsmith DJ (2013) Cardiovascular disease in chronic kidney disease: untying the Gordian knot. Int J Clin Pract 67:14–31

    CAS  PubMed  Google Scholar 

  5. McCullough PA, Steigerwalt S, Tolia K, Chen SC, Li S, Norris KC, Whaley-Connell A (2011) Cardiovascular disease in chronic kidney disease: data from the Kidney Early Evaluation Program (KEEP). Curr Diab Rep 11:47–55

    PubMed  PubMed Central  Google Scholar 

  6. Hemmelgarn BR, Clement F, Manns BJ, Klarenbach S, James MT, Ravani P, Pannu N, Ahmed SB, MacRae J, Scott-Douglas N, Jindal K, Quinn R, Culleton BF, Wiebe N, Krause R, Thorlacius L, Tonelli M (2009) Overview of the Alberta Kidney Disease Network. BMC Nephrol 10:30

    PubMed  PubMed Central  Google Scholar 

  7. Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT (2010) Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 375:2073–2081

    PubMed  PubMed Central  Google Scholar 

  8. van der Velde M, Matsushita K, Coresh J, Astor BC, Woodward M, Levey A, de Jong P, Gansevoort RT, Levey AS, de Jong PE, El-Nahas M, Eckardt KU, Kasiske BL, Ninomiya T, Chalmers J, Macmahon S, Tonelli M, Hemmelgarn B, Sacks F, Curhan G, Collins AJ, Li S, Chen SC, Hawaii Cohort KP, Lee BJ, Ishani A, Neaton J, Svendsen K, Mann JF, Yusuf S, Teo KK, Gao P, Nelson RG, Knowler WC, Bilo HJ, Joosten H, Kleefstra N, Groenier KH, Auguste P, Veldhuis K, Wang Y, Camarata L, Thomas B, Manley T (2011) Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int 79:1341–1352

    PubMed  Google Scholar 

  9. Verstuyf A, Carmeliet G, Bouillon R, Mathieu C (2010) Vitamin D: a pleiotropic hormone. Kidney Int 78:140–145

    CAS  PubMed  Google Scholar 

  10. Dusso AS, Tokumoto M (2011) Defective renal maintenance of the vitamin D endocrine system impairs vitamin D renoprotection: a downward spiral in kidney disease. Kidney Int 79:715–729

    CAS  PubMed  Google Scholar 

  11. Grant WB, Wimalawansa SJ, Holick MF, Cannell JJ, Pludowski P, Lappe JM, Pittaway M, May P (2015) Emphasizing the health benefits of vitamin D for those with neurodevelopmental disorders and intellectual disabilities. Nutrients 7:1538–1564

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Wimalawansa SJ (2012) Vitamin D in the new millennium. Curr Osteoporos Rep 10:4–15

    PubMed  Google Scholar 

  13. Holick MF, Frommer JE, McNeill SC, Richtand NM, Henley JW, Potts JT Jr (1977) Photometabolism of 7-dehydrocholesterol to previtamin D3 in skin. Biochem Biophys Res Commun 76:107–114

    CAS  PubMed  Google Scholar 

  14. Pike JW, Meyer MB (2010) The vitamin D receptor: new paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D(3). Endocrinol Metab Clin North Am 39:255–269

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Nair R, Maseeh A (2012) Vitamin D: the “sunshine” vitamin. J Pharmacol Pharmacother 3:118–126

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Liu S, Tang W, Zhou J, Stubbs JR, Luo Q, Pi M, Quarles LD (2006) Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. J Am Soc Nephrol 17:1305–1315

    CAS  PubMed  Google Scholar 

  17. Yu X, White KE (2005) FGF23 and disorders of phosphate homeostasis. Cytokine Growth Factor Rev 16:221–232

    CAS  PubMed  Google Scholar 

  18. Wali RK, Kong J, Sitrin MD, Bissonnette M, Li YC (2003) Vitamin D receptor is not required for the rapid actions of 1,25-dihydroxyvitamin D3 to increase intracellular calcium and activate protein kinase C in mouse osteoblasts. J Cell Biochem 88:794–801

    CAS  PubMed  Google Scholar 

  19. Haussler MR, Jurutka PW, Mizwicki M, Norman AW (2011) Vitamin D receptor (VDR)-mediated actions of 1alpha,25(OH)(2)vitamin D(3): genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab 25:543–559

    CAS  PubMed  Google Scholar 

  20. Heaney RP, Holick MF (2011) Why the IOM recommendations for vitamin D are deficient. J Bone Miner Res 26:455–457

    CAS  PubMed  Google Scholar 

  21. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B (2005) Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 293:2257–2264

    CAS  PubMed  Google Scholar 

  22. Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav EJ, Thoma A, Kiel DP, Henschkowski J (2009) Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med 169:551–561

    CAS  PubMed  Google Scholar 

  23. Priemel M, von Domarus C, Klatte TO, Kessler S, Schlie J, Meier S, Proksch N, Pastor F, Netter C, Streichert T, Puschel K, Amling M (2010) Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res 25:305–312

    CAS  PubMed  Google Scholar 

  24. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930

    CAS  PubMed  Google Scholar 

  25. Kumar J, Muntner P, Kaskel FJ, Hailpern SM, Melamed ML (2009) Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001-2004. Pediatrics 124:e362–e370

    PubMed  Google Scholar 

  26. Kumar J, McDermott K, Abraham AG, Friedman LA, Johnson VL, Kaskel FJ, Furth SL, Warady BA, Portale AA, Melamed ML (2016) Prevalence and correlates of 25-hydroxyvitamin D deficiency in the Chronic Kidney Disease in Children (CKiD) cohort. Pediatr Nephrol 31:121–129

    PubMed  Google Scholar 

  27. Seeherunvong W, Abitbol CL, Chandar J, Zilleruelo G, Freundlich M (2009) Vitamin D insufficiency and deficiency in children with early chronic kidney disease. J Pediatr 154:906–911 e901

    CAS  PubMed  Google Scholar 

  28. Kalkwarf HJ, Denburg MR, Strife CF, Zemel BS, Foerster DL, Wetzsteon RJ, Leonard MB (2012) Vitamin D deficiency is common in children and adolescents with chronic kidney disease. Kidney Int 81:690–697

    CAS  PubMed  Google Scholar 

  29. (2017) U.S. Renal Data System, USRDS 2017 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States

  30. Mitsnefes MM (2005) Cardiovascular disease in children with chronic kidney disease. Adv Chronic Kidney Dis 12:397–405

    PubMed  Google Scholar 

  31. 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

    CAS  PubMed  Google Scholar 

  32. Shroff R, Weaver DJ Jr, Mitsnefes MM (2011) Cardiovascular complications in children with chronic kidney disease. Nat Rev Nephrol 7:642–649

    CAS  PubMed  Google Scholar 

  33. Brady TM, Schneider MF, Flynn JT, Cox C, Samuels J, Saland J, White CT, Furth S, Warady BA, Mitsnefes M (2012) Carotid intima-media thickness in children with CKD: results from the CKiD study. Clin J Am Soc Nephrol 7:1930–1937

    PubMed  PubMed Central  Google Scholar 

  34. Reis JP, von Muhlen D, Miller ER 3rd, Michos ED, Appel LJ (2009) Vitamin D status and cardiometabolic risk factors in the United States adolescent population. Pediatrics 124:e371–e379

    PubMed  Google Scholar 

  35. Martins D, Wolf M, Pan D, Zadshir A, Tareen N, Thadhani R, Felsenfeld A, Levine B, Mehrotra R, Norris K (2007) Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 167:1159–1165

    CAS  PubMed  Google Scholar 

  36. Drechsler C, Pilz S, Obermayer-Pietsch B, Verduijn M, Tomaschitz A, Krane V, Espe K, Dekker F, Brandenburg V, Marz W, Ritz E, Wanner C (2010) Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients. Eur Heart J 31:2253–2261

    CAS  PubMed  PubMed Central  Google Scholar 

  37. de Boer IH, Kestenbaum B, Shoben AB, Michos ED, Sarnak MJ, Siscovick DS (2009) 25-Hydroxyvitamin D levels inversely associate with risk for developing coronary artery calcification. J Am Soc Nephrol 20:1805–1812

    PubMed  PubMed Central  Google Scholar 

  38. Abajo M, Betriu A, Arroyo D, Gracia M, Del Pino MD, Martinez I, Valdivielso JM, Fernandez E (2017) Mineral metabolism factors predict accelerated progression of common carotid intima-media thickness in chronic kidney disease: the NEFRONA study. Nephrol Dial Transplant 32:1882–1891

    CAS  PubMed  Google Scholar 

  39. 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

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Cardus A, Parisi E, Gallego C, Aldea M, Fernandez E, Valdivielso JM (2006) 1,25-Dihydroxyvitamin D3 stimulates vascular smooth muscle cell proliferation through a VEGF-mediated pathway. Kidney Int 69:1377–1384

    CAS  PubMed  Google Scholar 

  41. Zittermann A, Koerfer R (2008) Protective and toxic effects of vitamin D on vascular calcification: clinical implications. Mol Asp Med 29:423–432

    CAS  Google Scholar 

  42. Zittermann A, Koerfer R (2008) Vitamin D in the prevention and treatment of coronary heart disease. Curr Opin Clin Nutr Metab Care 11:752–757

    CAS  PubMed  Google Scholar 

  43. Carthy EP, Yamashita W, Hsu A, Ooi BS (1989) 1,25-Dihydroxyvitamin D3 and rat vascular smooth muscle cell growth. Hypertension 13:954–959

    CAS  PubMed  Google Scholar 

  44. Weng S, Sprague JE, Oh J, Riek AE, Chin K, Garcia M, Bernal-Mizrachi C (2013) Vitamin D deficiency induces high blood pressure and accelerates atherosclerosis in mice. PLoS One 8:e54625

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Wong MS, Delansorne R, Man RY, Vanhoutte PM (2008) Vitamin D derivatives acutely reduce endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol 295:H289–H296

    CAS  PubMed  Google Scholar 

  46. Ke L, Mason RS, Kariuki M, Mpofu E, Brock KE (2015) Vitamin D status and hypertension: a review. Integr Blood Press Control 8:13–35

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Witham MD, Nadir MA, Struthers AD (2009) Effect of vitamin D on blood pressure: a systematic review and meta-analysis. J Hypertens 27:1948–1954

    CAS  PubMed  Google Scholar 

  48. Wu SH, Ho SC, Zhong L (2010) Effects of vitamin D supplementation on blood pressure. South Med J 103:729–737

    PubMed  Google Scholar 

  49. Beveridge LA, Struthers AD, Khan F, Jorde R, Scragg R, Macdonald HM, Alvarez JA, Boxer RS, Dalbeni A, Gepner AD, Isbel NM, Larsen T, Nagpal J, Petchey WG, Stricker H, Strobel F, Tangpricha V, Toxqui L, Vaquero MP, Wamberg L, Zittermann A, Witham MD (2015) Effect of vitamin D supplementation on blood pressure: a systematic review and meta-analysis incorporating individual patient data. JAMA Intern Med 175:745–754

    PubMed  PubMed Central  Google Scholar 

  50. Mak RH (1992) Amelioration of hypertension and insulin resistance by 1,25-dihydroxycholecalciferol in hemodialysis patients. Pediatr Nephrol 6:345–348

    CAS  PubMed  Google Scholar 

  51. Shroff R, Aitkenhead H, Costa N, Trivelli A, Litwin M, Picca S, Anarat A, Sallay P, Ozaltin F, Zurowska A, Jankauskiene A, Montini G, Charbit M, Schaefer F, Wuhl E (2016) Normal 25-hydroxyvitamin D levels are associated with less proteinuria and attenuate renal failure progression in children with CKD. J Am Soc Nephrol 27:314–322

    CAS  PubMed  Google Scholar 

  52. de Zeeuw D, Agarwal R, Amdahl M, Audhya P, Coyne D, Garimella T, Parving HH, Pritchett Y, Remuzzi G, Ritz E, Andress D (2010) Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet 376:1543–1551

    PubMed  Google Scholar 

  53. Thadhani R, Appelbaum E, Pritchett Y, Chang Y, Wenger J, Tamez H, Bhan I, Agarwal R, Zoccali C, Wanner C, Lloyd-Jones D, Cannata J, Thompson BT, Andress D, Zhang W, Packham D, Singh B, Zehnder D, Shah A, Pachika A, Manning WJ, Solomon SD (2012) Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA 307:674–684

    CAS  PubMed  Google Scholar 

  54. 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 Phys 272:H1751–H1758

    Google Scholar 

  55. Simpson RU, Hershey SH, Nibbelink KA (2007) Characterization of heart size and blood pressure in the vitamin D receptor knockout mouse. J Steroid Biochem Mol Biol 103:521–524

    CAS  PubMed  Google Scholar 

  56. Patange AR, Valentini RP, Gothe MP, Du W, Pettersen MD (2013) Vitamin D deficiency is associated with increased left ventricular mass and diastolic dysfunction in children with chronic kidney disease. Pediatr Cardiol 34:536–542

    PubMed  Google Scholar 

  57. van Ballegooijen AJ, Snijder MB, Visser M, van den Hurk K, Kamp O, Dekker JM, Nijpels G, Stehouwer CD, Henry RM, Paulus WJ, Brouwer IA (2012) Vitamin D in relation to myocardial structure and function after eight years of follow-up: the Hoorn study. Ann Nutr Metab 60:69–77

    PubMed  Google Scholar 

  58. Park CW, Oh YS, Shin YS, Kim CM, Kim YS, Kim SY, Choi EJ, Chang YS, Bang BK (1999) Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients with secondary hyperparathyroidism. Am J Kidney Dis 33:73–81

    CAS  PubMed  Google Scholar 

  59. Wang AY, Fang F, Chan J, Wen YY, Qing S, Chan IH, Lo G, Lai KN, Lo WK, Lam CW, Yu CM (2014) Effect of paricalcitol on left ventricular mass and function in CKD—the OPERA trial. J Am Soc Nephrol 25:175–186

    CAS  PubMed  Google Scholar 

  60. Tamez H, Zoccali C, Packham D, Wenger J, Bhan I, Appelbaum E, Pritchett Y, Chang Y, Agarwal R, Wanner C, Lloyd-Jones D, Cannata J, Thompson BT, Andress D, Zhang W, Singh B, Zehnder D, Pachika A, Manning WJ, Shah A, Solomon SD, Thadhani R (2012) Vitamin D reduces left atrial volume in patients with left ventricular hypertrophy and chronic kidney disease. Am Heart J 164:902–909.e902

    CAS  PubMed  Google Scholar 

  61. Schaefer F, Doyon A, Azukaitis K, Bayazit A, Canpolat N, Duzova A, Niemirska A, Sozeri B, Thurn D, Anarat A, Ranchin B, Litwin M, Caliskan S, Candan C, Baskin E, Yilmaz E, Mir S, Kirchner M, Sander A, Haffner D, Melk A, Wuhl E, Shroff R, Querfeld U (2017) Cardiovascular phenotypes in children with CKD: the 4C Study. Clin J Am Soc Nephrol 12:19–28

    PubMed  Google Scholar 

  62. Samuels J, Ng D, Flynn JT, Mitsnefes M, Poffenbarger T, Warady BA, Furth S (2012) Ambulatory blood pressure patterns in children with chronic kidney disease. Hypertension 60:43–50

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Lerch C, Shroff R, Wan M, Rees L, Aitkenhead H, Kaplan Bulut I, Thurn D, Karabay Bayazit A, Niemirska A, Canpolat N, Duzova A, Azukaitis K, Yilmaz E, Yalcinkaya F, Harambat J, Kiyak A, Alpay H, Habbig S, Zaloszyc A, Soylemezoglu O, Candan C, Rosales A, Melk A, Querfeld U, Leifheit-Nestler M, Sander A, Schaefer F, Haffner D; 4C study consortium; ESPN CKD-MBD working group (2018) Effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism in children with chronic kidney disease. Nephrol Dial Transplant. https://doi.org/10.1093/ndt/gfy012

    CAS  Google Scholar 

  65. Apetrii M, Covic A (2016) Vitamin D and endothelial function in chronic kidney disease. In: Ureña Torres PA, Cozzolino M, Vervloet M (eds) Vitamin D in chronic kidney disease. Springer, Cham. https://doi.org/10.1007/978-3-319-32507-1_20 Request PDF. Available from: https://www.researchgate.net/publication/308500307_Vitamin_D_and_Endothelial_Function_in_Chronic_Kidney_Disease. Accessed 13 Sept 2018

    Chapter  Google Scholar 

  66. Merke J, Milde P, Lewicka S, Hugel U, Klaus G, Mangelsdorf DJ, Haussler MR, Rauterberg EW, Ritz E (1989) Identification and regulation of 1,25-dihydroxyvitamin D3 receptor activity and biosynthesis of 1,25-dihydroxyvitamin D3. Studies in cultured bovine aortic endothelial cells and human dermal capillaries. J Clin Invest 83:1903–1915

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Molinari C, Uberti F, Grossini E, Vacca G, Carda S, Invernizzi M, Cisari C (2011) 1alpha,25-Dihydroxycholecalciferol induces nitric oxide production in cultured endothelial cells. Cell Physiol Biochem 27:661–668

    CAS  PubMed  Google Scholar 

  68. Zhong W, Gu B, Gu Y, Groome LJ, Sun J, Wang Y (2014) Activation of vitamin D receptor promotes VEGF and CuZn-SOD expression in endothelial cells. J Steroid Biochem Mol Biol 140:56–62

    CAS  PubMed  Google Scholar 

  69. Stam F, van Guldener C, Becker A, Dekker JM, Heine RJ, Bouter LM, Stehouwer CD (2006) Endothelial dysfunction contributes to renal function-associated cardiovascular mortality in a population with mild renal insufficiency: the Hoorn study. J Am Soc Nephrol 17:537–545

    CAS  PubMed  Google Scholar 

  70. Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb DJ (2005) Endothelial function and dysfunction. Part I: methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens 23:7–17

    CAS  PubMed  Google Scholar 

  71. Shechter M, Issachar A, Marai I, Koren-Morag N, Freinark D, Shahar Y, Shechter A, Feinberg MS (2009) Long-term association of brachial artery flow-mediated vasodilation and cardiovascular events in middle-aged subjects with no apparent heart disease. Int J Cardiol 134:52–58

    PubMed  Google Scholar 

  72. Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM (2007) Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation 115:2390–2397

    PubMed  Google Scholar 

  73. Yilmaz MI, Stenvinkel P, Sonmez A, Saglam M, Yaman H, Kilic S, Eyileten T, Caglar K, Oguz Y, Vural A, Cakar M, Altun B, Yenicesu M, Carrero JJ (2011) Vascular health, systemic inflammation and progressive reduction in kidney function; clinical determinants and impact on cardiovascular outcomes. Nephrol Dial Transplant 26:3537–3543

    PubMed  Google Scholar 

  74. Zoccali C, Maio R, Tripepi G, Mallamaci F, Perticone F (2006) Inflammation as a mediator of the link between mild to moderate renal insufficiency and endothelial dysfunction in essential hypertension. J Am Soc Nephrol 17:S64–S68

    PubMed  Google Scholar 

  75. Wever R, Boer P, Hijmering M, Stroes E, Verhaar M, Kastelein J, Versluis K, Lagerwerf F, van Rijn H, Koomans H, Rabelink T (1999) Nitric oxide production is reduced in patients with chronic renal failure. Arterioscler Thromb Vasc Biol 19:1168–1172

    CAS  PubMed  Google Scholar 

  76. Kumar V, Yadav AK, Lal A, Kumar V, Singhal M, Billot L, Gupta KL, Banerjee D, Jha V (2017) A randomized trial of vitamin D supplementation on vascular function in CKD. J Am Soc Nephrol 28:3100–3108

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Zoccali C, Curatola G, Panuccio V, Tripepi R, Pizzini P, Versace M, Bolignano D, Cutrupi S, Politi R, Tripepi G, Ghiadoni L, Thadhani R, Mallamaci F (2014) Paricalcitol and endothelial function in chronic kidney disease trial. Hypertension 64:1005–1011

    CAS  PubMed  Google Scholar 

  78. Thethi TK, Bajwa MA, Ghanim H, Jo C, Weir M, Goldfine AB, Umpierrez G, Desouza C, Dandona P, Fang-Hollingsworth Y, Raghavan V, Fonseca VA (2015) Effect of paricalcitol on endothelial function and inflammation in type 2 diabetes and chronic kidney disease. J Diabetes Complicat 29:433–437

    Google Scholar 

  79. Kendrick J, Andrews E, You Z, Moreau K, Nowak KL, Farmer-Bailey H, Seals DR, Chonchol M (2017) Cholecalciferol, calcitriol, and vascular function in CKD: a randomized, double-blind trial. Clin J Am Soc Nephrol 12:1438–1446

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Zhang Q, Zhang M, Wang H, Sun C, Feng Y, Zhu W, Cao D, Shao Q, Li N, Xia Y, Tang T, Wan C, Liu J, Jin B, Zhao M, Jiang C (2018) Vitamin D supplementation improves endothelial dysfunction in patients with non-dialysis chronic kidney disease. Int Urol Nephrol 50:923–927

    CAS  PubMed  Google Scholar 

  81. Libby P, Ridker PM, Hansson GK (2009) Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 54:2129–2138

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340:115–126

    CAS  PubMed  Google Scholar 

  83. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D’Agostino RB, Wolf M, Vasan RS (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117:503–511

    CAS  PubMed  Google Scholar 

  84. Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE (1997) Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam study. Circulation 96:1432–1437

    CAS  PubMed  Google Scholar 

  85. Ng YM, Lim SK, Kang PS, Kadir KA, Tai MS (2016) Association between serum 25-hydroxyvitamin D levels and carotid atherosclerosis in chronic kidney disease patients. BMC Nephrol 17:151

    PubMed  PubMed Central  Google Scholar 

  86. Yadav AK, Banerjee D, Lal A, Jha V (2012) Vitamin D deficiency, CD4+CD28null cells and accelerated atherosclerosis in chronic kidney disease. Nephrology (Carlton) 17:575–581

    CAS  Google Scholar 

  87. Aytac MB, Deveci M, Bek K, Kayabey O, Ekinci Z (2016) Effect of cholecalciferol on local arterial stiffness and endothelial dysfunction in children with chronic kidney disease. Pediatr Nephrol 31:267–277

    PubMed  Google Scholar 

  88. Shroff R, Egerton M, Bridel M, Shah V, Donald AE, Cole TJ, Hiorns MP, Deanfield JE, Rees L (2008) A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol 19:1239–1246

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Alborzi P, Patel NA, Peterson C, Bills JE, Bekele DM, Bunaye Z, Light RP, Agarwal R (2008) Paricalcitol reduces albuminuria and inflammation in chronic kidney disease: a randomized double-blind pilot trial. Hypertension 52:249–255

    CAS  PubMed  Google Scholar 

  90. Agarwal R, Acharya M, Tian J, Hippensteel RL, Melnick JZ, Qiu P, Williams L, Batlle D (2005) Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney Int 68:2823–2828

    CAS  PubMed  Google Scholar 

  91. Fishbane S, Chittineni H, Packman M, Dutka P, Ali N, Durie N (2009) Oral paricalcitol in the treatment of patients with CKD and proteinuria: a randomized trial. Am J Kidney Dis 54:647–652

    CAS  PubMed  Google Scholar 

  92. Munoz Mendoza J, Isakova T, Ricardo AC, Xie H, Navaneethan SD, Anderson AH, Bazzano LA, Xie D, Kretzler M, Nessel L, Hamm LL, Negrea L, Leonard MB, Raj D, Wolf M (2012) Fibroblast growth factor 23 and inflammation in CKD. Clin J Am Soc Nephrol 7:1155–1162

    PubMed  PubMed Central  Google Scholar 

  93. Shlipak MG, Fried LF, Crump C, Bleyer AJ, Manolio TA, Tracy RP, Furberg CD, Psaty BM (2003) Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency. Circulation 107:87–92

    CAS  PubMed  Google Scholar 

  94. Zehnder D, Quinkler M, Eardley KS, Bland R, Lepenies J, Hughes SV, Raymond NT, Howie AJ, Cockwell P, Stewart PM, Hewison M (2008) Reduction of the vitamin D hormonal system in kidney disease is associated with increased renal inflammation. Kidney Int 74:1343–1353

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Bucharles S, Barberato SH, Stinghen AE, Gruber B, Piekala L, Dambiski AC, Custodio MR, Pecoits-Filho R (2012) Impact of cholecalciferol treatment on biomarkers of inflammation and myocardial structure in hemodialysis patients without hyperparathyroidism. J Ren Nutr 22:284–291

    CAS  PubMed  Google Scholar 

  96. Alvarez JA, Zughaier SM, Law J, Hao L, Wasse H, Ziegler TR, Tangpricha V (2013) Effects of high-dose cholecalciferol on serum markers of inflammation and immunity in patients with early chronic kidney disease. Eur J Clin Nutr 67:264–269

    CAS  PubMed  Google Scholar 

Download references

Funding

J.K. is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD009115) and Weill Cornell CTSC Pilot grant UL1-TR-002348.

Author information

Authors and Affiliations

  1. State University of New York Downstate Medical Center, Brooklyn, NY, 11203, USA

    Gurpreet Kaur

  2. Ross University School of Medicine, Portsmouth, Dominica

    Jatinder Singh

  3. New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY, USA

    Juhi Kumar

Authors
  1. Gurpreet Kaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jatinder Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Juhi Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juhi Kumar.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Answers

1. c; 2. a; 3. d; 4. e; 5. c

Key points

• Inadequate vitamin D levels (< 30 ng/ml) are highly prevalent in the adult and pediatric chronic kidney disease populations.

• Vitamin D deficiency is associated with hypertension, diabetes, proteinuria cardiac dysfunction, and dyslipidemia.

• Low vitamin D levels upregulate the renin-angiotensin-aldosterone system, increase inflammation, and cause endothelial dysfunction leading to higher cardiovascular risk.

• Clinical trials and meta-analyses data in adults have failed to show a benefit of vitamin D therapy on cardiovascular outcomes.

• Lack of randomized clinical trials and high-quality evidence in the pediatric CKD population makes it difficult to recommend the use of vitamin D therapy for reduction of cardiovascular disease burden.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaur, G., Singh, J. & Kumar, J. Vitamin D and cardiovascular disease in chronic kidney disease. Pediatr Nephrol 34, 2509–2522 (2019). https://doi.org/10.1007/s00467-018-4088-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-018-4088-y

Keywords

Search

Navigation