Skip to main content

Advertisement

SpringerLink
Log in

Intermittent cholecalciferol supplementation in children and teenagers followed in pediatric nephrology: data from a prospective single-center single-arm open trial

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Vitamin D deficiency is frequent in pediatric nephrology. The 2017 European guidelines recommend keeping 25OH vitamin D (25-D) levels within the 75–120 nmol/L range, ideally with daily supplementation. Intermittent supplementation with D3 has also been proposed. We aimed to assess the influence of our local protocol of intermittent vitamin D supplementation on the evolution of 25-D levels between baseline and 2 months. VITATOL is a prospective single-center study performed in our tertiary unit in children and teenagers followed for chronic kidney disease (CKD), kidney transplantation, or stable chronic nephrotic syndrome with 25-D levels below 75 nmol/L. Intermittent oral cholecalciferol (100,000 IU) was administered depending on baseline vitamin D levels and body weight. The primary outcome was the change in 25-D levels between baseline and 2 months. Secondary outcomes were the evolution of the main mineral biomarkers. Thirty-seven patients were included. Two months after beginning supplementation, corresponding to a median(min-max) of 46 (14–79) days after the last dose of vitamin D, 25-D levels increased from 50 to 76 nmol/L (p < 0.001), 18 patients having 25-D levels within the target range and 2 above. All patients displayed 25-D levels above 50 nmol/L. There were no significant changes in phosphate, PTH, alkaline phosphatase, and FGF23 levels before and after supplementation. Calcium levels increased from 2.39 to 2.44 mmol/L (p = 0.017), but no differences in calciuria and urinary calcium/creatinine ratio were observed.

Conclusion: This vitamin D supplementation protocol using intermittent moderate doses of cholecalciferol seems efficient in 54% of cases, with neither significant overdose nor hypercalciuria.

What is Known:

• Vitamin D deficiency is frequent in pediatric nephrology.

• The 2017 European guidelines recommend keeping 25OH vitamin D levels within the 75–120 nmol/L range ideally with daily supplementation, but intermittent supplementation with D3 has also been proposed.

What is New:

• We assessed the influence of a local protocol of intermittent vitamin D supplementation on the evolution of 25-D levels between baseline and 2 months in children and teenagers followed in pediatric nephrology.

• The intermittent cholecalciferol supplementation protocol seems efficient in 54% of cases, with neither significant overdose nor hypercalciuria.

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

Similar content being viewed by others

Abbreviations

ALP:

Alkaline phosphatase

UCa/creat:

Urinary calcium/creatinine ratio

CKD:

Chronic kidney disease

eGFR:

Estimated glomerular filtration rate

ESPN:

European Society of Pediatric Nephrology

FGF23:

Fibroblast growth factor 23

IRB:

Institutional Review Board

IU:

International unit

KDIGO:

Kidney disease improving global outcomes

KDOQI:

Kidney disease outcomes quality

PTH:

Parathormone

RCTs:

Randomized clinical trials

SDS:

Standard deviation scores

25-D:

25hydroxy vitamin D

1-25-D:

1-25 di-hydroxy vitamin D

References

  1. Bacchetta J, Ranchin B, Dubourg L, Cochat P (2010) Vitamin D revisited: a cornerstone of health? Arch Pediatr 17:1687–1695

    Article  CAS  Google Scholar 

  2. Menon S, Valentini RP, Hidalgo G, Peschansky L, Mattoo TK (2008) Vitamin D insufficiency and hyperparathyroidism in children with chronic kidney disease. Pediatr Nephrol 23:1831–1836

    Article  Google Scholar 

  3. Belostotsky V, Mughal MZ, Berry JL, Webb NJA (2008) Vitamin D deficiency in children with renal disease. Arch Dis Child 93:959–962

    Article  CAS  Google Scholar 

  4. Bacchetta J, Chun RF, Gales B, Zaritsky JJ, Leroy S, Wesseling-Perry K, Boregaard N, Rastogi A, Salusky IB, Hewison M (2014) Antibacterial responses by peritoneal macrophages are enhanced following vitamin D supplementation. PLoS One 9:e116530. https://doi.org/10.1371/journal.pone.0116530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Adams JS, Hewison M (2010) Update in vitamin D. J Clin Endocrinol Metab 95:471–478

    Article  Google Scholar 

  6. Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP (2002) 1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 110:229–238

    Article  CAS  Google Scholar 

  7. Bacchetta J, Pelletier S (2018) Vitamin D deficiency is associated with mortality in maintenance dialysis: moving forward from epidemiology to clinical trials. Nephrol Dial Transplant 33:1679–1682

    Article  CAS  Google Scholar 

  8. KDOQI Work Group (2009) KDOQI clinical practice guideline for nutrition in children with CKD: 2008 update. Executive summary Am J Kidney Dis 53:S11–S104

  9. Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, Moe SM, Shroff R, Tonelli MA, Toussaint ND, Vervloet MG, Leonard MB (2018) Diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder: synopsis of the kidney disease: improving global outcomes 2017 clinical practice guideline update. Ann Intern Med 168:422–430

    Article  Google Scholar 

  10. Shroff R, Wan M, Nagler EV, Bakkaloglu S, Cozzolino M, Bacchetta J, Edefonti A, Stefanidis CJ, Vande Walle J, Ariceta G, Klaus G, Haffner D, Schmitt CP ; European Society for Paediatric Nephrology Chronic Kidney Disease Mineral and Bone Disorders and Dialysis Working Groups (2017) Clinical practice recommendations for treatment with active vitamin D analogues in children with chronic kidney disease stages 2-5 and on dialysis. Nephrol Dial Transplant 32:1114–1127

  11. Shroff R, Wan M, Nagler EV, Bakkaloğlu S, Fischer D-C, Bishop N, Cozzolino M, Bacchetta J, Edefonti A, Stefanidis CJ, Vande Walle J, Haffner D, Klaus G, Schmitt CP ; European Society for Paediatric Nephrology Chronic Kidney Disease Mineral and Bone Disorders and Dialysis Working Groups (2017) Clinical practice recommendations for native vitamin D therapy in children with chronic kidney disease stages 2–5 and on dialysis. Nephrol Dial Transplant 32:1098–1113

  12. Daroux M, Shenouda M, Bacri J-L, Lemaitre V, Vanhille P, Bataille P (2013) Vitamin D2 versus vitamin D3 supplementation in hemodialysis patients: a comparative pilot study. J Nephrol 26:152–157

    Article  CAS  Google Scholar 

  13. Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, Chope G, Hyppönen E, Berry J, Vieth R, Lanham-New S (2012) Comparison of vitamin D2 and vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic review and meta-analysis. Am J Clin Nutr 95:1357–1364

    Article  CAS  Google Scholar 

  14. Courbebaisse M, Thervet E, Souberbielle JC, Zuber J, Eladari D, Martinez F, Mamzer-Bruneel MF, Urena P, Legendre C, Friedlander G, Prié D (2009) Effects of vitamin D supplementation on the calcium-phosphate balance in renal transplant patients. Kidney Int 75:646–651

    Article  CAS  Google Scholar 

  15. Benaboud S, Urien S, Thervet E, Prié D, Legendre C, Souberbielle JC, Hirt D, Friedlander G, Treluyer JM, Courbebaisse M (2013) Determination of optimal cholecalciferol treatment in renal transplant recipients using a population pharmacokinetic approach. Eur J Clin Pharmacol 69:499–506

    Article  CAS  Google Scholar 

  16. Vidailhet M, Mallet E, Bocquet A, Bresson J-L, Briend A, Chouraqui J-P, Darmaun D, Dupont C, Frelut ML, Ghisolfi J, Girardet JP, Goulet O, Hankard R, Rieu D, Simeoni U, Turck D; Comité de nutrition de la Société française de pédiatrie (2012) Vitamin D: still a topical matter in children and adolescents. A position paper by the Committee on Nutrition of the French Society of Paediatrics. Arch Pediatr 19:316–328

  17. Sempé M, Pédron G, Roy-Pernot M.P. (1997) Auxologie méthode et séquences, 2nd edn. Méditions, Paris

  18. Matos V, van Melle G, Boulat O, Markert M, Bachmann C, Guignard JP (1997) Urinary phosphate/creatinine, calcium/creatinine, and magnesium/creatinine ratios in a healthy pediatric population. J Pediatr 131:252–257

    Article  CAS  Google Scholar 

  19. Schwartz GJ, Work DF (2009) Measurement and estimation of GFR in children and adolescents. Clin J Am Soc Nephrol 4:1832–1843

    Article  Google Scholar 

  20. Armas LAG, Hollis BW, Heaney RP (2004) Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 89:5387–5391

    Article  CAS  Google Scholar 

  21. Lal BB, Alam S, Khanna R, Rawat D (2018) Weekly regimen of vitamin D supplementation is more efficacious than stoss regimen for treatment of vitamin D deficiency in children with chronic liver diseases. Eur J Pediatr 177:827–834

    Article  CAS  Google Scholar 

  22. Shroff R, Wan M, Gullett A, Ledermann S, Shute R, Knott C, Wells D, Aitkenhead H, Manickavasagar B, van’t Hoff W, Rees L (2012) Ergocalciferol supplementation in children with CKD delays the onset of secondary hyperparathyroidism: a randomized trial. Clin J Am Soc Nephrol 7:216–223

    Article  CAS  Google Scholar 

  23. Westerberg P-A, Sterner G, Ljunggren Ö, Isaksson E, Elvarson F, Dezfoolian H, Linde T (2018) High doses of cholecalciferol alleviate the progression of hyperparathyroidism in patients with CKD stages 3–4: results of a 12-week double-blind, randomized, controlled study. Nephrol Dial Transplant 33:466–471

    Article  CAS  Google Scholar 

  24. Yadav AK, Kumar V, Kumar V, Banerjee D, Gupta KL, Jha V (2018) The effect of vitamin D supplementation on bone metabolic markers in chronic kidney disease. J Bone Miner Res 33:404–409

    Article  CAS  Google Scholar 

  25. 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. 33:2208–2217

  26. Mitsnefes MM (2012) Cardiovascular disease in children with chronic kidney disease. J Am Soc Nephrol 23:578–585

    Article  CAS  Google Scholar 

  27. Jammal Addin MB, Young D, McCarrison S, Hunter L (2019) Dilated cardiomyopathy in a national paediatric population. Eur J Pediatr 178:1229–1235

    Article  Google Scholar 

  28. Basatemur E, Hunter R, Horsfall L, Sutcliffe A, Rait G (2017) Costs of vitamin D testing and prescribing among children in primary care. Eur J Pediatr 176:1405–1409

    Article  CAS  Google Scholar 

  29. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JPA (2014) Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 348:g2035

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank patients and their families for accepting to be part of the VITATOL study. They also would like to acknowledge Mrs. Tiphanie Ginhoux, project manager in EPICIME, for her technical help with the administrative duties, and Dr. Marie-Christine Carlier (PharmD, Hospices Civils de Lyon) for her help in biochemical assessment.

Funding

This study was supported by the Crinex laboratories, with a research grant of 3000 euros for biochemical markers assessment and the centralized delivery of cholecalciferol doses.

Author information

Authors and Affiliations

  1. Centre de référence des maladies rénales rares Service de Néphrologie Rhumatologie Dermatologie Pédiatriques, Néphrogones, Filières ORKiD, Hôpital Femme Mère Enfant, Hospices Civils de Lyon,, 59 Boulevard Pinel, 69677, Bron Cedex, France

    Manon Aurelle, Odile Basmaison, Bruno Ranchin, Anne-Laure Sellier-Leclerc, Aurélia Bertholet-Thomas & Justine Bacchetta

  2. Department of clinical epidemiology, EPICIME-CIC 1407 de Lyon, Inserm, CHU-Lyon, Bron, France

    Behrouz Kassai-Koupai

  3. Faculté de Médecine Lyon Est, Université Lyon 1, 69008, Lyon, France

    Behrouz Kassai-Koupai & Justine Bacchetta

  4. Centre de référence des maladies rares du calcium et du phosphate, Filières OSCAR, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, France

    Aurélia Bertholet-Thomas & Justine Bacchetta

  5. INSERM Research Unit 1033, Lyon, France

    Justine Bacchetta

Authors
  1. Manon Aurelle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Odile Basmaison
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bruno Ranchin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Behrouz Kassai-Koupai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anne-Laure Sellier-Leclerc
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aurélia Bertholet-Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Justine Bacchetta
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MA analyzed data and wrote the first draft of the manuscript.

OB, BR, ALSL, and ABT included patients and revised the manuscript.

BKK was involved in the study design and revised the manuscript.

JB designed the study, included patients, analyzed date and revised the manuscript.

Corresponding author

Correspondence to Justine Bacchetta.

Ethics declarations

Conflict of interest

This study was supported by the Crinex laboratories, with a research grant for biochemical markers assessment and the centralized delivery of cholecalciferol doses. The Crinex laboratories were not involved neither in the design and conduct of the study nor in data analysis.

Ethical approval

VITATOL was approved by the local IRB (Comité de Protection des Personnes Lyon Sud Est IV, session A13–329).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Communicated by Mario Bianchetti

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aurelle, M., Basmaison, O., Ranchin, B. et al. Intermittent cholecalciferol supplementation in children and teenagers followed in pediatric nephrology: data from a prospective single-center single-arm open trial. Eur J Pediatr 179, 661–669 (2020). https://doi.org/10.1007/s00431-019-03553-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-019-03553-y

Keywords

Search

Navigation