Vitamin D deficitent conditions and phosphorus-calcium disordes in children on dialysis and after kidney transplantation: diagnosis and treatment

Aim: to determine the prevalence of deficiency and insufficiency of vitamin D (vitD), secondary hyperparathyroidism and calcium-phosphorus disorders in children with chronic kidney disease stages 4-5 (CKD 4-5), on hemodialysis (HD), on peritoneal dialysis (PD), after kidney transplantation (Tx) and to assess changes of these parameters on the background of treatment with cholecalciferol (D3) and with phosphate-binding agents containing calcium carbonate and D3 (Ca-D3). Methods: serum levels of calcium, phosphorus, total 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (PTH) were determined in 106 children (age 12.4±4.8 years): Tx 53, PD 18, HD 23, CKD 4-5 without dialysis 12. If 25(OH)D in blood was <20 ng/ml - deficiency, if 20-29 ng/ml - insufficiency. Results: vitamin D deficiency and insufficiency of revealed in 86.8% Tx patients, 88.9% PD patients, 91.3% HD patients, and 75% of CKD 4-5 patients. The lowest values of 25(OH)D was detected in the PD group. Secondary hyperparathyroidism was found in 1.9% Tx patients, 44.4% PD patients, 47.8% HD patients, and 50% of CKD 4-5 patients. Seasonal variations of 25(OH)D levels and a decrease in its levels with time were found in Tx patients. Intake Ca-D3 for at least a year led to a normalization of phosphorus in 45.5% on PD patients with developing hypercalcemia in 31.8% of them and decreasing PTH levels below the target in 76.2% cases. 75% of children had high or toxic blood levels of 25(OH)D if a daily intake of D3 was 8000 ME. Conclusions: deficiency and insufficiency of vit D is widely prevalent in children on PD or HD, with CKD 4-5 and after Tx. It requires treatment and subsequent maintenance therapy with vitD.

витамин Д, гемодиализ, перитонеальный диализ, трансплантация почки, фосфорно-кальциевые нарушения, гиперпаратиреоз, лечение колекальциферолом, дети, vitamin D, hemodialysis, peritoneal dialysis, kidney transplantation, calcium-phosphorus disorders, hyperparathyroidism, treatment with cholecalciferol, children

1. Байко С.В., Сукало А.В., Руденко Э.В. и др. Методы диагностики и лечения дефицита витамина Д, костных и минеральных нарушений у детей с хронической болезнью почек: инструкция по применению. Минск, 2013. 23 с. Baiko S.V., Sukalo A.V., Rudenko E.V. i dr. Metody diagnostiki i lecheniya deficita vitamina D, kostnykh i mineralnykh narusheniy u detey s khronicheskoy boleznyu pochek: instrukciya po primeneniyu. Minsk, 2013. 23 s.

2. Байко С.В., Сукало А.В., Василенко Е.А. и др. Дефицит витамина Д, особенности фосфорно-кальциевого и костного обмена у здоровых детей. Известия Национальной академии наук Беларуси. Серия медицинских наук. 2015. 3: 14-18. Baiko S.V., Sukalo A.V., Vasilenko E.A. i dr. Deficit vitamina D, osobennosti fosforno-kalcievogo i kostnogo obmena u zdorovykh detey. Izvestiya Nacionalnoy akademii nauk Belarusi. Seriya medicinskikh nauk. 2015. 3: 14-18.

3. Байко С.В., Сукало А.В., Руденко Э.В. Дефицит витамина Д и особенности фосфорно-кальциевого обмена у здоровых детей. Медицинские новости. 2015. 254(11): 69-72. Baiko S.V., Sukalo A.V., Rudenko E.V. Deficit vitamina D i osobennosti fosforno-kalcievogo obmena u zdorovykh detey. Medicinskie novosti. 2015. 254(11): 69-72.

4. Ермоленко В.М., Волгина Г.В., Добронравов В.А. и др. Национальные рекомендации по минеральным и костным нарушениям при хронической болезни почек. Нефрология и диализ. 2011. 13(1): 33-51. Ermolenko V.M., Volgina G.V., Dobronravov V.A. i dr. Nacionalnye rekomendacii po mineralnym i kostnym narusheniyam pri khronicheskoy bolezni pochek. Nefrologiya i dializ. 2011. 13(1): 33-51.

5. Ляликов С.А., Сукало А.В., Кузнецов О.Е. и др. Центильные характеристики антропометрических и лабораторных показателей у детей в современный период: инструкция по применению. Гродно, 2009. 94 с. Lyalikov S.A., Sukalo A.V., Kuzneczov O.E. i dr. Centilnye kharakteristiki antropometricheskikh i laboratornykh pokazateley u detey v sovremennyy period: instrukciya po primeneniyu. Grodno, 2009. 94 s.

6. Мальцев С.В., Мансурова Г.Ш. Метаболизм витамина Д и пути реализации его основных функций. Практическая медицина. 2014. 85(9): 12-18. Malcev S.V., Mansurova G.Sh. Metabolizm vitamina D i puti realizacii ego osnovnykh funkciy. Prakticheskaya medicina. 2014. 85(9): 12-18.

7. Шестерикова В.В., Иванова И.Е., Стержанова Н.В. Современный взгляд на витамин Д. Лечение и профилактика. 2014. 9(1): 57-61. Shesterikova V.V., Ivanova I.E., Sterzhanova N.V. Sovremennyy vzglyad na vitamin D. Lechenie i profilaktika. 2014. 9(1): 57-61.

8. Adams J.S. Hewison M.J. Update in vitamin D. J. Clin. Endocrinol. Metab. 2010. 95(2): 471-478.

9. Bouillon, R., Bischoff-Ferrari H., Willett W. Vitamin D and health: perspectives from mice and man. J. Bone Miner. Res. 2008. 23(7): 974-979.

10. Cho H.Y., Hyun H.S., Kang H.G. et. al. Prevalence of 25(OH) vitamin D insufficiency and deficiency in pediatric patients on chronic dialysis. Perit. Dial. Int. 2013. 33(4): 398-404.

11. Chun R.F., Peercy B.E., Orwoll E.S. et al. Vitamin D and DBP: The free hormone hypothesis revisited. J. Steroid Biochem. Mol. Biol. 2014. 144PA: 132-137.

12. de Boer I.H., Kestenbaum B., Shoben A.B. et al. 25-Hydroxyvitamin D levels inversely associate with risk for developing coronary artery calcification. J. Am. Soc. Nephrol. 2009. 20(8): 1805-1812.

13. Dibas B.I., Warady B.A. Vitamin D status of children receiving chronic dialysis. Pediatr. Nephrol. 2012. 27(10): 1967-1973.

14. Ebbert K., Chow J., Krempien J. et al. Vitamin D insufficiency and deficiency in pediatric renal transplant recipients. Pediatr. Transplant. 2015. 19(5): 492-498.

15. Farah N.A., Lester M.A., Craig B.L. Vitamin D deficiency in children with chronic kidney disease: Uncovering an Epidemic. Pediatrics. 2009. 123(3): 791-796.

16. Franch H.A., Mitch W.E. Catabolism in uremia: the impact of metabolic acidosis. J. Am. Soc. Nephrol. 1998. 9(S12): 78-81.

17. González E.A., Sachdeva A., Oliver D.A. et al. Vitamin D insufficiency and deficiency in chronic kidney disease. A single center observational study. Am. J. Nephrol. 2004. 24(5): 503-510.

18. Green J., Kleeman C.R. Role of bone in regulation of systemic acidbase balance. Kidney Int. 1991. 39(1): 9-26.

19. Gupta A., Winer K., Econs M.J. et al. FGF-23 is elevated by chronic hyperphosphatemia. J. Clin. Endocrinol. Metab. 2004. 89(9): 4489-4492.

20. Hahn D., Hodson E.M., Craig J.C. Interventions for metabolic bone disease in children with chronic kidney disease. Cochrane Database Syst. Rev. 2015. 11: 1-90.

21. Hari P., Gupta N., Hari S. et al. Vitamin D insufficiency and effect of cholecalciferol in children with chronic kidney disease. Pediatr. Nephrol. 2010. 25(12): 2483-2488.

22. Haussler M.R., Whitfield G.K., Kaneko I. et. al. The role of vitamin D in the FGF23, klotho, and phosphate bone-kidney endocrine axis. Rev. Endocr. Metab. Disord. 2012. 13(1): 57-69.

23. Holick M.F. Vitamin D deficiency. N. Engl. J. Med. 2007. 357(3): 266-281.

24. Holick M.F., Binkley N.C., Bischoff-Ferrari H.A. et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 2011. 97(7): 1911-30.

25. K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am. J. Kidney Dis. 2005. 46(4, S1): 1-121.

26. Kaku Y., Ookawara S., Miyazawa H. et al. Approximation of Corrected Calcium Concentrations in Advanced Chronic Kidney Disease Patients with or without Dialysis Therapy. Nephron Extra. 2015. 5(2): 39-49.

27. Kalantar-Zadeh K., Shah A., Duong U. et al. Kidney bone disease and mortality in CKD: revisiting the role of vitamin D, calcimimetics, alkaline phosphatase, and minerals. Kidney Int. 2010. 78(S117): 10-21.

28. KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Inter-national. 2009. 76(S113): 1-130.

29. KDOQI clinical practice guideline for nutrition in children with CKD: 2008 Update. Am. J. Kidney Dis. 2009. 53(3, S2): 1-123.

30. Kestenbaum B., Sampson J.N., Rudser K.D. et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. J. Am. Soc. Nephrol. 2005. 16(2): 520-528.

31. Kraut J.A., Madias N.E. Metabolic Acidosis of CKD: An Update. Am. J. Kidney Dis. 2016. 67(2): 307-317.

32. Krieger N.S., Frick K.K., Bushinsky D.A. Mechanism of acidinduced bone resorption. Curr. Opin. Nephrol. Hypertens. 2004. 13(4): 423-436.

33. LaClair R.E., Hellman R.N., Karp S.L. et al. Prevalence of calcidiol deficiency in CKD: a cross-sectional study across latitudes in the United States. Am. J. Kidney Dis. 2005. 45(6): 1026-33.

34. Lee K.W., Lee S.T., Cho H. Optimal Vitamin D levels in Children with Chronic Kidney Disease. J. Nephrol. Ther. 2015. 5(4): 1-4.

35. Liu P.T. Tolllike receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006. 311(5768): 1770-1773.

36. Mahdavi H., Kuizon B.D., Gales B. et al. Sevelamer hydrochloride: an effective phosphate binder in dialyzed children. Pediatr. Nephrol. 2003. 18(12): 1260-1264.

37. Nigwekar S.U., Tamez H., Thadhani R.I. Vitamin D and chronic kidney disease-mineral bone disease (CKD-MBD). Bonekey Rep. 2014. 498(3): 1-6.

38. Payne R.B., Little A.J., Williams R.B. et al. Interpretation of serum calcium in patients with abnormal serum proteins. Br. Med. J. 1973. 5893(4): 643-646.

39. Peacock M. Calcium metabolism in health and disease. Clin. J. Am. Soc. Nephrol. 2010. 5(S1): 23-30.

40. Płudowski, P., Karczmarewicz E., Bayer M. et al. Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe -recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency. Endokrynologia Polska. 2013. 64(4): 319-327.

41. Prytuła A., Wells D., McLean T. et al. Urinary and dialysate losses of vitamin D-binding protein in children on chronic peritoneal dialysis. Pediatr. Nephrol. 2012. 27(4): 643-649.

42. Riccardi D., Brown E.M. Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am. J. Physiol. Renal. Physiol. 2010. 298(3): 485-499.

43. Sadlier D.M., Magee C.C. Prevalence of 25(OH) vitamin D (calcidiol) deficiency at time of renal transplantation: a prospective study. Clin. Transplant. 2007. 21(6): 683-688.

44. Salusky I.B., Goodman W.G., Sahney S. et al. Sevelamer controls parathyroid hormoneinduced bone disease as efficiently as calcium carbonate without increasing serum calcium levels during therapy with active vitamin D sterols. J. Am. Soc. Nephrol. 2005. 16(8): 2501-2508.

45. Seeherunvong W., Abitbol C.L., Chandar J. et al. Vitamin D insufficiency and deficiency in children with early chronic kidney disease. J. Pediatr. 2009. 154(6): 906-911.

46. Shah N., Bernardini J., Piraino B. Prevalence and correction of 25(OH) vitamin D deficiency in peritoneal dialysis patients. Perit. Dial. Int. 2005. 25(4): 362-366.

47. Shroff R., Wan M., Nagler E.V. et al. Clinical practice recommendations for native vitamin D therapy in children with chronic kidney disease Stages 2-5 and on dialysis. Nephrol. Dial. Transplant. 2017. 32(7): 1098-1113.

48. Shroff R., Wan M., Rees L. Can vitamin D slow down the progression of chronic kidney disease? Pediatr. Nephrol. 2012. 27(12): 2167-2173.

49. Spoto B., Pisano A., Zoccali C. Insulin resistance in chronic kidney disease: a systematic review. Am. J. Physiol. Renal. Physiol. 2016. 311(6): 1087-1108.

50. Stein D.R., Feldman H.A., Gordon C.M. Vitamin D status in children with chronic kidney disease. Pediatr. Nephrol. 2012. 27(8): 1341-1350.

51. Stubbs J.R., Egwuonwu S. Is fibroblast growth factor 23 a harbinger of mortality in CKD? Pediatr. Nephrol. 2012. 27(5): 697-703.

52. Tripkovic L., Lambert H., Hart K. et al. 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. 2012. 95(6): 1357-1364.

53. Wang C., Liu X., Zhou Y. New Conclusions Regarding Comparison of Sevelamer and Calcium-Based Phosphate Binders in Coronary-Artery Calcification for Dialysis Patients: A Meta-Analysis of Randomized Controlled Trials. PLoS One. 2015. 10(7): 1-15.

54. Wesseling K., Bakkaloglu S., Salusky I. Chronic kidney disease mineral and bone disorder in children. Pediatr. Nephrol. 2008. 23(2): 195-207.

55. Wesseling-Perry K. FGF-23 in bone biology. Pediatr. Nephrol. 2010. 25(4): 603-608.

56. Wesseling-Perry K., Salusky I.B. Chronic Kidney Disease: Mineral and Bone Disorder in Children. Semin. Nephrol. 2013. 33(2): 169-179.

57. Wolf M., Shah A., Gutierrez O. et al. Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int. 2007. 72(8): 1004-1013.