Preview

Osteoporosis and Bone Diseases

Advanced search

The effectiveness of nutritional vitamin D supplementation and selective vitamin D receptor agonists treatment on secondary hyperparathyroidism in chronic kidney diseases patients

Abstract

Background: secondary hyperparathyroidism (SHPT) is an early complication of chronic kidney disease (CKD). Maintaining the level of 25(OH)D and parathyroid hormone concentrations in the target range reduce its associated complications (fractures and cardiovascular calcification).


Aims: to examine the effectiveness of vitamin D supplementation and selective vitamin D receptor agonists treatment on SHPT in CKD.


Material and methods: prospective observational study to evaluate the efficacy and safety of vitamin D therapy SHPT in 54 in patients with CKD. The first phase (24 weeks) – treatment of suboptimal 25-hydroxycalciferol (25(OH)D) levels. The second (16 weeks) – treatment colecalciferol-resistant SHPT by combination of cholecalciferol with paricalcitol. Blood samples were taken to assess parathyroid hormone (PTH), 25(OH)D, creatinine, calcium, phosphorus levels and calcium excretion.


Results: After 8 weeks of cholecalciferol treatment all patients achieved 25(OH)D levels above 20 ng/ml, however 78% of patients still had SHPT. After 16 weeks, the decrease of PTH was achieved in all patients, but significantly only in patients with CKD 2 (19.2%, p< 0.01) and 3 (31%, p <0.05), compared with CKD 4 (17%, p >0.05). After 24 weeks of therapy, PTH normalized in all patients with CKD 2, in 15 (79%) with CKD 3 and in 9 (50%) patients with CKD 4. Cholecalciferol treatment resulted in a substantial increase in 25(OH)D levels with minimal or no impact on calcium, phosphorus levels and kidney function.


After 24 weeks we initiated combination therapy (cholecalciferol and paricalcitol) for patients with colecalciferol-resistant SHPT (n=13). PTH levels decreased from 149.1±13.4 to 118.2±14.1 pg/ml at 8 weeks, and to 93.1±9.7 pg/ml (p <0.05) at 16 weeks of treatment. No significant differences in serum calcium, phosphorus or urinary calcium levels. Normalization of PTH was achieved in all patients with CKD 3 and in 8 patients with stage 4. One patient with CKD 4 needed an increase in paricalcitol dose.


Conclusion: Cholecalciferol can be used in correcting vitamin D deficiency in patients with all stages of CKD, however, its effectiveness in reducing PTH in stage 4 is limited. Selective analogs, such as paricalcitol, were well-tolerated and effectively decreased PTH levels.

About the Authors

Lilit V. Egshatyan

Endocrinology Research Centre, Moscow, Russia; А.I. Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia


Russian Federation

MD, PhD



Natalya G. Mokrisheva

Endocrinology Research Centre


Russian Federation

MD, PhD



References

1. Vitamin D Deficiency. N. Engl. J. Med. 2007;357(19):1980-1982. doi: 10.1056/NEJMc072359.

2. Ravani P, Malberti F, Tripepi G, et al. Vitamin D levels and patient outcome in chronic kidney disease. Kidney Int. 2009;75(1):88-95. doi: 10.1038/ki.2008.501.

3. 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. doi: 10.1038/sj.ki.5002451.

4. Drechsler C, Pilz S, Obermayer-Pietsch B, et al. Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients. Eur. Heart J. 2010;31(18):2253-2261. doi: 10.1093/eurheartj/ehq246.

5. National Kidney F. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am. J. Kidney Dis. 2003;42(4 Suppl 3):S1-201.

6. Ketteler M, Block GA, Evenepoel P, et al. Executive summary of the 2017 KDIGO Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters. Kidney Int. 2017;92(1):26-36. doi: 10.1016/j.kint.2017.04.006.

7. Goldsmith DJA, Covic A, Fouque D, et al. Endorsement of the Kidney Disease Improving Global Outcomes (KDIGO) Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guidelines: a European Renal Best Practice (ERBP) commentary statement. Nephrology Dialysis Transplantation. 2010;25(12):3823-3831. doi: 10.1093/ndt/gfq513.

8. Kidney Disease: Improving Global Outcomes CKDMBDWG. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int. Suppl. 2009(113):S1-130. doi: 10.1038/ki.2009.188.

9. Alvarez JA, Law J, Coakley KE, et al. High-dose cholecalciferol reduces parathyroid hormone in patients with early chronic kidney disease: a pilot, randomized, double-blind, placebo-controlled trial. The American Journal of Clinical Nutrition. 2012;96(3):672-679. doi: 10.3945/ajcn.112.040642.

10. Dogan E, Erkoc R, Sayarlioglu H, et al. Effect of Depot Oral Cholecalciferol Treatment on Secondary Hyperparathyroidism in Stage 3 and Stage 4 Chronic Kidney Diseases Patients. Ren. Fail. 2009;30(4):407-410. doi: 10.1080/08860220801964210.

11. Oksa A, Spustova V, Krivosikova Z, et al. Effects of Long-Term Cholecalciferol Supplementation on Mineral Metabolism and Calciotropic Hormones in Chronic Kidney Disease. Kidney Blood Press. Res. 2008;31(5):322-329. doi: 10.1159/000157177.

12. Alvarez JA, Law J, Coakley KE, et al. High-dose cholecalciferol reduces parathyroid hormone in patients with early chronic kidney disease: a pilot, randomized, double-blind, placebo-controlled trial. The American Journal of Clinical Nutrition. 2012;96(3):672-679. doi: 10.3945/ajcn.112.040642.

13. Cupisti A, Egidi MF, Vigo V, et al. Vitamin D status and cholecalciferol supplementation in chronic kidney disease patients: an Italian cohort report. Int. J. Nephrol. Renovasc. Dis. 2015:151. doi: 10.2147/ijnrd.s90968.

14. Zisman AL, Hristova M, Ho LT, Sprague SM. Impact of Ergocalciferol Treatment of Vitamin D Deficiency on Serum Parathyroid Hormone Concentrations in Chronic Kidney Disease. Am. J. Nephrol. 2007;27(1):36-43. doi: 10.1159/000098561.

15. Gravesen E, Hofman-Bang J, Lewin E, Olgaard K. Ergocalciferol treatment and aspects of mineral homeostasis in patients with chronic kidney disease stage 4–5. Scand. J. Clin. Lab. Invest. 2013;73(2):107-116. doi: 10.3109/00365513.2012.744464.

16. Thimachai P, Supasyndh O, Chaiprasert A, Satirapoj B. Efficacy of High vs. Conventional Ergocalciferol Dose for Increasing 25-Hydroxyvitamin D and Suppressing Parathyroid Hormone Levels in Stage III-IV CKD with Vitamin D Deficiency/Insufficiency: A Randomized Controlled Trial. J. Med. Assoc. Thai. 2015;98(7):643-648.

17. Susantitaphong P, Nakwan S, Peerapornratana S, et al. A double-blind, randomized, placebo-controlled trial of combined calcitriol and ergocalciferol versus ergocalciferol alone in chronic kidney disease with proteinuria. BMC Nephrol. 2017;18(1). doi: 10.1186/s12882-017-0436-6.

18. Wetmore JB, Kimber C, Mahnken JD, Stubbs JR. Cholecalciferol v. ergocalciferol for 25-hydroxyvitamin D (25(OH)D) repletion in chronic kidney disease: a randomised clinical trial. Br. J. Nutr. 2017;116(12):2074-2081. doi: 10.1017/s000711451600427x.

19. Tokmak F, Quack I, Schieren G, et al. High-dose cholecalciferol to correct vitamin D deficiency in haemodialysis patients. Nephrology Dialysis Transplantation. 2008;23(12):4016-4020. doi: 10.1093/ndt/gfn367.

20. Jean G, Souberbielle JC, Chazot C. Monthly cholecalciferol administration in haemodialysis patients: a simple and efficient strategy for vitamin D supplementation. Nephrology Dialysis Transplantation. 2009;24(12):3799-3805. doi: 10.1093/ndt/gfp370.

21. Armas LAG, Andukuri R, Barger-Lux J, et al. 25-Hydroxyvitamin D Response to Cholecalciferol Supplementation in Hemodialysis. Clin. J. Am. Soc. Nephrol. 2012;7(9):1428-1434. doi: 10.2215/cjn.12761211.

22. Hewitt NA, O'Connor AA, O'Shaughnessy DV, Elder GJ. Effects of Cholecalciferol on Functional, Biochemical, Vascular, and Quality of Life Outcomes in Hemodialysis Patients. Clin. J. Am. Soc. Nephrol. 2013;8(7):1143-1149. doi: 10.2215/cjn.02840312.

23. Dusilová-Sulková S, Šafránek R, Vávrová J, et al. Low-dose cholecalciferol supplementation and dual vitamin D therapy in haemodialysis patients. Int. Urol. Nephrol. 2014;47(1):169-176. doi: 10.1007/s11255-014-0842-7.

24. Zitt E, Sprenger-Mähr H, Mündle M, Lhotta K. Efficacy and safety of body weight-adapted oral cholecalciferol substitution in dialysis patients with vitamin D deficiency. BMC Nephrol. 2015;16(1). doi: 10.1186/s12882-015-0116-3.

25. Shirazian S, Schanler M, Shastry S, et al. The Effect of Ergocalciferol on Uremic Pruritus Severity: A Randomized Controlled Trial. J. Ren. Nutr. 2013;23(4):308-314. doi: 10.1053/j.jrn.2012.12.007.

26. Bhan I, Dobens D, Tamez H, et al. Nutritional Vitamin D Supplementation in Dialysis: A Randomized Trial. Clin. J. Am. Soc. Nephrol. 2015;10(4):611-619. doi: 10.2215/cjn.06910714.

27. Miskulin DC, Majchrzak K, Tighiouart H, et al. Ergocalciferol Supplementation in Hemodialysis Patients With Vitamin D Deficiency: A Randomized Clinical Trial. J. Am. Soc. Nephrol. 2015;27(6):1801-1810. doi: 10.1681/asn.2015040468.

28. Heaney RP, Recker RR, Grote J, et al. Vitamin D3Is More Potent Than Vitamin D2in Humans. J. Clin. Endocr. Metab. 2011;96(3):E447-E452. doi: 10.1210/jc.2010-2230.

29. Khazai NB, Judd SE, Jeng L, et al. Treatment and Prevention of Vitamin D Insufficiency in Cystic Fibrosis Patients: Comparative Efficacy of Ergocalciferol, Cholecalciferol, and UV Light. J. Clin. Endocr. Metab. 2009;94(6):2037-2043. doi: 10.1210/jc.2008-2012.

30. Trang HM, Cole DE, Rubin LA, et al. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. The American Journal of Clinical Nutrition. 1998;68(4):854-858. doi: 10.1093/ajcn/68.4.854.

31. Zheng J-Q, Hou Y-C, Zheng C-M, et al. Cholecalciferol Additively Reduces Serum Parathyroid Hormone and Increases Vitamin D and Cathelicidin Levels in Paricalcitol-Treated Secondary Hyperparathyroid Hemodialysis Patients. Nutrients. 2016;8(11):708. doi: 10.3390/nu8110708.

32. Brown AJ, Finch J, Slatopolsky E. Differential effects of 19-nor-1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 on intestinal calcium and phosphate transport. J. Lab. Clin. Med. 2002;139(5):279-284. doi: 10.1067/mlc.2002.122819.

33. Coyne D, Acharya M, Qiu P, et al. Paricalcitol Capsule for the Treatment of Secondary Hyperparathyroidism in Stages 3 and 4 CKD. Am. J. Kidney Dis. 2006;47(2):263-276. doi: 10.1053/j.ajkd.2005.10.007.

34. Abboud H, Coyne D, Smolenski O, et al. A Comparison of Dosing Regimens of Paricalcitol Capsule for the Treatment of Secondary Hyperparathyroidism in CKD Stages 3 and 4. Am. J. Nephrol. 2006;26(1):105-114. doi: 10.1159/000092033.


Supplementary files

1. Fig. 1. Dynamics of the level of parathyroid hormone in patients with chronic kidney disease of the 3-4th stage during therapy with coralcaliferol and paricalcitol
Subject
Type Исследовательские инструменты
View (32KB)    
Indexing metadata ▾
2. Fig. 2. Dynamics of indicators of serum calcium and phosphorus, and daily calcium excretion in patients with chronic kidney disease of the 3-4th stage during therapy with co-calciferol and paricalcitol
Subject
Type Исследовательские инструменты
View (45KB)    
Indexing metadata ▾

Review

For citations:


Egshatyan L.V., Mokrisheva N.G. The effectiveness of nutritional vitamin D supplementation and selective vitamin D receptor agonists treatment on secondary hyperparathyroidism in chronic kidney diseases patients. Osteoporosis and Bone Diseases. 2018;21(2):12-22. (In Russ.)

Views: 4543


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2072-2680 (Print)
ISSN 2311-0716 (Online)