Vitamin D metabolism and current options for therapeutic activation of vitamin D receptor in patients with chronic kidney disease or renal failure
Authors:
S. Dusilová Sulková 1,2
Authors place of work:
Hemodialyzační středisko FN, Hradec Králové, vedoucí lékařka prof. MUDr. Sylvie Dusilová Sulková, DrSc., MBA
1; Klinika nefrologie, Transplantcentrum Institutu klinické a experimentální medicíny Praha, přednosta prof. MUDr. Ondřej Viklický, CSc.
2
Published in the journal:
Vnitř Lék 2012; 58(11): 839-849
Category:
Reviews
Summary
Chronic kidney disease (CKD), and chronic renal failure in particular, is associated with vitamin D deficiency and with a disorder of all metabolic processes that are associated with vitamin D. Calcidiol levels are often low. At present, efforts are made to test and to pharmacologically modulate its levels and thus to contribute to greater availability of the substrate for external calcitriol production. Calcitriol production is reduced in CKD patients not only as a consequence of diminishing functional renal parenchyma but also as a consequence of 1-α-hydroxylase inhibition by FGF-23 and other factors. On the other hand, although parathormone (PTH) increases renal production of calcitriol, it also causes secondary hyperparathyroidism. Synthetic calcitriol (or α-calcidiol) supresses PTH production and is used to treat secondary hyperparathyroidism. This approach is often associated with adverse increase in calcaemia and phosphataemia as the effect on parathyroid glands is associated with an effect on the gastrointestinal tract where calcium and phosphor absorption is increased by calcitriol. Synthetic analogues of vitamin D inhibit parathyroid gland but have significantly lower effect on gastrointestinal tract. Paricalcitol is a selective VDR (vitamin D receptor) activator, used for targeted suppression of parathyroid glands. Vitamin D deficiency in general population is associated, at least in epidemiological studies, with a range of medical complications and the same also applies to patients with renal disease. Although randomised studies are not available, clinical observational studies repeatedly showed treatment with VDR activators to be associated with better prognosis. As other fields of medicine, nephrology currently pays a great attention to vitamin D and vitamin D receptor activation.
Klíčová slova:
calcitriol – calcidiol – paricalcitol – chronic kidney disease – chronic renal failure – vitamin D receptor – secondary hyperparathyroidism
Zdroje
1. Vitamin D (příloha). Vnitř Lék 2012; 58: 378–416.
2. Dusilová Sulková S et al. Renální osteopatie. Praha: Maxdorf Jessenius, 2007.
3. Dusilová Sulková S. Kostní choroba při selhání ledvin a její moderní terapie. Vnitř Lék 2011; 57: 620–625.
4. Rodriguez M, Lorenzo V. Parathyroid hormone, a uremic toxin. Semin Dial 2009; 22: 363–368.
5. Go AS, Chertow GM, Fan D et al. Chronic kidney disease and the risk of death, cardiovascular events and hospitalization. N Engl J Med 2004; 351: 1296–1305.
6. Panichi V, Bigazzi R, Paoletti S et al. (RISCAVID Study Group) Impact of calcium, phosphate, PTH abnormalities and management on mortality in hemodialysis: results from the RISCAVID study. J Nephrol 2010; 23: 556–562.
7. LaClair RE, Hellman RN, Karp SL et al. Prevalence of calcidiol deficiency in CKD: a cross-sectional study across latitudes in United States. Am J Kidney Dis 2005; 45: 1026–1033.
8. Levin A, Bakris GL, Molitch M et al. 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 2007; 71: 31–38.
9. Jean G, Charra B, Chazot C. Vitamin D deficiency and associated factors in hemodialysis patients. J Ren Nutr 2008; 18: 395–399.
10. Ewers B, Gasbjerg A, Mølgaard Ch et al. Vitamin D status in kidney transplant patients: need for intensified routine supplementation. Am J Clin Nutr 2008; 87: 431–437.
11. Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357: 266–281.
12. Nigwekar SU, Bhan I, Thadhani R. Ergocalciferol and cholecalciferol in CKD. Am J Kidney Dis 2012; 60: 139–156.
13. Ala-Houhala MJ, Vahavihu K, Hasan T. Narrow-band ultraviolet B exposure increases serum vitamin D levels in haemodialysis patients. Nephrol Dial Transplant 2012; 27: 2435–2440.
14. Michaud J, Naud J, Quimet D et al. Reduced hepatic synthesis of calcidiol in uremia. J Am Soc Nephrol 2011; 21: 1488–1497.
15. Dusso AS. Kidney disease and vitamin D levels: 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and VDR activation. Kidney Int 2011; 79: (Suppl. 1): 136–141.
16. Dusso AS, Tokumoto M. Defective renal maintenance of the vitamin D endocrine system impairs vitamin D renoprotection: a downeard spiral in kidney disease. Kidney Int 2011; 79: 715–729.
17. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003; 42: (Suppl. 3): S1–S201.
18. Kidney Disease Improving Global Outcomes (KDIGO) CKD-MBD work group KDIGO clinical practice guideline for the diagnosis, evaluation, prevention and treatment of chronic kidney disease – mineral bone disorder (CKD-MBD). Kidney Int 2009; 76: (Suppl. 113): S1–S130.
19. Dusso AS, Brown AJ, Slatopolsky E. Vitamin D. Am J Physiol Renal Physiol 2005; 289: F8–F28.
20. Prie D, Friedlander G. Reciprocal control of 1,25-dihydroxyvitamin D and FGF-23 formation involving the FGF-23/Klotho system Clin J Am Soc Nephrol 2010; 5: 1717–1722.
21. Dusilová Sulková S, Kalousová M. Fibroblastový růstový faktor 23 (FGF-23, fibroblast growth factor 23) je molekulou s velkým významem pro klinickou, dialyzační i transplantační nefrologii – základní přehled současných poznatků. Aktuality v nefrologii 2011; 17: 17–22.
22. Sochorová K, Budinský V, Rožková D et al. Paricalcitol (19-nor-1,25dihydroxyvitamin D2) and calcitriol (1,25-dihydroxyvitamin D3) exert potent immunomodulatory effects on dendritic cells and inhibit induction of antigen-specific T cells. Clin Immunol 2009; 133: 69–77.
23. Patel T, Singh AK. Role of vitamin D in chronic kidney disease. Semin Nephrol 2009; 29: 113–121.
24. Andress DL. Vitamin D in chronic kidney disease: a systemic role for selective vitamin D receptor activation. Kidney Int 2006; 69: 33–43.
25. Bosworth CR, Levin G, Robinson-Cohen C et al. The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease. Kidney Int 2012; doi:10.1038/ki.2012.193.
26. Lee CT, Ng HY, Lien YH et al. Effects of cyclosporine, tacrolimus and rapamycin on renal calcium transport and vitamin D metabolism. Am J Nephrol 2011; 34: 87–94.
27. Brown AJ, Coyne DV. Bioavailable vitamin D in chronic kidney disease. Kidney Int 2012; 82: 5–7.
28. Bhan I, Powe CE, Berg AH et al. Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients. Kidney Int 2012; 82: 84–89.
29. London GM, Guerin AP, Marchais SJ et al. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 2003; 18: 1731–1740.
30. Mizobuchi M, Towler D, Slatopolsky E. Vascular calcification: The killer of patients with chronic kidney disease. J Am Soc Nephrol 2009; 20: 1453–1464.
31. Rodriguez M, Martinez-Moreno JM, Rodriguez-Ortiz ME. Vitamin D and vascular calcification in chronic kidney disease. Kidney Blood Press Res 2011; 34: 261–268.
32. Garcia-Canton C, Bosch E, Ramirez A et al. Vascular calcification and 25-hydroxyvitamin D in non-dialysis patients with chronic kidney disease stages 4 and 5. Nephrol Dial Transplant 2011; 26: 2250–2256.
33. Thadhani R, Appelbaum E, Pritchett Y et al. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. J Am Med Assoc 2012; 307: 674–684.
34. Alborzi P, Patel NA, Peterson C et al. Paricalcitol reduces albuminuria and inflammation in chronic kidney disease: a randomized double--blind pilot trial. Hypertension 2008; 52: 249–255.
35. Agarwal R. Vitamin D, proteinuria, diabetic nephropathy and progression of CKD. Clin J Am Soc Nephrol 2009; 4: 1523–1528.
36. Liu LJ, Lv JC, Shi SF et al. Oral calcitriol for reduction of proteinuria in patients with IgA nephropathy: a randomized controlled trial. Am J Kidney Dis 2012; 59: 67–74.
37. de Zeeuw D, Agarwal R, Amdahl M et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomized controlled trial. Lancet 2010; 376: 1543–1551.
38. Courbebaisse M, Souberbielle JC, Thervet E. Potential nonclassical effects of vitamin D in transplant recipients. Transplantation 2010; 89: 131–137.
39. Armas LAG, Andukuri R, Barger-Lux J et al. 25-hydroxyvitamin D response to cholekalciferol supplementation in hemodialysis. Clin J Am Soc Nephrol 2012; T: 1428-1434.
40. Cunningham J. Supplemental vitamin D: will do no harm and might do good. Nature Rev Nephrol 2009; 5: 614–615.
41. Kandula P, Dobre M, Schold JD et al. Vitamin D supplementation in chronic kidney disease: A systematic review and meta-analysis of observational studies and randomized controlled trials. Clin J Am Soc Nephrol 2011; 6: 50–62.
42. Jones G. Why Dialysis Patients Need Combination Therapy with Both Cholecalciferol and A Calcitriol Analogs. Semin Dial 2010; 23: 239–243.
43. Slatopolsky E, Weerts C, Thielan J et al. Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxycholecalciferol in uremic patients. J Clin Invest 1984; 74: 2136–2143.
44. Wu-Wong JR, Nakane M, Ma J et al. Effects of Vitamin D analogs on gene expression profiling in human coronary artery smooth muscle cells. Atherosclerosis 2006; 186: 20–28.
45. Martin JK, Gonzalez E, Lindgerg JS et al. Paricalcitol dosing according to body weight or severity of hyperparathyroidism: a double-blind, multicenter, randomized study. Am J Kidney Dis 2001; 38: (Supp. 5): S57–S63.
46. Cozzolino M, Brancaccio D. Emerging role for the vitamin D receptor activator (VDRA), paricalcitol, in the treatment of secondary hyperparathyroidism. Expert Opin Pharmacother 2008; 9: 947–954.
47. Ross EA, Tian J, Abboud H et al. Oral paricalcitol for the treatment of secondary hyperparathyroidism in patients on hemodialysis or peritoneal dialysis. Am J Nephrol 2008; 28: 97–106.
48. Coyne D, Acharva 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: 263–276.
49. Li YC. Vitamin D: roles in renal and cardiovascular protection. Curr Opin Nephrol Hypertens 2012; 21: 72–79.
50. Drechsler C, Verduijn M, Pilz S et al. Vitamin D status and clinical outcomes in incident dialysis patients: results from the NECOSAD study. Nephrol Dial Transplant 2011; 26: 1024–1032.
51. Wolf M, Shah A, Gutierrez O et al. Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 2007; 72: 1004–1013.
52. Oksa A, Spustová V, Krivosíková 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: 322–329.
53. Sulková S, Fořtová M, Uhrová J et al. Význam stanovení metabolitů vitaminu D u pacientů se sníženou funkcí ledvin. Vnitř Lék 2004; 50: 510–518.
54. Teng M, Wolf M, Lowrie E et al. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med 2003; 349: 446–456.
55. Teng M, Wolf M, Ofsthun MN et al. Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol 2005; 16: 1115–1125.
56. Kovesdy CP. Survival benefits with vitamin D receptor activation: New insights since 2003. Clin J Am Soc Nephrol 2010; 5: 1704–1709.
57. Naves-Díaz M, Alvarez-Hernández D, Passlick-Deetjen J et al. Oral active vitamin D is associated with improved survival in hemodialysis patients. Kidney Int 2008; 74: 1070–1078.
58. Shoben AB, Rudser KD, de Boer IH et al. Association of oral calcitriol with improved survival in nondialyzed CKD. J Am Soc Nephrol 2008; 19: 1613–1619.
59. Kalantar-Zadeh K, Kovesdy CP Clinical outcomes with active versus nutritional vitamin D compounds in chronic kidney disease. Clin J Am Soc Nephrol 2009; 4: 1529–1539.
60. Melamed ML, Thadhani RI. Vitamin D therapy in chronic kidney disease and end stage renal disease. Clin J Am Soc Nephrol 2012; 7: 358–365.
61. Cozzolino M, Brancaccio D, Cannella G et al. VDRA therapy is associated with improved survival in dialysis patients with serum intact PTH <=150 pg/mL: results of the Italian FARO Survey. Nephrol Dial Transplant 2012; 27:3588-3594.
62. Kovesdy CP, Lu JL, Malakuaskas S et al. Paricalcitol versus ergocalciferol for secondary hyperparathyroidism in CKD stages 3 and 4: A randomized controlled trial. Am J Kidney Dis 2012; 59: 58–66.
63. Ketteler M, Martin KJ, Cozzolino M et al. Paricalcitol versus cinacalcet plus low-dose vitamin D for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: study design and baseline characteristics of the IMPACT SHPT study. Nephrol Dial Transplant 2012; doi:10.1093/ndt/gfr531.
64. Ketteler M, Martin KJ, Wolf M et al. Paricalcitol versus cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: Results of the IMPACT SHPT study. Nephrol Dial Transpant 2012; 27: 1942-1949.
65. Cheng J, Zhang W, Zhang X et al. Efficacy and safety of paricalcitol therapy for chronic kidney disease: A meta-analysis. Clin J Am Soc Nephrol 2012; 7: 391–400.
Štítky
Diabetology Endocrinology Internal medicineČlánok vyšiel v časopise
Internal Medicine
2012 Číslo 11
Najčítanejšie v tomto čísle
- Coronary-subclavian steal syndrome, a complication following surgical revascularization of myocardium
- Vitamin D metabolism and current options for therapeutic activation of vitamin D receptor in patients with chronic kidney disease or renal failure
- Left ventricular myxoma – an unexpected cause of dyspnoea and fever in a young patient
- Carcinoid and its cardiac manifestation