The aim of the present study was to evaluate the dose of postdialysis cholecalciferol needed to maintain the 25-hydroxyvitamin D [25(OH)D] levels in the optimal range of 75–150？nmol/L. Twenty-six patients who had low baseline 25(OH)D levels (mean ？nmol/L) were studied. The 25(OH)D levels were measured every 2 months for one year. During the first two months, all the patients received 2000？IU of cholecalciferol after each hemodialysis (=6000？IU/wk). Thereafter, the dose was individualized and adapted every 2 months by administering 1 to 6 cholecalciferol tablets (2000？IU each) per week (total weekly dose = 2000–12000？IU/wk). During cholecalciferol supplementation, the 25(OH)D concentrations rapidly increased from baseline to ？nmol/L at month 6 and ？nmol/L at month 12. At month twelve, 86% of the patients had 25(OH)D levels within the target range with a mean dose of ？IU/wk of cholecalciferol; however, the amount needed to maintain these levels varied widely from 0 ( ) to 12000？IU/wk ( ). In conclusion, postdialysis cholecalciferol prescription is quite effective in correcting vitamin D deficiency/insufficiency, but the amount of cholecalciferol needed to maintain the 25(OH)D levels within the optimal range over the long-term varies widely among patients and must be individualized. 1. Introduction Recent important advances have been made in understanding vitamin D physiology, beyond its classic role in mineral and bone metabolism [1–11]. Indeed, recent studies have shown that several tissues, in addition to the kidneys, express the enzyme CYP27B1, which catalyzes the 1 -hydroxylation of 25(OH)D, and that the vitamin D receptor (VDR) is expressed ubiquitously [1–11]. It is now known that a conversion of 25(OH)D to 1 ,25-dihydroxyvitamin D (calcitriol, the active form of vitamin D) occurs in several extrarenal cells and may be associated with significant biological roles beyond those traditionally attributed to vitamin D [1–11]. As a consequence, there has been a great deal of interest in the study of these nonclassical autocrine/intracrine effects of vitamin D during the past few years and a significant body of information in the medical literature has shown that vitamin D deficiency/insufficiency is associated with several abnormalities such as an increased risk of cardiovascular, musculoskeletal and autoimmune diseases, cancer, infections, diabetes, and mortality [1–6, 12–27]. As a result, the possible benefits of vitamin D supplementation in patients with low levels became the focus of interest of the scientific community and studies have even reported
References
[1]
M. F. Holick, “Medical progress: vitamin D deficiency,” The New England Journal of Medicine, vol. 357, no. 3, pp. 266–281, 2007.
[2]
M. F. Holick and T. C. Chen, “Vitamin D deficiency: a worldwide problem with health consequences,” The American Journal of Clinical Nutrition, vol. 87, no. 4, pp. 1080S–1086S, 2008.
[3]
S. A. Stechschulte, R. S. Kirsner, and D. G. Federman, “Vitamin D: bone and beyond, rationale and recommendations for supplementation,” The American Journal of Medicine, vol. 122, no. 9, pp. 793–802, 2009.
[4]
J. Rojas-Rivera, C. de la Piedra, A. Ramos, A. Ortiz, and J. Egido, “The expanding spectrum of biological actions of vitamin D,” Nephrology Dialysis Transplantation, vol. 25, no. 9, pp. 2850–2865, 2010.
[5]
A. Verstuyf, G. Carmeliet, R. Bouillon, and C. Mathieu, “Vitamin D: a pleiotropic hormone,” Kidney International, vol. 78, no. 2, pp. 140–145, 2010.
[6]
J.-C. Souberbielle, J.-J. Body, J. M. Lappe et al., “Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: recommendations for clinical practice,” Autoimmunity Reviews, vol. 9, no. 11, pp. 709–715, 2010.
[7]
A. Hossein-Nezhad, A. Spira, and M. F. Holick, “Influence of vitamin D status and vitamin D3 supplementation on genome wide expression of white blood cells: a randomized double-blind clinical trial,” PloS ONE, vol. 8, Article ID e58725, 2013.
[8]
N. Binkley, R. Ramamurthy, and D. Krueger, “Low vitamin D status: definition, prevalence, consequences, and correction,” Endocrinology and Metabolism Clinics of North America, vol. 39, no. 2, pp. 287–301, 2010.
[9]
T. V. Patel and A. K. Singh, “Role of vitamin D in chronic kidney disease,” Seminars in Nephrology, vol. 29, no. 2, pp. 113–121, 2009.
[10]
S. U. Nigwekar, I. Bhan, and R. Thadhani, “Ergocalciferol and cholecalciferol in CKD,” The American Journal of Kidney Diseases, vol. 60, pp. 139–156, 2012.
[11]
I. Bhan, M. Hewison, and R. Thadhani, “Dietary vitamin D intake in advanced CKD/ESRD,” Seminars in Dialysis, vol. 23, no. 4, pp. 407–410, 2010.
[12]
M. L. Melamed, E. D. Michos, W. Post, and B. Astor, “25-hydroxyvitamin D levels and the risk of mortality in the general population,” Archives of Internal Medicine, vol. 168, no. 15, pp. 1629–1637, 2008.
[13]
I. H. de Boer, G. Levin, C. Robinson-Cohen et al., “Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults a cohort study,” Annals of Internal Medicine, vol. 156, no. 9, pp. 627–634, 2012.
[14]
J. H. Lee, J. H. O'Keefe, D. Bell, D. D. Hensrud, and M. F. Holick, “Vitamin D deficiency. An important, common, and easily treatable cardiovascular risk factor?” Journal of the American College of Cardiology, vol. 52, no. 24, pp. 1949–1956, 2008.
[15]
M. Wolf, A. Shah, O. Gutierrez et al., “Vitamin D levels and early mortality among incident hemodialysis patients,” Kidney International, vol. 72, no. 8, pp. 1004–1013, 2007.
[16]
N. Boudville, C. Inderjeeth, G. J. Elder, and P. Glendenning, “Association between 25-hydroxyvitamin D, somatic muscle weakness and falls risk in end-stage renal failure,” Clinical Endocrinology, vol. 73, no. 3, pp. 299–304, 2010.
[17]
C. Drechsler, M. Verduijn, S. Pilz et al., “Vitamin D status and clinical outcomes in incident dialysis patients: results from the NECOSAD study,” Nephrology Dialysis Transplantation, vol. 26, no. 3, pp. 1024–1032, 2011.
[18]
R. Mehrotra, D. A. Kermah, I. B. Salusky et al., “Chronic kidney disease, hypovitaminosis D, and mortality in the United States,” Kidney International, vol. 76, no. 9, pp. 977–983, 2009.
[19]
C. Drechsler, S. Pilz, B. Obermayer-Pietsch et al., “Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients,” European Heart Journal, vol. 31, no. 18, pp. 2253–2261, 2010.
[20]
S. Pilz, A. Tomaschitz, C. Friedl et al., “Vitamin D status and mortality in chronic kidney disease,” Nephrology Dialysis Transplantation, vol. 26, no. 11, pp. 3603–3609, 2011.
[21]
R. Krause, H.-J. Schober-Halstenberg, G. Edenharter, K. Haas, H. J. Roth, and U. Frei, “Vitamin D status and mortality of German hemodialysis patients,” Anticancer Research, vol. 32, no. 1, pp. 391–395, 2012.
[22]
D. Santoro, L. Gitto, A. Ferraro, E. Satta, V. Savica, and G. Bellinghieri, “Vitamin D status and mortality risk in patients with chronic kidney disease,” Renal Failure, vol. 33, no. 2, Article ID 553303, pp. 184–191, 2011.
[23]
S. Anand, G. A. Kaysen, G. M. Chertow et al., “Vitamin D deficiency, self-reported physical activity and health-related quality of life: the comprehensive dialysis study,” Nephrology Dialysis Transplantation, vol. 26, no. 11, pp. 3683–3688, 2011.
[24]
R. Fiedler, O. Dorligjav, E. Seibert, C. Ulrich, S. Markau, and M. Girndt, “Vitamin D deficiency, mortality, and hospitalization in hemodialysis patients with or without protein-energy wasting,” Nephron, vol. 119, no. 3, pp. c220–c226, 2011.
[25]
G. Jean, D. Lataillade, L. Genet et al., “Impact of hypovitaminosis D and alfacalcidol therapy on survival of hemodialysis patients: results from the French ARNOS study,” Nephron, vol. 118, no. 2, pp. c204–c210, 2011.
[26]
L. A. G. Armas and R. P. Heaney, “Vitamin D: the iceberg nutrient,” Journal of Renal Nutrition, vol. 21, no. 2, pp. 134–139, 2011.
[27]
K. Shaffi, H. Tighiouart, T. Scott et al., “Low 25-hydroxyvitamin D levels and cognitive impairment in hemodialysis patients,” Clinical Journal of the American Society of Nephrology, vol. 8, no. 6, pp. 979–986, 2013.
[28]
H.-C. Chang, C.-L. Chen, T.-L. Chiu, S.-I. Chen, A. M.-F. Yen, and T. H.-H. Chen, “Effectiveness of recombinant human erythropoietin, vitamin D3 and iron therapy on long-term survival of patients with end-stage renal disease receiving haemodialysis: analysis of 702 patients after 10-year follow-up,” Public Health Nutrition, vol. 12, no. 12, pp. 2410–2415, 2009.
[29]
L. Rejnmark, A. Avenell, T. Masud, et al., “Vitamin D with calcium reduces mortality: patient level pooled analysis of 70, 528 patients from eight major vitamin D trials,” The Journal of Clinical Endocrinology & Metabolism, vol. 97, pp. 2670–2681, 2012.
[30]
R. Vieth, “Why the minimum desirable serum 25-hydroxyvitamin D level should be 75 nmol/L (30？ng/ml),” Best Practice & Research, vol. 25, no. 4, pp. 681–691, 2011.
[31]
M. Audran and K. Briot, “Critical reappraisal of vitamin D deficiency,” Joint Bone Spine, vol. 77, no. 2, pp. 115–119, 2010.
[32]
M. F. Holick, “Evidence-based D-bate on health benefits of vitamin D revisited,” Dermato-Endocrinology, vol. 4, pp. 183–190, 2012.
[33]
H. A. Bischoff-Ferrari, A. Shao, B. Dawson-Hughes, J. Hathcock, E. Giovannucci, and W. C. Willett, “Benefit-risk assessment of vitamin D supplementation,” Osteoporosis International, vol. 21, no. 7, pp. 1121–1132, 2010.
[34]
M. F. Holick, N. C. Binkley, H. A. Bischoff-Ferrari et al., “Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline,” The Journal of Clinical Endocrinology & Metabolism, vol. 96, no. 1911, p. 1930, 2011.
[35]
E. M. Brouwer-Brolsma, H. A. Bischoff-Ferrari, R. Bouillon, et al., “Vitamin D: do we get enough? A discussion between vitamin D experts in order to make a step towards the harmonisation of dietary reference intakes for vitamin D across Europe,” Osteoporosis International, vol. 24, pp. 1567–1577, 2013.
[36]
C. L. Benhamou, J. C. Souberbielle, B. Cortet, P. Fardellone, J. B. Gauvain, and T. Thomas, “Vitamin D in adults: GRIO guidelines,” La Presse Médicale, vol. 40, pp. 673–682, 2011.
[37]
H. A. Bischoff-Ferrari, U. Keller, P. Burckhardt, et al., “Vitamin D deficiency: evidence, safety and recommendations for the Swiss population,” Forum Médical Suisse, vol. 12, pp. 775–778, 2012.
[38]
G. Jean, M.-H. Lafage-Proust, Z. A. Massy, and T. B. Drüeke, “Guidelines for vitamin D prescription in dialysis patients,” Nephrologie et Therapeutique, vol. 5, no. 6, pp. 520–532, 2009.
[39]
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 and bone disorder (CKD-MBD),” Kidney International Supplements, no. 113, pp. S1–S130, 2009.
[40]
A. Fournier, P. Fardellone, J. M. Achard et al., “Importance of vitamin D repletion in uraemia,” Nephrology Dialysis Transplantation, vol. 14, no. 4, pp. 819–823, 1999.
[41]
J. B. Cannata-Andía and C. Gómez Alonso, “Vitamin D deficiency: a neglected aspect of disturbed calcium metabolism in renal failure,” Nephrology Dialysis Transplantation, vol. 17, no. 11, pp. 1875–1878, 2002.
[42]
H. Taskapan, M. Wei, and D. G. Oreopoulos, “25(OH) vitamin D3 in patients with chronic kidney disease and those on dialysis: rediscovering its importance,” International Urology and Nephrology, vol. 38, no. 2, pp. 323–329, 2006.
[43]
A. Gal-Moscovici and S. M. Sprague, “Use of vitamin D in chronic kidney disease patients,” Kidney International, vol. 78, no. 2, pp. 146–151, 2010.
[44]
K. Kalantar-Zadeh and C. P. Kovesdy, “Clinical outcomes with active versus nutritional vitamin D compounds in chronic kidney disease,” Clinical Journal of the American Society of Nephrology, vol. 4, no. 9, pp. 1529–1539, 2009.
[45]
A. Dusso, E. A. González, and K. J. Martin, “Vitamin D in chronic kidney disease,” Best Practice & Research, vol. 25, pp. 647–655, 2011.
[46]
P. Kandula, M. Dobre, J. D. Schold, M. J. Schreiber Jr., R. Mehrotra, and S. D. Navaneethan, “Vitamin D supplementation in chronic kidney disease: a systematic review and meta-analysis of observational studies and randomized controlled trials,” Clinical Journal of the American Society of Nephrology, vol. 6, no. 1, pp. 50–62, 2011.
[47]
M. L. Melamed and R. I. Thadhani, “Vitamin D therapy in chronic kidney disease and end stage renal disease,” Clinical Journal of the American Society of Nephrology, vol. 7, no. 2, pp. 358–365, 2012.
[48]
E. Jakopin, B. Pecovnik Balon, R. Ekart, and M. Gorenjak, “High-dose cholecalciferol supplementation for vitamin D deficiency in haemodialysis patients,” Journal of International Medical Research, vol. 39, no. 3, pp. 1099–1106, 2011.
[49]
L. A. Armas, R. Andukuri, J. Barger-Lux, R. P. Heaney, and R. Lund, “25-Hydroxyvitamin D response to cholecalciferol supplementation in hemodialysis,” Clinical Journal of the American Society of Nephrology, vol. 7, pp. 1428–1434, 2012.
[50]
D. Blair, L. Byham-Gray, E. Lewis, and S. McCaffrey, “Prevalence of vitamin D [25(OH)D] deficiency and effects of supplementation with ergocalciferol (vitamin D2) in stage 5 chronic kidney disease patients,” Journal of Renal Nutrition, vol. 18, no. 4, pp. 375–382, 2008.
[51]
G. Jean, J.-C. Terrat, T. Vanel et al., “Daily oral 25-hydroxycholecalciferol supplementation for vitamin D deficiency in haemodialysis patients: effects on mineral metabolism and bone markers,” Nephrology Dialysis Transplantation, vol. 23, no. 11, pp. 3670–3676, 2008.
[52]
G. Jean, J.-C. Souberbielle, and C. Chazot, “Monthly cholecalciferol administration in haemodialysis patients: a simple and efficient strategy for vitamin D supplementation,” Nephrology Dialysis Transplantation, vol. 24, no. 12, pp. 3799–3805, 2009.
[53]
F. Tokmak, I. Quack, G. Schieren et al., “High-dose cholecalciferol to correct vitamin D deficiency in haemodialysis patients,” Nephrology Dialysis Transplantation, vol. 23, no. 12, pp. 4016–4020, 2008.
[54]
E. González-Parra, P. J. Avila, I. Mahillo-Fernández et al., “High prevalence of winter 25-hydroxyvitamin D deficiency despite supplementation according to guidelines for hemodialysis patients,” Clinical and Experimental Nephrology, vol. 16, pp. 945–951, 2012.
[55]
W. Y. Qunibi, A. Abdellatif, S. Sankar et al., “Treatment of vitamin D deficiency in CKD patients with ergocalciferol: are current K/DOQI treatment guidelines adequate?” Clinical Nephrology, vol. 73, no. 4, pp. 276–285, 2010.
[56]
H. Wasse, R. Huang, Q. Long, S. Singapuri, P. Raggi, and V. Tangpricha, “Efficacy and safety of a short course of very-high-dose cholecalciferol in hemodialysis,” The American Journal of Clinical Nutrition, vol. 95, no. 2, pp. 522–528, 2012.
[57]
E. Descombes, A. B. Hanck, and G. Fellay, “Water soluble vitamins in chronic hemodialysis patients and need for supplementation,” Kidney International, vol. 43, no. 6, pp. 1319–1328, 1993.
[58]
E. Descombes, O. Boulat, F. Perriard, and G. Fellay, “Water-soluble vitamin levels in patients undergoing high-flux hemodialysis and receiving long-term oral postdialysis vitamin supplementation,” Artificial Organs, vol. 24, no. 10, pp. 773–778, 2000.
[59]
E. Descombes, O. Boulat, L.-F. Bersier, and G. Fellay, “Difference in the homocysteine-lowering effect of folic acid in haemodialysis patients with and without occlusive vascular disease,” Nephrology Dialysis Transplantation, vol. 16, no. 3, pp. 585–589, 2001.
[60]
C. Hamatake, “The many forms and functions of essential Vitamin D for dialysis patients,” Journal of Renal Nutrition, vol. 23, no. 4, pp. e87–e88, 2013.
[61]
A. Bock and L. Luthi, “Simple and effective treatment of 25OH-vitamin D3 deficiency in hemodialysis patients,” Swiss Medical Weekly, vol. 138, supplement 167, p. 8, 2008.
[62]
M. Vogeser, “Quantification of circulating 25-hydroxyvitamin D by liquid chromatography-tandem mass spectrometry,” Journal of Steroid Biochemistry and Molecular Biology, vol. 121, no. 3-5, pp. 565–573, 2010.
[63]
B. Fellay, Y. Guillod, N. Jorand, G. Allemann, J. L. Magnin, and E. Descombes, “Accuracy of five 25-hydroxyvitamin D assays as compared to the reference method LC-MS/MS in chronic hemodialysis patients,” Swiss Medical Weekly, vol. 142, supplement 196, pp. 17–18, 2012.
[64]
I. Guessous, V. Dudler, N. Glat, et al., “Vitamin D levels and associated factors: a population-based study in Switzerland,” Swiss Medical Weekly, vol. 142, Article ID w13719, 2012.
[65]
G. Togni and D. Burki, “Vitamin D: deficiency and supplementation,” Le Vigaro, vol. 159, p. 1, 2011.
[66]
M. J. Bolland, W. W. Chiu, J. S. Davidson et al., “The effects of seasonal variation of 25-hydroxyvitamin D on diagnosis of vitamin D insufficiency,” New Zealand Medical Journal, vol. 121, no. 1286, pp. 63–74, 2008.
[67]
A. R. Webb, R. Kift, M. T. Durkin et al., “The role of sunlight exposure in determining the vitamin D status of the U.K. white adult population,” British Journal of Dermatology, vol. 163, no. 5, pp. 1050–1055, 2010.
[68]
T. C. Chen, F. Chimeh, Z. Lu et al., “Factors that influence the cutaneous synthesis and dietary sources of vitamin D,” Archives of Biochemistry and Biophysics, vol. 460, no. 2, pp. 213–217, 2007.
[69]
G. J. Elder, “Vitamin D levels, bone turnover and bone mineral density show seasonal variation in patients with chronic kidney disease stage 5,” Nephrology, vol. 12, no. 1, pp. 90–94, 2007.
[70]
S. Ish-Shalom, E. Segal, T. Salganik, B. Raz, I. L. Bromberg, and R. Vieth, “Comparison of daily, weekly, and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients,” The Journal of Clinical Endocrinology & Metabolism, vol. 93, no. 9, pp. 3430–3435, 2008.
[71]
M. F. Holick, R. M. Biancuzzo, T. C. Chen et al., “Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D,” The Journal of Clinical Endocrinology & Metabolism, vol. 93, no. 3, pp. 677–681, 2008.
[72]
P. Leventis and P. D. W. Kiely, “The tolerability and biochemical effects of high-dose bolus vitamin D2 and D3 supplementation in patients with vitamin D insufficiency,” Scandinavian Journal of Rheumatology, vol. 38, no. 2, pp. 149–153, 2009.
[73]
N. Binkley, D. Gemar, J. Engelke et al., “Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults,” The Journal of Clinical Endocrinology & Metabolism, vol. 96, no. 4, pp. 981–988, 2011.
[74]
V. F. Logan, A. R. Gray, M. C. Peddie, M. J. Harper, and L. A. Houghton, “Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months,” British Journal of Nutrition, vol. 109, pp. 1082–1088, 2013.
[75]
A. C. Heijboer, M. A. Blankenstein, I. P. Kema, and M. M. Buijs, “Accuracy of 6 routine 25-hydroxyvitamin D assays: influence of vitamin D binding protein concentration,” Clinical Chemistry, vol. 58, no. 3, pp. 543–548, 2012.
[76]
M. K. Koivula, N. Matinlassi, P. Laitinen, and J. Risteli, “Four automated 25-OH total vitamin D immunoassays and commercial liquid chromatography tandem-mass spectrometry in Finnish population,” Clinical Laboratory, vol. 59, no. 3-4, pp. 397–405, 2013.
[77]
A. R. Webb, B. R. DeCosta, and M. F. Holick, “Sunlight regulates the cutaneous production of vitamin D3 by causing its photodegradation,” The Journal of Clinical Endocrinology & Metabolism, vol. 68, no. 5, pp. 882–887, 1989.
[78]
N. Binkley, R. Novotny, D. Krueger et al., “Low vitamin D status despite abundant sun exposure,” The Journal of Clinical Endocrinology & Metabolism, vol. 92, no. 6, pp. 2130–2135, 2007.
[79]
L. Cuppari, A. B. Carvalho, and S. A. Draibe, “Vitamin D status of chronic kidney disease patients living in a sunny country,” Journal of Renal Nutrition, vol. 18, no. 5, pp. 408–414, 2008.
[80]
R. P. Heaney, M. J. Barger-Lux, M. S. Dowell, T. C. Chen, and M. F. Holick, “Calcium absorptive effects of vitamin D and its major metabolites,” The Journal of Clinical Endocrinology & Metabolism, vol. 82, no. 12, pp. 4111–4116, 1997.
[81]
G. Jean, T. Vanel, J.-C. Terrat, and C. Chazot, “Prevention of secondary hyperparathyroidism in hemodialysis patients: the key role of native vitamin D supplementation,” Hemodialysis International, vol. 14, no. 4, pp. 486–491, 2010.
