Background/Aims: Is cholecalciferol (D3) superior to ergocalciferol (D2) in treating nutritional vitamin D deficiency in chronic kidney disease (CKD)? The answer to this question has not been fully explored. Methods: A retrospective analysis of 57 patients with non-dialysis-requiring CKD was conducted to assess the relative effectiveness of D2 versus D3 replacement on circulating 25(OH)D levels. Levels of 25(OH) D were assessed at baseline, after attempted repletion with D2, and then after attempted repletion with D3. The relative paired differences of the drug treatment effects were tested using t-tests. Multiple regression modeling was used to determine the factors significantly associated with differential responsiveness to the drugs. Results: The mean (SEM) age was 66.4 ± 1.4 and mean eGFR was 40.5 ± 2.2 ml/min/1.73 m2. The baseline 25(OH)D level was 15.3 ± 0.8 ng/ml. After standardizing to 100,000 units of drug, increases after cholecalciferol (2.7 ± 0.3 ng/ml) were more than twice as great as those from ergocalciferol (1.1 ± 0.3 ng/ml) (p < 0.0001). A sensitivity analysis, which pooled the results of an additional 109 individuals treated with ergocalciferol alone, revealed similar findings (standardized change 2.7 ± 0.3 vs. 1.6 ± 0.3 ng/ml, p = 0.0025). Factors associated with a superior response to cholecalciferol were lower baseline 25(OH) D level at the start of therapy (p = 0.015) and the interaction of sex and age (p = 0.0048), with younger females tending to benefit relatively more from cholecalciferol than older males did. Conclusion: Cholecalciferol may be superior to ergocalciferol in treating nutritional vitamin D deficiency in non-dialysis CKD.

Keywords:
25-hydroxyvitamin D, Vitamin D, Cholecalciferol, Ergocalciferol, Mineral metabolism, Chronic kidney disease
1.
González EA, Sachdeva A, Oliver DA, Martin KJ: Vitamin D insufficiency and deficiency in chronic kidney disease. A single center observational study. Am J Nephrol 2004;24:503-510.
2.
Zehnder D, Landray MJ, Wheeler DC, Fraser W, Blackwell L, Nuttall S, et al: Cross-sectional analysis of abnormalities of mineral homeostasis, vitamin D and parathyroid hormone in a cohort of pre-dialysis patients. The chronic renal impairment in Birmingham (CRIB) study. Nephron Clin Pract 2007;107:c109-c116.
3.
Al-Badr W, Martin KJ: Vitamin D and kidney disease. Clin J Am Soc Nephrol 2008;3:1555-1560.
4.
Mehrotra R, Kermah D, Budoff M, Salusky IB, Mao SS, Gao YL, et al: Hypovitaminosis D in chronic kidney disease. Clin J Am Soc Nephrol 2008;3:1144-1151.
5.
Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, 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.
6.
Ishimura E, Nishizawa Y, Inaba M, Matsumoto N, Emoto M, Kawagishi T, et al: Serum levels of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, and 25-hydroxyvitamin D in nondialyzed patients with chronic renal failure. Kidney Int 1999;55:1019-1027.
7.
Melamed ML, Astor B, Michos ED, Hostetter TH, Powe NR, Muntner P: 25-hydroxyvitamin D levels, race, and the progression of kidney disease. J Am Soc Nephrol 2009;20:2631-2639.
8.
LaClair RE, Hellman RN, Karp SL, Kraus M, Ofner S, Li Q, et al: Prevalence of calcidiol deficiency in CKD: a cross-sectional study across latitudes in the United States. Am J Kidney Dis 2005;45:1026-1033.
9.
de Boer IH, Ioannou GN, Kestenbaum B, Brunzell JD, Weiss NS: 25-hydroxyvitamin D levels and albuminuria in the third national health and nutrition examination survey (NHANES III). Am J Kidney Dis 2007;50:69-77.
10.
Helvig CF, Cuerrier D, Hosfield CM, Ireland B, Kharebov AZ, Kim JW, et al: Dysregulation of renal vitamin D metabolism in the uremic rat. Kidney Int 2010;78:463-472.
11.
Smogorzewski MJ, Massry SG: Liver metabolism in CRF. Am J Kidney Dis 2003;41(3 Suppl 1):S127-S132.
12.
Dusso AS, Brown AJ, Slatopolsky E: Vitamin D. Am J Physiol Renal Physiol 2005;289:F8-F28.
13.
Ritter CS, Armbrecht HJ, Slatopolsky E, Brown AJ: 25-hydroxyvitamin D(3) suppresses PTH synthesis and secretion by bovine parathyroid cells. Kidney Int 2006;70:654-659.
14.
Dusso AS, Sato T, Arcidiacono MV, Alvarez-Hernandez D, Yang J, Gonzalez-Suarez I, et al: Pathogenic mechanisms for parathyroid hyperplasia. Kidney Int Suppl 2006;102:S8-S11.
15.
Ford ES, Ajani UA, McGuire LC, Liu S: Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care 2005;28:1228-1230.
16.
Liu S, Song Y, Ford ES, Manson JE, Buring JE, Ridker PM: Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older U.S. women. Diabetes Care 2005;28:2926-2932.
17.
Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Körfer R, Stehle P: Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 2003;41:105-112.
18.
Martins D, Wolf M, Pan D, Zadshir A, Tareen N, Thadhani R, et al: Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the third national health and nutrition examination survey. Arch Intern Med 2007;167:1159-1165.
19.
Zittermann A: Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr 2003;89:552-572.
20.
Cantorna MT, Zhu Y, Froicu M, Wittke A: Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system. Am J Clin Nutr 2004;80(6 Suppl):1717S-1720S.
21.
Cantorna MT, Mahon BD: Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med (Maywood) 2004;229:1136-1142.
22.
Peterlik M, Cross HS: Vitamin D and calcium deficits predispose for multiple chronic diseases. Eur J Clin Invest 2005;35:290-304.
23.
National Kidney Foundation: K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42(4 Suppl 3):S1-S201.
24.
Sanchez I, Mangoo-Karim R, Stubbs JR, Yanev GP, Wetmore JB: Ethnic differences in 25-hydroxyvitamin D levels and response to treatment in CKD. Int Urol Nephrol 2013;45:181-189.
25.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al: A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-612.
26.
Al-Aly Z, Qazi RA, González EA, Zeringue A, Martin KJ: Changes in serum 25-hydroxyvitamin D and plasma intact PTH levels following treatment with ergocalciferol in patients with CKD. Am J Kidney Dis 2007;50:59-68.
27.
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;27:36-43.
28.
Glendenning P, Chew GT, Seymour HM, Gillett MJ, Goldswain PR, Inderjeeth CA, et al: Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol. Bone 2009;45:870-875.
29.
Logan VF, Gray AR, Peddie MC, Harper MJ, Houghton LA: Long-term vitamin D3 supplementation is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the winter months. Br J Nutr 2013;109:1082-1088.
30.
Armas LA, Hollis BW, Heaney RP: Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab 2004;89:5387-5391.
31.
Lehmann U, Hirche F, Stangl GI, Hinz K, Westphal S, Dierkes J: Bioavailability of vitamin D(2) and D(3) in healthy volunteers, a randomized placebo-controlled trial. J Clin Endocrinol Metab 2013;98:4339-4345.
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2015
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