The role of nutritional vitamin D in chronic kidney disease-mineral and bone disorder in children and adults with chronic kidney disease, on dialysis, and after kidney transplantation-a European consensus statement. - 2025
The role of nutritional vitamin D in chronic kidney disease-mineral and bone disorder in children and adults with chronic kidney disease, on dialysis, and after kidney transplantation-a European consensus statement.
chronic kidney disease–mineral and bone disorder; kidney transplantation; parathyroid hormone; renal osteodystrophy; vitamin D; Vitamin D; Adult; Child; Humans; Consensus; Dietary Supplements; Europe; Practice Guidelines as Topic; Review Literature as Topic; Chronic Kidney Disease-Mineral and Bone Disorder/etiology; Chronic Kidney Disease-Mineral and Bone Disorder/prevention & control; Kidney Transplantation/adverse effects; Renal Dialysis/adverse effects; Renal Insufficiency, Chronic/therapy; Renal Insufficiency, Chronic/complications; Vitamin D/therapeutic use; Vitamin D/administration & dosage; Vitamin D Deficiency/etiology; Vitamin D Deficiency/prevention & control; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin D Deficiency; Vitamins; Nephrology; Transplantation
Abstract :
[en] Vitamin D deficiency is common in patients with chronic kidney disease (CKD) and associates with poor outcomes. Current clinical practice guidelines recommend supplementation with nutritional vitamin D as for the general population. However, recent large-scale clinical trials in the general population failed to demonstrate a benefit of vitamin D supplementation on skeletal or non-skeletal outcomes, fueling a debate on the rationale for screening for and correcting vitamin D deficiency, both in non-CKD and CKD populations. In a collaboration between the European Renal Osteodystrophy initiative of the European Renal Association (ERA) and the European Society for Paediatric Nephrology (ESPN), an expert panel performed an extensive literature review and formulated clinical practice points on vitamin D supplementation in children and adults with CKD and after kidney transplantation. These were reviewed by a Delphi panel of members from relevant working groups of the ERA and ESPN. Key clinical practice points include recommendations to monitor for, and correct, vitamin D deficiency in children and adults with CKD and after kidney transplantation, targeting 25-hydroxyvitamin D levels >75 nmol/l (>30 ng/ml). Although vitamin D supplementation appears well-tolerated and safe, it is recommended to avoid mega-doses (≥100 000 IU) and very high levels of 25 hydroxyvitamin D (>150-200 nmol/l, or 60-80 ng/ml) to reduce the risk of toxicity. Future clinical trials should investigate the benefit of vitamin D supplementation on patient-relevant outcomes in the setting of vitamin D deficiency across different stages of CKD.
Disciplines :
Laboratory medicine & medical technology Urology & nephrology
Author, co-author :
Jørgensen, Hanne Skou ; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark ; Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark
Vervloet, Marc ; Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
Cavalier, Etienne ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Bacchetta, Justine ; Department of Pediatric Nephrology, Reference Center for Rare Diseases of Calcium and Phosphate, INSERM1033 Research Unit, Hospices Civils de Lyon, Université Lyon 1, Lyon, France
de Borst, Martin H ; Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Bover, Jordi; Department of Nephrology, University Hospital Germans Trias i Pujol, Badalona (Barcelona), Catalonià, Spain
Cozzolino, Mario ; Department of Health Sciences, Renal Division, University of Milan, Milan, Italy
Ferreira, Ana Carina ; Nephrology Department, Hospital Curry Cabral | ULS São José, Lisbon, Portugal and Nova Medical School, Lisbon, Portugal
Hansen, Ditte ; Department of Nephrology, Copenhagen University Hospital-Herlev, Copenhagen, Denmark ; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Herrmann, Markus; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
de Jongh, Renate; Department of Endocrinology and Metabolism, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Mazzaferro, Sandro ; Department of Translation and Precision Medicine, Sapienza University of Rome, Rome, Italy
Wan, Mandy; Institute of Pharmaceutical Science, King's College London, London, UK and Department of Evelina Pharmacy, Guys' & St Thomas' NHS Foundation Trust, London, UK
Shroff, Rukshana ; Renal Unit, UCL Great Ormond Street Hospital for Children, University College London, London, UK
Evenepoel, Pieter ; Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium
The role of nutritional vitamin D in chronic kidney disease-mineral and bone disorder in children and adults with chronic kidney disease, on dialysis, and after kidney transplantation-a European consensus statement.
This consensus work was supported by an unrestricted educational grant by Vifor CSL. CSL-Vifor had no role in the design of the study, data analysis, or data interpretation for this manuscript. This consensus work was supported by an unrestricted educational grant by Vifor CSL. CSL-Vifor had no role in the design of the study, nor in data analysis and data interpretation.
J-DAVID Investigators, Shoji T, Inaba M, Fukagawa M et al. Effect of oral alfacalcidol on clinical outcomes in patients without secondary hyperparathyroidism receiving maintenance hemodialysis: the J-DAVID randomized clinical trial. JAMA 2018;320:2325–34. https://doi.org/10.1001/jama.2018.17749
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. JAMA 2012;307:674–84. https://doi.org/10.1001/jama.2012. 120
Wang AY-M, Fang F, Chan J et al. Effect of paricalcitol on left ventricular mass and function in CKD—the OPERA trial. J Am Soc Nephrol 2014;25:175–86. https://doi.org/10.1681/ASN. 2013010103
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;92:26–36. https://doi.org/10.1016/j.kint.2017.04.006
Shroff R, Wan M, Nagler EV et al. Clinical practice recommendations for treatment with active vitamin D analogues in children with chronic kidney disease stages 2–5 and on dialysis. Nephrol Dial Transplant 2017;32:1114–27. https://doi.org/10.1093/ndt/gfx080
Leboff MS, Chou SH, Ratliff KA et al. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med 2022;387:299–309. https://doi.org/10.1056/NEJMoa2202106
Leboff MS, Chou SH, Murata EM et al. Effects of supplemental vitamin D on bone health outcomes in women and men in the VITamin D and OmegA-3 TriaL (VITAL). J Bone Miner Res 2020;35:883–93. https://doi.org/10.1002/jbmr.3958
Giustina A, Bilezikian JP, Adler RA et al. Consensus statement on vitamin D status assessment and supplementation: whys, whens, and hows. Endocr Rev 2024; 45:625–54. https://doi.org/10.1210/endrev/bnae009
Cummings SR, Rosen C. VITAL findings—a decisive verdict on vitamin D supplementation. N Engl J Med 2022;387:368–70. https://doi.org/10.1056/NEJMe2205993
Bouillon R, LeBoff MS, Neale RE. Health effects of vitamin D supplementation: lessons learned from randomized controlled trials and mendelian randomization studies. J Bone Miner Res 2023; 38:1391–403. https://doi.org/10.1002/jbmr.4888
Bouillon R, Manousaki D, Rosen C et al. The health effects of vitamin D supplementation: evidence from human studies. Nat Rev Endocrinol 2022;18:96–110. https://doi.org/10.1038/ s41574-021-00593-z
Charoenngam N, Shirvani A, Holick MF. The ongoing D-lemma of vitamin D supplementation for nonskeletal health and bone health. Curr Opin Endocrinol Diabetes Obes 2019;26:301–5. https://doi.org/10.1097/MED.0000000000000508
Vervloet MG, Hsu S, de Boer IH. Vitamin D supplementation in people with chronic kidney disease. Kidney Int 2023; 104: 698–706. https://doi.org/10.1016/j.kint.2023.07.010
Cavalier E, Makris K, Heijboer AC et al. Vitamin D: analytical advances, clinical impact, and ongoing debates on health perspectives. Clin Chem 2024; 70:1104–21. https://doi.org/10.1093/clinchem/hvae056
Melamed ML, Chonchol M, Gutiérrez OM et al. The role of vitamin D in CKD stages 3 to 4: report of a scientific workshop sponsored by the National Kidney Foundation. Am J Kidney Dis 2018;72:834–45. https://doi.org/10.1053/j.ajkd.2018.06.031
Bouillon R. Comparative analysis of nutritional guidelines for vitamin D. Nat Rev Endocrinol 2017;13:466–79. https://doi.org/10.1038/nrendo.2017.31
Freisling H, Fahey MT, Moskal A et al. Region-specific nutrient intake patterns exhibit a geographical gradient within and between European countries. J Nutr 2010;140:1280–6. https://doi.org/10.3945/jn.110.121152
Bouillon R, Bikle D. Vitamin D metabolism revised: fall of dogmas. J Bone Miner Res 2019;34:1985–92. https://doi.org/10.1002/jbmr.3884
Roizen JD, Long C, Casella A et al. Obesity decreases hepatic 25-hydroxylase activity causing low serum 25-hydroxyvitamin D. J Bone Miner Res 2019;34:1068–73 [doi]. https://doi.org/10.1002/jbmr.3686
Aatsinki S-M, Elkhwanky M-S, Kummu O et al. Fasting-induced transcription factors repress vitamin D bioactivation, a mechanism for vitamin D deficiency in diabetes. Diabetes 2019;68: 918–31. https://doi.org/10.2337/db18-1050
Bikle DD, Patzek S, Wang Y. Physiologic and pathophysiologic roles of extra renal CYP27b1: case report and review. Bone Reports 2018;8:255–67. https://doi.org/10.1016/j.bonr.2018.02.004
Shimada T, Hasegawa H, Yamazaki Y et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 2004;19:429–35. https://doi.org/10.1359/JBMR.0301264
Viaene L, Evenepoel P, Meijers B et al. Uremia suppresses immune signal-induced CYP27B1 expression in human monocytes. Am J Nephrol 2012;36:497–508. https://doi.org/10.1159/ 000345146
Bacchetta J, Sea JL, Chun RF et al. Fibroblast growth factor 23 inhibits extrarenal synthesis of 1,25-dihydroxyvitamin D in human monocytes. J Bone Miner Res 2013;28:46–55. https://doi.org/10.1002/jbmr.1740
Somjen D, Weisman Y, Kohen F et al. 25-hydroxyvitamin D3-1alpha-hydroxylase is expressed in human vascular smooth muscle cells and is upregulated by parathyroid hormone and estrogenic compounds. Circulation 2005;111:1666–71. https://doi.org/10.1161/01.CIR.0000160353.27927.70
Kanemoto Y, Hayakawa A, Sawada T et al. Transcriptional regulation of 25-hydroxyvitamin D-24-hydroxylase (CYP24A1) by calcemic factors in keratinocytes. J Nutr Sci Vitaminol (Tokyo) 2021;67:424–8. https://doi.org/10.3177/jnsv.67.424
Meyer MB, Lee SM, Carlson AH et al. A chromatin-based mechanism controls differential regulation of the cytochrome P450 gene Cyp24a1 in renal and non-renal tissues. J Biol Chem 2019;294:14467–81. https://doi.org/10.1074/jbc.RA119.010173
Armbrecht HJ, Hodam TL, Boltz MA et al. Induction of the vitamin D 24-hydroxylase (CYP24) by 1,25-dihydroxyvitamin D3 is regulated by parathyroid hormone in UMR106 osteoblastic cells. Endocrinology 1998;139:3375–81. https://doi.org/10.1210/endo.139.8.6134
Jørgensen HS, De Loor H, Billen J et al. Vitamin D metabolites before and after kidney transplantation in patients who are anephric. Am J Kidney Dis 2024;84:427–436.e1. https://doi.org/10.1053/j.ajkd.2024.03.025
Stoffels K, Overbergh L, Giulietti A et al. Immune regulation of 25-hydroxyvitamin-D3-1alpha-hydroxylase in human monocytes. J Bone Miner Res 2006;21:37–47. https://doi.org/10.1359/JBMR.050908
Bikle DD. The free hormone hypothesis: when, why, and how to measure the free hormone levels to assess vitamin D, thyroid, sex hormone, and cortisol status. JBMR Plus 2021;5:e10418. https://doi.org/10.1002/jbm4.10418
Christakos S, Dhawan P, Verstuyf A et al. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev 2016;96:365–408. https://doi.org/10.1152/physrev.00014.2015
Pike JW, Meyer MB. The unsettled science of nonrenal calcitriol production and its clinical relevance. J Clin Invest 2020;130:4519–21. https://doi.org/10.1172/JCI141334
Meyer MB, Benkusky NA, Kaufmann M et al. Targeted genomic deletions identify diverse enhancer functions and generate a kidney-specific, endocrine-deficient Cyp27b1 pseudo-null mouse. J Biol Chem 2019;294:9518–35. https://doi.org/10.1074/jbc.RA119.008760
Dusso A, Brown A, Slatopolsky E. Extrarenal production of calcitriol. Semin Nephrol 1994;14:144–55.
Braegger C, Campoy C, Colomb V et al. Vitamin D in the healthy European paediatric population. J Pediatr Gastroenterol Nutr 2013;56:692–701. https://doi.org/10.1097/MPG. 0b013e31828f3c05
Feldman D, Pike JW. Feldman and Pike’s Vitamin D. 5th edition edn. Elsevier, 2023.
Herrick KA, Storandt RJ, Afful J et al. Vitamin D status in the United States, 2011–2014. Am J Clin Nutr 2019;110:150–7. https://doi.org/10.1093/ajcn/nqz037
Bouillon R, Carmeliet G. Vitamin D insufficiency: definition, diagnosis and management. Best Pract Res Clin Endocrinol Metab 2018;32:669–84. https://doi.org/10.1016/j.beem.2018.09.014
Munns CF, Shaw N, Kiely M et al. Global consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab 2016;101:394–415. https://doi.org/10.1210/jc.2015-2175
Need AG, O’loughlin PD, Morris HA et al. Vitamin D metabolites and calcium absorption in severe vitamin D deficiency. J Bone Miner Res 2008;23:1859–63. https://doi.org/10.1359/jbmr.080607
Lips P, Duong T, Oleksik A et al. A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. J Clin Endocrinol Metab 2001;86:1212–21. https://doi.org/10.1210/jcem.86.3.7327
Malabanan A, Veronikis IE, Holick MF. Redefining vitamin D insufficiency. Lancet 1998;351:805–6. https://doi.org/10.1016/ S0140-6736(05)78933-9
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. https://doi.org/10.1038/sj.ki.5002009
Wolf M, Shah A, Gutierrez O et al. Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 2007;72:1004–13. https://doi.org/10.1038/sj.ki.5002451
Ureña-Torres P, Metzger M, Haymann JP et al. Association of kidney function, vitamin D deficiency, and circulating markers of mineral and bone disorders in CKD. Am J Kidney Dis 2011;58:544–53. https://doi.org/10.1053/j.ajkd.2011.04.029
Barragry JM, Carter ND, Beer M et al. Vitamin-D metabolism in nephrotic syndrome. Lancet 1977;310:629–32. https://doi.org/10.1016/S0140-6736(77)92498-9
Grymonprez A, Proesmans W, Van Dyck M et al. Vitamin D metabolites in childhood nephrotic syndrome. Pediatr Nephrol 1995;9:278–81. https://doi.org/10.1007/BF02254183
Joffe P, Heat JG. Vitamin D and vitamin-D-binding protein kinetics in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Perit Dial Int 1989;9:281–4. https://doi.org/10.1177/089686088900900410
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;27:643–9. https://doi.org/10.1007/ s00467-011-2045-0
Michaud J, Naud J, Ouimet D et al. Reduced hepatic synthesis of calcidiol in uremia. J Am Soc Nephrol 2010;21:1488–97. https://doi.org/10.1681/ASN.2009080815
Cani PD, Amar J, Iglesias MA et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes 2007;56:1761–72. https://doi.org/10.2337/db06-1491
Evenepoel P, Stenvinkel P, Shanahan C et al. Inflammation and gut dysbiosis as drivers of CKD-MBD. Nat Rev Nephrol 2023;19:646–57. https://doi.org/10.1038/s41581-023-00736-7
Mithal A, Wahl DA, Bonjour J-P et al. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int 2009;20:1807–20. https://doi.org/10.1007/s00198-009-0954-6
Tobias DK, Luttmann-Gibson H, Mora S et al. Association of body weight with response to vitamin D supplementation and metabolism. JAMA Netw Open 2023;6:e2250681. https://doi.org/10.1001/jamanetworkopen.2022.50681
Kim SM, Choi HJ, Lee JP et al. Prevalence of vitamin D deficiency and effects of supplementation with cholecalciferol in patients with chronic kidney disease. J Ren Nutr 2014;24:20–25. https://doi.org/10.1053/j.jrn.2013.07.003
Hasegawa H, Nagano N, Urakawa I et al. Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease. Kidney Int 2010;78:975–80. https://doi.org/10.1038/ki.2010.313
Bosworth C, de Boer IH. Impaired vitamin D metabolism in CKD. Semin Nephrol 2013;33:158–68. https://doi.org/10.1016/j.semnephrol.2012.12.016
Gallieni M, Kamimura S, Ahmed A et al. Kinetics of monocyte 1 alpha-hydroxylase in renal failure. Am J Physiol Renal Physiol 1995;268:F746–53. https://doi.org/10.1152/ajprenal.1995.268.4. F746
Glorieux G, Vanholder R. Blunted response to vitamin D in uremia. Kidney Int Suppl 2001;78:S182–185. https://doi.org/10.1046/j.1523-1755.2001.59780182.x
Sawaya BP, Koszewski NJ, Qi Q et al. Secondary hyperparathyroidism and vitamin D receptor binding to vitamin D response elements in rats with incipient renal failure. J Am Soc Nephrol 1997;8:271–8. https://doi.org/10.1681/ASN.V82271
Perrin P, Caillard S, Javier RM et al. Persistent hyperparathyroidism is a major risk factor for fractures in the five years after kidney transplantation. Am J Transplant 2013;13:2653–63. https://doi.org/10.1111/ajt.12425
Torres A, Torregrosa V, Marcen R et al. Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: the role of gender (EMITRAL study). Nefrología 2016;36:255–67. https://doi.org/10.1016/j.nefro.2016.03.004
Yin S, Wang X, Li L et al. Prevalence of vitamin D deficiency and impact on clinical outcomes after kidney transplantation: a systematic review and meta-analysis. Nutr Rev 2022;80: 950–61. https://doi.org/10.1093/nutrit/nuab058
Perrin P, Kiener C, Javier R-M et al. Recent changes in chronic kidney disease–mineral and bone disorders and associated fractures after kidney transplantation. Transplantation 2017;101:1897–905. https://doi.org/10.1097/TP. 0000000000001449
Evenepoel P, Naesens M, Claes K et al. Tertiary ‘hyperphosphatoninism’ accentuates hypophosphatemia and suppresses calcitriol levels in renal transplant recipients. Am J Transplant 2007;7:1193–200. https://doi.org/10.1111/j.1600-6143.2007.01753.x
Evenepoel P, Meijers BKI, De Jonge H et al. Recovery of hyperphosphatoninism and renal phosphorus wasting one year after successful renal transplantation. Clin J Am Soc Nephrol 2008;3:1829–36. https://doi.org/10.2215/CJN.01310308
Wolf M, Weir MR, Kopyt N et al. A prospective cohort study of mineral metabolism after kidney transplantation. Transplantation 2016;100:184–93. https://doi.org/10.1097/TP. 0000000000000823
Cavalier E, Lukas, P, Beaert, A-C et al. Analytical and clinical evaluation of the new Fujirebio Lumipulse(R)G noncompetitive assay for 25(OH)-vitamin D and three immunoassays for 25(OH)D in healthy subjects, osteoporotic patients, third trimester pregnant women, healthy African subjects, hemodialyzed and intensive care patients. Clin Chem Lab Med 2016;54:1347–55.
Depreter B, Heijboer AC, Langlois MR. Accuracy of three automated 25-hydroxyvitamin D assays in hemodialysis patients. Clin Chim Acta 2013;415:255–60. https://doi.org/10.1016/j.cca.2012.10.056
Hsu S, Zelnick LR, Lin YS et al. Validation of the 24,25-dihydroxyvitamin D(3) to 25-hydroxyvitamin D(3) ratio as a biomarker of 25-hydroxyvitamin D(3) clearance. J Steroid Biochem Mol Biol 2022;217:106047. https://doi.org/10.1016/j.jsbmb.2021.106047
Ginsberg C, Hoofnagle AN, Katz R et al. The vitamin D metabolite ratio is independent of vitamin D binding protein concentration. Clin Chem 2021;67:385–93. https://doi.org/10.1093/clinchem/hvaa238
De Boer IH, Sachs MC, Chonchol M et al. Estimated GFR and circulating 24,25-dihydroxyvitamin D3 concentration: a participant-level analysis of 5 cohort studies and clinical trials. Am J Kidney Dis 2014;64:187–97. https://doi.org/10.1053/j.ajkd.2014.02.015
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;82:693–700. https://doi.org/10.1038/ki.2012.193
Graeff-Armas LA, Kaufmann M, Lyden E et al. Serum 24,25-dihydroxyvitamin D(3) response to native vitamin D(2) and D(3) supplementation in patients with chronic kidney disease on hemodialysis. Clin Nutr 2018;37:1041–5. https://doi.org/10.1016/j.clnu.2017.04.020
Stubbs JR, Zhang S, Friedman PA et al. Decreased conversion of 25-hydroxyvitamin D 3 to 24,25-dihydroxyvitamin D 3 following cholecalciferol therapy in patients with CKD. Clin J Am Soc Nephrol 2014;9:1965–73. https://doi.org/10.2215/CJN. 03130314
Lee S, Chung HJ, Jung S et al. 24,25-Dihydroxy vitamin D and vitamin D metabolite ratio as biomarkers of vitamin D in chronic kidney disease. Nutrients 2023; 15:578. https://doi.org/10.3390/ nu15030578
Hsu S, Zelnick LR, Lin YS et al. Differences in 25-hydroxyvitamin D clearance by eGFR and race: a pharmacokinetic study. J Am Soc Nephrol 2021;32:188–98. https://doi.org/10.1681/ASN. 2020050625
Hsu S, Zelnick LR, Bansal N et al. Vitamin D metabolites and risk of cardiovascular disease in chronic kidney disease: the CRIC study. J Am Heart Assoc 2023;12:e028561. https://doi.org/10.1161/JAHA.122.028561
Bikle DD, Schwartz J. Vitamin D binding protein, total and free vitamin D levels in different physiological and pathophysiological conditions. Front Endocrinol 2019;10:317. https://doi.org/10.3389/fendo.2019.00317
Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999;84:3666–72. https://doi.org/10.1210/jcem.84.10.6079
Henderson CM, Lutsey PL, Misialek JR et al. Measurement by a novel LC-MS/MS methodology reveals similar serum concentrations of vitamin D-binding protein in blacks and whites. Clin Chem 2016;62:179–87. https://doi.org/10.1373/clinchem.2015. 244541
Heureux N, Lindhout E, Swinkels L. A direct assay for measuring free 25-hydroxyvitamin D. J AOAC Int 2017;100:1318–22. https://doi.org/10.5740/jaoacint.17-0084
Ishimine N, Wu S, Ota R et al. Development of free 25-hydroxyvitamin D3 assay method using liquid chromatography–tandem mass spectrometry. Biosci Rep 2022;42. https://doi.org/10.1042/BSR20221326
Van Hoof H, De Sevaux R, Van Baelen H et al. Relationship between free and total 1,25-dihydroxyvitamin D in conditions of modified binding. Eur J Endocrinol 2001;144:391–6. https://doi.org/10.1530/eje.0.1440391
Chen X, Lu Y-P, Luo T et al. Free 25-vitamin D is correlated with cardiovascular events in prevalent hemodialysis patients but not with markers of renal mineral bone disease. Kidney Blood Press Res 2019;44:344–53. https://doi.org/10.1159/000499878
Zeng S, Bachert D, Pavkovic M et al. Free vitamin D is independently associated with systolic blood pressure in diabetic patients with impaired kidney function. Clin Nephrol 2022;97:63–69. https://doi.org/10.5414/CN110549
Ennis JL, Worcester EM, Coe FL et al. Current recommended 25-hydroxyvitamin D targets for chronic kidney disease management may be too low. J Nephrol 2016;29:63–70. https://doi.org/10.1007/s40620-015-0186-0
Dhillon-Jhattu S, Mcgill RL, Ennis JL et al. Vitamin D and parathyroid hormone levels in CKD. Am J Kidney Dis 2023;81:122–4. https://doi.org/10.1053/j.ajkd.2022.06.006
Christodoulou M, Aspray TJ, Schoenmakers I. Vitamin D supplementation for patients with chronic kidney disease: a systematic review and meta-analyses of trials investigating the response to supplementation and an overview of guidelines. Calcif Tissue Int 2021;109:157–78. https://doi.org/10.1007/ s00223-021-00844-1
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. Am J Clin Nutr 2012;96:672–9. https://doi.org/10.3945/ajcn.112.040642
Gravesen E, Hofman-Bang J, Lewin E et al. Ergocalciferol treatment and aspects of mineral homeostasis in patients with chronic kidney disease stage 4–5. Scand J Clin Lab Invest 2013;73:107–16. https://doi.org/10.3109/00365513.2012.744464
Petchey WG, Hickman IJ, Prins JB et al. Vitamin D does not improve the metabolic health of patients with chronic kidney disease stage 3–4: a randomized controlled trial. Nephrology 2013;18:26–35. https://doi.org/10.1111/j.1440-1797.2012.01662.x
Marckmann P, Agerskov H, Thineshkumar S et al. Randomized controlled trial of cholecalciferol supplementation in chronic kidney disease patients with hypovitaminosis D. Nephrol Dial Transplant 2012;27:3523–31. https://doi.org/10.1093/ndt/gfs138
Westerberg P-A, Sterner G, Ljunggren Ö et al. High doses of cholecalciferol alleviate the progression of hyperparathyroidism in patients with CKD stages 3–4: results of a 12-week double-blind, randomized, controlled study. Nephrol Dial Transplant 2018;33:466–71. https://doi.org/10.1093/ndt/gfx059
Yadav AK, Kumar V, Kumar V et al. The effect of vitamin D supplementation on bone metabolic markers in chronic kidney disease. J Bone Miner Res 2018;33:404–9. https://doi.org/10.1002/jbmr.3314
Kumar V, Yadav AK, Lal A et al. A randomized trial of vitamin D supplementation on vascular function in CKD. J Am Soc Nephrol 2017;28:3100–8. https://doi.org/10.1681/ASN.2017010003
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 2008;30:407–10. https://doi.org/10.1080/08860220801964210
Chandra P, Binongo JNG, Ziegler TR et al. Cholecalciferol (vitamin D3) therapy and vitamin D insufficiency in patients with chronic kidney disease: a randomized controlled pilot study. Endocr Pract 2008;14:10–17. https://doi.org/10.4158/EP.14.1.10
Wetmore JB, Kimber C, Mahnken JD et al. Cholecalciferol v. ergocalciferol for 25-hydroxyvitamin D (25(OH)D) repletion in chronic kidney disease: a randomised clinical trial. Br J Nutr 2016;116:2074–81. https://doi.org/10.1017/S000711451600427X
Matuszkiewicz-Rowińska J, Kulicki P, Zebrowski P et al. Cholecalciferol vs. small doses of alfacalcidol vs. placebo in chronic kidney disease patients on hemodialysis: a randomized parallel group study. Front Med (Lausanne) 2021;8:781191. https://doi.org/10.3389/fmed.2021.781191
Brimble KS, Ganame J, Margetts P et al. Impact of bioelectrical impedance-guided fluid management and vitamin D supplementation on left ventricular mass in patients receiving peritoneal dialysis: a randomized controlled trial. Am J Kidney Dis 2022;79:820–31. https://doi.org/10.1053/j.ajkd.2021.08.022
Alshahawey M, El Borolossy R, El Wakeel L et al. The impact of cholecalciferol on markers of vascular calcification in hemodialysis patients: a randomized placebo controlled study. Nutr Metab Cardiovasc Dis 2021;31:626–33. https://doi.org/10.1016/j.numecd.2020.09.014
Zheng C-M, Wu C-C, Hung C-F et al. Cholecalciferol additively reduces serum parathyroid hormone levels in severe secondary hyperparathyroidism treated with calcitriol and cinacalcet among hemodialysis patients. Nutrients 2018;10:196. https://doi.org/10.3390/nu10020196
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 hyper-parathyroid hemodialysis patients. Nutrients 2016;708. https://doi.org/10.3390/nu8110708
Wang Y, Liu Y, Lian Y et al. Efficacy of high-dose supplementation with oral vitamin D3 on depressive symptoms in dialysis patients with vitamin D3 insufficiency: a prospective, randomized, double-blind study. J Clin Psychopharmacol 2016;36:229–35. https://doi.org/10.1097/JCP.0000000000000486
Massart A, Debelle FD, Racapé J et al. Biochemical parameters after cholecalciferol repletion in hemodialysis: results from the VitaDial randomized trial. Am J Kidney Dis 2014;64:696–705. https://doi.org/10.1053/j.ajkd.2014.04.020
Li L, Lin M, Krassilnikova M et al. Effect of cholecalciferol supplementation on inflammation and cellular alloimmunity in hemodialysis patients: data from a randomized controlled pilot trial. PLoS One 2014;9:e109998. https://doi.org/10.1371/journal.pone.0109998
Hewitt NA, O’Connor AA, O’Shaughnessy DV et al. Effects of cholecalciferol on functional, biochemical, vascular, and quality of life outcomes in hemodialysis patients. Clin J Am Soc Nephrol 2013;8:1143–9. https://doi.org/10.2215/CJN.02840312
Delanaye P, Weekers L, Warling X et al. Cholecalciferol in haemodialysis patients: a randomized, double-blind, proof-of-concept and safety study. Nephrol Dial Transplant 2013;28:1779–86. https://doi.org/10.1093/ndt/gft001
Dreyer G, Tucker AT, Harwood SM et al. Ergocalciferol and microcirculatory function in chronic kidney disease and concomitant vitamin D deficiency: an exploratory, double blind, randomised controlled trial. PLoS One 2014;9:e99461. https://doi.org/10.1371/journal.pone.0099461
Bhan I, Dobens D, Tamez H et al. Nutritional vitamin D supplementation in dialysis: a randomized trial. Clin J Am Soc Nephrol 2015;10:611–9. https://doi.org/10.2215/CJN.06910714
Zhang D, Li H, Yin D et al. Ergocalciferol versus calcitriol for controlling chronic kidney disease mineral bone disorder in stage 3 to 5 CKD: a randomized controlled trial. Eur J Pharmacol 2016;789:127–33. https://doi.org/10.1016/j.ejphar.2016.07.019
Batacchi Z, Robinson-Cohen C, Hoofnagle AN et al. Effects of vitamin D(2) supplementation on vitamin D(3) metabolism in health and CKD. Clin J Am Soc Nephrol 2017;12:1498–506. https://doi.org/10.2215/CJN.00530117
Sprague SM, Crawford PW, Melnick JZ et al. Use of extended-release calcifediol to treat secondary hyperparathyroidism in stages 3 and 4 chronic kidney disease. Am J Nephrol 2016;44:316–25. https://doi.org/10.1159/000450766
Sprague SM, Silva AL, Al-Saghir F et al. Modified-release calcifediol effectively controls secondary hyperparathyroidism associated with vitamin D insufficiency in chronic kidney disease. Am J Nephrol 2014;40:535–45. https://doi.org/10.1159/ 000369939
Strugnell SA, Csomor P, Ashfaq A et al. Evaluation of therapies for secondary hyperparathyroidism associated with vitamin D insufficiency in chronic kidney disease. Kidney Dis (Basel) 2023;9:206–17. https://doi.org/10.1159/000529523
Strugnell SA, Sprague SM, Ashfaq A et al. Rationale for raising current clinical practice guideline target for serum 25-hydroxyvitamin D in chronic kidney disease. Am J Nephrol 2019;49:284–93. https://doi.org/10.1159/000499187
Shroff R, Wan M, Gullett A et al. Ergocalciferol supplementation in children with CKD delays the onset of secondary hyperparathyroidism: a randomized trial. Clin J Am Soc Nephrol 2012;7:216–23. https://doi.org/10.2215/CJN.04760511
Jean G, Souberbielle JC, Chazot C. Monthly cholecalciferol administration in haemodialysis patients: a simple and efficient strategy for vitamin D supplementation. Nephrol Dial Transplant 2009;24:3799–805. https://doi.org/10.1093/ndt/gfp370
Jean G, Terrat J-C, Vanel T et al. Daily oral 25-hydroxycholecalciferol supplementation for vitamin D deficiency in haemodialysis patients: effects on mineral metabolism and bone markers. Nephrol Dial Transplant 2008;23:3670–6. https://doi.org/10.1093/ndt/gfn339
Matias PJ, Jorge C, Ferreira C et al. Cholecalciferol supplementation in hemodialysis patients: effects on mineral metabolism, inflammation, and cardiac dimension parameters. Clin J Am Soc Nephrol 2010;5:905–11. https://doi.org/10.2215/CJN.06510909
Huish SA, Jenkinson C, Dunn JA et al. Low serum 1,25(OH)2D3 in end-stage renal disease: is reduced 1alpha-hydroxylase the only problem? Endocr Connect 2021;10:1291–8. https://doi.org/10.1530/EC-21-0372
Shroff R, Wan M, Nagler EV 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;32:1098–113. https://doi.org/10.1093/ndt/gfx065
Hari P, Gupta N, Hari S et al. Vitamin D insufficiency and effect of cholecalciferol in children with chronic kidney disease. Pediatr Nephrol 2010;25:2483–8. https://doi.org/10.1007/ s00467-010-1639-2
Iyengar A, Kamath N, Reddy HV et al. Determining the optimal cholecalciferol dosing regimen in children with CKD: a randomized controlled trial. Nephrol Dial Transplant 2022;37:326–34. https://doi.org/10.1093/ndt/gfaa369
Kamath N, Iyengar A, Reddy HV et al. Changes in bone biomarkers in response to different dosing regimens of cholecalciferol supplementation in children with chronic kidney disease. Pediatr Nephrol 2023;38:1907–13. https://doi.org/10.1007/ s00467-022-05790-0
DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 2004;80:1689S–96S. https://doi.org/10.1093/ajcn/80.6.1689S
Bhan A, Qiu S, Rao SD. Bone histomorphometry in the evaluation of osteomalacia. Bone Reports 2018;8:125–34. https://doi.org/10.1016/j.bonr.2018.03.005
Yeung W-CG, Palmer SC, Strippoli GFM et al. Vitamin D therapy in adults with CKD: a systematic review and meta-analysis. Am J Kidney Dis 2023;82:543–58. https://doi.org/10.1053/j.ajkd.2023.04.003
Bosworth C, Boer IHD, Targher G et al. The effect of combined calcium and cholecalciferol supplementation on bone mineral density in elderly women with moderate chronic kidney disease. Clin Nephrol 2012;77:358–65. https://doi.org/10.5414/ CN107180
Priemel M, Von Domarus C, Klatte TO et al. Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res 2010;25:305–12. https://doi.org/10.1359/jbmr.090728
Coen G, Mantella D, Manni M et al. 25-hydroxyvitamin D levels and bone histomorphometry in hemodialysis renal osteodystrophy. Kidney Int 2005;68:1840–8. https://doi.org/10.1111/j.1523-1755.2005.00603.x
Hamdy NAT, Kanis JA, Beneton MNC et al. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure. BMJ 1995;310:358–63. https://doi.org/10.1136/bmj.310.6976.358
Cannella G, Bonucci E, Rolla D et al. Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol. Kidney Int 1994;46:1124–32. https://doi.org/10.1038/ki.1994.375
Heaf J, Tvedegaard E, Kanstrup I-L et al. Bone loss after renal transplantation: role of hyperparathyroidism, acidosis, cyclosporine and systemic disease. Clin Transplant 2000;14:457–63. https://doi.org/10.1034/j.1399-0012.2000.140503.x
Jørgensen HS, Behets G, Bammens B et al. Patterns of renal osteodystrophy 1 year after kidney transplantation. Nephrol Dial Transplant 2021;36:2130–9. https://doi.org/10.1093/ndt/gfab239
Courbebaisse M, Bourmaud A, Souberbielle J-C et al. Nonskeletal and skeletal effects of high doses versus low doses of vitamin D(3) in renal transplant recipients: results of the VITALE (VITamin D supplementation in renAL transplant recipients) study, a randomized clinical trial. Am J Transplant 2023;23:366–76. https://doi.org/10.1016/j.ajt.2022.12.007
Tsujita M, Doi Y, Obi Y et al. Cholecalciferol supplementation attenuates bone loss in incident kidney transplant recipients: a prespecified secondary endpoint analysis of a randomized controlled trial. J Bone Miner Res 2020;37:303–11. https://doi.org/ 10.1002/jbmr.4469
Courbebaisse M, Thervet E, Souberbielle JC et al. Effects of vitamin D supplementation on the calcium–phosphate balance in renal transplant patients. Kidney Int 2009;75:646–51. https://doi.org/10.1038/ki.2008.549
Wissing KM, Broeders N, Moreno-Reyes R et al. A controlled study of vitamin D3 to prevent bone loss in renal-transplant patients receiving low doses of steroids. Transplantation 2005;79:108–15. https://doi.org/10.1097/01.TP.0000149322.70295.A5
Talalaj M, Gradowska, L, Marcinowska-Suchowierska, E et al. Efficiency of preventive treatment of glucocorticoidinduced osteoporosis with 25-hydroxyvitamin D3 and calcium in kidney transplant patients. Transplant Proc 1996;28: 3485–7.
Courbebaisse M, Bourmaud A, Souberbielle J-C et al. Nonskeletal and skeletal effects of high doses versus low doses of vitamin D3 in renal transplant recipients: results of the VITALE (VITamin D supplementation in renAL transplant recipients) study, a randomized clinical trial. Am J Transplant 2023; 23:366–76. https://doi.org/10.1016/j.ajt.2022.12.007
Pike JW, Meyer MB, Lee SM et al. The vitamin D receptor: contemporary genomic approaches reveal new basic and translational insights. J Clin Invest 2017;127:1146–54. https://doi.org/10.1172/JCI88887
Zhang R, Li B, Gao X et al. Serum 25-hydroxyvitamin D and the risk of cardiovascular disease: dose–response meta-analysis of prospective studies. Am J Clin Nutr 2017;105:810–9. https://doi.org/10.3945/ajcn.116.140392
Herrmann M, Keppel MH, Zelzer S et al. The role of functional vitamin D deficiency and low vitamin D reservoirs in relation to cardiovascular health and mortality. Clin Chem Lab Med 2024; 63:208–19. https://doi.org/10.1515/cclm-2024-0391
Zhang Y, Darssan D, Pascoe EM et al. Vitamin D status and mortality risk among patients on dialysis: a systematic review and meta-analysis of observational studies. Nephrol Dial Transplant 2018;33:1742–51. https://doi.org/10.1093/ndt/gfy016
Pilz S, Iodice S, Zittermann A et al. Vitamin D status and mortality risk in CKD: a meta-analysis of prospective studies. Am J Kidney Dis 2011;58:374–82. https://doi.org/10.1053/j.ajkd.2011.03.020
Duranton F, Rodriguez-Ortiz ME, Duny Y et al. Vitamin D treatment and mortality in chronic kidney disease: a systematic review and meta-analysis. Am J Nephrol 2013;37:239–48. https://doi.org/10.1159/000346846
Manson JE, Cook NR, Lee I-M et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med 2019;380:33–44. https://doi.org/10.1056/NEJMoa1809944
Scragg R, Stewart AW, Waayer D et al. Effect of monthly high-dose vitamin D supplementation on cardiovascular disease in the vitamin D assessment study: a randomized clinical trial. JAMA Cardiol 2017;2:608–16. https://doi.org/10.1001/jamacardio.2017.0175
Trivedi DP. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 2003;326:469. https://doi.org/10.1136/bmj.326.7387.469
Neale RE, Baxter C, Romero BD et al. The D-Health Trial: a randomised controlled trial of the effect of vitamin D on mortality. Lancet Diabetes Endocrinol 2022;10:120–8. https://doi.org/10.1016/S2213-8587(21)00345-4
Sutherland JP, Zhou A, Hyppönen E. Vitamin D deficiency increases mortality risk in the UK Biobank: a nonlinear mendelian randomization study. Ann Intern Med 2022;175:1552–9. https://doi.org/10.7326/M21-3324
Lips P, Wiersinga A, Van Ginkel FC et al. The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects. J Clin Endocrin Metab 1988;67:644–50. https://doi.org/10.1210/jcem-67-4-644
Limonte CP, Zelnick LR, Hoofnagle AN et al. Effects of vitamin D(3) supplementation on cardiovascular and cancer outcomes by eGFR in VITAL. Kidney360 2022;3:2095–105. https://doi.org/10.34067/KID.0006472022
NIHR, N. I. f. H. a. C. R. Survival Improvement with Cholecalciferol in Patients on Dialysis the SIMPLIFIED Registry Trial, https://fundingawards.nihr.ac.uk/award/14/49/127
Levin A, Tang M, Perry T et al. Randomized controlled trial for the effect of vitamin D supplementation on vascular stiffness in CKD. Clin J Am Soc Nephrol 2017;12:1447–60. https://doi.org/10.2215/CJN.10791016
Das S, Selvarajan S, Kamalanathan S et al. A randomized double-blind placebo-controlled trial evaluating the efficacy of oral cholecalciferol in improving renal and vascular functions in vitamin D-deficient patients with type 2 diabetes mellitus. J Diet Suppl 2023;20:44–54. https://doi.org/10.1080/19390211.2021.1958041
Samaan F, Carvalho AB, Pillar R et al. The effect of long-term cholecalciferol supplementation on vascular calcification in chronic kidney disease patients with hypovitaminosis D. J Ren Nutr 2019;29:407–15. https://doi.org/10.1053/j.jrn.2018.12.002
Banerjee D, Chitalia N, Ster IC et al. Impact of vitamin D on cardiac structure and function in CKD patients with hypovitaminosis D, a randomised controlled trial and meta-analysis. Eur Heart J Cardiovasc Pharmacother 2019; 7:302–11. https://doi.org/10.1093/ehjcvp/pvz080
Liyanage GC, Lekamwasam S, Weerarathna TP et al. Effects of high-dose parenteral vitamin D therapy on lipid profile and blood pressure in patients with diabetic nephropathy: a randomized double-blind clinical trial. Diabetes Metab Syndr 2017;11 Suppl 2:S767–70. https://doi.org/10.1016/j.dsx.2017.05. 013
Krummel T, Ingwiller M, Keller N et al. Effects of high-vs low-dose native vitamin D on albuminuria and the renin–angiotensin–aldosterone system: a randomized pilot study. Int Urol Nephrol 2022;54:895–905. https://doi.org/10.1007/ s11255-021-02950-3
Zittermann A, Berthold HK, Pilz S. The effect of vitamin D on fibroblast growth factor 23: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr 2021;75:980–7. https://doi.org/10.1038/s41430-020-00725-0
Daroux M, Shenouda M, Bacri J-L et al. Vitamin D2 versus vitamin D3 supplementation in hemodialysis patients: a comparative pilot study. J Nephrol 2013;26:152–7. https://doi.org/10.5301/jn.5000123
Balachandar R, Pullakhandam R, Kulkarni B et al. Relative efficacy of vitamin D(2) and vitamin D(3) in improving vitamin D status: systematic review and meta-analysis. Nutrients 2021; 3:3328. https://doi.org/10.3390/nu13103328
van den Heuvel EG, Lips P, Schoonmade LJ et al. Comparison of the effect of daily vitamin D2 and vitamin D3 supplementation on serum 25-hydroxyvitamin D concentration (total 25(OH)D, 25(OH)D2, and 25(OH)D3) and importance of body mass index: a systematic review and meta-analysis. Adv Nutr 2024;15:100133. https://doi.org/10.1016/j.advnut.2023.09.016
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;95:1357–64. https://doi.org/10.3945/ajcn.111.031070
Behairy MA, Elsharabasy RM, El Shaarawy AB et al. Oral versus intramuscular cholecalciferol replacement in hemodialysis patients with vitamin D deficiency. J Nephropharmacol 2022;11:e07. https://doi.org/10.34172/npj.2022.07
Gupta N, Farooqui KJ, Batra CM et al. Effect of oral versus intramuscular vitamin D replacement in apparently healthy adults with vitamin D deficiency. Indian J Endocrinol Metab 2017;21: 131–6. https://doi.org/10.4103/2230-8210.196007
Tellioglu A, Basaran S, Guzel R et al. Efficacy and safety of high dose intramuscular or oral cholecalciferol in vitamin D deficient/insufficient elderly. Maturitas 2012;72:332–8. https://doi.org/10.1016/j.maturitas.2012.04.011
Albinsson E, Grönlund AB, Paulsson M et al. Unpredictable supplementation of vitamin D to infants in the neonatal intensive care unit: an experimental study. Acta Paediatr 2024; https://doi.org/10.1111/apa.17351
Wan M, Patel A, Patel JP et al. Quality and use of unlicensed vitamin D preparations in primary care in England: retrospective review of national prescription data and laboratory analysis. Br J Clin Pharmacol 2021;87:1338–46. https://doi.org/10.1111/bcp.14521
Garg S, Sabri D, Kanji J et al. Evaluation of vitamin D medicines and dietary supplements and the physicochemical analysis of selected formulations. J Nutr Health Aging 2013;17:158–61. https://doi.org/10.1007/s12603-012-0090-4
Verkaik-Kloosterman J, Seves SM, Ocké MC. Vitamin D concentrations in fortified foods and dietary supplements intended for infants: implications for vitamin D intake. Food Chem 2017;221:629–35. https://doi.org/10.1016/j.foodchem.2016.11. 128
Khadgawat R, Ramot R, Chacko KM et al. Disparity in cholecalciferol content of commercial preparations available in India. Indian J Endocrinol Metab 2013;17:1100–3. https://doi.org/10.4103/2230-8210.122638
LeBlanc ES, Perrin N, Johnson JD, Jr et al. Over-the-counter and compounded vitamin D: is potency what we expect? JAMA Intern Med 2013;173:585–6. https://doi.org/10.1001/jamainternmed.2013.3812
Nimalaratne C, Sun C, Wu J et al. Quantification of selected fat soluble vitamins and carotenoids in infant formula and dietary supplements using fast liquid chromatography coupled with tandem mass spectrometry. Food Res Int 2014;66:69–77.
Huang Z, You T. Personalise vitamin D(3) using physiologically based pharmacokinetic modelling. CPT: Pharmacometrics Syst Pharmacol 2021;10:723–34. https://doi.org/10.1002/psp4. 12640
Wan M, Green B, Iyengar AA et al. Population pharmacokinetics and dose optimisation of colecalciferol in paediatric patients with chronic kidney disease. Br J Clin Pharmacol 2022;88:1223–34. https://doi.org/10.1111/bcp.15064
de Oliveira LF, de Azevedo LG, da Mota Santana J et al. Obesity and overweight decreases the effect of vitamin D supplementation in adults: systematic review and meta-analysis of randomized controlled trials. Rev Endocr Metab Disord 2020;21: 67–76. https://doi.org/10.1007/s11154-019-09527-7
Shroff R, Aitkenhead H, Costa N et al. Normal 25-hydroxyvitamin D levels are associated with less proteinuria and attenuate renal failure progression in children with CKD. J Am Soc Nephrol 2016;27:314–22. https://doi.org/10.1681/ ASN.2014090947
Aloni Y, Shany S, Chaimovitz C. Losses of 25-hydroxyvitamin D in peritoneal fluid: possible mechanism for bone disease in uremic patients treated with chronic ambulatory peritoneal dialysis. Miner Electrolyte Metab 1983;9:82–86.
National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42:S1–201.
Nadeem S, Tangpricha V, Ziegler TR et al. Randomized trial of two maintenance doses of vitamin D in children with chronic kidney disease. Pediatr Nephrol 2022;37:415–22. https://doi.org/10.1007/s00467-021-05228-z
Feng Z, Lu K, Ma Y et al. Effect of a high vs. standard dose of vitamin D3 supplementation on bone metabolism and kidney function in children with chronic kidney disease. Front Pediatr 2022;10:990724. https://doi.org/10.3389/fped.2022.990724
Nata N, Kanchanasinitth J, Tasanavipas P et al. Efficacy of weekly split versus single doses of ergocalciferol on serum 25-hydroxyvitamin D among patients on continuous ambulatory peritoneal dialysis: a randomized controlled trial. Int J Nephrol 2021;2021:1. https://doi.org/10.1155/2021/5521689
Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ et al. Monthly high-dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial. JAMA Intern Med 2016;176:175–83. https://doi.org/10.1001/jamainternmed.2015.7148
Sanders KM, Stuart AL, Williamson EJ et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA 2010;303:1815–22. https://doi.org/10.1001/jama.2010.594
Morrone L, Palmer SC, Saglimbene VM et al. Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial. J Nephrol 2022;35:517–25. https://doi.org/10.1007/ s40620-021-01104-z
Donati S, Marini F, Giusti F et al. Calcifediol: why, when, how much? Pharmaceuticals (Basel) 2023; 6:637. https://doi.org/10.3390/ph16050637
Pérez-Castrillón JL, Dueñas-Laita A, Brandi ML et al. Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial. J Bone Miner Res 2020;36:1967–78. https://doi.org/10.1002/jbmr.4387
Cashman KD, Seamans KM, Lucey AJ et al. Relative effectiveness of oral 25-hydroxyvitamin D3 and vitamin D3 in raising wintertime serum 25-hydroxyvitamin D in older adults. Am J Clin Nutr 2012;95:1350–6. https://doi.org/10.3945/ajcn.111. 031427
Fadda G, Germain MJ, Broumand V et al. Real-world assessment: clinical effectiveness and safety of extended-release calcifediol. Am J Nephrol 2021;52:798–807. https://doi.org/10.1159/ 000518545
Germain MJ, Paul SK, Fadda G et al. Real-world assessment: effectiveness and safety of extended-release calcifediol and other vitamin D therapies for secondary hyperparathyroidism in CKD patients. BMC Nephrology 2022;23:362. https://doi.org/10.1186/s12882-022-02993-3
Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B et al. Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES. J Clin Endocrinol Metab 2013;98:3001–9. https://doi.org/10.1210/jc.2013-1333
Durup D, Jørgensen HL, Christensen J et al. A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study. J Clin Endocrinol Metab 2012;97:2644–52. https://doi.org/10.1210/ jc.2012-1176
Durup D, Jørgensen HL, Christensen J et al. A reverse J-shaped association between serum 25-hydroxyvitamin D and cardiovascular disease mortality: the CopD study. J Clin Endocrinol Metab 2015;100:2339–46. https://doi.org/10.1210/jc.2014-4551
Zhao S, Chen X, Wan Z et al. Associations of serum 25-hydroxyvitamin D and vitamin D receptor polymorphisms with risks of cardiovascular disease and mortality among patients with chronic kidney disease: a prospective study. Am J Clin Nutr 2024; 119:1397–404. https://doi.org/10.1016/j.ajcnut.2024.04.001
Tantiyavarong P, Kramer A, Heaf JG et al. Changes in clinical indicators related to the transition from dialysis to kidney transplantation—data from the ERA-EDTA Registry. Clin Kidney J 2020;13:188–98. https://doi.org/10.1093/ckj/sfz062
Rolighed L, Rejnmark L, Sikjaer T et al. Vitamin D treatment in primary hyperparathyroidism: a randomized placebo controlled trial. J Clin Endocrinol Metab 2014;99:1072–80. https://doi.org/10.1210/jc.2013-3978
Holick MF, Binkley NC, Bischoff-Ferrari HA et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911–30. https://doi.org/10.1210/jc.2011-0385
Lips P, Cashman KD, Lamberg-Allardt C et al. Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency: a position statement of the European Calcified Tissue Society. Eur J Endocrinol 2019;180:P23–54. https://doi.org/10.1530/EJE-18-0736
Kaur J, Khosla S, Farr JN. Effects of diabetes on osteocytes. Curr Opin Endocrinol Diabetes Obes 2022;29:310–7. https://doi.org/10.1097/MED.0000000000000733
Liyanage P, Lekamwasam S, Weerarathna TP et al. Effect of vitamin D therapy on urinary albumin excretion, renal functions, and plasma renin among patients with diabetic nephropathy: a randomized, double-blind clinical trial. J Postgrad Med 2018;64:10–15. https://doi.org/10.4103/jpgm.JPGM_598_16
Nata N, Siricheepchaiyan W, Supasyndh O et al. Efficacy of high versus conventional dose of ergocalciferol supplementation on serum 25-hydroxyvitamin D and interleukin-6 levels among hemodialysis patients with vitamin D deficiency: a multicenter, randomized, controlled study. Ther Apher Dial 2022;26:378–86. https://doi.org/10.1111/1744-9987.13722
Mager DR, Jackson ST, Hoffmann MR et al. Vitamin D(3) supplementation, bone health and quality of life in adults with diabetes and chronic kidney disease: results of an open label randomized clinical trial. Clin Nutr 2017;36:686–96. https://doi.org/10.1016/j.clnu.2016.05.012
