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12 Which Vitamin D Should We Use? Native Vitamin D or Active VDRA Compound? D2 or D3?

12 Which Vitamin D Should We Use? Native Vitamin D or Active VDRA Compound? D2 or D3?

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Vitamin D and Mortality Risk in Chronic Kidney Disease



Unmet Need

Studies capable of demonstrating a positive effect of treatment with vitamin D compounds at the patient level are difficult to undertake if sufficiently robust. Thus virtually all of the available data to hand at the moment fall some way short of being

able to establish clear cut cause and effect in regard to mortality, and also in regard

to specific patient level outcomes that are themselves likely to impact on mortality.

Thus far interventional studies have focused largely on biochemical end points,

although some have examined other surrogates such as mortality and morbid events

that may be closer to the holy grail of patient level outcomes that really matter.

Nevertheless we still lack convincing data from randomized intervention controlled

trials demonstrating that any formulation of vitamin D results in improved patient

level outcomes, although some are planned or are in progress. To be set against this

negative view are the background plausibility as outlined above, and the experimental data and the extensive observational clinical data currently available.

The same limitations apply when it comes to making recommendations in regard

to the indications for vitamin D treatment beyond the classical ones related to bone

and mineral metabolism. This somewhat negative and cautious conclusion that

applies to patients with CKD is close to that drawn by the Institute of Medicine

when making recommendations regarding vitamin D supplementation [72]. That

organisation considered how to ensure that the vitamin D requirements of the general population should be met and concluded that there was sufficiently robust evidence of beneficial effects in relation to classical bone mineral and skeletal

indications to justify current strategies, albeit at slightly higher dose than historically recommended. The Institute of Medicine stopped short of recommending

higher doses such as have been considered in the setting of the pleiotropic actions

of cholecalciferol and also stopped short of routinely recommending treatment with

vitamin D for indications related to infection, autoimmunity or cancer.

For the nephrologist one thing is clear. We need patient level outcome data from

properly designed intervention studies capable of establishing, or refuting, cause and

effect. Less clear is what we should do in the meantime [73]. A pragmatic view, based

on the principle of “do good if you can, provided you do no harm”, is to use active

vitamin D compounds in appropriate pharmacological doses, often supraphysiological, for established indications based on the classical actions of vitamin D on the parathyroids, bone and mineral metabolism. This then leaves two important unanswered

questions. First, should all CKD patients, whether or not manifesting an established

indication, be offered physiological doses of active vitamin D in the hope of reaping

the benefit implied in the results of the many large observational studies already published? Second, should generous supplementation with native vitamin D be offered to

all CKD patients with the aim of supporting widespread extra renal generation of calcitriol and facilitating the putative pleotropic effects of vitamin D that could mitigate

some of the cardiovascular and other attrition faced by these patients (Fig. 24.1)? Such

an approach appears extraordinarily unlikely to do harm and so, for the time being at

least, a cautious and provisional “yes” to both questions appears justified.

J. Cunningham


Unless contraindicated, default to:

Generous D3 supplementation

to 75 - 150nM

(typically 10,000 – 30,000 units/week)

Physiological replacement of deficient calcitriol

(alfacalcidol/calcitriol 0.125 - 0.25mcg/d)

Residual hyperparathyroidism?


Pharmacological VDRA

and/or calcimimetic


continue as above

Fig. 24.1 An approach to vitamin D management in CKD. This presumes that the clinician is

willing to make a decision on the basis of likely risk vs. possible, but unproven, benefit. It reflects

widely adopted clinical practice. It is not based on hard evidence or current published guidance


1. Holick MF, Schnoes HK, DeLuca HF. Identification of 1,25-dihydroxycholecalciferol, a form of

vitamin D3 metabolically active in the intestine. Proc Natl Acad Sci U S A. 1971;68(4):803–4.

2. Brickman AS, Coburn JW, Norman AW. Action of 1,25-dihydroxycholecalciferol, a potent,

kidney-produced metabolite of vitamin D, in uremic man. N Engl J Med. 1972;287(18):


3. Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003;349(5):446–56.

4. Teng M, Wolf M, Ofsthun MN, Lazarus JM, Hernán MA, Camargo CA, Thadhani R. Activated

injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol.


5. Wolf M, Shah A, Gutierrez O, Ankers E, Monroy M, Tamez H, et al. Vitamin D levels and

early mortality among incident hemodialysis patients. Kidney Int. 2007;72(8):1004–13.

6. Naves-Díaz M, Alvarez-Hernández D, Passlick-Deetjen J, Guinsburg A, Marelli C, RodriguezPuyol D, Cannata-Andía JB. Oral active vitamin D is associated with improved survival in

hemodialysis patients. Kidney Int. 2008;74(8):1070–8.

7. Tentori F, Hunt WC, Stidley CA, Rohrscheib MR, Bedrick EJ, Meyer KB, et al. Mortality risk

among hemodialysis patients receiving different vitamin D analogs. Kidney Int. 2006;70(10):


8. Shoben AB, Rudser KD, de Boer IH, Young B, Kestenbaum B. Association of oral calcitriol

with improved survival in nondialyzed CKD. J Am Soc Nephrol. 2008;19(8):1613–9.


Vitamin D and Mortality Risk in Chronic Kidney Disease


9. Kovesdy CP, Ahmadzadeh S, Anderson JE, Kalantar-Zadeh K. Association of activated vitamin D treatment and mortality in chronic kidney disease. Arch Intern Med. 2008;168(4):


10. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.

11. Schottker B, Jorde R, Peasey A, Thorand B, Jansen EHJM, Groot LD, et al. Vitamin D and

mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ. 2014;348:g3656.

12. 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(4):1144–51.

13. Chonchol M, Kendrick J, Targher G. Extra-skeletal effects of vitamin D deficiency in chronic

kidney disease. Ann Med. 2011;43(4):273–82.

14. Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, Chowdhury S, Kiefte-de-Jong JC,

et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903.

15. London GM, Guérin AP, Verbeke FH, Pannier B, Boutouyrie P, Marchais SJ, Mëtivier

F. Mineral metabolism and arterial functions in end-stage renal disease: potential role of

25-hydroxyvitamin D deficiency. J Am Soc Nephrol. 2007;18(2):613–20.

16. Isakova T, Gutiérrez OM, Patel NM, Andress DL, Wolf M, Levin A. Vitamin D deficiency,

inflammation, and albuminuria in chronic kidney disease: complex interactions. J Ren Nutr.


17. Chitalia N, Recio-Mayoral A, Kaski JC, Banerjee D. Vitamin D deficiency and endothelial dysfunction in non-dialysis chronic kidney disease patients. Atherosclerosis. 2012;220(1):265–8.

18. Chitalia N, Ismail T, Tooth L, Boa F, Hampson G, Goldsmith D, et al. Impact of vitamin D

supplementation on arterial vasomotion, stiffness and endothelial biomarkers in chronic kidney disease patients. PLoS ONE. 2014;9(3), e91363.

19. Dreyer G, Tucker AT, Harwood SM, Pearse RM, Raftery MJ, Yaqoob MM. Ergocalciferol and

microcirculatory function in chronic kidney disease and concomitant vitamin d deficiency: an

exploratory, double blind, randomised controlled trial. PLoS ONE. 2014;9(7), e99461.

20. Shroff R, Egerton M, Bridel M, Shah V, Donald AE, Cole TJ, et al. A bimodal association of

vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19(6):


21. Patange AR, Valentini RP, Du W, Pettersen MD. Vitamin D deficiency and arterial wall stiffness in children with chronic kidney disease. Pediatr Cardiol. 2012;33(1):122–8.

22. de Boer IH, Kestenbaum B, Shoben AB, Michos ED, Sarnak MJ, Siscovick DS.

25-hydroxyvitamin D levels inversely associate with risk for developing coronary artery calcification. J Am Soc Nephrol. 2009;20(8):1805–12.

23. Razzaque MS. The dualistic role of vitamin D in vascular calcifications. Kidney Int. 2011;


24. Levin A, Perry T, De Zoysa P, Sigrist MK, Humphries K, Tang M, Djurdjev O. A randomized

control trial to assess the impact of vitamin D supplementation compared to placebo on vascular stiffness in chronic kidney disease patients. BMC Cardiovasc Disord. 2014;14:156.

25. Melamed ML, Muntner P, Michos ED, Uribarri J, Weber C, Sharma J, Raggi P. Serum

25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease: results from

NHANES 2001 to 2004. Arterioscler Thromb Vasc Biol. 2008;28(6):1179–85.

26. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503–11.

27. Vaidya A, Forman JP. Vitamin D and vascular disease: the current and future status of vitamin

D therapy in hypertension and kidney disease. Curr Hypertens Rep. 2012;14(2):111–9.

28. Rostand SG. Ultraviolet light may contribute to geographic and racial blood pressure differences. Hypertension. 1997;30(2):150–6.

29. Krause R, Bühring M, Hopfenmüller W, Holick MF, Sharma AM. Ultraviolet B and blood

pressure. Lancet. 1998;352(9129):709–10.

30. Li YC, Kong J, Wei M, Chen Z-F, Liu SQ, Cao L-P. 1,25-dihydroxyvitamin D3 is a negative

endocrine regulator of the renin-angiotensin system. J Clin Investig. 2002;110(2):229–38.


J. Cunningham

31. Xiang W, Kong J, Chen S, Cao L-P, Qiao G, Zheng W, et al. Cardiac hypertrophy in vitamin D

receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am

J Physiol Endocrinol Metab. 2005;288(1):E125–32.

32. Zhou C, Lu F, Cao K, Xu D, Goltzman D, Miao D. Calcium-independent and 1,25(OH)2d3dependent regulation of the renin-angiotensin system in 1alpha-hydroxylase knockout mice.

Kidney Int. 2008;74(2):170–9.

33. Pilz S, Tomaschitz A, Ritz E, Pieber TR. Vitamin D status and arterial hypertension: a systematic review. Nat Rev Cardiol. 2009;6(10):621–30.

34. Patange AR, Valentini RP, Gothe MP, Du W, Pettersen MD. Vitamin D deficiency is associated

with increased left ventricular mass and diastolic dysfunction in children with chronic kidney

disease. Pediatr Cardiol. 2013;34(3):536–42.

35. Thadhani R, Appelbaum E, Pritchett Y, Chang Y, Wenger J, Tamez H, et al. Vitamin D therapy

and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA. 2012;307(7):674–84.

36. Tamez H, Zoccali C, Packham D, Wenger J, Bhan I, Appelbaum E, et al. Vitamin D reduces

left atrial volume in patients with left ventricular hypertrophy and chronic kidney disease. Am

Heart J. 2012;164(6):902–9.e2.

37. de Borst MH, Hajhosseiny R, Tamez H, Wenger J, Thadhani R, Goldsmith DJA. Active vitamin D treatment for reduction of residual proteinuria: a systematic review. J Am Soc Nephrol.


38. Kim MJ, Frankel AH, Donaldson M, Darch SJ, Pusey CD, Hill PD, et al. Oral cholecalciferol

decreases albuminuria and urinary tgf-β1 in patients with type 2 diabetic nephropathy on

established renin-angiotensin-aldosterone system inhibition. Kidney Int. 2011;80(8):


39. De Zeeuw D, Agarwal R, Amdahl M, Audhya P, Coyne D, Garimella T, et al. Selective

vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients

with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet.


40. Shroff R, Aitkenhead H, Costa N, Trivelli A, Litwin M, Picca S, 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(1):314–22.

41. Andress DL. Vitamin D, in chronic kidney disease: a systemic role for selective vitamin D

receptor activation. Kidney Int. 2006;69(1):33–43.

42. Shroff R, Wan M, Rees L. Can vitamin D slow down the progression of chronic kidney disease? Pediatr Nephrol. 2012;27(12):2167–73.

43. Chertow GM, Block GA, Correa-Rotter R, Drüeke TB, Floege J, Goodman WG, et al. Effect

of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med.


44. Cunningham J, Zehnder D. New vitamin D analogs and changing therapeutic paradigms.

Kidney Int. 2011;79(7):702–7.

45. de Boer IH, Kestenbaum B. Vitamin D in chronic kidney disease: is the jury in? Kidney Int.


46. Kovesdy CP, Kalantar-Zadeh K. Vitamin D receptor activation and survival in chronic kidney

disease. Kidney Int. 2008;73(12):1355–63.

47. Cozzolino M, Ketteler M, Zehnder D. The vitamin D system: a crosstalk between the heart and

kidney. Eur J Heart Fail. 2010;12(10):1031–41.

48. Kovesdy CP. Survival benefits with vitamin D receptor activation: new insights since 2003.

Clin J Am Soc Nephrol. 2010;5(9):1704–9.

49. Heaf JG, Joffe P, Marckmann P. Vitamin d and stage 5 chronic kidney disease: a new paradigm? Semin Dial. 2012;25(1):50–8.

50. Tentori F, Albert JM, Young EW, Blayney MJ, Robinson BM, Pisoni RL, et al. The survival

advantage for haemodialysis patients taking vitamin D is questioned: findings from the dialysis outcomes and practice patterns study. Nephrol Dial Transplant. 2009;24(3):963–72.


Vitamin D and Mortality Risk in Chronic Kidney Disease


51. Nigwekar SU, Thadhani RI. Shining light on vitamin D trials in chronic kidney disease.

Kidney Int. 2013;83(2):198–200.

52. Mann MC, Hobbs AJ, Hemmelgarn BR, Roberts DJ, Ahmed SB, Rabi DM. Effect of oral

vitamin D analogs on mortality and cardiovascular outcomes among adults with chronic kidney disease: a meta-analysis. Clin Kidney J. 2015;8(1):41–8.

53. Li X-H, Feng L, Yang Z-H, Liao Y-H. The effect of active vitamin D on cardiovascular outcomes in predialysis chronic kidney diseases: a systematic review and meta-analysis.

Nephrology (Carlton). 2015;20(10):706–714.

54. Duranton F, Rodriguez-Ortiz ME, Duny Y, Rodriguez M, Daurès J-P, Argilés A. Vitamin D

treatment and mortality in chronic kidney disease: a systematic review and meta-analysis. Am

J Nephrol. 2013;37(3):239–48.

55. Pilz S, Iodice S, Zittermann A, Grant WB, Gandini S. Vitamin D status and mortality risk in

CKD: a meta-analysis of prospective studies. Am J Kidney Dis. 2011;58(3):374–82.

56. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of

a vitamin d-mediated human antimicrobial response. Science. 2006;311(5768):1770–3.

57. Yamshchikov AV, Desai NS, Blumberg HM, Ziegler TR, Tangpricha V. Vitamin D for treatment and prevention of infectious diseases: a systematic review of randomized controlled trials. Endocr Pract. 2009;15(5):438–49.

58. Gombart AF, Bhan I, Borregaard N, Tamez H, Camargo CA, Koeffler HP, Thadhani R. Low

plasma level of cathelicidin antimicrobial peptide (hcap18) predicts increased infectious

disease mortality in patients undergoing hemodialysis. Clin Infect Dis. 2009;


59. Alvarez JA, Zughaier SM, Law J, Hao L, Wasse H, Ziegler TR, Tangpricha V. Effects of highdose cholecalciferol on serum markers of inflammation and immunity in patients with early

chronic kidney disease. Eur J Clin Nutr. 2013;67(3):264–9.

60. Moe SM, Zekonis M, Harezlak J, Ambrosius WT, Gassensmith CM, Murphy CL, et al. A

placebo-controlled trial to evaluate immunomodulatory effects of paricalcitol. Am J Kidney

Dis. 2001;38(4):792–802.

61. Sterling KA, Eftekhari P, Girndt M, Kimmel PL, Raj DS. The immunoregulatory function

of vitamin D: implications in chronic kidney disease. Nat Rev Nephrol. 2012;8(7):


62. Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health

outcomes: a reanalysis of the women’s health initiative (WHI) limited-access data set. Am

J Clin Nutr. 2011;94(4):1144–9.

63. Gallicchio L, Moore LE, Stevens VL, Ahn J, Albanes D, Hartmuller V, et al. Circulating

25-hydroxyvitamin D and risk of kidney cancer: cohort consortium vitamin D pooling project

of rarer cancers. Am J Epidemiol. 2010;172(1):47–57.

64. Lee JE, Li H, Chan AT, Hollis BW, Lee I-M, Stampfer MJ, et al. Circulating levels of vitamin

D and colon and rectal cancer: the physicians’ health study and a meta-analysis of prospective

studies. Cancer Prev Res (Phila). 2011;4(5):735–43.

65. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium

supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr.


66. Dusso A, González EA, Martin KJ. Vitamin D in chronic kidney disease. Best Pract Res Clin

Endocrinol Metab. 2011;25(4):647–55.

67. Fleet JC, DeSmet M, Johnson R, Li Y. Vitamin D and cancer: a review of molecular mechanisms. Biochem J. 2012;441(1):61–76.

68. Birkeland SA, Storm HH. Cancer risk in patients on dialysis and after renal transplantation.

Lancet. 2000;355(9218):1886–7.

69. Marquardt P, Krause R, Schaller M, Bach D, von Gersdorff G. Vitamin D status and cancer

prevalence of hemodialysis patients in Germany. Anticancer Res. 2015;35(2):1181–7.

70. Gröber U, Spitz J, Reichrath J, Kisters K, Holick MF. Vitamin D: update 2013: from rickets

prophylaxis to general preventive healthcare. Dermatoendocrinology. 2013;5(3):331–47.


J. Cunningham

71. Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3

increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr.


72. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, et al. The 2011 report

on dietary reference intakes for calcium and vitamin D from the institute of medicine: what

clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–8.

73. Goldsmith DJA, Cunningham J. Mineral metabolism and vitamin D in chronic kidney disease – more questions than answers. Nat Rev Nephrol. 2011;7(6):341–6.

Part IV

Kidney Transplantation

Chapter 25

Vitamin D in Kidney Transplantation

Pieter Evenepoel

Abstract Renal transplantation restores renal functional mass and corrects metabolic and hormonal disturbances underlying the altered vitamin D metabolism in

chronic kidney disease. As a consequence, concentrations of 1,25 dihydroxyvitamin

D rapidly recover after successful renal transplantation. Remarkably however, concentrations remain often at the lower range in the early posttransplant period despite

the presence of hyperparathyroidism and hypophosphatemia, conditions known to

stimulate increased calcitriol synthesis. Also 25-hydroxyvitamin D concentrations

increase following transplantation but, overall, these increases are modest.

25-hydroxyvitamin D deficiency and insufficiency thus remain very common

among renal transplant recipients. Hypovitaminosis D may contribute to persistent

hyperparathyroidism and posttransplant bone and vascular disease. Limited epidemiological evidence also suggest that hypovitaminosis D may foster malignancies

and infections in renal transplant recipients. Disappointingly, intervention studies

with vitamin D supplementations studies are scanty. They moreover did not yield

unequivocal results. Hard endpoint intervention studies are lacking at all.

Keywords Vitamin D • Renal transplantation • CKD-MBD



For patients with end stage renal disease, kidney transplantation undoubtedly is the

best treatment option. Worldwide, the numbers of transplanted kidneys rise steadily.

In the US alone, more than 17,500 kidneys are transplanted annually. The development of novel immunosuppressive therapies has led to a tremendous increase in the

1-year survival rates of renal allografts [1]. Accordingly, improving the long-term

survival and quality of life for renal transplant recipients has become a major focus

P. Evenepoel, MD

Division of Nephrology, Dialysis and Renal Transplantation, Department of Medicine,

University Hospital Leuven, Leuven, Belgium

e-mail: Pieter.Evenepoel@uzleuven.be

© Springer International Publishing Switzerland 2016

P.A. Ureña Torres et al. (eds.), Vitamin D in Chronic Kidney Disease,

DOI 10.1007/978-3-319-32507-1_25



P. Evenepoel

of post-transplantation patient care and includes prevention of cardiovascular

complications, diabetes mellitus, infections, cancer, and fractures associated with

bone disease. The increased awareness that vitamin D deficiency, being common

among renal transplant recipients may be involved in the pathogenesis of each of

these complications, fueled interest in posttransplant vitamin D metabolism and

triggered several interventional studies specifically exploring the pivotal benefits of

vitamin D supplementation on bone metabolism and beyond. The present review

aims to present a state of the art on vitamin D metabolism and its association with

non-renal outcomes in kidney transplant recipients.



Vitamin D Metabolism in Health, Chronic Kidney

Disease and Renal Transplantation

Vitamin D Metabolism in Health

Vitamin D is a steroid hormone whose primary function is to regulate calcium

homeostasis and bone mineralization; however, it is increasingly thought to exert

important effects on other tissues such as vascular endothelium and cells of the

immune system. It is a unique vitamin in that it can be sourced from the diet or

synthesized in the skin by ultraviolet B (UVB) sunlight. Most people depend on

solar synthesis of vitamin D to achieve adequate body stores, with dietary vitamin

D normally contributing only 10–20 % of the recommended intake. The formation

of fully active vitamin D out of the prohormones ergocalciferol (vitamin D2) and

cholecalciferol (vitamin D3) requires a further two-step hydroxylation process.

Hepatocytes mediate the first hydroxylation on carbon 25 (by the action of CYP2R1)

to produce 25-hydroxyvitamin D (25(OH)D), also known as calcidiol), which binds

the vitamin D receptor (VDR) with only a modest affinity. The complete activation

of vitamin D requires further hydroxylation on carbon 1 by the enzyme CYP27B1,

resulting in the formation of calcitriol or 1,25 dihydroxyvitamin D (1,25(OH)2D).

This last step takes place mainly in the proximal tubular cells of the kidney. Both

25(OH)D and 1,25(OH)2D undergo catabolism via multiple side chain hydroxylations. Vitamin D catabolism is mediated mainly by renal CYP24A1. Evidence suggests that CYP3A4, i.e. the most abundant cytochrome P450 enzyme in the liver,

may also be involved. The quantitative contribution of CYP3A4 to vitamin D catabolism, compared to CYP24A1, is poorly defined.

Production and catabolism of 1,25(OH)2D by the kidney is tightly regulated

through a complex system of hormones that together maintain calcium and phosphorus homeostasis. These hormones include parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and 1,25(OH)2D itself. While 1,25(OH)2D is

considered the biologically active form of vitamin D, 25(OH)D is the major circulating form and is considered the more reliable measure of vitamin D status.


Vitamin D in Kidney Transplantation



Vitamin D Metabolism in Chronic Kidney Disease

In CKD, 1,25(OH)2D production is reduced owing to alterations in CYP

abundances, CYP activity, and delivery of substrate to CYP enzymes (for review

see [2]). PTH and FGF23 exert opposite effect on CYP27B1 expression. The net

effect is uncertain, as evidenced by experimental and clinical data. Impaired

delivery of 25(OH)D to CYP27B1 and/or decreased CYP27B1 activity may prove

more important than decreased enzymatic mass in CKD. Circulating 25(OH)D

levels in CKD patients are often low as a result of low sun exposure, decreased

cutaneous synthesis, and limited dietary intake. Moreover, reabsorption of filtered

25(OH)D in the proximal tubule may be impaired in CKD as a consequence of

decreased megalin expression. CKD also disrupts vitamin D catabolism. PTH

suppresses, while FGF23 stimulates CYP24A1 expression and activity. The net

effect remains, as for CYP27B1, incompletely understood. Most recent data suggest that CKD should be considered a state of stagnant vitamin D metabolism

characterized by reduced vitamin D catabolism and turnover in addition to reduced

1,25(OH)2D production. In this paradigm, competing effects of PTH and FGF23

on the expression of CYP27B1 and CYP24A1 either balance each other or are

superseded by a general decrease in vitamin D metabolic function of the kidney,

caused either by impaired uptake of 25(OH)D, diminished metabolic activity of

proximal tubular cells, or a simple reduction in the number of functioning nephrons (for review see [2]).


Vitamin D Metabolism in Renal Transplant Recipients

Renal transplantation restores, at least partly, renal functional mass and corrects

metabolic and hormonal disturbances underlying the altered vitamin D metabolism

in CKD [3].

25(OH)D Levels in Renal Transplant Recipients

Following renal transplantation, serum 25(OH)D levels commonly follow a

biphasic pattern characterized by an early decrease followed by a modest recovery

[4–8]. Several mechanisms may be hypothesized to contribute to the early decline

[9]; first, tubular dysfunction (related to ischemia-reperfusion injury) associates

with overload proteinuria which may result in substantial urinary losses of the

Vitamin D- Vitamin D binding protein complex. Second, vitamin D catabolism

may be enhanced in the posttransplant period, due to upregulation of CYP24A1

either by inappropriately high FGF23 levels [10] or by glucocorticoids [11].

Despite a slight recovery of 25(OH)D levels later on, 25(OH)D levels remain

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