Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 2087 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 


 
Table of Contents   
ORIGINAL ARTICLE  
Year : 2016  |  Volume : 27  |  Issue : 5  |  Page : 929-935
Prevalence of hypovitaminosis D and the different-dose cholecalciferol supplementation effects on renal transplant recipients


Department of Medicine, Santa Casa de Sao Paulo School of Medical Sciences, São Paulo, Brazil

Click here for correspondence address and email

Date of Web Publication22-Sep-2016
 

   Abstract 

High prevalence of hypovitaminosis D has been observed in patients with chronic kidney disease. However, there is not much data about its prevalence in kidney transplant recipients (KTRs). The study included 83 adult KTRs at a single center to calculate the prevalence of hypovitaminosis D. Among the 83 patients, those with incomplete data were excluded leaving 22 patients available for study. The demographic and biochemical data were analyzed retrospectively. Serum concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), phosphorus, calcium, and creatinine were evaluated. The 22 selected patients were divided into two groups: (1) those who received 10,000 IU of cholecalciferol orally per week, and (2) those who received 10,000-20,000 IU/week. The Vitamin D level rate was calculated to evaluate the time necessary to reach serum values ≥30 ng/mL. Hypovitaminosis D was present in 80.7% (67/83) of the patients. Eleven patients received 10,000 IU/week of cholecalciferol, and the other 11 patients received 10,000-20,000 IU/week (approximately 64,000 IU/month). The calcium, phosphorus, and PTH values did not show any differences between the two groups. We estimate that a dose of approximately 64,000 IU/month of cholecalciferol was sufficient to reach values of ≥30 ng/mL of 25(OH)D in approximately 2.1 months in the insufficient and 4.3 months in Vitamin D-deficient patients. The prevalence of hypovitaminosis D was high among Brazilian KTR, and low-level doses of cholecalciferol (approximately 64,000 IU/month) were sufficient to control hypovitaminosis D.

How to cite this article:
Poli de Figueiredo SM, Magalhães AO, Malafronte P, de Souza JF, Sens YA. Prevalence of hypovitaminosis D and the different-dose cholecalciferol supplementation effects on renal transplant recipients. Saudi J Kidney Dis Transpl 2016;27:929-35

How to cite this URL:
Poli de Figueiredo SM, Magalhães AO, Malafronte P, de Souza JF, Sens YA. Prevalence of hypovitaminosis D and the different-dose cholecalciferol supplementation effects on renal transplant recipients. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2019 Oct 14];27:929-35. Available from: http://www.sjkdt.org/text.asp?2016/27/5/929/190839

   Introduction Top


Vitamin D plays an important role in calcium homeostasis. Various studies show a worldwide high prevalence of hypovitaminosis D in the general population and in patients with chronic kidney disease (CKD). However, there is limited data on its prevalence in kidney transplant recipients (KTRs). The main sources of Vitamin D available to humans are from direct exposure to sunlight and from the diet, varying in different populations and regions. Vitamin D from skin and diet is metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], which is the main circulating form of Vitamin D. The serum levels of 25(OH)D are markers for Vitamin D insufficiency, deficiency, or intoxication. [1] The 25(OH)D released in the liver is transported to the kidneys, where it is metabolized and converted into its active form. [1] Several factors can decrease the production of cutaneous Vitamin D. [2] Individuals from high latitude and low sunlight exposure geographic areas may be at increased risk for Vitamin D deficiency, but hypovitaminosis D has also been described in latitudes with abundant sunlight. [3] Afro-descendants require greater exposure to sunlight to synthesize the same quantity that Caucasian people do. [4] The skin's efficiency in synthesizing Vitamin D decreases with aging; individuals over 70 produce 30% less Vitamin D than young adults. [5] Even though 25(OH)D serum levels in the healthy population have not yet been definitively established, the level considered adequate is between 30 and 50 ng/mL, 15-30 ng/mL being insufficient, and under 15 ng/mL being deficient. [6]

A successful renal transplant usually corrects or improves mineral metabolism disturbances and bone disease present in CKD. However, some patients continue having these abnormalities which result from a complex interaction of different factors. [7],[8],[9] The 25(OH)D insufficiency is present in approximately 85% of renal transplant recipients [10] and may be caused by poor graft function, immunosuppressive drugs which increase Vitamin D catabolism, [11] persistent hypersecretion of fibroblast growth factor 23 following the transplant, [12] as well as decreased sun exposure recommended for these patients due to their immunosuppressor-induced skin cancer risk. [13]

In Brazil, a tropical country with year-round sunshine, there is a scarcity of studies evaluating the prevalence of hypovitaminosis D in renal transplant recipients, as well a lack of a well-established Vitamin D dose and supplementation safety for these patients. Baxmann et al found 65% of hypovitaminosis D in renal transplant receptors in Brazil, indicating insufficiency in 53% and deficiency in 12% of them. [14]

Considering this data, the aim of this study was to evaluate the prevalence of hypovitaminosis D and the effect of different dose cholecalciferol supplementation on renal transplant recipients in a single center in Brazil.


   Methods Top


Patient medical file data of a cohort of renal transplant recipients were collected retrospectively at the Santa Casa de São Paulo Nephrology Outpatient Unit, from July 2013 to July 2014. The inclusion criteria were patients over 18 years old, on renal transplantation for more than six months, treatment naïve of Vitamin D or calcium supplement, and without infectious episodes in the six months before serum Vitamin D dosage. Eighty-three KTRs were included in the study to calculate the prevalence of hypovitaminosis D. Then, among the 83 patients those with incomplete data were excluded and 22 patients that had dosage Vitamin D reported within the period of one year after the cholecalciferol supplementation were selected. The demographic and biochemical data were analyzed, as well as the etiology of renal failure before transplantation. The 22 selected patients were subdivided into two groups: (1) those who received 10,000 IU of cholecalciferol orally per week, and (2) those who received 10,000-20,000 IU/ week. The Vitamin D increases rate (final value−initial value of Vitamin D/ supplementation time) was calculated to evaluate the time needed to reach serum values ≥30 ng/mL. Serum concentrations of calcium, phosphorus, creatinine, 25(OH)D, and parathyroid hormone (PTH) were evaluated before and after cholecalciferol supplementation. All analyses were performed according to the current laboratory standards. Both serum concentrations of 25 (OH)D and PTH were determined by the chemiluminescence assay periodically every three months. The level of the Vitamin D between 30 and 50 ng/mL was considered normal, 15-30 ng/mL being insufficient, and under 15 ng/ mL being deficient. [6] The Ethics Committee of the Institution approved the study protocol (no. 177/2011), and informed consent was obtained from every participant.


   Statistical Analysis Top


Data are expressed as the mean ± standard deviation or frequencies. Paired relationships were analyzed by the paired Student's t-test. Analyses were performed using the Statistical Package for the Social Sciences (SPSS) for Windows version 21.0 (SPSS Inc, Chicago, IL., USA), and P <0.05 was considered statistically significant.


   Results Top


The prevalence of hypovitaminosis D in 83 renal transplant recipients was 80.7% (67/83): 60.2% presented insufficiency and 20.5% deficiency in 25(OH)D. The mean value of Vitamin D was 23.2 ± 12.0 ng/mL.

Twenty-two patients were tested for Vitamin D dosages after cholecalciferol supplementation. The demographic and clinical characteristics of these patients are shown in [Table 1]. The serum Vitamin D concentrations in these patients were 18.3 ± 5.6 ng/mL, 68.2% patients being insufficient (21.5 ± 3.8 ng/mL) and 31.8% deficient (12.4 ± 2.5 ng/mL).
Table 1: Demographic and clinical characteristics of the 22 renal transplant recipients with hypovitaminosis D.

Click here to view


In the 22 patients with hypovitaminosis D, who received cholecalciferol (10,000 IU orally/ week to 20,000 IU orally/week), the average dose was 13,000 ± 4,000 IU/week for 7.2 ± 4.8 months. The comparison of biochemical data before and after cholecalciferol supplementation did not show significant differences in serum concentrations of calcium, phosphorus, creatinine, and PTH during the period of the study [Table 2].
Table 2: Comparison of biochemical data of 22 renal transplant recipients before and after cholecalciferol supplementation (13,000±4000 UI orally/week).

Click here to view


[Table 3] shows that the patient group who received 10,000 IU/week (40,000 IU/month) of cholecalciferol (n=11) initially presented with levels of 25(OH)D of 19.2 ± 5.1 ng/mL and following supplementation had an increase to 32.5 ± 4.2 ng/mL over 9.5 ± 4.7 months. The other group of 11 patients received cholecalciferol dose greater than 10,000 IU up to 20,000 IU/week, an average of 16,000 ± 3000 IU/week (approximately 64,000 IU/month). They presented initial levels of Vitamin D of 18.4 ± 6.0 ng/mL and following supplementation, there was an increase to 38.7 ± 9.9 ng/mL over 5.1 ± 4.1 months. The values of calcium, phosphorus, creatinine, and PTH did not show statistically significant alterations during the study period.
Table 3: Comparison of biochemical data of 22 renal transplant receptors before and after cholecalciferol supplementation divided into two groups.

Click here to view


Thus, it was calculated (final value−initial value of Vitamin D/supplementation time) that the cholecalciferol 10,000 IU/week dosage group had an increase of 1.46 ng/mL/month, whereas the group with cholecalciferol dosage of 16,000 ± 3000 IU/week had an increase of 4.05 ng/mL/month.

With the vitamin increase rate, it was possible to estimate that the time needed for patients with Vitamin D insufficiency (21.5 ± 3.8 ng/mL) to reach normal values (≥30 ng/ mL) of 25(OH)D is 2.1 months and for those with Vitamin D deficiency (12.4 ± 2.5 ng/mL) is 4.3 months with a 16,000 IU/week cholecalciferol dosage.


   Discussion Top


This study found high hypovitaminosis D prevalence in renal transplant recipients from a single center in São Paulo city. Despite the high sun exposure in Brazil, hypovitaminosis D was not prevented. Baxmann et al found 65% of hypovitaminosis D in renal transplant recipients in Brazil, Unger et al observed 77.4% rate of hypovitaminosis in healthy individuals, and Diniz et al reported 72.6% of hypovitaminosis in patients with CKD. [14],[15],[16] In this study, the prevalence of hypovitaminosis D in renal transplant recipients was similar to those found in other geographic regions of the world. [9],[17],[18],[19] In a region of Spain with high sun exposure, the prevalence of hypovitaminosis D in renal transplant receptors was also high (96.3%). [9] In Denmark, a country with lower sun exposure, the prevalence of Vitamin D insufficiency was 51% and deficiency was 24% in renal transplant recipients. [18] The factors responsible for this high prevalence of hypovitaminosis D after the kidney transplant, even in high sun exposure areas, are unclear. Vitamin D deficiency promotes a reduction in bowel absorption of calcium, leading to high levels of PTH that exacerbates the secondary hyperparathyroidism and bone disease which may be present even in a well-functioning allograft. Renal transplant recipients have a higher prevalence of atherosclerotic and cardiovascular disease, which is the main cause of death in this population. [20] Even in healthy male individuals, the risk of myocardial infarction is higher with lower Vitamin D levels (15 ng/mL) than the ones with Vitamin D between 25 and 30 ng/mL. [21] Clinical and animal studies show that Vitamin D reduces inflammation and controls metalloproteins responsible for vascular calcification, promoting improvement in endothelial function. [22] There is also evidence that suggests a relation between Vitamin D deficiency and arterial hypertension. [23] Other effects of Vitamin D are: possible anticarcinogenic property, improves innate immune response, and increases infection defenses, [24] and its deficiency is related to auto-immune disease development, diabetes, musculoskeletal alterations, and psychiatry diseases such as schizophrenia and dementia. [20],[25],[26]

Although hypovitaminosis D was the aim of many studies, still there is not a consensus about the cholecalciferol dosage, especially in renal transplant receptors. The Kidney Disease Outcome Quality Initiative gave recommendations concerning the treatment of Vitamin D deficiency in both CKD and renal transplant recipients, suggesting treatment strategies applied to the general population. [27] The Endocrine Society suggests that adults with hypovitaminosis D should be treated with 50,000 IU/week (200,000 IU/month) of cholecalciferol for eight weeks. [28] In patients with CKD and hypovitaminosis D, a randomized and controlled trial concluded that the use of 160,000/month (40,000 IU orally/week) of cholecalciferol for eight weeks was effective. [29] Another study in CKD in hemodialysis compared the treatment with cholecalciferol 50,000 IU/month with 200,000 IU/month (50,000 IU/ week) and concluded that both groups of patients reached 25(OH)D higher than 32 ng/ mL, without alterations in serum calcium, phosphorus, or PTH. [30] On the other hand, in thirty patients with metabolic bone disease and hypovitaminosis D, the treatment with 150,000 IU/month (5,000 IU orally/day) was more effective than 60,000 IU/month (2,000 IU orally/day) to normalize the serum Vitamin D. [31]

In this study, the dosage of 64,000 IU/month of oral cholecalciferol was more effective than 40,000 IU/month dosage, being enough to reach 25(OD)D sufficiency (≥30 ng/mL) in approximately 2.1 months in insufficient patients and in 4.3 months in deficient patients, without any toxicity or hypercalcemia. There was not a significant reduction in PTH values in the period studied. Furthermore, in renal transplant recipients with hypovitaminosis D, Courbebaisse et al used 200,000/month (100,000 each two weeks) of cholecalciferol for two months, and Vitamin D increased above 30 ng/mL and PTH decreased without hypercalcemia. [32] In another study in a similar population, Wissing et al proposed a single monthly dosage of 25,000 IU of cholecalciferol, but it was not enough to correct hypovitaminosis D. [33]

The results obtained in this study show that not very high doses of 25(OH)D (approximately 64,000 IU/month) can be sufficient to control hypovitaminosis D, contributing to the current literature to determinate a standard dose in the renal transplant recipients population. The limitations of this study include data being collected retrospectively from a single center limiting the number of patients, and the absence of a fixed cholecalciferol dosage in the group of patients that received more than 40,000 IU/month.


   Conclusions Top


Hypovitaminosis D is common in KTRs and the dosage of approximately 64.000 IU/month was sufficient to restore normal serum Vitamin D values without causing hypercalcemia in the population studied.

There is a need for prospective multicenter studies with a large number of patients to compare the effect of different cholecalciferol dosage, minimizing costs, promoting safety and efficacy in the treatment of this risk population, and preventing important comorbidities.


   Acknowledgments Top


The study received financial support in Brazil from Conselho Nacional de Desenvolvimento Científico e Tecnológico.

Conflict of interest: None declared.

 
   References Top

1.
Holick MF. Vitamin D: A D-lightful health perspective. Nutr Rev 2008;66 10 Suppl 2: S182-94.  Back to cited text no. 1
    
2.
Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81.  Back to cited text no. 2
[PUBMED]    
3.
Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D. Vitamin D status in Andhra Pradesh: A population based study. Indian J Med Res 2008;127:211-8.  Back to cited text no. 3
[PUBMED]  Medknow Journal  
4.
Holick MF. McCollum award lecture, 1994: Vitamin D - New horizons for the 21st century. Am J Clin Nutr 1994;60:619-30.  Back to cited text no. 4
[PUBMED]    
5.
Lips P. Vitamin D physiology. Prog Biophys Mol Biol 2006;92:4-8.  Back to cited text no. 5
[PUBMED]    
6.
Levi R, Silver J. Vitamin D supplementation after renal transplantation: How much Vitamin D should we prescribe? Kidney Int 2009;75: 576-8.  Back to cited text no. 6
[PUBMED]    
7.
Courbebaisse M, Alberti C, Colas S, et al. VITamin D supplementation in renAL transplant recipients (VITALE): A prospective, multicentre, double-blind, randomized trial of Vitamin D estimating the benefit and safety of Vitamin D3 treatment at a dose of 100,000 UI compared with a dose of 12,000 UI in renal transplant recipients: Study protocol for a double-blind, randomized, controlled trial. Trials 2014;15:430.  Back to cited text no. 7
[PUBMED]    
8.
Torres A, Rodríguez AP, Concepción MT, et al. Parathyroid function in long-term renal transplant patients: Importance of pretransplant PTH concentrations. Nephrol Dial Transplant 1998;13 Suppl 3:94-7.  Back to cited text no. 8
    
9.
Kanter Berga J, Crespo Albiach J, Beltran Catalan S, et al. Vitamin D deficiency in a renal transplant population: Safe repletion with moderate doses of calcidiol. Transplant Proc 2010;42:2917-20.  Back to cited text no. 9
[PUBMED]    
10.
Courbebaisse M, Souberbielle JC, Thervet E. Potential nonclassical effects of Vitamin D in transplant recipients. Transplantation 2010;89: 131-7.  Back to cited text no. 10
[PUBMED]    
11.
Pascussi JM, Robert A, Nguyen M, et al. Possible involvement of pregnane X receptorenhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest 2005;115:177-86.  Back to cited text no. 11
[PUBMED]    
12.
Bhan I, Shah A, Holmes J, et al. Post-transplant hypophosphatemia: Tertiary 'HyperPhosphatoninism'? Kidney Int 2006;70:148694.  Back to cited text no. 12
    
13.
Reichrath J. Dermatologic management, sun avoidance and Vitamin D status in organ transplant recipients (OTR). J Photochem Photobiol B 2010;101:150-9.  Back to cited text no. 13
[PUBMED]    
14.
Baxmann AC, Menon VB, Medina-Pestana JO, Carvalho AB, Heilberg IP. Overweight and body fat are predictors of hypovitaminosis D in renal transplant patients. Clin Kidney J 2015;8:49-53.  Back to cited text no. 14
[PUBMED]    
15.
Unger MD, Cuppari L, Titan SM, et al. Vitamin D status in a sunny country: Where has the sun gone? Clin Nutr 2010;29:784-8.  Back to cited text no. 15
[PUBMED]    
16.
Diniz HF, Romão MF, Elias RM, Romão Júnior JE. Vitamin D deficiency and insufficiency in patients with chronic kidney disease. J Bras Nefrol 2012;34:58-63.  Back to cited text no. 16
    
17.
Stavroulopoulos A, Cassidy MJ, Porter CJ, Hosking DJ, Roe SD. Vitamin D status in renal transplant recipients. Am J Transplant 2007;7: 2546-52.  Back to cited text no. 17
[PUBMED]    
18.
Ewers B, Gasbjerg A, Moelgaard C, Frederiksen AM, Marckmann P. Vitamin D status in kidney transplant patients: Need for intensified routine supplementation. Am J Clin Nutr 2008;87:431-7.  Back to cited text no. 18
[PUBMED]    
19.
Tripathi SS, Gibney EM, Gehr TW, King AL, Beckman MJ. High prevalence of Vitamin D deficiency in African American kidney transplant recipients. Transplantation 2008;85:76770.  Back to cited text no. 19
    
20.
Souberbielle JC, Body JJ, Lappe JM, et al. Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice. Autoimmun Rev 2010;9:709-15.  Back to cited text no. 20
[PUBMED]    
21.
Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: A prospective study. Arch Intern Med 2008;168:1174-3  Back to cited text no. 21
    
22.
Fleet JC. Molecular actions of Vitamin D contributing to cancer prevention. Mol Aspects Med 2008;29:388-96.  Back to cited text no. 22
[PUBMED]    
23.
Ullah MI, Uwaifo GI, Nicholas WC, Koch CA. Does Vitamin D deficiency cause hypertension? Current evidence from clinical studies and potential mechanisms. Int J Endocrinol 2010;2010:579640.  Back to cited text no. 23
[PUBMED]    
24.
Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a Vitamin D-mediated human antimicrobial response. Science 2006; 311:1770-3.  Back to cited text no. 24
[PUBMED]    
25.
Baeke F, van Etten E, Gysemans C, Overbergh L, Mathieu C. Vitamin D signaling in immunemediated disorders: Evolving insights and therapeutic opportunities. Mol Aspects Med 2008;29:376-87.  Back to cited text no. 25
[PUBMED]    
26.
Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: New aetiological and therapeutic considerations. Ann Rheum Dis 2007;66:1137-42.  Back to cited text no. 26
[PUBMED]    
27.
Improving Global Outcomes (KDIGO) CKDMBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, and treatment of chronic clinical disease-mineral and bone disorder (CKD-MBD). Chapter 5: Evaluation and treatment of kidney transplant bone disease. Kidney Int 2009;76 Suppl 113: S100-10.  Back to cited text no. 27
    
28.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of Vitamin D deficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911-30.  Back to cited text no. 28
[PUBMED]    
29.
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.  Back to cited text no. 29
    
30.
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.  Back to cited text no. 30
[PUBMED]    
31.
Diamond T, Wong YK, Golombick T. Effect of oral cholecalciferol 2,000 versus 5,000 IU on serum Vitamin D, PTH, bone and muscle strength in patients with Vitamin D deficiency. Osteoporos Int 2013;24:1101-5.  Back to cited text no. 31
[PUBMED]    
32.
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.  Back to cited text no. 32
[PUBMED]    
33.
Wissing KM, Broeders N, Moreno-Reyes R, Gervy C, Stallenberg B, Abramowicz D. A controlled study of Vitamin D3 to prevent bone loss in renal-transplant patients receiving low doses of steroids. Transplantation 2005; 79:108-15.  Back to cited text no. 33
[PUBMED]    

Top
Correspondence Address:
Sergio Mazzola Poli de Figueiredo
Santa Casa de Sao Paulo School of Medical Sciences, São Paulo
Brazil
Login to access the Email id


DOI: 10.4103/1319-2442.190839

PMID: 27752000

Rights and Permissions



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
   
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
   Introduction
   Methods
   Statistical Analysis
   Results
   Discussion
   Conclusions
   Acknowledgments
    References
    Article Tables
 

 Article Access Statistics
    Viewed2649    
    Printed7    
    Emailed0    
    PDF Downloaded302    
    Comments [Add]    

Recommend this journal