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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 6  |  Issue : 1  |  Page : 1-5

25(OH) vitamin D: Serum levels and related factors in hemodialysis patients


Cursos de Farmácia e Medicina, University of Southern Santa Catarina, Tubarão, SC, Brazil

Date of Submission26-Jun-2018
Date of Decision18-Aug-2018
Date of Acceptance28-Aug-2018
Date of Web Publication26-Feb-2021

Correspondence Address:
Prof. Thiago Mamôru Sakae
University of Southern Santa Catarina, Tubarao, SC
Brazil
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jina.jina_9_18

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  Abstract 


Background and Objective: Advanced chronic renal failure leads to changes in calcium metabolism that cause disturbances in the parathyroid, vascular system, and bones. The 25(OH) Vitamin D plays a key role in regulating calcium metabolism and preventing these complications. The objective of this study was to determine 25(OH) Vitamin D levels in dialysis patients and to relate to clinical and sociodemographic characteristics. Methods: This was a cross-sectional study. The data collection was given by interview and consultation in electronic records, and the dosage of 25(OH) Vitamin D was performed on heparinized plasma samples collected at the beginning of the dialysis session. Results: Of the 77 patients studied, noted that seven (9.1%) showed poor values of 25(OH) Vitamin D and 19 (24.7%) showed insufficient values. As for the presence of comorbidities, 31 (40.3%) reported having diabetes mellitus, and 54 (70.1%) reported having arterial hypertension. It was also observed that the serum levels of 25(OH) Vitamin D are inferior in the carriers of diabetes mellitus and decrease with the increase of age and with the elevation of serum creatinine. The use of Vitamin D supplements presented positive correlation with serum calcium levels. Conclusion: The insufficiency of 25(OH) Vitamin D is frequent in dialysis patients especially in the carriers of diabetes mellitus.

Keywords: Chronic renal failure, diabetes mellitus, dialysis, secondary hyperparathyroidism, Vitamin D


How to cite this article:
Nascimento Dd, Luz MC, Remor KV, Sakae TM, Machado Md. 25(OH) vitamin D: Serum levels and related factors in hemodialysis patients. J Integr Nephrol Androl 2019;6:1-5

How to cite this URL:
Nascimento Dd, Luz MC, Remor KV, Sakae TM, Machado Md. 25(OH) vitamin D: Serum levels and related factors in hemodialysis patients. J Integr Nephrol Androl [serial online] 2019 [cited 2021 Aug 1];6:1-5. Available from: http://www.journal-ina.com/text.asp?2019/6/1/1/310180




  Introduction Top


In Brazil, it is estimated that 122,825 patients were in dialysis treatment in 2016, with hemodialysis being the predominant form of this treatment. Among these patients, it has been observed that the majority presents serum levels of the parathyroid hormone (PTH) increased, reflecting deficiency of adequacy and control of the indicators of mineral[1] metabolism.

Secondary hyperparathyroidism is a consequence of renal failure, generated by the loss of the homeostasis of calcium metabolism and phosphorus. In the term of renal failure, calcium loss and phosphorus retention occur in the renal tubules, reflecting on the serum levels of these minerals. The reduction of serum calcium stimulates the release of PTH that in turn activates bone reabsorption to restore serum calcium.[2],[3]

The chronic renal failure observes the elevation of the growth factor levels of fibroblasts 23 a hormone that inhibits the enzyme activity of the alpha-1-hydroxylase, responsible for the renal activation of the 25(OH) Vitamin D3. The reduction of serum levels of 25(OH) Vitamin D linked to decreased renal activation contributes to the secondary hyperparathyroidism framework by decreased intestinal absorption and renal reabsorption of calcium.[4] The progression of secondary hyperparathyroidism is marked by parathyroid hyperplasia, and by the inability of its cells to adequately respond to ambient calcium and/or 1,25(OH)2Vitamina D, due to the alteration in the sensitivity of its receptors.[3],[4]

Some bone diseases are particularly monitored in patients with chronic renal failure. Increased bone turnover and cystic fibrosis osteitis are characterized by the increased activities of osteoblasts and osteoclasts and peritrabecular fibrosis. The defective mineralization of the newly formed osteoid is called osteomalacia. Osteopenia and osteoporosis are bone diseases generated by decreased turnover. The combination of these changes in bone metabolism is called renal osteoarthritis and represents the manifestations of secondary hyperparathyroidism to renal dysfunction.[4],[5],[6]

In addition to the participation of 1,25(OH)2Vitamina D in bone metabolism, there are other functions of this recently described vitamin that contribute to the prevention of complications of chronic renal failure. Among them, it stands out its protective role against vascular calcifications, by precipitates of phosphate and calcium complexes.[7]

In clinical practice, despite the emergence of new effective treatment options, it has been perceived difficulties in the management and monitoring of the deficiency of 25(OH) Vitamin D and its implicações.[8] This reality is translated into the data of the Brazilian census of 2016.[1] Therefore, this work aims to characterize a group of patients with renal failure in hemodialysis treatment regarding the clinical and sociodemographic aspects and to determine the serum levels of the 25(OH) Vitamin D. In this way, it will be possible to associate the serum levels of 25(OH) Vitamin D with renal lesion, with the metabolism of calcium and phosphorus and with the clinical and sociodemographic characteristics. This data can help to prevent the complications of chronic renal failure in clinical practice.


  Methods Top


The research had a cross-sectional and observational outline. This work was approved by the Ethics Committee on Research of UNISUL, according to protocol number n° 384.577, and followed the ethical requirements established by resolution n°. 466/2012 of the National Health Council (Guidelines and Regulatory Research norms involving human beings).

Patients with renal insufficiency were included in hemodialysis treatment at the renal Disease Clinic of shark-SC, which carried out their periodic examinations at the Laboratory of Clinical Analyses UNISUL, aged >18 years old. The exclusion criteria adopted were as follows: refusal of the patient to participate in the study, patients with cognitive impairment, and absent patients to dialysis sessions in at least three previously scheduled visits. The sampling method adopted was the census of all patients who had respected inclusion/exclusion criteria in the study period. The sample size was 77 patients.

The data collection was held between June and December of 2013. The clinical data were obtained through questionnaires and views to the electronic chart. The dosage of 25(OH) Vitamin D was performed through amplified chemiluminescence method (Vitros Roche) in heparinized plasma samples of these patients, collected and dosed by the Laboratory of Clinical Analyses UNISUL at the beginning of the dialysis session.

The statistical analysis was performed in the software SPSS version 20.0. The mean, median, and standard deviation (SD) were calculated for the continuous variables and proportions for the categorical variables. To test the association between categorical variables was used the Pearson Chi-Square test or Fisher's Exact test, when appropriate. For the association of numerical variables, given the normal distribution of data evidenced by the Kolmogorov–Smirnov-test, the comparison was performed using the t-test for independent samples and the correlation using the correlation coefficient of Pearson. The association between the categorical variables was quantified by the prevalence ratio, observing the confidence interval. The level of statistical significance adopted was 95% (P = 0.05).


  Results Top


During the research period, 101 patients were assisted by the clinic of kidney diseases in Tubarão – SC and carried out heparinized plasma collection by Laboratory of Clinical Analyses UNISUL concomitantly. During the data collection, there were three deaths, two refusals, two dispensations of the hemodialysis treatment, four absences to the sessions, and one patient with cognitive impairment, totaling 12 losses and 89 participants. Of these samples, we obtained 77 dosages of 25(OH) Vitamin D valid and 12 losses due to the analytical problems generated by software failures.

The sample was composed of 77 dialysis patients, of which 30 (39%) were female, and 65 (84.4%) were Caucasian. The age ranged from 21 to 88 years, with a mean of 56.6 years and the schooling ranged from 0 to 16 years of study, with a mean of 6.3 years of study. Only 21 (27.3%) patients informed to use supplement in some form of Vitamin D, and the dialysis time ranged from 1 to 180 months, with a mean of 34.78 months. Regarding comorbidities, 31 (40.3%) reported having diabetes mellitus, and 54 (70.1%) reported having arterial hypertension.

The laboratory data of the sample are presented in [Table 1]. As for the dosage of 25(OH) Vitamin D, he noted that seven (9.1%) patients showed poor values and 19 (24.7%) patients showed insufficient values. The dosage of 25(OH) Vitamin D showed inversely proportional and statistically significant correlation with serum creatinine levels (P = 0.021) and age (P = 0.034).
Table 1: Biochemical markers associate to metabolism and/or kidney, hepatic, and bone function

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In the comparison between groups, it was observed that serum levels of 25(OH) Vitamin D were superior in males (mean = 43.27; SD = 16.68) compared to female (mean = 33.32; SD = 13.72) (P = 0.008). It was also observed that patients with diabetes mellitus had a lower mean of 25(OH) Vitamin D (mean = 32.84; SD = 14.81) when compared with patients not carrying diabetes mellitus (mean = 43.82; SD = 15.82) (P = 0.003). Diabetic patients also presented a prevalence 65% lower use of Vitamin D supplements (RP = 0.349; IC = 0.130–0.939) (P = 0.017).

Calcium serum levels in patients using Vitamin D supplements (mean = 9.26; SD = 0.76) were statistically higher than in those who were not receiving this supplement (mean = 8.67; SD = 0.86) (P = 0.009).


  Discussion Top


The population studied presents sociodemographic characteristics concordant with Brazilian Chronic Dialysis Survey of 2016, where we find 57% of male patients and 65.7% of patients aged between 20 and 64 years. The present study is also corroborated by the Brazilian census regarding the diagnosis of primary renal disease, where the most frequent in 2016 were arterial hypertension (34%) and diabetes mellitus (30%).[1]

As for the color of the skin, the auto-referenced caucasian was prevalent, and this fact is concordant with local colonization. However, Hall and employees, discussing this aspect, present evidence that medical distrust may be linked to racism and compose a risk factor for renal failure.[9]

It is also known that the cutaneous synthesis of precursors of Vitamin D directly proportional to the sun exposure and inversely proportional to the skin pigmentation since melanin reduces the effects of UV rays. Exposure to the sun is influenced by the lifestyle, and it is also a consensus that sick and/or elderly patients often present some degree of dependence on caregivers to expose themselves to the sun.[10]

As for schooling, some studies reviewed by Hall and employees showed that low schooling is associated with greater risk of disease, within the context of renal failure. This inverse correlation between schooling and risk of aggravated health seems to be related to at least two factors: Life habits such as smoking, alcoholism, among others, and knowledge to participate in the choice of treatment, for example, the selection of dialysis mode.[9]

Local studies in several populations have shown that the lack of 25(OH) Vitamin D is a clinical condition of high prevalence in the studied population as follows: in patients with low-energy fractures, there was a prevalence of 72%, disability, and 25% of insufficiency of 25(OH) Vitamin D;[11] in patients with obesity in Grade 2 and 3, a prevalence of 23.5%, deficiency was found, and 45.3% insufficiency of 25(OH) Vitamin D;[12] in pregnant women, a study evaluated the inadequacy of Vitamin D intake in two cohorts, and concluded that the prevalence of the inadequacy of Vitamin D intake ranged from 97.1% to 99.7% in the different quarters of pregnancy.[13] Data strengthen the hypothesis that the lifestyle of the studied population does not offer satisfactory amount of Vitamin D. However, the lack of 25(OH) Vitamin D in renal failure carriers can occur or worsen by factors related to the disease, and the reduction of levels of 25(OH) Vitamin D and calcium, in turn, are related to the development of secondary hyperparathyroidism.[3]

International studies also showed that the lack of 25(OH) Vitamin D is a clinical condition of high prevalence in chronic renal failure, and presented some similarities with this study in the correlation tests. Restrepo and employees, in a sample of 331 patients with chronic renal failure, found 70.1% insufficiency and 8.8% deficiency, and negative correlation between Vitamin D and creatinine levels.[14] Bansal and employees found 6.7% insufficiency and 88.9% deficiency of 25(OH) Vitamin D in 44 patients on hemodialysis and negative correlation between Vitamin D and female and presence of diabetes mellitus.[15]

Feng and employees studied 152 patients with chronic renal failure in the 3–5 stages, and concluded that advanced renal insufficiency and hypoalbuminemia are independent risk factors for deficiency of 25(OH) Vitamin D.[16] In our study, we consider increment serum creatinine and urea to evidence of renal function loss. Renal failure in diabetics courses with proteinuria, which can be evidenced at various stages of the disease through microalbuminuria, which in turn consists of an independent risk factor for cardiovascular disease these findings gain importance when we consider that 20%–40% of diabetes mellitus sufferers develop renal disease and this is the main cause of morbidity and mortality in these patients.[17]

The relationship between the use of Vitamin D supplements and calcemia is an interesting finding. The use of calcitriol (active Vitamin D) is recommended in patients with advanced renal disease. Calcium supplementation and 25(OH) Vitamin D are also frequent in these patients, while thyroidectomy is a resource only for refractory patients to supplements.[4],[8] In a cohort study with 15,755 patients with chronic renal failure, Janmaat and employees showed that higher values of basal serum calcium were associated with slower renal function decline, and this association was eliminated in patients in use of Vitamin D supplement. In addition, this same cohort suggests that the corrected serum calcium is indicative of the deficiency of 25(OH) Vitamin D.[18]

The reference values of the 25(OH) Vitamin D are still debatable, both for the general population and for the carriers of chronic renal disease. Calcium absorption and PTH suppression are the main factors influencing the definition of reference values.[4],[5]

In fact, the elevation of serum creatinine is evidence of the loss of renal function, and one of the functions of the kidneys is the conversion of 25(OH) Vitamin D into 1, 25(OH)2 Vitamin D. The loss of renal function also leads to the accumulation of phosphate in the blood, which also contributes to the inhibition of the enzyme 1 α-hydroxylase and consequently inhibition of the activation of the 25(OH) Vitamin D. Both the inactivity of the 25(OH) Vitamin D and the hyperphosphatemia, they contribute to the reduction of serum calcium levels, due to lack of intestinal absorption and crystallization in soft tissues, respectively. The reduction of the calcemia stimulates the release of the PTH, modifying the bone turnover, with greater reabsorption of calcium and phosphate, process feasible by the alkaline phosphatase. The result of these changes is the development of the secondary hyperparathyroidism, increasing the risk of renal osteoarthritis and vascular rigidity.[5],[6],[19],[20]


  Conclusion Top


This study demonstrated that the insufficiency of 25(OH) Vitamin D is a frequent clinical condition in patients with chronic renal failure especially in the carriers of diabetes mellitus. It was also observed that the serum levels of 25(OH) Vitamin D decrease with the increase of the age and the elevation of serum creatinine. Finally, the use of Vitamin D supplements presented positive correlation with serum levels of calcium.

Acknowledgment

The authors would like to thank the Renal Disease Clinic of Tubarão/SC, the Ortho Clinical Diagnostics, and the Laboratory of Clinical Analyses of UNISUL, collaboration, reagents for 25(OH) Vitamin D dosage, and infrastructure.

Financial support and sponsorship

National Schoolaarship Artigo 171. Dosage Reagents of 25(OH) Vitamin D donated by Ortho Clinical Diagnostics. Blood collection and dosages of 25(OH) Vitamin D performed by the laboratory of clinical analyses of UNISUL.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Sesso RC, Lopes AA, Thomé FS, Lugon JR, Martins CT. Brazilian chronic dialysis survey 2016. J Bras Nefrol 2017;39:261-6.  Back to cited text no. 1
    
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Goltzman D, Mannstadt M, Marcocci C. Physiology of the calcium-parathyroid hormone-Vitamin D axis. Front Horm Res 2018;50:1-3.  Back to cited text no. 2
    
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Romagnani P, Remuzzi G, Glassock R, Levin A, Jager KJ, Tonelli M, et al. Chronic kidney disease. Nat Rev Dis Primers 2017;3:17088.  Back to cited text no. 3
    
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Cipriani C, Pepe J, Colangelo L, Minisola S. Vitamina D and secondary hyperparathyreoid status. Giustina A, Bilezikian JP (eds): Vitamin D in Clinical Medicine. Front Horm Res. Basel, Karger 2018, 50: 138–148. doi: 10.1159/000486077 https://www.karger.com/Article/Abstract/486077.  Back to cited text no. 4
    
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Molina P, Carrero JJ, Bover J, Chauveau P, Mazzaferro S, Torres PU, et al. Vitamin D, a modulator of musculoskeletal health in chronic kidney disease. J Cachexia Sarcopenia Muscle 2017;8:686-701.  Back to cited text no. 5
    
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Lamb EJ, Delaney MP. Does PTH offer additive value to ALP measurement in assessing CKD-MBD? Perit Dial Int 2014;34:687-91.  Back to cited text no. 6
    
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Akdam H, Alp A. Arterial stiffness and 25-hydroxyVitamin D levels in chronic kidney disease patients. Rev Assoc Med Bras (1992) 2017;63:910-6.  Back to cited text no. 7
    
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Kdigo CKD Work Group. KDIGO 2017 Clinical practice guideline update for the diagnosis, evaluation, prevention and treatmente of chronic kidney disease-mineral and boné disorder (CKD-MBD). Kidney Int. Suppl. 2017, 7: 1–59. doi: 10.1016/j.kisu. 2017.04.001 http://kdigo.org/wp-content/uploads/2017/02/2017-KDIGO-CKD-MBD-GL-Update.pdf.  Back to cited text no. 8
    
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Hall YN. Social determinants of health: Addressing unmet needs in nephrology. Am J Kidney Dis 2018; pii: S0272-6386(18)30107-0.  Back to cited text no. 9
    
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Jablonski NG, Chaplin G. The roles of Vitamin D and cutaneous Vitamin D production in human evolution and health. Int J Paleopathol 2018;30133: S1879-9817. https://doi.org/10.1016/j.ijpp.2018.01.005.  Back to cited text no. 10
    
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Veiga FS, Elpo JA, Correa CG, Nardin GD, Ronsoni MF, Coral MHC, et al. [Serum 25(OH)-Vitamin D in patients with grade 2 and 3 obesity]. Arq. Catarin Med. 2016, 45 (1): 23-36. ISNN 18064280 http://www.acm.org.br/acm/seer/index.php/arquivos/article/view/59  Back to cited text no. 12
    
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Gomes CB, Malta MB, Corrente JE, Benício MHD, Carvalhaes, MABL. [High prevalence of inadequate calcium and Vitamin D dietary intake in two cohorts of pregnant women]. Cad Saúde Pública 2016, 32 (12): e00127815. doi: 10.1590/0102-311X00127815 http://dx.doi.org/10.1590/0102-311x00127815.  Back to cited text no. 13
    
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Restrepo VCA, Aguirre AJV. Vitamin D (25(OH) D) in patients with chronic kidney disease stages 2–5. Colom Med (Cali) 2016, 47 (3): 160–6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091275/  Back to cited text no. 14
    
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Janmaat CJ, van Diepen M, Gasparini A, Evans M, Qureshi AR, Ärnlöv J, et al. Lower serum calcium is independently associated with CKD progression. Sci Rep 2018, 8 (1): 5148. doi: 10.1038/s41598-018-23500-5 https://www.ncbi.nlm.nih.gov/pubmed/29581540.  Back to cited text no. 18
    
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Vervloet MG, Brandenburg VM, CKD-MBD working group of ERA-EDTA. Circulating markers of bone turnover. J Nephrol 2017;30:663-70.  Back to cited text no. 19
    
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