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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2016  |  Volume : 27  |  Issue : 3  |  Page : 460-466
Is there an association between Vitamin D level and inflammatory markers in hemodialysis patients? A cross-sectional study


Department of Nephrology, Alhada Military Hospital, Taif, Saudi Arabia

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Date of Web Publication13-May-2016
 

   Abstract 

Vitamin D deficiency is very prevalent among the patients with end-stage renal disease. The etiology of this is multifactorial, including nutritional deficiency, insufficient expo- sure to sunlight, race, obesity and not the least, impaired Vitamin D synthesis and metabolism in chronic kidney disease patients. We hypothesized that lower Vitamin D level will be associated with higher inflammatory burden and low immunological response to hepatitis B vaccination in hemodialysis (HD) population. The study was carried out in March 2013 among 100 HD patients who were identified to be eligible for the study. This was a cross-sectional study analyzing the relationship between Vitamin D level and inflammatory markers in HD patients. A relationship between Vitamin D level and markers of mineral bone disorder was also analyzed. We also analyzed the relationship between Vitamin D level and hemoglobin and erythropoietin dosage. Hemoglobin, transferrin saturation, and erythropoietin dose were used to study the relationship between Vitamin D and markers of anemia. Antibodies to hepatitis B surface antigen were measured to study the response between Vitamin D level and immune response to hepatitis B vaccine. Vitamin D levels were significantly lower in females compared to males (P = 0.009) and diabetics compared to non-diabetics (P = 0.02). No significant association was observed between Vitamin D levels with immune response to hepatitis B vaccine (P = 0.89), C-reactive protein (P = 0.19), serum albumin (P = 0.17), hemoglobin level (P = 0.18,) and erythropoietin requirement (P = 0.87), parathyroid hormone (PTH) levels (P = 0.57), calcium levels (P = 0.79) and phosphate level (P = 0.1).

How to cite this article:
Mohiuddin SA, Marie M, Ashraf M, Hussein M, Almalki N. Is there an association between Vitamin D level and inflammatory markers in hemodialysis patients? A cross-sectional study. Saudi J Kidney Dis Transpl 2016;27:460-6

How to cite this URL:
Mohiuddin SA, Marie M, Ashraf M, Hussein M, Almalki N. Is there an association between Vitamin D level and inflammatory markers in hemodialysis patients? A cross-sectional study. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2022 Aug 7];27:460-6. Available from: https://www.sjkdt.org/text.asp?2016/27/3/460/182377

   Introduction Top


Vitamin D deficiency is a pandemic and it is estimated that nearly 1 billion people world-wide have Vitamin D deficiency or insuffi- ciency.[1]According to recent studies, 20-60% of healthy men and women in the UK have Vitamin D deficiency.[2]This problem is further exacerbated in patients with end-stage renal failure, and evidence suggests that 76-92%[3],[4]of this population is deficient. The etiology of this is multifactorial, including nutritional deficiency, insufficient exposure to sunlight, race, obesity and not the least, impaired Vita- min D synthesis and metabolism in chronic kidney disease patients.

The role of Vitamin D in the regulation of calcium and phosphate and thereby bone metabolism is well-known, and deficiency in Vitamin D leads to conditions such as hyper- parathyroid bone disease, rickets, osteoma- lacia, osteoporosis, and fractures. However, recently there has been a body of evidence from studies which has suggested that Vitamin D has diverse biological effects beyond its calcium and phosphate homeostasis, and Vita- min D status is vital for optimal function of many organs including kidneys, heart, brain, and the immune system.[5]Several studies have highlighted the nephroprotective effect of Vitamin D through various mechanisms,[6],[7],[8]and more importantly, it has been implicated in the progression of chronic kidney disease.[9],[10]Moreover, Vitamin D has been associated with increased overall mortality in chronic kidney patients[11]cardiovascular mortality,[12],[13],[14]low mood and maintenance of cognitive function,[15],[16],[17]auto- immune conditions,[18],[19]and malignancy.[20],[21]

Vitamin D has also been linked to systemic inflammatory processes and it has been sug- gested it plays an important role both directly and indirectly in the regulation, proliferation, differentiation, and the function of various cell lines including dendritic cells, macrophages, T-cells, and B-cells.[7],[22],[23]Several studies exa- mining relationships between Vitamin D defi- ciency and inflammatory biomarkers have shown a positive association.[13],[24],[25],[26]Further- more, in a randomized control trial, supple- mentation of Vitamin D was found to attenuate inflammation.[27]

The majority of studies examining the asso- ciation between Vitamin D and inflammation have excluded patients with severe renal im- pairment, especially patients on hemodialysis (HD) who tend to have unexplained high inflammatory biomarkers such as C-reactive protein (CRP) in the absence of sepsis. We hypothesized that lower Vitamin D level will be associated with higher inflammatory burden and low immunological response to hepatitis B vaccination in HD population. We also deci- ded to analyze the association between Vita- min D level and markers of mineral bone dis- order and anemia.


   Materials and Methods Top


This is a cross-sectional study analyzing the relationship between Vitamin D level and in- flammatory markers in HD patients. A rela- tionship between Vitamin D level and markers of mineral bone disorder was also analyzed. We also analyzed the relationship between Vitamin D level and hemoglobin and erythro- poietin dosage.

Inclusion criteria

All patients on HD in the dialysis unit were included in the study.

Exclusion criteria

All patients who were admitted in the hos- pital at the time of study or patients with active infection or malignancy were excluded from the study.

Patient selection

A total of 100 patients were identified to be eligible for the study. The study was carried out in March 2013.

Vitamin D deficiency was defined as total 25 hydroxy Vitamin D level <10 ng/mL, level between 10 and 29 defined insufficiency, and level ≥30 was regarded as normal.

CRP and albumin were used to assess the inflammatory burden. Hemoglobin, transferrin saturation (TSAT), and erythropoietin dose were used to study the relationship between Vitamin D and markers of anemia.

Antibodies to hepatitis B surface antigen were measured to study the response between Vitamin D level and immune response to hepatitis B vaccine. Intact parathyroid hor- mone (PTH) assay was done by in vitro che- miluminescent microparticle immunoassay for the quantitative determination of intact PTH in serum.

Confidentiality

All data were stored and analyzed in pass- word protected hospital computers.


   Data Analysis Top


Data were cleaned, coded, and analyzed using Stata version 11 (www.statacorp.com). Median and interquartile (IQR) range were used to describe quantitative variables with asymmetrical distribution. Mean and standard deviation were used for quantitative variables with symmetrical distribution. Quantitative va- riables were analyzed using Student's t-test or Wilcoxin rank-sum test depending on distri- bution of the variables. Categorical variables were analyzed using Chi-square test. Linear regression was used to analyze relationship between quantitative variables.


   Results Top


One hundred HD patients (fifty males, fifty females) with a median age of 55 years (IQR 44, 68) were studied [Table 1]. Median dia-

lysis vintage was 4 years (IQR 3, 7). Forty-one percent of the patients had diabetes. Forty-five percent of the patients were dialyzing using dialysis catheters and 13% of the patients had hepatitis C.
Table 1. Baseline characteristics of study population

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Vitamin D levels were significantly lower in females compared to males (P = 0.009). Com- pared to patients without diabetes, diabetics had lower Vitamin D levels (P = 0.02). No significant association was observed between CRP and Vitamin D levels (P = 0.19, [Figure 1]. No significant association was found bet- ween Vitamin D level and serum albumin (P = 0.17). There was no significant association bet- ween Vitamin D levels and hemoglobin level (P = 0.18, [Figure 2] or erythropoietin require- ment (P = 0.87, [Figure 3]. No significant asso- ciation was seen between Vitamin D level and immune response to hepatitis B vaccine (P = 0.89). PTH level was also found to be not associated with Vitamin D level (P = 0.57). Calcium was not associated with Vitamin D levels (P = 0.79). There was no association between Vitamin D and phosphate level (P = 0.1).
Figure 1. Relation between C-reactive protein and Vitamin D level

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Figure 2. Relation between hemoglobin and Vitamin D level

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Figure 3. Relation between erythropoietin dose and Vitamin D level

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   Discussion Top


This study confirms the high prevalence of Vitamin D deficiency among patients with the end-stage renal disease, on HD. Only one pa- tient had Vitamin D level in the normal range. The total percentage of patients with Vitamin D insufficiency and deficiency was 99%, which is higher than reported in previous studies.[3],[4]In this study, Vitamin D levels were measured at the beginning of spring, which is likely to provide an accurate assessment of Vitamin D status in this population. Vitamin D levels were lower in diabetics and women. No signi- ficant association was seen between CRP and Vitamin D levels. No association was observed between Vitamin D level and serum albumin, which is in contrast to one previous study that showed that lower levels of albumin in HD patients corresponded with lower Vitamin D levels.[28]No association was found between hemoglobin level or erythrocyte-stimulating agents dose and Vitamin D level. In one pre- vious study, lower Vitamin D levels were associated with high inflammatory markers (personal communication). However, sample size was much larger in that study (704 pa- tients). Second reason for not observing an association between inflammatory markers and Vitamin D levels in present study may be the narrow clustering of Vitamin D levels around their median and only one patient had normal Vitamin D level. Both these factors prevent adequate comparison between patients with Vitamin D deficiency, insufficiency, and Vitamin D sufficient populations. Unexplained elevated levels of CRP is a common pheno- menon among HD patients, and a number of hypothesis has been proposed such as an increase in cytokine production and retention[29]and also, the types of dialysis membrane used were thought to play an important role in inflammation.[30]However, the exact mechanism, which leads to a high CRP in dialysis patients, is yet to be established.

No association was seen between Vitamin D levels and markers of mineral bone disorders. Narrow clustering of Vitamin D and lack of enough number of patients in the group with adequate Vitamin D levels may again explain this.

Vitamin D has recently enjoyed a great deal of attention and the discovery that most cells in the body possess Vitamin D receptors (VDRs) has revolutionized our understanding about the important functions of Vitamin D beyond its skeletal role. More specifically, it has been implicated in the regulation of the immune system. The metabolic actions of Vitamin D occur when it binds to VDR, which results in the inhibition of pro-inflammatory cytokines that in turn reduces inflammation.[22],[31]It has been suggested that activation of VDR results in both upregulation and downregu- lation of vital proteins, which control the pro- cess of inflammation. For example, Vitamin D can selectively suppress key effect or func- tions of interferon-γ (INF-γ) activated macro- phages and thereby, suppression of important IFN-γ-induced genes which control the inflam- matory responses of activated macrophages.[32]The majority of the studies examining the association between Vitamin D and inflamma- tion have been on nonchronic kidney disease patients. However, there are a small number of studies done of HD patients, which show that Vitamin D supplementation attenuates inflam- mation.[33],[34]

To the best of our knowledge, this is the largest study in Saudi Arabia quantifying the prevalence of Vitamin D deficiency in HD population and trying to link Vitamin D defi- ciency with inflammatory and anemia mar- kers. Limitations of this study include, it is a cross-sectional study and our data are also limited by the fact that biochemical measure- ments were only performed once, which does not take into account time and season depen- dent changes of Vitamin D levels. It is also limited by the fact that only one patient had normal Vitamin D level, therefore providing inadequate control group for the Vitamin D insufficiency and deficiency groups. Sample size was also relatively small.[35]

Conclusions

Vitamin D deficiency is highly prevalent in HD population in Saudi Arabia. A randomized controlled trial to see the effect of its replace- ment is recommended.

Acknowledgment

The authors would like to thank the Head Nurse Dialysis Unit, Marylin Wee.

Conflict of interest: None.

 
   References Top

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Correspondence Address:
Mohamed Marie
Department of Nephrology, Alhada Military Hospital, Taif
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.182377

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