|Year : 2022 | Volume
| Issue : 3 | Page : 163-167
Study of vitamin D3 level in Egyptian hemodialysis patients and the effect of replacement therapy
Alaa A. A. Sabry1, Mohamed Elazazy2, Ahmed Abd El Wahab1
1 Mansoura Nephrology and Dialysis Unit, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Ministry of Health, Mansoura, Egypt
|Date of Submission||07-Jan-2022|
|Date of Acceptance||02-Apr-2022|
|Date of Web Publication||22-Jul-2022|
Dr. Alaa A. A. Sabry
Department of Nephrology, Mansoura School of Medicine, Mansoura University, Mansoura 35111
Source of Support: None, Conflict of Interest: None
Background The ability of extrarenal tissues to convert 25-hydroxyvitamin D into 1,25-hydroxyvitamin D and its dependence on substrate levels provide the rationale for supplementing vitamin D in dialysis patients who usually have severe depletion of both calcitriol and vitamin D. The primary aim of the study was to detect serum vitamin D3 levels in a cohort of Egyptian hemodialysis patients and to check the effect of 12-week therapy of cholecalciferol on serum calcium, phosphate, and parathyroid hormone (PTH) in vitamin D-naïve hemodialysis patients with vitamin D deficiency. Patients and methods A total of 40 patients (25 males and 15 females) with chronic kidney disease on regular hemodialysis, attending the Nephrology Unit of internal Medicine Department, Mansoura University Hospital, during the period from January to June 2017, were included. According to laboratory investigations and clinical examination, deficient patients were treated with Devarol-S (cholecalciferol) for 3 months and then revaluated. Deficient patients received intramuscular injection of 50 000 IU monthly for 3 consecutive months. Results The patient group included 40 persons, comprising 27 (73%) male patients and 13 (27%) female patients. Their mean age was 47.16 ± 14.92 years. The mean dialysis duration was 4.68 ± 2.42 years. At 3 months after vitamin D replacement, significant increase in serum calcium (8.33–8.89 mg/dl), phosphorous (4.99–5.85 mg/dl), and vitamin D3 (4.01–28.43 ng/ml) levels were observed compared with pretreatment levels. There was also significant decrease in PTH level (419.30–377.20 pg/ml). After 3 months of follow-up, there were no significant changes in the levels of hemoglobin, Kt/v, albumin, and alkaline phosphatase in the study group. Conclusions In most patients, treatment with cholecalciferol in a 50 000 IU/month dose permits safe correction of vitamin D deficiency and control of PTH level, yet serum phosphorus should be monitored.
Keywords: Egyptians, hemodialysis, supplementation, vitamin D level
|How to cite this article:|
Sabry AA, Elazazy M, El Wahab AA. Study of vitamin D3 level in Egyptian hemodialysis patients and the effect of replacement therapy. J Egypt Soc Nephrol Transplant 2022;22:163-7
|How to cite this URL:|
Sabry AA, Elazazy M, El Wahab AA. Study of vitamin D3 level in Egyptian hemodialysis patients and the effect of replacement therapy. J Egypt Soc Nephrol Transplant [serial online] 2022 [cited 2023 Jun 8];22:163-7. Available from: http://www.jesnt.eg.net/text.asp?2022/22/3/163/351707
| Introduction|| |
According to the current knowledge, vitamin D regulates the function of many organs and systems, not only mineral and bone metabolism. Moreover, it has been postulated that its deficiency may be associated with an increased risk for nearly all major human diseases. Both 1-alpha-hydroxylase (CYP27B1) and vitamin D receptor (VDR) are present in almost every human tissue, and vitamin D may exert its actions via two ways: (a) the endocrine way with 1,25-hydroxyvitamin D [1,25(OH)2D] as a hormone produced in kidneys, and (b) paracrine, autocrine, and intracrine ways, in which its precursor – 25-hydroxyvitamin D [25(OH)D] – is converted locally by CYP27B1 to 1,25(OH)2D in the target cell, which activates the VDR and downstream gene expression in the same or a neighboring VDR-expressing cell [1–3].
The recognition of the ability of extrarenal tissues to produce calcitriol and the suggestions that many of the significant biological consequences of dysregulated vitamin D balance may be associated with changes in the extracellular concentration of substrate 25(OH)D together with the fact of severe deficiency of both, 1,25(OH)2D and 25(OH)D in patients with end-stage renal disease, especially those on long-term dialysis therapy, provided a rationale to the study.
The primary outcome of the study was the effect of 12-week therapy of cholecalciferol on serum calcium, phosphate, and parathyroid hormone (PTH) in vitamin D-naïve hemodialysis patients with vitamin D deficiency.
| Patients and methods|| |
This interventional study was carried out on 40 patients (25 males and 15 females) on regular hemodialysis attending the Nephrology Unit of Internal Medicine Department, Mansoura University Hospital, during the period from January to June 2017.
Ethical approval had been obtained from the Medical Research Ethics Committee of Faculty of Medicine, Mansoura University. Patients signed written consents after detailed explanation of the study protocol.
- (1) We excluded the following patients based on history, clinical assessment, and investigations done before enrollment: those with cognitive impairment, cancer, active hepatitis or any liver disease, and those who had inflammation or active infection.
- (2) The following investigations were done at the start of the study and repeated after 3 months of cholecalciferol treatment: complete blood picture, serum albumin, PTH, alkaline phosphatase, serum calcium, phosphorus, and vitamin D3. Kt/v was assessed in the same manner.
- (3) Cholecalciferol (Devarol-S) was given as intramuscular injection of 50 000 IU monthly for 3 consecutive months.
Data were tabulated, coded, and then analyzed using the computer program SPSS (Statistical package for social science), version 23.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were calculated in the form of following:
- (1) Mean±SD.
- (2) Median and interquartile range.
- (3) Frequency (number-percent).
Student t test (paired) was used to compare between mean of two related groups of numerical (parametric) data. Wilcoxon signed-rank test was used to compare between two related groups of numerical (nonparametric) data. Mann–Whitney test was used to compare between mean of two different groups of numerical (nonparametric) data. Intergroup comparison of categorical data was performed using χ2 test. Pearson correlation coefficient test was used for correlating different parameters. A P value less than 0.05 was considered statistically significant.
| Results|| |
A total of 40 patients on regular hemodialysis were included in our study. There were 29 (73%) males and 11 (27%) females, with mean age of 47.16 ± 14.92 years. The mean dialysis duration was 4.68 ± 2.42 years. Hypertension and diabetes were the commonest causes of chronic kidney disease (CKD) (65 and 17.5%, respectively), as shown in [Table 1]. Vitamin D deficiency was present in all studied patients (median=4.01, interquartile range was 0.79–8.17).
At the end of the study, there was significant increase in serum calcium (8.33 to 8.89 mg/dl; P=0.008), serum phosphorous (4.99–5.85 mg/dl; P=0.01) and vitamin D3 (4.01–28.43 ng/ml; P<0.001) compared with pretreatment levels. There was also significant decrease in PTH level (419.30–377.20 pg/ml; P<0.001), as shown in [Table 2]b.
|Table 2: Comparison between laboratory variables before and after vitamin D3 supplementation|
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After 3 months of follow-up, there was no significant change in the levels of hemoglobin, Kt/v, albumin, and alkaline phosphatase in the study group (P=0.7, 0.4, 0.29, and 0.59, respectively), as shown in [Table 2]a.
| Discussion|| |
The rapidly aging dialysis population with a high burden of comorbid illnesses, insufficiently exposed to the sun, or affected by malnutrition, is particularly vulnerable to bone fractures owing to profound disturbances in mineral metabolism. Combining these factors together with defective cutaneous cholecalciferol synthesis and the effects of a variety of medications that prevent its intestinal absorption or interfere with its metabolism [4–6], vitamin D deficiency is a common finding in this population, ranging from 38 to 95%, depending on the definition, geographic latitude, and season of the year [7–9].
Vitamin D affects significantly the bony skeleton and extraskeletal tissues. Vitamin D deficiency will elevate PTH level which in turn increases bone turnover and reduces mineralization, causing different mineral bone disorders such as osteoporosis and osteomalacia .
In the past decade, research studies have spotlighted the pluripotent effects of vitamin D on different tissues of the human body. There is also underestimation of the real size of deficient individuals in general population and patients with chronic kidney [11,12].
Patients with CKD having vitamin D deficiency will end up developing secondary hyperparathyroidism and mineral bone disease syndrome .
Our work aims to assess vitamin D levels among patients with CKD treated by hemodialysis and the effect of cholecalciferol replacement therapy on serum calcium, phosphorus, PTH, and vitamin D levels.
Results from our study showed that all 40 patients were vitamin D deficient (100%). Vitamin D deficiency is defined as serum 25(OH)D less than 20 ng/ml . All patients did not exceed 13.5 ng/ml, and most of them (70%) were below 7 ng/ml when they were assessed before the replacement therapy. This observation agrees with what was reported previously by Ngai et al. , where more than 80% of CKD nontransplant patients had low serum 25(OH)D levels.
Kim et al. , reported that the prevalence of vitamin D deficiency was 85.7% in stage 5 CKD. Restrepo Valencia and Aguirre Arango , showed that in patients with CKD (stages 2–5), 70.1% were insufficient and 8.8% were within deficit range. Possible causes for vitamin D deficiency are nutritional and sunlight exposure deficits, race, sex, age, obesity, and impaired vitamin D synthesis and metabolism [18,19].
Despite the alarming results of the studies evaluating vitamin D deficiency in dialysis population worldwide, the current nephrology societies leave us without a clear guideline on that issue. In 2009 and 2017, KDIGO proposed, with a low quality of evidence, guidelines measuring 25(OH)D serum and treating its deficiency as in the general population, however, without any suggestion concerning the dosing and the target threshold [20,21]. With such a weak and imprecise recommendation, many patients undergoing dialysis remain without vitamin D supplementation.
The main argument for neglecting vitamin D supplementation in patients on dialysis has been the fact that there is weak 1,25(OH)2D production by severely damaged kidneys. However, the discovery of extrarenal synthesis of calcitriol points to the importance of vitamin D supplementation in those with end-stage kidney disease undergoing dialysis [22–26]. Our results showed that treatment was safe; there were no episodes of hypercalcemia. Serum vitamin D concentrations did not exceed 60 ng/ml in any patient in our study.
The study showed significant increase in 25(OH)D from 4.01 ± 0.97 to 28.43 ± 23.64 ng/ml (P<0.001) after a monthly dose of 50 000 IU of cholecalciferol for 3 consecutive months, which agrees with Matias et al. , who reported an increase in 25(OH)D from 22.3 to 42.0 ng/ml after 6 months of cholecalciferol supplementation with dose of 50 000 IU once to thrice weekly according to the previous status of vitamin D deficiency. Another study reported an increase of 25(OH)D after two doses of 300 000 IU 8 weeks apart, which effectively replenished the stores up to 70 ng/ml after 16 weeks .
Results of our study showed that serum PTH concentrations significantly decreased from baseline after the replacement therapy from 419.3 to 377.2 pg/ml (P<0.001). This observation agrees with what was reported by Okša and colleagues, who administered cholecalciferol treatment with either 5000 or 20 000 IU/week for 12 months in patients with CKD stages 2–4, and also agrees with Alvarez and colleagues, who showed reduction in PTH with cholecalciferol replacement therapy after 12 weeks (mean PTH concentration: 89.1 ± 49.3–70.1 ± 24.8 pg/ml). Our results were in disagreement with what was reported by Mose and colleagues, who showed that there was no change in the level of PTH concentration before and after replacing vitamin D probably owing to potential changes in plasma concentrations of PTH, which are most likely concealed by medication changes [29–31].
The results of our study showed significant increase in serum calcium (8.33–8.89 mg/dl; P=0.008), which was in accordance with Bansal et al. , who showed that calcium levels increased significantly at 6 weeks in the intervention group and no patient developed hypercalcemia despite being on active vitamin D analogs as well. In contrast, Chandra et al. ; Kandula et al. ; and Massart et al. , showed no significant difference in serum calcium level from the baseline, mostly because they were on noncalcium-containing phosphate binders.
Regarding phosphorous, it showed significant increase from 4.99 to 5.85 mg/dl (P=0.01), which disagrees with Hewitt et al. , who reported no change in bone-related minerals including serum phosphorus because patients were on calcium-based phosphate binders.
Our study has certain limitations: small patient number, absence of bone biopsy, lack of assessment of dietary intake of calcium and phosphorous, the short duration of intervention and follow-up, and the small patient group.
In conclusion, the results of our study allow us to conclude a high prevalence of vitamin D deficiency in hemodialysis patients, and this alarming finding should be investigated in Egypt on a wide scale.
It also shed light on the cost effectiveness of a cheap product as cholecalciferol in replenishing the stores of vitamin D and its possible role in treating its deficiency without serious adverse effect in one of the most vulnerable categories of patients such as hemodialysis patients.
Financial support and sponsorship
Conflicts of interest
The authors declare no conflict of interest.
| References|| |
Hewison M Vitamin D and immune function: autocrine, paracrine or endocrine? Scand J Clin Lab Invest 2012; 243(Suppl):92–102.
Hamdy NA, Kanis JA, Beneton MN, Brown CB, Juttmann JR, Jordans JG, et al
. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure. BMJ 1995; 310:358–363.
Shoji T, Shinohara K, Kimoto E, Emoto M, Tahara H, Koyama H, et al
. Lower risk for cardiovascular mortality in oral 1alpha-hydroxy vitamin D3 users in a haemodialysis population. Nephrol Dial Transplant 2004; 19:179–184.
Jacob AI, Sallman A, Santiz Z, Hollis BW Defective photo production of cholecalciferol in normal and uremic humans. J Nutr 1984; 114:1313–1319.
Michaud J, Naud J, Ouimet D, Demers C, Petit J-L, Leblond FA, et al
. Reduced hepatic synthesis of calcidiol in uremia. J Am Soc Nephrol 2010; 21:1488–1497.
Susantitaphong P, Jaber BL Potential interaction between sevelamer and fat soluble vitamins: a hypothesis. Am J Kidney Dis 2012; 59:165–167.
Cuppari L, Carvalho AB, Draibe SA Vitamin D status of chronic kidney disease patients living in a sunny country. J Ren Nutr 2008; 18:408–414.
Del Valle E, Negri AL, Aguirre C, Fradinger E, Zanchetta JR Prevalence of 25(OH) vitamin D insufficiency and deficiency in chronic kidney disease stage 5 patients on hemodialysis. Hemodial Int 2007; 11:315–321.
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; 3:1144–1151.
Grober U, Spitz J, Reichrath J, Kisters K, Holick M Vitamin D: update 2013: from rickets prophylaxis to general preventive healthcare. Dermatoendocrinology 2013; 5:331–347.
Jones G Expanding role for vitamin D in chronic kidney disease: importance of blood 25-OH-D levels and extra-renal 1alpha-hydroxylase in the classical and nonclassical actions of 1alpha, 25-dihydroxyvitamin D3. Semin Dial 2007; 20:316–324.
Al-Badr W, Martin KJ Vitamin D and kidney disease. Clin J Am Soc Nephrol 2008; 3:1555–1560.
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; 3:1144–1151.
Holick MF Vitamin D deficiency. N Engl J Med 2007; 357:266–281.
Ngai M, Lin V, Wong HC, Vathsala A, How P Vitamin D status and its association with mineral and bone disorder in a multi-ethnic chronic kidney disease population. Clin Nephrol 2014; 82:231–239.
Kim SM, Choi HJ, Lee JP, Kim DK, Oh YK, Kim YS 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.
Restrepo Valencia CA, Aguirre Arango JV Vitamin D (25 (OH) D) in patients with chronic kidney disease stages 2-5. Colombia Méd 2016; 47:160–166.
Mitchell D, Henao M, Finkelstein J, Burnett-Bowie SA Prevalence and predictors of vitamin D deficiency in healthy adults. Endocr Pract 2012; 18:914–923.
Guessous I, McClellan W, Kleinbaum D, Vaccarino V, Zoller O, Theler JM, et al
. Comparisons of serum vitamin D levels, status, and determinants in populations with and without chronic kidney disease not requiring renal dialysis: a 24-hour urine collection population-based study. J Ren Nutr 2014; 24:303–312.
Moe SM, Drüeke TB, Block GA, Cannata-Andía JB, Elder GJ, Fukagawa M et al.; KDIGO CKD-MBD working group. KDIGO, clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int 2009; 113(Suppl. 76):1–130.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 2017; 7:1–59.
Bentata Y Benefit-risk balance of native vitamin D supplementation in chronic hemodialysis: what can we learn from the major clinical trials and international guidelines?. Ren Fail 2019; 41:607–615.
Massart A, Debelle FD, Racapé J, Gervy C, Husson C, Dhaene M, et al
. Biochemical parameters after cholecalciferol repletion in hemodialysis: results from the VitaDial randomized trial. Am J Kidney Dis 2014; 64:696–705.
Mieczkowski M, Żebrowski P, Wojtaszek E, Stompór T, Przedlacki J, Bartoszewicz Z, et al
. Long-term cholecalciferol administration in hemodialysis patients: a single-center randomized pilot study. Med Sci Monit 2014; 20:2228–2234.
Hewitt NA, O’Connor AA, O’Shaughnessy DV, Elder GJ Effects of cholecalciferol on functional, biochemical, vascular, and quality of life outcomes in hemodialysis patients. Clin J Am Soc Nephrol 2013; 8:1143–1149.
Armas LAG, Andukuri R, Barger-Lux J, Heaney RP, Lund R 25-hydroxyvitamin D response to cholecalciferol supplementation in hemodialysis. Clin J Am Soc Nephrol 2012; 7:1428–1434.
Matias PJ, Jorge C, Ferreira C, Borges M, Aires I, Amaral T, et al
. Cholecalciferol supplementation in hemodialysis patients: effects on mineral metabolism, inflammation, and cardiac dimension parameters. Clin J Am Soc Nephrol 2010; 5:905–911.
Yadav AK, Kumar V, Banerjee D, Gupta KL, Jha V The effect of vitamin D supplementation on bone metabolic markers in chronic kidney disease. J Bone Miner Res 2017; 33:404–409.
Okša A, Spustová V, Krivošíková Z, Gazdíková K, Fedelešová V, Lajdová I, et al
. Effects of long-term cholecalciferol supplementation on mineral metabolism and calciotropic hormones in chronic kidney disease. Kidney Blood Press Res 2008; 31:322–329.
Alvarez JA, Law J, Coakley KE, Zughaier SM, Hao L, Shahid Salles K, 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; 96:672–679.
Mose FH, Vase H, Larsen T, Kancir AS, Kosierkiewic R, Jonczy B, et al
. Cardiovascular effects of cholecalciferol treatment in dialysis patients – a randomized controlled trial. BMC Nephrol 2014; 15:50.
Bansal B, Bansal SB, Mithal A, Kher V, Marwaha R, Singh P et al
. A randomized controlled trial of cholecalciferol supplementation in patients on maintenance hemodialysis. Indian J Endocrinol Metab 2014; 18:655.
Chandra P, Binongo J, Ziegler T, Schlanger L, Wang W, Someren J 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.
Kandula P, Dobre M, Schold JD, Schreiber MJ, Mehrotra R, Navaneethan SD Vitamin D supplementation in chronic kidney disease: a systematic review and meta-analysis of observational studies and randomized controlled trials. Clin J Am Soc Nephrol 2011; 6:50–62.
[Table 1], [Table 2]