|Year : 2016 | Volume
| Issue : 2 | Page : 233-240
|Serum magnesium level and vascular stiffness in children with chronic kidney disease on regular hemodialysis
Manal Mohamed Zaher1, Manal Abdel-Salam1, Ragaa Abdel-Salam1, Randa Sabour2, Amal Abd El-Aleem Morsy3, Dina Gamal1
1 Department of Pediatrics, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
2 Department of Radiology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
3 Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
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|Date of Web Publication||11-Mar-2016|
| Abstract|| |
Chronic kidney disease (CKD) patients have a high prevalence of vascular calcifications, and cardiovascular disease is the leading cause of death in this population. Magnesium (Mg) depletion may be the missing link between multiple cardiovascular risk factors and the development of atherosclerosis. In this study, we aimed to assess the relationship between serum Mg levels and vascular stiffness in children with CKD on regular hemodialysis (HD). The study included 25 children with CKD on regular HD in our center; the study included also 25 healthy children age-and sex-matched as a control group. Serum Mg levels were measured, and Doppler ultrasound assessment of the intima-media thickness (IMT) and the peak systolic velocities (PSVs) of the main arteries including the (aorta, carotid, and femoral) arteries were recorded in the study patients. There were significantly lower serum Mg levels in children on regular HD than in the controls (1.7 ± 0.43 mg/dL vs. 2.31 ± 0.12 mg/dL, respectively, P = 0.001). There was a significant increase in the aorta and carotid IMT in the study group than in the controls (0.45 ± 0.07 mm vs. 0.40 ± 0.09 mm; 0.98 ± 0.57 mm vs. 0.55 ± 0.1 mm, P = 0.034 and 0.001, respectively), whereas there were no significant differences regarding the PSV of the carotid, aorta, and femoral arteries between the study patients and the controls (P >0.05). A negative correlation was found between serum Mg level with aortic IMT (AIMT) (r = −0.682; P = 0.000). In addition, a significant negative correlation was found between the AIMT with systolic and diastolic blood pressure (r = 0.447, P = 0.025, 0.472, P = 0.017), respectively. We conclude that lower serum Mg levels were associated with vascular calcification in chronic HD children. Confirmation of our results warrants further study.
|How to cite this article:|
Zaher MM, Abdel-Salam M, Abdel-Salam R, Sabour R, Morsy AA, Gamal D. Serum magnesium level and vascular stiffness in children with chronic kidney disease on regular hemodialysis. Saudi J Kidney Dis Transpl 2016;27:233-40
|How to cite this URL:|
Zaher MM, Abdel-Salam M, Abdel-Salam R, Sabour R, Morsy AA, Gamal D. Serum magnesium level and vascular stiffness in children with chronic kidney disease on regular hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2020 Jan 27];27:233-40. Available from: http://www.sjkdt.org/text.asp?2016/27/2/233/178205
| Introduction|| |
Chronic kidney disease (CKD) patients have a high prevalence of vascular calcifications (VC), and cardiovascular disease (CVD) is the leading cause of death in this population.
However, the molecular mechanisms of vascular calcification, which are multifactorial, cell-mediated, and dynamic, are not yet fully understood.  They include "traditional factors," such as older age, hypertension, diabetes, and dyslipidemia besides a number of other "nontraditional" factors, such as mineral metabolism abnormalities, extreme parathyroid hormone (PTH) serum levels, excess administration of calcium salts, inflammation, malnutrition, and oxidative stress.  Understanding the pathogenesis of VC is essential, as it is a frequent cause of morbidity and mortality of CKD patients. Indeed, vascular calcification occurs in all ages and stages of CKD. ,
Interestingly, not all dialysis patients develop arterial calcification, and importantly do not develop calcification with the increased duration of dialysis. These findings imply that there are protective factors, either in the blood vessels or in the circulation, or both. 
Magnesium (Mg) is one of the major intracellular cations. It is a vital element in human metabolism and general body function. Developments in methods to monitor this element have provided an improved understanding of its role in various diseases, particularly in CVD 5. 
In moderate CKD (Stage 1-3), an increase in fractional excretion of Mg compensates for the loss of renal function, such that Mg levels are maintained within the normal range. In more advanced CKD (Stage 4 and 5), renal compensatory mechanisms become inadequate. 
However, there is a wide variability in Mg balance in dialysis patients and it is not surprising that Mg balance may be normal or even low in this population.  The mechanisms by which Mg may influence VC are unclear. It is known that in vitro, Mg impairs hydroxyapatite crystal growth. ,
In addition to its involvement in the functions of many enzymes, Mg plays a role in skeletal and mineral metabolism and vascular tone. Data from observational clinical studies suggest that serum Mg levels are inversely related with the presence of VC or atherosclerosis. ,
There are unanswered questions about Mg balance and its effects in both CKD and dialysis patients and the development of atherosclerosis in children.
In this study, we aimed to assess the relationship between serum Mg levels and vascular stiffness in chronic hemodialysis (HD) children.
| Patients and Methods|| |
This is a cross-sectional comparative study carried out in the HD unit of Al-zahraa Hospital, Al-Azhar University, Cairo, Egypt. The study included 25 children with CKD on regular HD, in 4 h sessions, three times weekly. They were 10 males and 15 females with an age range from 4 to 18 years. A group of 25 apparently healthy children with matched age and sex with the study group served as controls. The adequacy of dialysis was assessed by clearance time/volume (Kt/V). The most common cause of CKD in the patients group was unknown (44%) followed by focal segmental glomerulosclerosis (20%). Children with congenital, structural, or primary vascular diseases, and with other chronic illness were excluded from the study.
Informed consent was obtained from the participating parents in adherence with the guidelines of the Ethical Committee of our University.
Five milliliters fasting (for 12 h) venous blood samples were withdrawn from all the patients and the controls. The samples were left to clot and sera were separated without delay for the biochemical parameters to be done on the same day. Other portions of the serum sample were stored frozen at −20°C after careful labeling till the time of assay of PTH.
Serum levels of urea, creatinine, calcium, phosphorus, PTH, cholesterol, and triglycerides were done on HITACHII auto analyzer except serum PTH was done on Elecsys 1010 electro-chemiluminescence autoanalyzer. Serum Mg was done on Cobas C311 autoanalyzer using Roche reagent kits. 
Intima-media thickness (IMT) and peak systolic velocity (PSV) of the main arteries including the aorta, carotid, and femoral arteries were measured using the Doppler ultrasound. The IMT and PSV were measured by grayscale ultrasound. The IMT was measured as the distance between the leading edge of the lumen-intima interface and the media-adventitia interface on the far wall of the artery, and the PVC was measured through B mode and color mode of the Doppler examination.
The technique of examination of the assessed arteries
For the examination of the common carotid artery, the patients were examined in the supine position with the neck extended and the chin turned contra lateral to the side being examined. Examination of the carotid artery was done first in a transverse plane and then longitudinally. For the examination of the aorta, the patients were examined in the supine position using 5.5 MHz probe. The abdominal aorta was examined in the upper abdomen and scanning was continued distally to the aortic bifurcation. For the examination of the femoral artery, the patients were examined in the supine position, with the leg in slight external rotation and the groin area was exposed, using probe 7.5 MHz. Longitudinal scan was started at the groin and continued distally. 
| Statistical Analysis|| |
Data were collected, revised, coded, and entered into the Statistical Package for Social Science (SPSS) version 17. Pearson and Spearman correlation coefficients were used to assess the relations between two quantitative parameters in the same group.
P value was considered significant if P <0.05 and highly significant if P <0.01.
| Results|| |
[Table 1] shows demographic data and the Z score for anthropometric measurements. There was a significant decrease in the study patients' Z scores for weight compared to the controls, whereas there was no significant difference regarding the height and BMI. In addition, there was a higher significant increase in the systolic blood pressure in the patients group than in the controls, but there was no significant difference between them regarding the diastolic pressure.
|Table 1: Demographic and clinical characteristics of the studied groups.|
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[Table 2] shows the comparison between the patients group and the controls regarding laboratory data revealed a highly significant increase in the serum (urea, creatinine, phosphorous, PTH, cholesterol, and triglycerides) levels and decrease in the serum Ca and Mg levels in the patients group than in the controls. [Table 3] shows the comparison between the patients group and the controls regarding IMT of the (carotid, aorta, and femoral) arteries and their PSV. There was a significant increase in the [carotid IMT (CIMT) and aortic IMT (AIMT)] in the patients group compared to the controls and there was no significant differences between the two studied groups regarding the PSV of the (carotid, aorta, and femoral) arteries.
|Table 2: Comparison between the two studied groups regarding laboratory data.|
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|Table 3: Comparison between the two studied groups regarding intima-media thickness of the (carotid, aorta, and femoral) arteries and their peak systolic velocity.|
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[Table 4] shows the correlation among the CIMT, AIMT, and FIMT, and the studied parameters in the patients group: It revealed a negative correlation between the AIMT and serum Mg level [Figure 1], whereas there was a positive correlation between the AIMT and blood pressure [Figure 2]. Finally, there were no correlations regarding the other studied parameters.
|Figure 1: Demonstrates a negative correlation between the AIMT thickness and serum magnesium level in the patients' group.|
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|Figure 2: Demonstrates a positive correlation between aortic AIMT and the systolic blood pressure in the patients group.|
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|Table 4: Correlation among CIMT, AIMT, and FIMT, and the studied parameters in the patients group.|
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| Discussion|| |
The results of this study suggest that there is a correlation between Mg levels in vascular calcification in children on chronic HD. Factors promoting calcification include abnormalities in mineral metabolism, particularly high phosphate levels. Inorganic phosphate (Pi) is a classical inducer of in vitro VC. 
In our study, serum phosphate, alkaline phosphatase, and PTH, levels were significantly more elevated, whereas serum calcium levels were significantly lower in the study patients than the healthy controls; this in agreement with other reports with the same findings. , Hyperphosphatemia and hypocalcemia may increase serum PTH levels, which stimulate inflammatory markers such as interleukin-6 that plays a role in the induction of VC. ,
Other risk factors of VC include atherosclerosis, hypertension, and dyslipidemia. The total cholesterol and triglycerides were significantly higher in in our study patients. Hyperlipidemia is a frequent finding in the pediatric patients treated with chronic HD and renal transplantation and may be associated with premature coronary artery disease.  A key question is what drives the development and maintenance, or progression, of abnormal calcification in CKD patients.
Mg's role in the pathogenesis of VC has not been extensively studied. Nonetheless, several in vitro and animal studies point toward a protective role of Mg through multiple molecular mechanisms. Hypermagnesemia may develop due to loss of the renal ability to excrete Mg. In spite of this, Mg balance may be normal or even low in dialysis patients. 
In the present study, we found a significant decrease in the serum Mg levels in children with CKD on regular HD than in the controls. We found in our study that the mean of CIMT as well as AIMT were larger in the HD patients than the controls. Several studies have reported similar findings that VC in CKD patients are frequently localized in high-caliber arteries, such as the aorta, medium arteries, including coronary arteries and also in small caliber arteries. ,,,,,
Our results revealed a significant negative correlation between the AIMT and Mg levels in dialysis children. A study reported existing relationships between Mg, inhibition of VC on calcification-induced aortic rings of rats, and clinical biomarkers.  Another study showed that increasing Mg concentrations reduced the calcium deposition in calcification-induced bovine VSMC and modulated calcification markers. 
Our results are in the same line with Tzanakis et al  who showed a strong inverse relationship between serum and intracellular Mg and carotid IMT. Each 0.5 mmol/L increase in Mg serum levels was associated with a 0.35 mm reduction in the carotid IMT. The same authors in a prospective study evaluated the mitral annular calcification by the M mode and 2dimensional echocardiography in HD patients.  Another study reported lower mortality risk associated with higher Mg levels. A serum Mg level >1.15 mmol/L was associated with a reduced risk of mortality in dialysis patients.  Furthermore, serum Mg levels were higher in patients with slow progression of VC compared to patients with rapid progression.  Increased systolic blood pressure is a pathological process that ultimately results in reduced elasticity of the blood vessel wall.  It is not surprising in our study to find a strong positive association between AIMT in dialysis children with systolic blood pressure.
We found no significant correlation between serum Mg levels and serum calcium, PTH, atherogenic lipids, and the other studied parameters including anthropometry. This may be attributed to small number of patients and short duration of CKD and dialysis.  By using multivariate analysis, our study found a strong association of AIMT with serum Mg level.
In conclusion, structural abnormalities in the large vessels are associated with low serum Mg levels occur in children with CKD on HD. Further study is warranted to find the cause- effect relationship between these two phenomena in large cohort studies.
Conflict of interest : None declared.
| References|| |
M de Francisco AL, Rodríguez M. Magnesium - Its role in CKD. Nefrologia 2013;33:389-99.
Nitta K. Vascular calcification in patients with chronic kidney disease. Ther Apher Dial 2011; 15:513-21.
Shroff R, Egerton M, Bridel M, et al. A bimodal association of Vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol 2008;19:1239-46.
de Oliveira RB, Okazaki H, Stinghen AE, Drüeke TB, Massy ZA, Jorgetti V. Vascular calcification in chronic kidney disease: A review. J Bras Nefrol 2013;35:147-61.
Covic AC. Magnesium in chronic kidney disease - More than just phosphate binding. Eur Nephrol 2010;4:28-36.
Spiegel DM. Magnesium in chronic kidney disease: Unanswered questions. Blood Purif 2011;31:172-6.
Ennever J, Vogel JJ. Magnesium inhibition of apatite nucleation by proteolipid. J Dent Res 1981;60:838-41.
Boskey AL, Posner AS. Effect of magnesium on lipid-induced calcification: An in vitro model for bone mineralization. Calcif Tissue Int 1980;32:139-43.
Ishimura E, Okuno S, Kitatani K, et al. Significant association between the presence of peripheral vascular calcification and lower serum magnesium in hemodialysis patients. Clin Nephrol 2007;68:222-7.
Turgut F, Kanbay M, Metin MR, Uz E, Akcay A, Covic A. Magnesium supplementation helps to improve carotid intima media thickness in patients on hemodialysis. Int Urol Nephrol 2008;40:1075-82.
Wilson K, Walker J. Principle and Technology of Biochemistry and Molecular Biology. 6th ed. Cambridge, UK: Cambridge University Press 2005.
Chavhan GB, Parra DA, Mann A, Navarro OM. Normal Doppler spectral waveforms of major pediatric vessels: Specific patterns. Radiographics 2008;28:691-706.
Louvet L, Büchel J, Steppan S, PasslickDeetjen J, Massy ZA. Magnesium prevents phosphate-induced calcification in human aortic vascular smooth muscle cells. Nephrol Dial Transplant 2013;28:869-78.
Ali YF, Abdel-Latif AM, El-Koumi MA, Ghorab AA, Labib HA. Bone activity biomarkers and bone mineral density in children with chronic kidney disease. Arab J Nephrol Transplant 2010;3:29-35.
Delucchi A, Dinamarca H, Gainza H, Whitttle C, Torrealba I, Iñiguez G. Carotid intima-media thickness as a cardiovascular risk marker in pediatric end-stage renal disease patients on dialysis and in renal transplantation. Transplant Proc 2008;40:3244-6.
Wu CC, Chang JH, Chen CC, et al. Calcitriol treatment attenuates inflammation and oxidative stress in hemodialysis patients with secondary hyperparathyroidism. Tohoku J Exp Med 2011;223:153-9.
Neven E, D'Haese PC. Vascular calcification in chronic renal failure: what have we learned from animal studies? Circ Res 2011;108:249-64.
Pennisi AJ, Heuser ET, Mickey MR, Lipsey A, Malekzadeh MH, Fine RN. Hyperlipidemia in pediatric hemodialysis and renal transplant patients. Associated with coronary artery disease. Am J Dis Child 1976;130:957-61.
Sánchez C, Aranda P, Pérez de la Cruz A, Llopis J. Magnesium and zinc status in patients with chronic renal failure: Influence of a nutritional intervention. Magnes Res 2009;22: 72-80.
Román-García P, Rodríguez-García M, CabezasRodríguez I, López-Ongil S, Díaz-López B, Cannata-Andía JB. Vascular calcification in patients with chronic kidney disease: Types, clinical impact and pathogenesis. Med Princ Pract 2011;20:203-12.
Dursun I, Poyrazoglu HM, Gunduz Z, et al. The relationship between circulating endothelial microparticles and arterial stiffness and atherosclerosis in children with chronic kidney disease. Nephrol Dial Transplant 2009;24:2511-8.
Querfeld U, Anarat A, Bayazit AK, et al. The cardiovascular comorbidity in children with chronic kidney disease (4C) study: Objectives, design, and methodology. Clin J Am Soc Nephrol 2010;5:1642-8.
Ossareh S. Vascular calcification in chronic kidney disease: Mechanisms and clinical implications. Iran J Kidney Dis 2011;5:285-99.
Dvoráková HM, Szitányi P, Dvorák P, et al. Determinants of premature atherosclerosis in children with end-stage renal disease. Physiol Res 2012;61:53-61.
Salem S, Bruck H, Bahlmann FH, et al. Relationship between magnesium and clinical biomarkers on inhibition of vascular calcification. Am J Nephrol 2012;35:31-9.
Kircelli F, Peter ME, Sevinc Ok , et al. Magnesium reduces calcification in bovine vascular smooth muscle cells in a dose-dependent manner. Nephrol Dial Transplant 2012; 27:514-21.
Tzanakis I, Virvidakis K, Tsomi A, et al. Intraand extracellular magnesium levels and atheromatosis in haemodialysis patients. Magnes Res 2004;17:102-8.
Tzanakis I, Pras A, Kounali D, et al. Mitral annular calcifications in haemodialysis patients: A possible protective role of magnesium. Nephrol Dial Transplant 1997;12:2036-7.
Lacson EK, Wang W, Lazarus M, et al. Magnesium and mortality risk in hemodialysis patients. San Diego, CA: American Society of Nephrology (Renal Week); 2009.
Tamashiro M, Iseki K, Sunagawa O, et al. Significant association between the progression of coronary artery calcification and dyslipidemia in patients on chronic hemodialysis. Am J Kidney Dis 2001;38:64-9.
Guérin AP, London GM, Marchais SJ, Metivier F. Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant 2000;15:1014-21.
Khatami MR, Mirchi E, Khazaeipour Z, Abdollahi A, Jahanmardi A. Association between serum magnesium and risk factors of cardiovascular disease in hemodialysis patients. Iran J Kidney Dis 2013;7:47-52.
Department of Pediatrics, Faculty of Medicine, Al-Azhar University, Cairo
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]
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