Menoufia Medical Journal

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 33  |  Issue : 3  |  Page : 772--777

Serum magnesium, parathormone levels, and cardiovascular calcification in chronic hemodialysis patients


Hassan A. M. Attia1, Said S. A. Khamis1, Ahmed M Zahran1, Khaled M El-Zorkany1, Waleed A Ebrahim2, Mohammad S Amer3,  
1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Cardiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Internal Medicine, Benha Teaching Hospital, Ministry of Health, Kalyopia, Egypt

Correspondence Address:
Mohammad S Amer
Benha Teaching Hospital, Benha, Kalyopia 13512
Egypt

Abstract

Objectives To elucidate the correlation between serum magnesium (Mg) and intact parathormone hormone (iPTH) levels and between serum Mg and cardiac calcification in chronic hemodialysis patients. Background Patients with chronic kidney disease (CKD) have various complications, one of which is mineral and bone disorder. iPTH is a major player in CKD-mineral and bone disorder and it may have a relation with Mg. Also, lower serum Mg levels may BE associated with cardiac calcification in CKD. Patients and methods Medical charts of 50 hemodialysis patients were reviewed retrospectively. Demographic and laboratory analyses were recorded. Echocardiographic findings were collected, with stressing on valve calcification (VC). We investigated their serum Mg levels and the correlation between iPTH and serum Mg levels, and other clinical parameters. Results Regarding dividing patients into two groups according to Mg level: iPTH, abdominal aortic radiography calcification, carotid intima thickness, BMI, age, and VC were lower in patients with high Mg than other patients (306.36 ± 69.53 vs. 365.36 ± 116.72 pg/ml; P = 0.042) in multiple regression analysis according to the serum Mg level. the iPTH level was an independent variable after adjustment for other factors. VC was found in 31 (62.2%) patients and significantly increased with older age (P = 0.018). Also, aortic calcification, lower serum Mg, and high low-density lipoprotein levels were found in patients with VC. Conclusion The results of this study indicate a significant negative correlation between serum Mg and iPTH in regular hemodialysis patients, and it was an independent factor among other significant parameters according to serum Mg levels. Also, low Mg level is frequent in regular hemodialysis patients with VC.



How to cite this article:
Attia HA, Khamis SS, Zahran AM, El-Zorkany KM, Ebrahim WA, Amer MS. Serum magnesium, parathormone levels, and cardiovascular calcification in chronic hemodialysis patients.Menoufia Med J 2020;33:772-777


How to cite this URL:
Attia HA, Khamis SS, Zahran AM, El-Zorkany KM, Ebrahim WA, Amer MS. Serum magnesium, parathormone levels, and cardiovascular calcification in chronic hemodialysis patients. Menoufia Med J [serial online] 2020 [cited 2021 Mar 4 ];33:772-777
Available from: http://www.mmj.eg.net/text.asp?2020/33/3/772/296692


Full Text



 Introduction



Patients with chronic kidney disease (CKD) have various complications, one of which is mineral and bone metabolism disorder, which comprises abnormal levels of calcium (Ca), phosphate (P), and intact parathyroid hormone (iPTH), and altered vitamin D metabolism. The most important factors involved in the regulation of PTH synthesis and secretion are Ca, vitamin D, andP [1]. Secondary hyperparathyroidism is manifested early in the course of CKD and its progression is enhanced by the progress of renal impairment [2].

Magnesium (Mg), the fourth most abundant cation in the body, plays an important role in numerous enzyme reactions, transport processes, and synthesis of proteins, DNA and RNA. In contrast to its physiological role, the clinical importance of Mg is often underestimated in CKD patients. Louvet et al. [3] showed that increasing Mg levels significantly reduced vascular calcification, improved cell viability, and modulated secretion of vascular calcification markers on cultured human aortic vascular smooth muscle cells.

Also, the connection between Mg and serum PTH is complex. PTH increases serum Mg by enhancing its intestinal absorption, bone resorption, and renal reabsorption. On the other hand, Mg influences the synthesis, secretion, and tissue sensitivity to PTH. Hypermagnesemia, like hypercalcemia suppresses PTH secretion, but its effect is 2.5–3 times lower than that of Ca. Also, lower serum Mg levels are associated with vascular calcification and cardiovascular mortality among patients with end-stage renal disease [4].

So among several mechanisms of the favorable effects of Mg on vascular function, recent studies have focused on its anticalcification property [5]. Also, a cross-sectional study in the general population showed that a higher Mg intake is associated with lower coronary artery calcification scores [6]. A significant association between hypomagnesemia and increased risk for fatal and nonfatal cardiovascular disease (CVD) events was also reported in patients with predialysis CKD [7]. Associations between hypomagnesemia or low Mg intake and the incidence of CVD events, including sudden cardiac death, have been reported in the general population as well as in patients with predialysis CKD [8] and those undergoing hemodialysis [9].

The aim of this study was to study the effect of Mg in patients with end-stage renal disease on regular hemodialysis, in order to evaluate the correlation between Mg and cardiovascular calcification, and between Mg and iPTH.

 Patients and Methods



This cross-sectional study was carried out on 50 patients in Menoufia University Hospital from May 2017 to May 2018. Patients with at least 1 year duration on regular dialysis were included. The study followed the ethical standard of the hospital and it was approved by the ethics committee, as well as informed consent was obtained from all patients. The following patients were excluded from the study, patients with rheumatic or congenital heart disease, patients receiving drugs that may affect the serum Mg levels, for example, tonic/vitamins and Mg-containing P binders, were asked to stop such drugs before the lab assessment by 10 days. All included patients were subjected to the following: full history with stress on: age, sex, and smoking habit. History of renal disease with determination of primary renal disease. History of CVD. Drug history/medications such as Mg-containing drugs, vitamin D, cinacalcet. Dialysis history including: hemodialysis vintage, and date of starting hemodialysis. Number of dialysis sessions per week. Duration of each dialysis session (hr/week). Dialysate concentrate including Mg concentration. Dialysis procedures: the patients were dialyzed three times weekly (4 h per session) using a 1.7 m 2 surface area dialyzer with bicarbonate-based dialysate (sodium 105 mmol/l; bicarbonate cartridge; potassium, 2 mEq/l; Ca, 1.75 mmol/l; and Mg, 0.5 mmol/l) on FRESENIUS 4008B (Fresenius Medical Care, Hamburg, Germany) Dialysis Machine. Detailed clinical examination of all body systems with stressing on: blood pressure, BMI (kg/m 2), type of vascular access. Also, they underwent laboratory investigations including hemoglobin (g/d), ht value, blood urea and serum creatinine, serum Ca and phosphorus and potassium blood sugar – random, glycated hemoglobin. Total lipid profile C-reactive protein, serum albumin, alkaline phosphatase, serum Mg level, iPTH. Corrected serum Ca has made when serum albumin less than 4 g/dl = measured serum Ca (mg/dl) [4-serum albumin level (g/dl)], ECG, echocardiography: transthoracic echocardiography was done to all patients using a General Electric Divid 9 (General Electric, Boston, Massachusetts, United States) 2.5 MHZ transducer probe with stressing on: ejection fraction, valve calcification (VC), and left ventricular mass, mass index, echo-Doppler study of carotid arteries with stressing on measurement of carotid intima–media thickness of carotid arteries through ultrasonographic examination of carotid artery using General Electric Divid 9 using duplex probe (11 L) in the laboratory of Cardiology Department, Menoufia University. Plain radiography of abdominal aorta (lateral view on lumbosacral spine) to detect calcification of abdominal aorta was done for all patients. Serum Mg level normal range was 1.6–2.5 mg/dl. The normal value of iPTH was 10–65 pg/ml. The patients were divided according to cardiac calcification into two groups, those with cardiac calcification and those without. Comparison of clinical, laboratory, and radiological data was done between the two groups. The same cohort was divided again according low and high normal Mg into two groups, those with low normal and high normal serum Mg and the same comparison was done between the two groups.

Statistical analysis

Clinical data were recorded on a report form. These data were tabulated and analyzed using the computer program Microsoft Office 2003 (Excel) and the Statistical Package for the Social Sciences, version 16 IBM (SPSS Inc., Chicago, Illinois, USA) to obtain: descriptive data. Descriptive statistics were calculated for the data in the form of mean ± SD for quantitative data and frequency and distribution for qualitative data. Analytical statistics in the statistical comparison between the different groups, the significance of difference was tested using one of the following tests: Student's t test and Mann–Whitney test: used to compare the mean of two groups of quantitative data of parametric and nonparametric, respectively. Intergroup comparison of categorical data was performed by using χ2 test.

Correlation coefficient: to find the relationships between variables. Receiver operating characteristic curve: to find the validity of Mg value. A P value of less than 0.05 was considered statistically significant while more than 0.05 statistically insignificant. P value less than 0.01 was considered highly significant.

 Results



This study included 50 patients with end-stage renal disease on regular hemodialysis for more than 1 year. Epidemiological data and baseline characteristics are shown in [Table 1]. The cohort was divided according to cardiac calcification into two groups, those without cardiac calcifications and the other group with cardiac calcification. [Table 2] shows the comparison between the studied groups. Age, serum Mg level, low-density lipoprotein (LDL), and abdominal aortic radiography calcification were the only parameters that showed a significantt difference when compared patients according to the presence or absence of calcification.{Table 1}{Table 2}

Logistic regression analysis was done among the significant parameters to detect the best predictor of vascular calcification and it showed that abdominal aortic radiography calcification is the predictor of vascular calcification with a P value of 0.022 [Table 3]. ROC curve was constructed to detect the cut off value of serum Mg to detect cardiac calcification [Figure 1]. It showed the best cut off value of 1.95 mg/ml with area under the curve of 0.744 and a P value of 0.006. It showed 71% sensitivity, 68.4% specificity, 78.6% positive predictive value, and 59.1% negative predictive value.{Table 3}{Figure 1}

The cohort was divided again to low and high median Mg level. A comparison between the studied groups is shown in [Table 4], as age, weight, BMI, hypertension, cardiac calcification, abdominal aortic radiography calcification, carotid intima thickness, iPTH, and LDL level were the only parameters that showed a significant difference among the studied groups. Logistic regression analysis was done among the significant parameters to detect the predictor of relative hypomagnesemia where a high iPTH was found to be the best predictor of relative hypomagnesemia with a P value of 0.028.{Table 4}

 Discussion



Patients with CKD have a high prevalence of vascular calcification, and CVD is the leading cause of death in this population. However, the mechanisms of cardiovascular calcification, which are multifactorial, cell-mediated and dynamic, are not yet fully understood [9]. Mg plays an essential role in many biological processes. Mg deficiency is known to be involved in various pathological conditions especially CVDs [10]. In community prospective studies, low serum Mg was a significant risk factor for CVD [11]. The significant association of lower serum Mg with an increased cardiovascular risk is also found in patients before starting regular hemodialysis in CKD patients [2], and those undergoing regular hemodialysis [8]. Also, there is a significant correlation between serum Mg and iPTH levels. Furthermore, the serum Mg level was an independent factor apart from the other factors regulating iPTH. And it is one of the factors regulating serum iPTH level in uremic patients [12].

In our study, we found that 29 (58%) of 50 patients has cardiac calcification as detected by transthoracic echocardiography. There are some reports that showed a higher prevalence than our results. In one study included 129 (33.3%) hemodialysis patients identified cardiac calcification by echocardiography of patients and other different studies of different percentage 25.5 [13], 32.7 [14], and 57.5% [15]. Comparison between patients with cardiac calcification and those without cardiac calcifications showed that Mg level, abdominal aortic radiography calcification, age, and LDL level were significantly higher in hemodialysis patients with cardiac calcification. On the other hand, our results did not show any significant difference among the two groups regarding the duration of dialysis, BMI, serum Ca, phosphorus, iPTH, albumen, urea prehemodialysis or posthemodialysis, urea, LDL, carotid intima thickness, comorbidities, or other lab data, this agrees with Strózecki et al. [16] in the study done on 65 patient on hemodialysis and he found 29% of patients with cardiac calcification and no significant relation with PTH, Ca, andP (phosphorous) and with disagreement with Sayarlioglu et al. [17] who found a relation to albumin which have a significant reverse relation with calcification but also found no relation with PTH and also no significant relation with LDL which is against our study; however, he had more patients in his study.

Hwang et al. [18] found a significant relation between vascular calcification which is detected by abdominal lateral radiography and cardiovascular mortality, left ventricular hypertrophy, and events in regular hemodialysis patients which agree with our finding. The ROC curve in [Figure 1] and [Table 4] demonstrated that serum Mg level was the predictor of cardiac calcification with a cutoff value of 1.95 mg/dl and area under the curve of 0.744. In our study, the cohort was divided again according to serum Mg. Comparison between patients with high median level and those with low median Mg level showed that there was a significant difference between the two groups regarding abdominal aortic radiography calcification, carotid intima thickness, iPTH, BMI, age, and cardiac calcification. On the other hand, there was not any significant difference between the two groups regarding age, duration of dialysis, serum Ca, and comorbidities. Regression analysis [Table 5] demonstrated that iPTH is the only predictor of relative hypomagnesemia. Some studies [8],[19] were found similar to our results, as there is a reverse relation between Mg and PTH and this relation had good outcome within limits.{Table 5}

In our study, cardiac calcifications as regards valve calcification were present in 29 (62%) patients. Out of 31 hemodialysis patients with cardiac calcifications there were 22 (70.9%) hemodialysis patients with low median hypomagnesemia. It means there is high association between cardiac calcification and relative hypomagnesemia in accordance with Dritsa et al. [20], who suggests that treatment with Mg salts may reduce stenosis of aortic valves and also show that in order to reduce the progression of calcification of aortic valves, treatment of patients with Mg salts is needed and it can be explained by substitution of Ca 2+ cations by Mg 2+ cations which leads to the formation of amorphous hydroxyapatite, preventing aortic valve stenosis. Also this agrees with Silva et al. [21] who found that Mg levels might have a significant clinical relevance as a marker or predictor of mitral VC as well as intimal medial thickness as a measure of VC and last but not least, a therapeutic role for Mg should be considered, and this appeared in other studies [8],[22],[23].

There are some limitations of this study, first the small number of the studied group, second observational view of the study. Third, absence of mortality relation with our finding.

 Conclusion



Cardiac calcification and relative hypomagnesemia is prevalent in hemodialysis patients, patients with upper high normal magnesia have less cardiac calcification and this effect occurs either by anticalcific properties of Mg or by inhibition of parathormone hormone. Follow up of serum Mg in hemodialysis patients with control of level to a high normal level may decrease both cardiac calcification and hazard of hyperparathyroidism. Cutoff value of serum Mg at 1.95 mg/dl may be the target goal in hemodialysis patients. We recommend future meta-analysis studies with long-term follow-up to estimate mortality risk and other comorbidities [Table 6].{Table 6}

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Silver J, Naveh-Many T. Phosphate and the parathyroid. Kidney Int 2009; 75:898–905.
2Kanbay M, Yilmaz M, Apetrii M, Saglam M, Yaman H. Relationship between serum magnesium levels and cardiovascular events in chronic kidney disease patients. Am J Nephrol 2012; 36:228–237.
3Louvet L, Büchel J, Steppan S, Passlick-Deetjen J, Massy ZA. Magnesium prevents phosphate-induced calcification in human aortic vascular smooth muscle cells. Nephrol Dial Transplant 2013; 28:869–878.
4Kanbay M, Goldsmith D, Uyar M. Magnesium in chronic kidney disease: challenges and opportunities. Blood Purif 2010; 29:280–292.
5Van Laecke S, Van Biesen W, Vanholder R. Hypomagnesaemia, the kidney and the vessels. Nephrol Dial Transplant 2012; 27:4003–4010.
6Hruby A, O'Donnell CJ, Jacques PF, Meigs JB, Hoffmann U. Magnesium intake is inversely associated with coronary artery calcification: the Framingham Heart Study. JACC Cardiovasc Imaging 2014; 7:59–69.
7Khan A, Lubitz S, Sullivan L. Low serum magnesium and the development of atrial fibrillation in the community: the Framingham Heart Study. Circulation 2013; 127:33–38.
8Sakaguchi Y, Fujii N, Shoji T, Hayashi T, Rakugi H. Hypomagnesemia is a significant predictor of cardiovascular and non-cardiovascular mortality in patients undergoing hemodialysis. Kidney Int 2014; 85:174–181.
9Massy Z, Drüeke T. Magnesium and outcomes in patients with chronic kidney disease: focus on vascular calcification, atherosclerosis and survival. Clin Kidney J 2012; 5:52–61.
10Maier JA. Endothelial cells and magnesium: implications in atherosclerosis. Clin Sci 2012; 122:397–407.
11Del Gobbo L, Imamura F, Wu J, de Oliveira Otto M, Chiuve S. Circulating and dietary magnesium and risk of cardiovascular disease: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr 2013; 98:160–173.
12Ohya M, Negi S, Sakaguchi T. Significance of serum magnesium as an independent correlative factor on the parathyroid hormone level in uremic patients. J Clin Endocrinol Metab 2014; 99:3873–3878.
13Chen X, Chen Z, Ma X. Aortic artery and cardiac valve calcification are associated with mortality in Chinese hemodialysis patients: a 3.5 years follow-up. Chin Med J 2015; 128:2764–2771.
14Li ZL, He CS, Chen YH. Association of heart valve calcification with cardiovascular outcomes in patients on maintenance hemodialysis. J South Med Univ 2016; 36:941–946.
15Raggi P, Bellasi A, Gamboa C. All-cause mortality in hemodialysis patients with heart valve calcification. Clin J Am Soc Nephrol 2011; 6:1990–1995.
16Strózecki P, Odrowaz-Sypniewska G, Manitius J. Cardiac valve calcifications and left ventricular hypertrophy in hemodialysis patients. Ren Fail 2005; 27:733–738.
17Sayarlioglu H, Acar G, Sahin M. Prevalence and risk factors of valvular calcification in hemodialysis patients. Iran J Kidney Dis 2013; 7:129–134.
18Hwang H, Cho J, Hong Y, Chang Y, Kim S, Shin S. Vascular calcification and left ventricular hypertrophy in hemodialysis patients: interrelationship and clinical impacts. Int J Med Sci 2018; 15:557–563.
19Baradarn A, Nasri H. Correlation of serum magnesium with serum parathormone levels in patients on regular hemodialysis. Saudi J Kidney Dis Transplant 2006;17:344–350.
20Dritsa V, Pissaridi K, Koutoulakis E, Mamarelis I, Kotoulas C, Anastassopoulou J. An infrared spectroscopic study of aortic valve. A possible mechanism of calcification and the role of magnesium salts. In Vivo 2014; 84:91–98.
21Silva AP, Gundlach K, Büchel J. Low magnesium levels and FGF-23 dysregulation predict mitral valve calcification as well as intima media thickness in predialysis diabetic patients. Int J Endocrinol 2015; 30:81–90.
22Reffelmann T, Ittermann T, Dorr M, Volzke H, Reinthaler M, Petersmann A, et al. Low serum magnesium concentrations predict cardiovascular and all-cause mortality. Atherosclerosis 2011; 219:280–284.
23van Laecke S, Nagler E, Verbeke F, van Biesen W, Vanholder R. Hypomagnesemia and the risk of death and GFR decline in chronic kidney disease. Am J Med 2013; 126:825–831.