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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2006  |  Volume : 17  |  Issue : 3  |  Page : 344-350
Correlation of Serum Magnesium with Serum Parathormone Levels in Patients on Regular Hemodialysis


1 Department of Biochemistry, Center of Research and Reference Laboratory of Iran, Hospital Bu Ali, Shahrekord, Iran
2 Internist and Nephrologist, Shahrekord University of Medical Sciences, Hajar Medical, Educational and Therapeutic Center, (Hemodialysis Department), Shahrekord, Iran

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   Abstract 

Secondary hyperparathyroidism (SHPT) is a common, important, and treatable complication of end-stage renal disease. This study was conducted to investigate the role of serum magnesium (Mg) in regulating the secretion of parathyroid hormone (PTH) by the parathyroid gland in patients on maintenance hemodialysis (HD). Pre-dialysis serum levels of calcium (Ca), phosphorus (P), Mg, alkaline phosphatase (ALP), intact serum PTH (iPTH), serum 25-hydroxy Vitamin D (25-OH Vit D) and plasma bicarbonate (HCO3) were measured. The Urea Reduction Rate as well as duration and dosage of HD treatment were noted. Our study did not show any significant correlation between serum Mg levels and duration of HD treatment, levels of serum ALP, and plasma HCO3, Ca and P. An inverse correlation, albeit insignificant, was found between the serum Mg levels and iPTH (r=-0.30 p=0.079); also, a significant positive correlation was found between serum Mg levels and serum 25-OH Vit D levels (r= 0.40 p= 0.009). Our findings are in agreement with previous data, which suggest that factors other than serum Mg are more important in the regulation of PTH secretion in HD patients. A positive and strong association between serum Mg with 25-OH Vit D needs to be studied in greater detail.

Keywords: Hemodialysis, Magnesium, Secondary hyperparathyroidism, Parathormone, 25-Hydroxy vitamin D.

How to cite this article:
Baradaran A, Nasri H. Correlation of Serum Magnesium with Serum Parathormone Levels in Patients on Regular Hemodialysis. Saudi J Kidney Dis Transpl 2006;17:344-50

How to cite this URL:
Baradaran A, Nasri H. Correlation of Serum Magnesium with Serum Parathormone Levels in Patients on Regular Hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2006 [cited 2019 Jun 24];17:344-50. Available from: http://www.sjkdt.org/text.asp?2006/17/3/344/35766

   Introduction Top


Secondary hyperparathyroidism (SHPT) is a common, important, and treatable compli­cation of end-stage renal disease (ESRD).[1],[2]],[3] Hyperphosphatemia, hypocalcemia, decreased expression of calcium and vitamin D receptors, and resistance to the action of parathyroid hor­mone (PTH) are the main causative factors.[3],[4],[5],[6],[7],[8],[9] The fact that many complications of SHPT are poorly reversible in the long-term [10],[11],[12],[13] emphasizes the need for early management of its causative factors. [2] In fact, independent of the factors mentioned above, which regulate parathyroid gland function, it has been believed that serum magnesium (Mg) levels play an important role in regulating the secretion of PTH. [14] It is thought that Mg may be able to modulate PTH secretion in a way similar to calcium (Ca). [15] Since renal excretion is the major route of elimination of Mg from the body, a positive Mg balance would be expected in patients with renal insufficiency. [16] However, the Mg balance may be normal or even decreased in uremic patients. This is probably due to decreased dietary intake combined with impaired intestinal absorption. Impaired absorption of Mg seems to be related to deficient synthesis of the active metabolite of vitamin D by the non­functioning kidney. [16] Following the institution of chronic hemodialysis (HD) treatment, the major determinant of Mg balance is the concentration of Mg in the dialysate. Thus, in patients with chronic renal failure (CRF), although reduced nutritional intake, impaired absorption from the intestine, vomiting, diarrhea, the use of diuretics, and acidosis may result in a negative balance of Mg, as mentioned above, reduced renal excretion may cause accumulation of Mg, [17],[18] resulting in increased Mg concentration in serum and red cells in CRF patients. Bone concentrations and total body Mg also appear to be increased. [17]

Studies have shown that infusion of Mg decreases the secretion of PTH. However, the effect of chronic hyper-magnesemia on PTH levels in dialysis patients is not well established. [19] Uncertainty about the inter­relationship between serum Mg levels, and boyh serum 25-hydroxy vitamin D (25-OH Vit D) levels, and PTH levels in patients on maintenance HD, prompted us to undertake this study.


   Patients and Methods Top


This is a cross-sectional study performed in the HD section of The Hajar Medical Edu­cational and Therapeutic Center of Shahrekord University of Medical Sciences in Shahrekord, Iran. It involved patients with ESRD on regular maintenance HD treatment, using acetate bath dialysate and a polysulfone membrane dialyzer. All patients received treatment with oral active vitamin D 3 (Rocaltrol) and calcium carbonate or sevelamer (Renagel) at various doses, according to the severity of the SHPT. In addition, patients received intravenous (i.v.) iron therapy with iron sucrose (Venofer), administered after each dialysis session, apart from folic acid, L-carnitine, oral vitamin B­complex, and i.v. recombinant human ery­thropoietin (rHuEPO) (Eprex) in appro­priate doses.

Patients with active infection were excluded from the study. The serum calcium (Ca), phos­phorus (P), Mg, and alkaline phosphatase (ALP) levels were measured using standard kits. Intact serum PTH (iPTH) was measured by the RIA method using DSL-8000 of the USA. Serum 25-OH Vit D levels were measured by the ELISA method using DRG of Germany (normal range, 25 to 125 nmol/L). Plasma HCO3 was measured by arterial blood gas. The efficacy of HD was assessed by calculating the urea reduction rate (URR). [20]

For statistical analysis, descriptive data are expressed as mean ± SD. Comparison bet­ween the groups was done using a Student's t-test. Statistical correlations were assessed using a partial correlation test. Statistical analysis was performed separately on the study group as a whole, females, males, diabetics, and non-diabetics. All statistical analyses were performed using SPSS (version 11.5.00). Statistical significance was fixed at a p value < 0.05.


   Results Top


A total of 41 patients (males=26, females =15) were studied. Of them, there were 29 non-diabetic (M=18, F=11) and 12 diabetic patients (M=8, F=4). [Table - 1] shows the demographic features, the length of the time patients had been on HD, the dialysis dosage, and the results of the laboratory tests. The mean ± SD age of the study patients was 46 (± 17.6) years. The length of the time the patients had been on HD was 29.5 (± 34.7) months. The mean values of serum Mg, serum 25-OH Vit D, and serum iPTH were 2.48 (±0.41) mg/dl, 7.6 (± 9.45) nmol/L, and 408 (± 44) pg/ml, respectively. No significant difference was seen in the levels of serum Mg, Ca, P, HCO3, ALP, and 25-OH Vit D between diabetics and non-diabetics. A signi­ficant difference in the serum iPTH levels (r=0.012) as well as the URR (r=0.046) was seen between diabetic and non-diabetic patients. No significant differences were seen between males and females in the levels of serum iPTH, Mg, Ca, P, plasma HCO3, ALP, and serum 25-OH Vit D or in the duration of time on dialysis, dialysis dosage, and the age of the patients. There was no significant correlation between serum Mg levels and such variables including duration of time on HD, serum ALP, plasma HCO3, serum Ca, and P in the study patients. After adjusting for age, duration, and dosage of dialysis, as well as serum Ca, P, and ALP levels, a near signi­ficant inverse correlation of serum Mg with serum iPTH (r= -0.30 p=0.079; [Figure - 1]) was found. A significant positive correlation was found between serum levels of Mg and 25­OH Vit D (r= 0.40 p= 0.009; [Figure - 2]). This significant association was strongly positive in non-diabetic, diabetic, female, and male groups individually. A near significant positive correlation between serum Mg and dialysis dosage was found (r= 0.27 p=0.096). In non­diabetic HD patients, a near significant positive correlation of serum Mg with plasma HCO3 (r= 0.33 p= 0.085) and a near significant inverse correlation of serum Mg with dialysis adequacy were seen (r= - 0.33 p = 0.083; [Figure - 3]).


   Discussion Top


In this study, we found no significant cor­relation of serum Mg levels with duration of time on HD treatment and levels of serum ALP, plasma HCO3, and serum Ca and P. Also, a near significant inverse correlation of serum Mg with iPTH levels and a significant positive correlation of serum Mg with serum 25- OH Vit D levels were found for the study patients.

Studies concerning the relationship between serum Mg and serum iPTH have revealed some interesting results. In the study conducted by Gohda et al on 86 HD patients not treated with vitamin D, serum iPTH levels cor­related negatively with serum Mg and the authors concluded that serum Mg level could predict the serum iPTH levels. [21] On the contrary, Gonella et al. studied 22 uremic patients on chronic HD, using different con­centrations of Mg in the dialysate. After a six-month period, they did not find any significant changes in the serum PTH levels; they concluded that the serum Mg levels do not appreciably influence PTH secretion in uremic patients on regular HD. [22] In a study on 110 HD patients not receiving vitamin D, Navarro et al. demonstrated that serum Mg levels were inversely correlated with PTH levels and that PTH levels were influenced by Mg levels. Navarro concluded that patients with inadequately low PTH levels showed higher serum Mg concentrations, suggesting that chronic hypermagnesemia might decrease PTH secretion and/or synthesis. [19] In another study of 126 patients to determine the patho­genesis of relative hypoparathyroidism (PTH< 200 pg/mL) in HD patients, Guh et al showed that time-dependent PTH levels were inversely correlated with serum Mg levels. [15] McGonigle et al. studied 20 patients on regular HD therapy to assess the influence of Mg on circulating plasma iPTH levels. Plasma levels of iPTH and 25-OH Vit D were measured before and 10 weeks after the Mg concentration in the dialysate was increased from 0.75 to 1.50 mmol/L. They showed a 36% rise in the mean pre-dialysis plasma Mg concentration and a 23% fall in the mean plasma iPTH concentration. Also, the mean plasma concen­trations of 25-OH Vit D levels decreased, although this was not significant. The authors concluded that a rise in plasma Mg concen­tration reduces the circulating plasma iPTH levels in normo-calcemic, uremic patients with initially both normal and raised plasma PTH levels. [23] In contrast to this study, which implies an inverse correlation between serum Mg and 25-OH Vit D levels, we found a strong positive correlation between serum Mg and 25 OH Vit D levels. This association remained strongly positive in non-diabetic, diabetic, female, and male groups studied individually.

In conclusion, we found a near significant and inverse correlation of serum Mg with serum iPTH levels. Our findings suggest that factors other than serum Mg may be more important in the regulation of PTH secretion. We also found a positive association bet­ween serum Mg with 25-OH Vit D levels, which is in contrast to some earlier studies.


   Acknowledgements Top


We would like to thank the Research Department at our university, especially Dr. Yussefi, who helped provide the facilities to conduct this study.

 
   References Top

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5.Yamamoto M, Igarashi T, Muramatsu M, Fukagawa M, Motokura T, Ogata E. Hypocalcemia increases and hypercalcemia decreases the steady state level of parathyroid hormone messenger RNA in the rat. J Clin Invest 1989;83:1053-6.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
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9.Llach F, Massry SG, Singer FR, Kurokawa K, Kaye JH, Coburn JW. Skeletal resistance to endogenous parathyroid hormone in patients with early renal failure. A possible cause for secondary hyperparathyroidism. J Clin Endocrinol Metab 1975;41:339-45.  Back to cited text no. 9    
10.Nasri H, Baradaran A, Naderi AS. Close association between parathyroid hormone and left ventricular function and structure in end-stage renal failure patients under maintenance hemodialysis. Acta Med Austriaca 2004;31(3):67-72.  Back to cited text no. 10    
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12.Nasri H. Intensification of anemia by secondary hyperparathyroidism in hemodialysis patients. Iran J Med Sci. 2003;28:( http://www.sums.ac.ir).  Back to cited text no. 12    
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14.Cho MS, Lee KS, Lee YK, Ma SK, Ko JH, Kim SW, Kim NH, Choi KC. Relationship between the serum parathyroid hormone and magnesium levels in continuous ambulatory peritoneal dialysis (CAPD) patients using low-magnesium peritoneal dialysate. Korean J Intern Med 2002;17(2):114-21.  Back to cited text no. 14    
15.Guh JY, Chen HC, Chuang HY, Huang SC, Chien LC, Lai YH.Risk factors and risk for mortality of mild hypoparathyroidism in hemodialysis patients. Am J Kidney Dis 2002;39(6):1245-54.  Back to cited text no. 15    
16.Mountokalakis TD. Magnesium metabolism in chronic renal failure. Magnes Res 1990;3(2):121-7.  Back to cited text no. 16    
17.Lindeman RD. Chronic renal failure and magnesium metabolism. Magnesium 1986;5(5-6):293-300.  Back to cited text no. 17    
18.Nasri H, Baradaran A. Correlation of serum magnesium with dyslipidemia in maintenance hemodialysis patients. Acta Medica (Hradec Kralove) 2004;47(4):263-­5.  Back to cited text no. 18    
19.Navarro JF, Mora C, Jimenez A, Torres A, Macia M, Garcia J.Relationship between serum magnesium and parathyroid hormone levels in hemodialysis patients. Am J Kidney Dis 1999;34(1):43-8.  Back to cited text no. 19    
20.Boag JT. Basic truths in optimal hemo­dialysis. Dial Transplant 1994;23(11): 636.  Back to cited text no. 20    
21.Gohda T, Shou I, Fukui M, et al. Parathyroid hormone gene polymorphism and secondary hyperparathyroidism in hemodialysis patients. Am J Kidney Dis 2002;39(6):1255-60.  Back to cited text no. 21    
22.Gonella M, Bonaguidi F, Buzzigoli G, v Bartolini, Mariani G.On the effect of magnesium on the PTH secretion in uremic patients on maintenance hemodialysis. Nephron 1981;27(1):40-2.  Back to cited text no. 22    
23.McGonigle RJ, Weston MJ, Keenan J, Jackson DB, Parsons V.Effect of hypermagnesemia on circulating plasma parathyroid hormone in patients on regular hemodialysis therapy. Magnesium 1984;3(1):1-7.  Back to cited text no. 23    

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Correspondence Address:
Hamid Nasri
Internist, Nephrologist, Assistant Professor of Shahrekord University of Medical Sciences, Hajar Medical, Educational and Therapeutic Center, (Hemodialysis Department), P.O. Box: 88155-468, Shahrekord
Iran
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