Magnesium in Chronic Kidney Disease – More than Just Phosphate Binding
Table 1: Overview of Clinical Studies Assessing the Effect of Magnesium Levels on Arterial Calcification in Patients Receiving Dialysis for Stage 5 Chronic Kidney Disease
Authors, Year
Spiegel et al., 200943 Turgut et al., 200842 Ishimura et al., 200741 Tzanakis et al., 200440
No. Patients (Dialysis Type)
7 (haemodialysis) 47 (haemodialysis) 390 (haemodialysis)
93 (haemodialysis) and 182 age- and sex-
Tzanakis et al., 199739 Meema et al., 198768
matched healthy controls 56 (haemodialysis)
44 (CAPD)
Study Design
Prospective, follow-up over 18 months
Prospective, follow-up over 2 months
Prospective, single-blind, follow-up over 4 months Cross-sectional analysis
Retrospective analysis of 8 years
Prospective follow-up
*p-values are for the association between magnesium levels and arterial calcification. CAPD = continuous ambulatory peritoneal dialysis.
Parameter Determined
Coronary artery calcification
Intima-media thickness of the carotid artery Calcification of the hand arteries
Carotid intima-media thickness
Mitral annular calcification
Progression/regression of arterial calcification
Assessment Technique p-value*
Electron-beam tomography Ultrasound
Radiographic findings of the hands
B-mode ultrasound Doppler
echocardiography Radiographic survey
0.0737 0.014 0.036 0.001 0.008 <0.001
receiving haemodialysis and 102 patients not receiving haemodialysis who had suspected CVD, CT scanning showed that coronary artery calcification scores were 2.5- to five-fold higher in patients receiving dialysis compared with those who were not.37
A multiple regression
analysis of the results indicated that increased age and hypertension were both significant risk factors for the development of cardiovascular calcification. Theredfore, in patients with CKD stage 5, vascular calcification starts at a younger age and is more widely distributed throughout the body compared with individuals with normal kidney function.
The importance of Mg levels in the development of CVD in patients with CKD stage 5 has been recognised in several cardiovascular studies. One such study examined the effect of Mg on cardiac valve calcification in a group of 56 patients (34 males and 22 females) who were receiving haemodialysis.39
M-mode, 2D and Doppler echocardiograms indicated
that patients with serum Mg levels <1.2mmol/l were twice as likely to have mitral annular calcification than those with Mg levels above this concentration (Chi square = 6.98; p=0.008).
Another prospective study included 93 stable chronic haemodialysis patients and 182 age- and sex-matched healthy controls. B-mode ultrasound revealed that both serum and lymphocyte intracellular Mg levels were strongly negatively associated with intimal thickness in the common carotid arteries (p=0.001 and 0.003, respectively).40
A
striking finding in this study was that for each 0.5mmol/l increase in serum Mg levels there was a 0.35mm reduction in intima-media thickness in the common carotid arteries. This suggests that Mg may play a protective role, slowing atherosclerosis development in patients with CKD stage 5.
This beneficial effect of moderate hypermagnesaemia is supported by the results of a study from Japan that investigated the association of serum Mg levels with vascular calcification in 390 non-diabetic patients with CKD stage 5 who were receiving haemodialysis.41
Hand
roentgenography showed that 52 (13.3%) of these patients had arterial calcification and 338 (86.7%) did not. Serum Mg levels were significantly lower in patients with calcification than in those without: 2.69±0.28mg/dl (1.12±0.12mmol/l) versus 2.78±0.33mg/dl (1.14±0.14mmol/l; p<0.05). Multivariate logistic regression analysis
EUROPEAN NEPHROLOGY
showed that serum Mg concentration was a significant independent risk factor for vascular calcification (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.09–0.92mg/dl for an increase in serum Mg of 1mg/dl [0.41mmol/l]; p=0.036).41
In addition, serum phosphorus
(p=0.0002), but not Ca (p=0.809) or parathyroid hormone (PTH) levels (p=0.726), were significantly associated with calcification in multivariate logistic regression analysis. It was concluded that higher serum Mg levels could have an important protective role against calcification in patients receiving haemodialysis and that dialysate concentrations should be altered to address this.
A study conducted in Turkey reached a similar conclusion regarding the protective role of Mg.42
A population of 47 patients receiving
haemodialysis with Ca acetate as phosphate binder treatment were randomised to receive 610mg Mg citrate every other day for two months or to the control group. The bilateral carotid intimal thickness was significantly improved for Mg- compared with Ca-treated patients (p=0.001 and 0.002 for the left and right carotid, respectively). PTH levels were also significantly lower in Mg-treated patients. The authors stated that further studies were warranted to assess the role of Mg in atherosclerotic regression.
The findings of a recent small study in the US point in the same direction.43
Seven patients receiving haemodialysis were treated with
a combination of magnesium carbonate (MgCO3) and calcium carbonate (CaCO3) over a period of 18 months. During this time, phosphorus levels were well controlled and electron-beam CT
scanning showed a small, non-significant increase in coronary artery calcification (CAC) of p=0.0737. This was despite the fact that all patients had baseline CAC scores >30 and were followed up for a relatively long time. This is remarkable as the progression of CAC scores in individuals with baseline CAC scores >30 in other trials was demonstrated to be between 6 and 41% after 12 months.44–46
There
was also no significant change in bone mineral density recorded (p=0.6525). The data from this study are promising but are taken from a very limited group of patients; the authors suggested that larger studies should be undertaken to confirm their findings.
Further investigations are required in order to clarify the mechanisms by which hypermagnesaemia retards the development of arterial
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