Research Article
Blood Purif
DOI: 10.1159/000509788
Continuous Observation of Serum Total
Magnesium Level in Patients Undergoing
Hemodialysis
Wenfang Yang a Erli Wang b Wenxiu Chen a Chunming Chen a
Shanying Chen a  
aDepartment of Nephrology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China;
bClinical
Laboratory, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China
Keywords
Continuous observation · Hypermagnesemia · Initiating
hemodialysis · Magnesium · Maintenance hemodialysis
Abstract
Background: Magnesium is an indispensable cation and
plays an important physiological role in the body. Most previ-
ous studies focused on the single measurement of serum
magnesium in patients undergoing hemodialysis. However,
scant studies focused on continuous observations of serum
magnesium levels. Objective: To provide continuous obser-
vations of serum magnesium levels in patients on mainte-
nance hemodialysis (MHD). The levels of magnesium in pa-
tients initiating hemodialysis are also recorded and analyzed
in the present study. Methods: In this retrospective study, we
serially investigated the measurements of serum total mag-
nesium in MHD patients and patients initiating hemodialysis.
Our data were followed up for one year. We provided real-
time update on the levels of serum magnesium in patients on
hemodialysis. Results: On January 1, 2019, a total of 356 end-
stage renal disease patients were receiving hemodialysis in
our hospital. On December 31, 2019, the number had in-
creased to 383. We found that serum total magnesium levels
were in the normal range before initiating hemodialysis. With
karger@karger.com © 2020 S. Karger AG, Basel
www.karger.com/bpu
Received: March 20, 2020
Accepted: June 28, 2020
Published online: August 31, 2020
the initiation of hemodialysis, the levels of serum total mag-
nesium increased. In patients on MHD, hypermagnesemia
was very common. Hypomagnesemia was rare when 0.5
mmol/L magnesium dialysate was used. We did not find pro-
ton pump inhibitor associated hypomagnesemia. Conclu-
sion: We find that serum total magnesium levels are in the
normal range before initiating hemodialysis. However, in pa-
tients on MHD, hypermagnesemia is common when 0.5
mmol/L magnesium dialysate is used. Hypomagnesemia is
very rare. Hypomagnesemia in patients on MHD is an indica-
tor of poor condition. © 2020 S. Karger AG, Basel
Introduction
The patients with end-stage renal disease (ESRD) of-
ten have a series of metabolic disorders because of losing
the regulation function of normal kidney [1]. Although
much attention has been focused on electrolytes includ-
ing potassium, calcium, and phosphorus in dialysis pa-
tients [2], magnesium has long been referred to as “the
neglected cation” [1]. In fact, magnesium is an indispens-
able cation and plays an important physiological role in
the body [3]. Magnesium is a cofactor in more than 300
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Shanying Chen
Department of Nephrology
Zhangzhou Affiliated Hospital of Fujian Medical University
59 # Shengli Xi Road, Zhangzhou 363000 (China)
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enzymatic reactions [4]. About 99% of total body magne-
sium is stored in bones, skeletal muscles, and soft tissues
[2, 3]. Extracellular magnesium only accounts for about
1% of total body magnesium [2, 3]. Magnesium homeo-
stasis is maintained by the intestine, the bone, and the
kidneys [2, 3]. The kidneys are crucial in magnesium ho-
meostasis [2, 3]. With the loss of kidney function, the
magnesium homeostasis may be out of balance [2].
Sakaguchi et al. [5] conducted a cohort study of 142,555
hemodialysis patients. This is the first published study to
demonstrate the significant association between hypo-
magnesemia and mortality in patients undergoing hemo-
dialysis [5]. Thereafter, several studies based on large
samples focus on the association between magnesium
levels and mortality in dialysis patients [1, 6, 7]. Normal
serum total magnesium level ranges from 0.7 to 1.0
mmol/L [1]. The previous study has indicated that an in-
creased level of magnesium (2.8–3.1 mg/dL) is optimal
for hemodialysis patients [5]. However, the previous
large-scale studies focused on the single measurement of
serum magnesium and usually used baseline level of se-
rum magnesium as a predictor [6, 7]. Since the levels of
electrolytes in the body often fluctuate, a single measure-
ment of electrolytes may be not a good indicator.
To the best of our knowledge, scant studies focused on
continuous observations of serum magnesium levels in
patients undergoing hemodialysis. We performed this
retrospective study to provide continuous observations of
serum magnesium levels in patients on maintenance he-
modialysis (MHD). The levels of magnesium in patients
initiating dialysis were also recorded and analyzed in the
present study.
Materials and Methods
Data Collection
Our hospital had two hemodialysis centers. Information regis-
tration and medical records have been established in hemodialysis
centers. Medical records included patient name, age, gender, pri-
mary diseases, dialysis treatment information, history, pharmacol-
ogy therapies, and so on. Using out-patient clinical laboratory sys-
tem, we collected laboratory data on hemodialysis patients. Ac-
cording to Chinese Blood Purification Standard Operating
Procedure (SOP) 2010 [8], it is recommended to examine labora-
tory variables including electrolytes, serum creatinine, and blood
urea every 1–3 months in patients on hemodialysis. In our hemo-
dialysis centers, we had a monthly measurement of the level of
electrolytes, serum creatinine, and blood urea. We also measured
postdialysis blood urea every three months. We also recommend-
ed to re-examine postdialysis electrolytes according to conditions.
The residual urine volume was calculated as the average of 24-h
urine volume on a dialysis day and a non-dialysis day.
2 Blood Purif
DOI: 10.1159/000509788
The study period was from January 1, 2019, to December 31,
2019. In this study, weinvestigated the data of two groups: MHD
patients and patients initiating hemodialysis. Inclusion criteria for
MHD patients were as follows: (1) ESRD confirmed by nephrolo-
gists; (2) receiving hemodialysis; and (3) undergoing dialysis ther-
apy >90 days. Exclusion criteria were (1) age < 18 years and (2)
acute kidney injury (AKI).
Inclusion criteria for patients initiating hemodialysis were as
follows: (1) ESRD confirmed by nephrologists and (2) initiating
hemodialysis from January 1, 2019, to October 31, 2019. Exclusion
criteria were (1) age < 18 years; (2) AKI; (3) transfer to hemodialy-
sis after peritoneal dialysis therapy; and (4) patients who had re-
ceived hemodialysis in other medical institutions.
Some pharmacology therapies may affect magnesium metabo-
lism [9–12], so history of pharmacology therapies in 2019 was in-
vestigated. Pharmacology therapies which may affect magnesium
metabolism included proton pump inhibitors (PPIs) [9, 10], calci-
neurin inhibitors [11], diuretics [12], and magnesium-containing
preparations. We reviewed medical records and imaging reports
(chest CT or X-ray) to diagnose aortosclerosis and coronary calci-
fication. Echocardiography reports were reviewed to diagnose cal-
cification of the aorta or mitral valve.
Laboratory Variables
Predialysis samples were collected from the fistula needle,
avoiding heparin or saline infusion before samples were collected.
Postdialysis samples were collected before the end of hemodialysis.
To avoid the influence of hemodialysis vascular access recycling,
the method of postdialysis sample collection was as follows [8]:
(1) set the ultrafiltration speed to 0; (2) then set the dialysate as
bypass; (3) maintain extracorporeal circulation for 3–5 min at nor-
mal speed; and (4) extract blood samples from the extracorporeal
pipeline. Heparin or other anticoagulation was stopped for at least
30 min before the end of dialysis. Fasting was not required prior to
the collection of blood samples.
The blood sample was centrifuged within 2 h, and the plasma
was separated. The level of total serum magnesium was measured
using the Arsenazo I method (Beckman AU 5800). According to
the recommendation of our laboratory, the normal level of serum
total magnesium ranged from 0.6 to 1.1 mmol/L. Hypomagnese-
mia and hypermagnesemia were defined as the level of total se-
rum magnesium <0.6 mmol/L or >1.1 mmol/L, respectively. For
the patients initiating hemodialysis, the baseline serum magne-
sium value was the last measurement of serum magnesium before
receiving the first hemodialysis therapy. Based on the Japanese
large-scale study [5], a higher level of serum total magnesium
(2.8–3.1 mg/dL) was associated with the lowest mortality in he-
modialysis patients. In the present study, the optimal level of
magnesium was defined as 1.1–1.3 mmol/L (2.6–3.1 mg/dL). Se-
vere hypermagnesemia was defined as the level of serum total
magnesium ≥1.3 mmol/L. Persistence of severe hypermagnese-
mia  was defined as serum total magnesium ≥1.3 mmol/L at least
two consecutive months. Recurrence of severe hypermagnesemia 
was defined if the level of serum total magnesium increased to 1.3
mmol/L after decreasing below 1.3 mmol/L from severe hyper-
magnesemia . According to the reference provided by the labora-
tory, the normal level of plasma albumin was 35–55 g/L, so hy-
poalbuminemia was defined if the level of plasma albumin was
<35 g/L. The normal level of intact parathyroid hormone was
12–88 pg/mL.
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 Table 1. The level of serum total magnesium in MHD patients

N Mean ± SD, Magnesium <0.6 mmol/L 1.1–1.3 mmol/L ≥1.3 mmol/L

mmol/L range, mmol/L (%) (%) (%)

1 246 1.13±0.15 0.67–1.68 0 119 (48.37) 30 (12.20)

2 265 1.13±0.17 0.63–1.69 0 122 (46.03) 37 (13.96)
3 229 1.16±0.15 0.59–1.80 1 (0.44) 105 (45.85) 22 (9.60)
4 214 1.13±0.15 0.61–1.83 0 95 (44.39) 24 (11.21)
5 233 1.20±0.17 0.66–1.95 0 113 (48.50) 58 (24.89)
6 249 1.13±0.16 0.52–1.66 2 (0.80) 111 (44.58) 33 (13.25)
7 270 1.13±0.18 0.13–1.67 2 (0.74) 126 (46.67) 37 (13.70)
8 268 1.12±0.15 0.70–1.94 0 120 (44.78) 26 (9.70)
9 231 1.16±0.15 0.64–1.82 0 105 (45.45) 40 (17.32)
10 294 1.17±0.16 0.72–1.66 0 141 (47.96) 55 (18.71)
11 227 1.15±0.15 0.71–1.58 0 121 (53.30) 35 (15.42)
12 255 1.12±0.16 0.60–1.59 0 105 (41.17) 28 (10.98)

MHD, maintenance hemodialysis.

Data Analysis
We used Excel to complete data input and collection. Stata sta-
tistical software (version 12.0) was used to perform data analysis.
The levels of serum total magnesium in patients undergoing MHD
were calculated monthly. The prevalence of hypomagnesemia, hy-
permagnesemia, and severe hypermagnesemia was calculated
monthly. We also calculated the ratio of the optimal level of serum
total magnesium. The multiple linear regression model was used
for test factors associated with the level of serum total magnesium.
The model was adjusted for age, gender, diabetes, plasma albumin,
blood urea, the level of serum potassium, hemoglobin, total calci-
um, phosphorus, and parathyroid hormone [5–7]. Because hemo-
dialysis twice a week was not a conventional hemodialysis therapy,
the therapy may lead to a different magnesium balance. In the re-
gression models, the cases receiving hemodialysis twice a week
were excluded. Before data analysis, we made a logarithmic trans-
formation and deal the variables with skew distribution.
In the patients initiating hemodialysis between January 1, 2019,
and October 31, 2019, the baseline magnesium measurements and
serum total magnesium measurements in three consecutive
months after initiating dialysis were collected. The paired t test was
used for comparing predialysis and postdialysis serum total mag-
nesium.
Results
Basic Information about the Patients Undergoing
Hemodialysis
A total of 464 ESRD patients had received hemodialy-
sis in our hospital. Age ranged from 12 to 99 years with a
mean of 53 years. The ratio of male/female was 277/187.
The average of body mass index was 21.29 ± 3.60 kg/m2.
On January 1, 2019, a total of 356 ESRD patients were
receiving hemodialysis in our hospital. On December 31,
2019, the number had increased to 383. The total number
of ESRD patients receiving hemodialysis in our hospital
is listed in Appendix 1 by month. On December 31, 2019,
a total of 371 patients were undergoing MHD (dialysis
>90 days) treatment in our hospital. In the following data,
the data of two patients <18 years were excluded. Age
ranged from 21 to 89 years with a mean of 51 years. The
ratio of male/female was 211/158. The most common pri-
mary disease was glomerulonephritis (36.86%), followed
by diabetic nephropathy (26.02%). Other primary diseas-
es include hypertensive nephropathy, polycystic kidney
disease, lupus nephritis, purpura nephritis, ANCA-asso-
ciated vasculitis, and obstructive nephropathy.
Other Clinical Information and Therapies
The median of residual urine volume in December
2019 was 0 mL/24 h (25%: 0, 75%: 250 mL/24 h). The per-
centage of vascular access of adult patients receiving
MHD in our hospital was as follows: autogenous arterio-
venous fistula (92.95%), graft arteriovenous fistula
(3.25%), and cuffed hemodialysis catheter (3.79%). About
96% patients received hemodialysis or hemodiafiltration
three times a week. Other patients received treatment
twice a week. The target value of on-line monitoring Kt/V
was 1.2–1.4. Physicians and nurses adjusted treatment in
time to ensure treatment compliance. Bicarbonate dialy-
sate (from Kangcheng Healthcare, Guangzhou, China;
Mg2+ 0.50 mmol/L, Ca2+ 1.50 mmol/L) was used in our
hospital.
Major pharmacology therapies of 462 HD patients >18
years are listed in Appendix 2. Among 239 patients having
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Magnesium in Hemodialysis Blood Purif 3

DOI: 10.1159/000509788
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used PPIs, 134 patients were prescribed 1–4 times (3–14 Table 2. The level of serum total magnesium in patients initiating
days for one prescription). Thirty-four patients had re- hemodialysis
ceived magnesium-containing preparations; however, 50%
N Mean ± SD, Magnesium range,
of the patients took them for a short time (only 1 prescrip- mmol/L mmol/L
tion). In 2019, 256 patients received chest CT or chest X-ray
examination. Thirty-two patients had aortosclerosis or cor- Initiation 72 0.88±0.19 0.53–1.24
onary arteriosclerosis. Among 184 patients who received 1st month 48 1.03±0.13 0.77–1.29
echocardiography, calcification of the aorta or mitral valve 2nd month 49 1.08±0.12 0.85–1.43
3rd month 46 1.10±0.15 0.52–1.34
was observed in 60 patients. In December 2019, 242 of 369
MHD patients received serum albumin tests. Among these
242 cases, 100 cases (41.32%) had a serum albumin level of
>40 g/L, and 22 cases had hypoalbuminemia (9.09%).
Table 3. Predialysis and postdialysis serum total magnesium in
patients with severe hypermagnesemia
The Level of Serum Total Magnesium in MHD
Patients (Table 1) Predialysis Postdialysis p value
In every month, 57–77% cases undergoing MHD re- serum total serum total
ceived measurements of predialysis serum total magne- magnesium, magnesium,
sium. The means of serum total magnesium were 1.12– mmol/L mmol/L
1.20 mmol/L, which were higher than the normal level. In February (N = 33) 1.40±0.09 1.07±0.13 <0.001
the monthly evaluation, 41.17–53.3% of MHD patients May (N = 51) 1.41±0.12 1.11±0.10 <0.001
receiving measurement had the optimal level of serum August (N = 21) 1.41±0.14 1.06±0.14 <0.001
magnesium. However, 9.6–24.89% of MHD patients had November (N = 18) 1.40±0.07 1.12±0.08 <0.001
severe hypermagnesemia. In contrast, hypomagnesemia
was very rare. Only 4 patients suffered from hypomagne-
semia during the study period. The factors associated
with serum total magnesium in multivariate regression hypomagnesemia. One patient had metastatic bladder
analyses are listed in Appendix 3. cancer with recurrent bleeding and poor appetite. An-
other patient was converted from peritoneal dialysis to
The Level of Serum Total Magnesium in Patients hemodialysis. Recurrent abdominal pain led to poor ap-
Initiating Hemodialysis (Table 2) petite. The other two patients were complicated with hep-
From January 1 to October 31, 2019, 98 patients initiated atitis B. One had taken adefovir and tacrolimus for long
hemodialysis therapy in our hospital. Patients who had re- term before initiating hemodialysis. One patient had cir-
ceived hemodialysis in other medical institutions or perito- rhosis. No patients were taking PPIs or diuretics.
neal dialysis were excluded. Data of 72 patients initiating Hypermagnesemia was common in MHD patients.
hemodialysis were included in the present study. The mean Even severe hypermagnesemia was not seldom. Overall,
age was 55.60 ± 14.4 years, with 43 male and 29 female pa- 94 patients experienced severe hypermagnesemia any-
tients. The levels of serum total magnesium in baseline, the time in 2019. During follow-up, 28 patients and 66 pa-
first month, the second month, and the third month are tients had recurrence of severe hypermagnesemia and
listed in Table 2. Compared with the baseline level of serum persistence of severe hypermagnesemia, respectively.
magnesium, the level of serum magnesium increased sig- Among these patients, seven patients had taken medi-
nificantly after receiving hemodialysis (p < 0.05). Before ini- cines containing magnesium. The results of statistical
tiating hemodialysis, the mean value of plasma albumin was analysis indicated significant remission of severe hyper-
29.3 g/L, and the mean value of plasma albumin in the first magnesemia after hemodialysis treatment (Table 3).
month, the second month, and the third month was 32.4 Reviewing medical records, we did not find severe
g/L, 38.8 g/L, and 34.3 g/L, respectively. clinical manifestations associated with magnesium me-
tabolism disorders, including severe arrhythmia, convul-
Hypomagnesemia and Hypermagnesemia in MHD sion, epilepsy, or delirium [1–4]. However, nausea, vom-
Patients iting, anorexia, and asthenia are common symptoms of
In MHD patients, hypomagnesemia was very rare. In uremia [8], and it was difficult to define whether they
the present study, only four patients were diagnosed as were caused by magnesium metabolism disorders.
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4 Blood Purif Yang/Wang/Chen/Chen/Chen

DOI: 10.1159/000509788
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 Discussion
In the present study, we follow up the level of serum
total magnesium in hemodialysis patients for one year.
We find that serum total magnesium levels are in the nor-
mal range before initiating hemodialysis. With the under-
going of hemodialysis, the level of serum total magne-
sium increases. In patients on MHD, hypermagnesemia
is very common. In the monthly evaluation, 41.17–53.3%
of MHD patients have optimal level of serum magnesium
(1.1–1.3 mmol/L). Even 9.6–24.89% of MHD patients
had severe hypermagnesemia (>1.3 mmol/L). Hypomag-
nesemia is rare when 0.5 mmol/L magnesium dialysate is
used. Hypomagnesemia in patients on MHD is an indica-
tor of poor condition. In the present study, we did not
find PPI-associated hypomagnesemia.
Magnesium homeostasis depends on intestinal up-
take, renal excretion, and storage in bones and skeletal
muscles [13]. The majority of magnesium is absorbed in
the small intestine by a passive paracellular mechanism
[2, 3]. A minority of magnesium is transported via the
transcellular transporters transient receptor potential
channel melastatin member (TRPM) 6 and TRPM7 [2, 3].
The kidneys regulate the reabsorption and excretion of
magnesium cation within a sizeable range [2, 3]. In 24 h,
approximately 2,400 mg of magnesium is filtered by the
glomeruli [2, 3]. About 95% of filtered magnesium is re-
absorbed in the proximal tubule, the thick ascending limb
of the loop of Henle, and the distal convoluted tubule [2].
Only 3–5% of filtered magnesium excreted in the urine
[2, 3]. Hormones, including parathyroid hormone, play a
minor role in magnesium homeostasis [2, 3].
A variety of causes lead to magnesium deficiency and
hypomagnesemia [14]. In a retrospective study [15],
overall frequency of hypomagnesemia was 20.1%. Hypo-
magnesemia can be a useful tool in predicting morbidity
and mortality [15], while hypomagnesemia is not com-
mon in patients undergoing dialysis [16, 17]. With the
progression of renal failure, residual renal function is in-
adequate to maintain magnesium homeostasis and hy-
permagnesemia may occur [2, 13, 16]. In patients under-
going dialysis, dialysate magnesium concentration is also
a major determinant of magnesium balance [16]. The
previous study based on a group of Chinese peritoneal
dialysis patients indicates that hypomagnesemia is rare
while using Mg2+ 0.56 mmol/L dialysate [18]. In the past
several years, several large-scale studies have been per-
formed focusing on the level of magnesium in dialysis
patients [5–7]. In Sakaguchi et al.’s study [5], of 142,555
hemodialysis patients for whom baseline serum magne-
Magnesium in Hemodialysis
sium level data were available, only 20.18% (28,764) pa-
tients had a relatively low serum magnesium level (<2.3
mg/dL). 19,071 (13.3%) patients had a higher level of se-
rum magnesium (>3.1 mg/dL) [5]. In the present study,
the results also indicated that the patients with MHD had
a relatively high level of serum magnesium. The mean of
serum magnesium was 1.12–1.20 mmol/L. In the month-
ly evaluation, 9.6–24.89% of MHD patients had severe
hypermagnesemia (>1.3 mmol/L). The result is consis-
tent with the conclusion of previous studies that dialysis
patients often have higher serum magnesium levels than
the general population [16, 17]. In the other two large
studies performed in the United States, the baseline mag-
nesium levels in patients initiating dialysis were available
[6, 7]. Of 9,359 patients on hemodialysis and 10,692 pa-
tients receiving peritoneal dialysis, the mean serum mag-
nesium level of the cohort was 2.1 mg/dL (median 2.1 mg/
dL [IQR, 1.8–2.3 mg/dL]) and 2.1 mg/dL (median 2.1 mg/
dL [IQR, 1.9–2.3-mg/dL]), respectively [6, 7]. In the pres-
ent study, the level of serum magnesium of 72 patients
initiating hemodialysis during the study period was ana-
lyzed. Before hemodialysis was initiated, the mean of se-
rum magnesium level was 0.88 ± 0.19 mmol/L. We do not
find that ESRD patients who have not received dialysis
have a higher level of magnesium. In the latest report [19],
serum magnesium, mortality, and disease progression in
10,568 patients with estimated glomerular filtration rate
between 15 and 59 mL/min/1.73 m2 were investigated. In
9,049 patients, serum magnesium ranged from 1.7 to 2.6
mg/dL [19]. Only 205 patients had a higher level of mag-
nesium (>2.6 mg/dL) [19]. The results of the latest report
[19] and the present study indicate that chronic kidney
disease may not attribute to hypermagnesemia.
However, in the present study, with undergoing he-
modialysis, the level of magnesium increased, and the dif-
ference was statistically significant. How to explain an in-
crease of serum magnesium after undergoing hemodialy-
sis? Serum magnesium will be eliminated by hemodialysis,
only when 0.5 mmol/L or lower magnesium dialysate is
used [16]. Other factors may play an important role in
determining serum magnesium levels in dialysis patients
[16]. It is estimated that daily requirement for magne-
sium in adults is about 200–400 mg [20, 21]. Patients with
ESRD were found to have a severe depression of intestinal
magnesium absorption, presumably due to deficiency of
1,25-dihydroxycholecalciferol [22]. Active vitamin D can
increase intestinal magnesium absorption [22, 23]. After
initiating hemodialysis, the patient’s condition can be im-
proved. We speculate that the intake of magnesium and
intestinal magnesium absorption increase due to condi-
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Blood Purif 5
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tion improvement and vitamin D supplementation. This
may be a potential explanation. In the present study, plas-
ma albumin levels increased after initiating hemodialysis.
The result supports our explanation.
Another increasing concern is the concentration of
magnesium cation in dialysate [2, 23, 24]. During hemo-
dialysis therapy, rapid magnesium equilibration between
dialysate and serum is achieved [2, 23]. The concentra-
tion of magnesium cation in dialysate is a major determi-
nant of serum magnesium levels for patients on hemodi-
alysis [16, 23]. Different concentrations for magnesium
cation (0.375, 0.5, or 0.75 mmol/L) are available in clinical
practice [1, 2, 23, 24]. It is found that lower serum mag-
nesium levels are associated with a higher mortality in
hemodialysis patients, including those with hypoalbu-
minemia [6]. Maintaining a higher level of serum magne-
sium may be beneficial to dialysis patients [5, 6]. In a sin-
gle-center, randomized, double-blinded, controlled clini-
cal trial [24], a total of 59 hemodialysis patients were
randomized to two groups: standard dialysate magne-
sium group (0.5 mmol/L) and increased dialysate magne-
sium group (1.0 mmol/L). After 28-day therapy, increas-
ing dialysate magnesium decreased calcification propen-
sity in subjects undergoing MHD [24]. Increasing
dialysate magnesium is a simple and effective method to
improve hypomagnesemia in hemodialysis patients [23].
Whether further raising dialysate magnesium concentra-
tion is benefit for hemodialysis patients needs to be fur-
ther demonstrated. Approximately 25% and 8% of serum
total magnesium are bound to albumin and globulin, re-
spectively [25]. Only non-protein-bound serum magne-
sium is ultrafilterable in hemodialysis [2]. However, an
obvious drawback in the previous studies is that only se-
rum total magnesium is measured [5–7].
Although the association of hypomagnesemia and
mortality has been demonstrated in patients on dialysis
[5–7], causality cannot be determined in these observa-
tional studies. The previous study indicates that the as-
sociation between mortality and the level of serum mag-
nesium is attenuated after adjusted for albumin [6]. The
decreased level of serum magnesium may indicate mal-
nutrition [6]. However, we did not find the association
of the level of magnesium and albumin. In our study, the
prevalence of hypoalbuminemia is not high. A small
sample size and the low incidence of malnutrition may
affect the results. In the present study, only four patients
had hypomagnesemia. Metastatic malignant tumor, cir-
rhosis, and poor appetite are the causes of hypomagne-
semia. Hypomagnesemia is an indicator of poor condi-
tion.
6 Blood Purif
DOI: 10.1159/000509788
A higher level of magnesium may improve the prog-
nosis of patients on hemodialysis [5–7]. However, a Japa-
nese study also found the U-shape association between
the serum magnesium level and mortality [5]. Both the
Japanese study [5] and the present study find that severe
hypermagnesemia is not seldom in patients on hemodi-
alysis. In the present study, using 0.50 mmol/L magne-
sium dialysate can decrease postdialysis serum magne-
sium in patients with severe hypermagnesemia, while se-
vere hypermagnesemia persists or recurs in these patients.
Whether lower magnesium concentration dialysate
should be provided for the patients with severe hyperma-
gnesemia is unknown. Floege [23] proposed “Magnesium
Concentration in Dialysate: Is Higher Better?”. Our study
cannot answer this question. On account of the high prev-
alence of hypermagnesemia in hemodialysis patients, the
higher concentration of magnesium dialysate should be
cautious.
A variety of medicines can affect magnesium balance
[9–12]. Magnesium-containing preparations may lead to
an increase in serum magnesium levels. In the present
study, only seven patients with severe hypermagnesemia
intermittently took magnesium-containing preparations.
Taking magnesium-containing preparations is unlikely
the major cause of severe hypermagnesemia. Previous
studies have reported hypomagnesemia induced by PPIs
in the general population and dialysis patients [10]. How-
ever, in the present study, we did not report hypomagne-
semia induced by PPIs. In the latest survey, PPI prescrip-
tion for hemodialysis patients in Japan was investigated
by a questionnaire survey [26]. PPI prescription is often
long-term use in hemodialysis patients [26]. After eight
weeks treatment for peptic ulcer or gastroesophageal re-
flux disease, 112 (60%) physicians prefer to continuously
prescribe PPIs [26]. In Alhosaini et al.’s study [27], use of
PPIs is associated with hypomagnesemia. In this previous
study, 22 patients took omeprazole (20–80 mg/day), and
7 patients were treated with pantoprazole (40–80 mg/
day) [27]. Duration of PPI use ranged from one to nine
years [27]. In the present study, although PPI use was
common, only 16 patients were prescribed >20 times (3–
14 days for one prescription) in 2019. In our dialysis cen-
ter, we prescribe oral omeprazole (20–40 mg/day), esome-
prazole (20–40 mg/day), pantoprazole (20–40 mg/day),
or abeprazole (10–20 mg/day). Relatively short-term and
low-dose use of PPIs may explain that we did not find
PPI-associated hypomagnesemia. One case with hypo-
magnesemia may be related to tacrolimus.
The advantages and limitations of the present study are
discussed here. Our data were followed up for one year. In
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every month, 57–77% cases with MHD received measure-
ments of serum magnesium levels. Compared with previ-
ous studies, the present study provides real-time update
on the levels of serum magnesium in patients on hemodi-
alysis. As we know, no similar research has been reported.
The present study also included MHD patients and pa-
tients initiating hemodialysis. Serum total magnesium but
not ionized magnesium is measured in the present study.
It is a definite limitation of the present study and previous
studies [2, 5–7]. Some factors affecting magnesium are not
included in the present study. A single-center study can-
not represent general patients. Scientific value of retro-
spective observational studies is limited.
Statement of Ethics
The Declaration of Helsinki of the World Medical Association
was strictly followed in the present study. The present study was
approved by the ethics committee of Zhangzhou Affiliated Hospi-
tal of Fujian Medical University (ethics paper number:
2020LWB019). The ethics committee of the hospital waived the
need for written informed consent from the patients in this retro-
spective study. All personal information of the patients was confi-
dential.
Conflict of Interest Statement
The authors declare that they have no conflicts of interest.

Conclusion Funding Source

We find that serum total magnesium levels are in the
normal range before initiating dialysis. However, in pa-
tients on MHD, hypermagnesemia is very common when
0.5 mmol/L magnesium dialysate is used. Hypomagnese-
mia is rare. Hypomagnesemia in patients on MHD may
be an indicator of poor condition. In the present study,
we do not report PPI-associated hypomagnesemia.
The authors did not receive any funding.
Author Contributions
W.Y., E.W., W.C., C.C. collected the data. W.Y. drafted the ini-
tial manuscript. S.C. designed the study and reviewed and edited
the manuscript. All authors approved the final manuscript.

Appendix 1 Appendix 2

The Total Number of Hemodialysis Patients in 2019 by Month Major Pharmacology Therapy of Hemodialysis Patients

N N

1 Jan 2019 356 Antihypertensive drugs

31 Jan 2019 359 Calcium antagonist 358
28 Feb 2019 366 ACEI/ARB 31/129
31 Mar 2019 372 β-Blocker 195
30 Apr 2019 374 Clonidine 236
31 May 2019 370 α-Receptor blocker 151
30 Jun 2019 372 Calcitriol 157
31 Jul 2019 367 Calcium carbonate 174
31 Aug 2019 366 Sevelamer 145
30 Sep 2019 373 Proton pump inhibitors 239
31 Oct 2019 379 Magnesium-containing preparations 34
30 Nov 2019 378
31 Dec 2019 383 ACEI, angiotensin-converting enzyme inhibitor; ARB, angio-
tensin receptor blocker.
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Magnesium in Hemodialysis Blood Purif 7

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 Appendix 3

The Factors Associated with Serum Total Magnesium in

Multivariate Regression Analyses

Adjusted model coefficient p value

February data
Age −0.0007 (−0.003, 0.002) 0.51
Gender 0.02 (−0.04, 0.07) 0.55
Diabetes 0.007 (−0.06, 0.07) 0.84
Hemoglobin 0.0009 (−0.0009, 0.003) 0.34
Predialysis blood urea 0.0001 (−0.005, 0.005) 0.98
Predialysis serum total calcium 0.16 (0.03, 0.29) 0.02
Predialysis serum phosphorus 0.04 (−0.02, 0.10) 0.21
Predialysis serum potassium 0.02 (−0.02, 0.05) 0.31
Parathyroid hormone (log) 0.005 (−0.03, 0.03) 0.76
Plasma albumin 0.007 (−0.003, 0.02) 0.18
May data
Age −0.001 (−0.004, 0.001) 0.35
Gender 0.02 (−0.004, 0.08) 0.55
Diabetes −0.006 (−0.07, 0.06) 0.98
Hemoglobin 0.002 (−0.0004, 0.005) 0.09
Predialysis blood urea 0.005 (0.000, 0.01) 0.05
Predialysis serum total calcium 0.22 (0.06, 0.37) 0.007
Predialysis serum phosphorus 0.02 (−0.04, 0.08) 0.53
Predialysis serum potassium 0.05 (0.008, 0.08) 0.02
Parathyroid hormone (log) 0.005 (−0.03, 0.04) 0.78
Plasma albumin 0.009(−0.002, 0.02) 0.10
August data
Age −0.000 (−0.002, 0.002) 0.93
Gender 0.02 (−0.03, 0.07) 0.39
Diabetes −0.04 (−0.09, 0.02) 0.18
Hemoglobin 0.002 (0.0005, 0.004) 0.01
Predialysis blood urea 0.002 (−0.002, 0.006) 0.24
Predialysis serum total calcium 0.17(0.04, 0.30) 0.009
Predialysis serum phosphorus 0.04 (−0.01, 0.08) 0.14
Predialysis serum potassium 0.05 (0.002, 0.08) 0.001
Parathyroid hormone (log) 0.01 (−0.01, 0.04) 0.30
Plasma albumin 0.007 (−0.002, 0.03) 0.15
November data
Age −0.0001 (−0.002, 0.002) 0.91
Gender −0.02 (−0.03, 0.07) 0.49
Diabetes −0.03 (−0.08, 0.02) 0.25
Hemoglobin 0.002 (0.0004, 0.004) 0.02
Predialysis blood urea 0.003 (−0.001, 0.006) 0.18
Predialysis serum total calcium 0.16 (0.03, 0.29) 0.02
Predialysis serum phosphorus 0.03 (−0.01, 0.08) 0.13
Predialysis serum potassium 0.05 (−0.01, 0.08) <0.001
Parathyroid hormone (log) 0.008 (−0.02, 0.03) 0.52
Plasma albumin 0.005 (−0.004, 0.01) 0.26

Model: Adjusted for age, gender, diabetes, hemoglobin, predialysis blood urea, predi-
alysis  serum total calcium, predialysis  serum phosphorus, predialysis serum potassium,
parathyroid hormone (log) and plasma albumin.
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8 Blood Purif Yang/Wang/Chen/Chen/Chen

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