Introduction: The association between magnesium level and progression to acute kidney disease (AKD) in acute kidney injury (AKI) patients was not well studied. With AKI transition to AKD, the burden of the disease on mortality, morbidity, and healthcare costs increases. Serum magnesium disturbances are linked with a decline in renal function and increased risk of death in CKD and hemodialysis patients. This study aims to assess the significance of magnesium derangements as a risk factor for the progression of AKI to AKD in critically ill patients. Methods: This study was conducted among patients with AKI admitted to the intensive care units at Mayo Clinic from 2007 to 2017. Serum magnesium at AKI onset was categorized into five groups of <1.7, 1.7–1.9, 1.9–2.1, 2.1–2.3, and ≥2.3 mg/dL, with 1.9–2.1 mg/dL as the reference group. AKD was defined as AKI that persisted >7 days following the AKI onset. Logistic regression was used to evaluate the association between magnesium and AKD. Results: Among 20,198 critically ill patients with AKI, the mean age was 66 ± 16 years, and 57% were male. The mean serum magnesium at AKI onset was 1.9 ± 0.4 mg/dL. The overall incidence of AKD was 31.4%. The association between serum magnesium and AKD followed a U-shaped pattern. In multivariable analysis, serum magnesium levels were associated with increased risk of AKD with the odds ratio of 1.17 (95% CI: 1.07–1.29), 1.13 (95% CI: 1.01–1.26), and 1.65 (95% CI: 1.48–1.84) when magnesium levels were <1.7, 2.1–2.3, and ≥2.3 mg/dL, respectively. Conclusion: Among patients with AKI, magnesium level derangement was an independent risk for AKD in critically ill AKI patients. Monitoring serum magnesium and proper correction in critically ill patients with AKI should be considered an AKD preventive intervention in future trials.

1.
Kellum
JA
,
Sileanu
FE
,
Bihorac
A
,
Hoste
EA
,
Chawla
LS
.
Recovery after acute kidney injury
.
Am J Respir Crit Care Med
.
2017
;
195
(
6
):
784
91
.
2.
James
MT
,
Bhatt
M
,
Pannu
N
,
Tonelli
M
.
Long-term outcomes of acute kidney injury and strategies for improved care
.
Nat Rev Nephrol
.
2020
;
16
(
4
):
193
205
.
3.
James
MT
,
Levey
AS
,
Tonelli
M
,
Tan
Z
,
Barry
R
,
Pannu
N
, et al
.
Incidence and prognosis of acute kidney diseases and disorders using an integrated approach to laboratory measurements in a universal health care system
.
JAMA Netw Open
.
2019
;
2
(
4
):
e191795
.
4.
See
EJ
,
Polkinghorne
KR
,
Toussaint
ND
,
Bailey
M
,
Johnson
DW
,
Bellomo
R
.
Epidemiology and outcomes of acute kidney diseases: a comparative analysis
.
Am J Nephrol
.
2021
;
52
(
4
):
342
50
.
5.
Su
CC
,
Chen
JY
,
Chen
SY
,
Shiao
CC
,
Neyra
JA
,
Matsuura
R
, et al
.
Outcomes associated with acute kidney disease: a systematic review and meta-analysis
.
EClinicalMedicine
.
2023
;
55
:
101760
.
6.
Xu
L
,
Li
C
,
Li
N
,
Zhao
L
,
Zhu
Z
,
Zhang
X
, et al
.
Incidence and prognosis of acute kidney injury versus acute kidney disease among 71,041 inpatients
.
Clin Kidney J
.
2023
;
16
(
11
):
1993
2002
.
7.
Lertussavavivat
T
,
Kulvichit
W
,
Peerapornratana
S
,
Lumlertgul
N
,
Bhumitrakul
J
,
Tungsanga
K
, et al
.
The epidemiology and long-term outcomes of acute kidney disease in a resource-limited setting
.
J Nephrol
.
2022
;
35
(
9
):
2283
92
.
8.
Pickkers
P
,
Darmon
M
,
Hoste
E
,
Joannidis
M
,
Legrand
M
,
Ostermann
M
, et al
.
Acute kidney injury in the critically ill: an updated review on pathophysiology and management
.
Intensive Care Med
.
2021
;
47
(
8
):
835
50
.
9.
Swaminathan
R
.
Magnesium metabolism and its disorders
.
Clin Biochem Rev
.
2003
;
24
(
2
):
47
66
.
10.
Saris
N-EL
,
Mervaala
E
,
Karppanen
H
,
Khawaja
JA
,
Lewenstam
A
.
Magnesium: an update on physiological, clinical and analytical aspects
.
Clin Chim Acta
.
2000
;
294
(
1–2
):
1
26
.
11.
Jahnen-Dechent
W
,
Ketteler
M
.
Magnesium basics
.
Clin Kidney J
.
2012
;
5
(
Suppl 1
):
i3
i14
.
12.
Leenders
NHJ
,
Vervloet
MG
.
Magnesium: a magic bullet for cardiovascular disease in chronic kidney disease
.
Nutrients
.
2019
;
11
(
2
):
455
.
13.
Azem
R
,
Daou
R
,
Bassil
E
,
Anvari
EM
,
Taliercio
JJ
,
Arrigain
S
, et al
.
Serum magnesium, mortality and disease progression in chronic kidney disease
.
BMC Nephrol
.
2020
;
21
(
1
):
49
.
14.
Sakaguchi
Y
,
Shoji
T
,
Hayashi
T
,
Suzuki
A
,
Shimizu
M
,
Mitsumoto
K
, et al
.
Hypomagnesemia in type 2 diabetic nephropathy: a novel predictor of end-stage renal disease
.
Diabetes Care
.
2012
;
35
(
7
):
1591
7
.
15.
Maier
JAM
,
Malpuech-Brugère
C
,
Zimowska
W
,
Rayssiguier
Y
,
Mazur
A
.
Low magnesium promotes endothelial cell dysfunction: implications for atherosclerosis, inflammation and thrombosis
.
Biochim Biophys Acta
.
2004
;
1689
(
1
):
13
21
.
16.
Kanbay
M
,
Goldsmith
D
,
Uyar
ME
,
Turgut
F
,
Covic
A
.
Magnesium in chronic kidney disease: challenges and opportunities
.
Blood Purif
.
2010
;
29
(
3
):
280
92
.
17.
Markaki
A
,
Kyriazis
J
,
Stylianou
K
,
Fragkiadakis
GA
,
Perakis
K
,
Margioris
AN
, et al
.
The role of serum magnesium and calcium on the association between adiponectin levels and all-cause mortality in end-stage renal disease patients
.
PLoS One
.
2012
;
7
(
12
):
e52350
.
18.
Van Laecke
S
,
Van Biesen
W
,
Vanholder
R
.
Hypomagnesaemia, the kidney and the vessels
.
Nephrol Dial Transplant
.
2012
;
27
(
11
):
4003
10
.
19.
Cheungpasitporn
W
,
Thongprayoon
C
,
Qian
Q
.
Dysmagnesemia in hospitalized patients: prevalence and prognostic importance
.
Mayo Clin Proc
.
2015
;
90
(
8
):
1001
10
.
20.
Joosten
MM
,
Gansevoort
RT
,
Bakker
SJ
;
PREVEND Study Group
.
Low plasma magnesium and risk of developing chronic kidney disease: results from the PREVEND Study
.
Kidney Int
.
2015
;
87
(
6
):
1262
3
.
21.
Van Laecke
S
,
Nagler
EV
,
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
(
9
):
825
31
.
22.
Massy
ZA
,
Drüeke
TB
.
Magnesium and cardiovascular complications of chronic kidney disease
.
Nat Rev Nephrol
.
2015
;
11
(
7
):
432
42
.
23.
Tin
A
,
Grams
ME
,
Maruthur
NM
,
Astor
BC
,
Couper
D
,
Mosley
TH
, et al
.
Results from the Atherosclerosis Risk in Communities study suggest that low serum magnesium is associated with incident kidney disease
.
Kidney Int
.
2015
;
87
(
4
):
820
7
.
24.
Molnar
AO
,
Biyani
M
,
Hammond
I
,
Harmon
JP
,
Lavoie
S
,
McCormick
B
, et al
.
Lower serum magnesium is associated with vascular calcification in peritoneal dialysis patients: a cross sectional study
.
BMC Nephrol
.
2017
;
18
(
1
):
129
.
25.
Ferrè
S
,
Li
X
,
Adams-Huet
B
,
Maalouf
NM
,
Sakhaee
K
,
Toto
RD
, et al
.
Association of serum magnesium with all-cause mortality in patients with and without chronic kidney disease in the Dallas Heart Study
.
Nephrol Dial Transplant
.
2018
;
33
(
8
):
1389
96
.
26.
Thongprayoon
C
,
Hansrivijit
P
,
Petnak
T
,
Mao
MA
,
Bathini
T
,
Duriseti
P
, et al
.
Impact of serum magnesium levels at hospital discharge and one-year mortality
.
Postgrad Med
.
2022
;
134
(
1
):
47
51
.
27.
Thongprayoon
C
,
Cheungpasitporn
W
,
Hansrivijit
P
,
Thirunavukkarasu
S
,
Chewcharat
A
,
Medaura
J
, et al
.
Association of serum magnesium level change with in-hospital mortality
.
BMJ Evid Based Med
.
2020
;
25
(
6
):
206
12
.
28.
Wu
H
,
Li
Q
,
Fan
L
,
Zeng
D
,
Chi
X
,
Guan
B
, et al
.
Prognostic value of serum magnesium in mortality risk among patients on hemodialysis: a meta-analysis of observational studies
.
Kidney Dis
.
2021
;
7
(
1
):
24
33
.
29.
Cheungpasitporn
W
,
Thongprayoon
C
,
Bathini
T
,
Hansrivijit
P
,
Vaitla
P
,
Medaura
J
, et al
.
Impact of admission serum magnesium levels on long-term mortality in hospitalized patients
.
Hosp Pract
.
2020
;
48
(
2
):
80
5
.
30.
Cheungpasitporn
W
,
Thongprayoon
C
,
Chewcharat
A
,
Petnak
T
,
Mao
MA
,
Davis
PW
, et al
.
Hospital-acquired dysmagnesemia and in-hospital mortality
.
Med Sci
.
2020
;
8
(
3
):
37
.
31.
Negrea
L
,
DeLozier
SJ
,
Janes
JL
,
Rahman
M
,
Dobre
M
.
Serum magnesium and cardiovascular outcomes and mortality in CKD: the chronic renal insufficiency cohort (CRIC)
.
Kidney Med
.
2021
;
3
(
2
):
183
92.e1
.
32.
Stevens
JS
,
Moses
AA
,
Nickolas
TL
,
Husain
SA
,
Mohan
S
.
Increased mortality associated with hypermagnesemia in severe COVID-19 illness
.
Kidney360
.
2021
;
2
(
7
):
1087
94
.
33.
Khwaja
A
.
KDIGO clinical practice guidelines for acute kidney injury
.
Nephron Clin Pract
.
2012
;
120
(
4
):
c179
c184
.
34.
Thongprayoon
C
,
Cheungpasitporn
W
,
Harrison
AM
,
Kittanamongkolchai
W
,
Ungprasert
P
,
Srivali
N
, et al
.
The comparison of the commonly used surrogates for baseline renal function in acute kidney injury diagnosis and staging
.
BMC Nephrol
.
2016
;
17
:
6
.
35.
Pickering
JW
,
Endre
ZH
.
Back-calculating baseline creatinine with MDRD misclassifies acute kidney injury in the intensive care unit
.
Clin J Am Soc Nephrol
.
2010
;
5
(
7
):
1165
73
.
36.
Chawla
LS
,
Bellomo
R
,
Bihorac
A
,
Goldstein
SL
,
Siew
ED
,
Bagshaw
SM
, et al
.
Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup
.
Nat Rev Nephrol
.
2017
;
13
(
4
):
241
57
.
37.
Santos
MS
,
Seguro
AC
,
Andrade
L
.
Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury
.
Braz J Med Biol Res
.
2010
;
43
(
3
):
316
23
.
38.
Alves
SC
,
Tomasi
CD
,
Constantino
L
,
Giombelli
V
,
Candal
R
,
Bristot
MDL
, et al
.
Hypomagnesemia as a risk factor for the non-recovery of the renal function in critically ill patients with acute kidney injury
.
Nephrol Dial Transplant
.
2013
;
28
(
4
):
910
6
.
39.
Bellomo
R
,
Ronco
C
,
Kellum
JA
,
Mehta
RL
,
Palevsky
P
;
Acute Dialysis Quality Initiative workgroup
.
Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group
.
Crit Care
.
2004
;
8
(
4
):
R204
12
.
40.
Altura
BM
,
Altura
BT
,
Carella
A
,
Gebrewold
A
,
Murakawa
T
,
Nishio
A
.
Mg2+-Ca2+ interaction in contractility of vascular smooth muscle: Mg2+ versus organic calcium channel blockers on myogenic tone and agonist-induced responsiveness of blood vessels
.
Can J Physiol Pharmacol
.
1987
;
65
(
4
):
729
45
.
41.
Dibaba
DT
,
Xun
P
,
Song
Y
,
Rosanoff
A
,
Shechter
M
,
He
K
.
The effect of magnesium supplementation on blood pressure in individuals with insulin resistance, prediabetes, or noncommunicable chronic diseases: a meta-analysis of randomized controlled trials
.
Am J Clin Nutr
.
2017
;
106
(
3
):
921
9
.
42.
Kawano
Y
,
Matsuoka
H
,
Takishita
S
,
Omae
T
.
Effects of magnesium supplementation in hypertensive patients: assessment by office, home, and ambulatory blood pressures
.
Hypertension
.
1998
;
32
(
2
):
260
5
.
43.
Correa
S
,
Guerra-Torres
XE
,
Waikar
SS
,
Mc Causland
FR
.
Serum magnesium, blood pressure, and risk of hypertension and chronic kidney disease progression in the CRIC study
.
Hypertension
.
2021
;
78
(
6
):
1771
80
.
44.
ter Braake
AD
,
Shanahan
CM
,
de Baaij
JH
.
Magnesium counteracts vascular calcification
.
Arterioscler Thromb Vasc Biol
.
2017
;
37
(
8
):
1431
45
.
45.
Ter Braake
AD
,
Tinnemans
PT
,
Shanahan
CM
,
Hoenderop
JGJ
,
de Baaij
JHF
.
Magnesium prevents vascular calcification in vitro by inhibition of hydroxyapatite crystal formation
.
Sci Rep
.
2018
;
8
(
1
):
2069
.
46.
Sakaguchi
Y
,
Hamano
T
,
Isaka
Y
.
Magnesium and progression of chronic kidney disease: benefits beyond cardiovascular protection
.
Adv Chronic Kidney Dis
.
2018
;
25
(
3
):
274
80
.
47.
Termine
JD
,
Posner
AS
.
Calcium phosphate formation in vitro. I. Factors affecting initial phase separation
.
Arch Biochem Biophys
.
1970
;
140
(
2
):
307
17
.
48.
Rodríguez-Ortiz
ME
,
Gómez-Delgado
F
,
Arenas de Larriva
AP
,
Canalejo
A
,
Gómez-Luna
P
,
Herencia
C
, et al
.
Serum Magnesium is associated with Carotid Atherosclerosis in patients with high cardiovascular risk (CORDIOPREV Study)
.
Sci Rep
.
2019
;
9
(
1
):
8013
.
49.
Sakaguchi
Y
,
Hamano
T
,
Nakano
C
,
Obi
Y
,
Matsui
I
,
Kusunoki
Y
, et al
.
Association between density of coronary artery calcification and serum magnesium levels among patients with chronic kidney disease
.
PLoS One
.
2016
;
11
(
9
):
e0163673
.
50.
Kroll
MH
,
Elin
RJ
.
Relationships between magnesium and protein concentrations in serum
.
Clin Chem
.
1985
;
31
(
2
):
244
6
.
You do not currently have access to this content.