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10.1080/0886022X.2024.2401137
2401137
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Research Article
Acute Kidney Injury
Association between serum calcium level and the risk of acute kidney injury in patients with acute myocardial infarction: evidences from the MIMIC-IV database
Y. Wang et al.
Wang Ya a
Lu Yuli b
Liu Chen a
Xiao Jiandong a
a Department of Cardiology, Hengshui People’s Hospital, Hengshui, Hebei, China
b Department of Endocrinology, Hengshui People’s Hospital, Hengshui, Hebei, China
Supplemental data for this article can be accessed online at https://doi.org/10.1080/0886022X.2024.2401137.

CONTACT Ya Wang wyyelegant@outlook.com Department of Cardiology, Hengshui People’s Hospital, No.180 Renmin Road, Taocheng District, Hengshui, Hebei 053000, China
9 9 2024
2024
9 9 2024
46 2 240113720 6 2024
14 8 2024
1 9 2024
KnowledgeWorks Global Ltd.9 9 2024
published online in a building issue9 9 2024
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
2024
The Author(s)
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

Abstract

Objective

This cohort study was to assess the association between serum calcium levels and the risk of acute kidney injury (AKI) in acute myocardial infarction (AMI) patients.

Methods

This study was analyzed using data of 1286 AMI patients aged ≥18 years who stayed in ICU more than 24 h in Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Univariable logistic regression model was established to identify potential covariates. Univariate and multivariable logistic regression models were used to analyze the association between serum calcium and the risk of AKI in patients with AMI. The association between serum calcium and the risk of AKI in patients with AMI was also shown by restricted cubic spline (RCS) plot. Odds ratio (OR) and 95% confidence interval (CI) were calculated.

Results

The median follow-up time was 1.61 (1.23, 2.30) days, and 436 (33.90%) participants had AKI at the end of follow-up. After adjusting for covariates, elevated level of serum calcium level was related to reduced risk of AKI in AMI patients (OR = 0.88, 95%CI: 0.80–0.98). Decreased risk of AKI was found in AMI patients with serum calcium level of 8.40–8.90 mg/dL (OR = 0.54, 95%CI: 0.34–0.86) or ≥8.90 mg/dL (OR = 0.60, 95%CI: 0.37–0.99). The RCS plot depicted that serum calcium level was negatively correlated with the risk of AKI in patients with AMI.

Conclusions

AMI patients with AKI had lower serum calcium levels compared with those without AKI. Increased serum calcium level was associated with decreased risk of AKI in patients with AMI.

Keywords

Serum calcium
acute kidney injury
acute myocardial infarction
association
Science and Technology Research and Development Plan Project of Hengshui 2022014057Z This study got the fund from Science and Technology Research and Development Plan Project of Hengshui (2022014057Z).
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pmcIntroduction

Acute kidney injury (AKI) is a common complication in patients with acute myocardial infarction (AMI) in critically ill patients [1]. The reported incidence of AKI in patients hospitalized for AMI varied significantly, ranging from 10% to 30%, across different studies [2–4]. The in-hospital mortality in patients with AMI who developed AKI during hospitalization was three times higher than patients without a diagnosis of AKI [3]. AKI occurrence seriously affected the short-term and long-term prognosis of AMI patients [2, 5]. Over the past few decades, significant advancements have been made in both interventional and medical treatment of AMI while there has been limited progress in the prevention of AKI during the same time period [6]. The prevention and management of AKI can be considered as a crucial factor impeding improvements in outcomes for patients with AMI [7]. To identify more reliable biomarkers related to the risk of AKI in AMI patients is of great value.

Previously, studies revealed that serum calcium was closely related to the risk of AKI in non-critically ill hospitalized patients, and both high or low baseline serum calcium levels may be associated with an increased risk of AKI [8]. High serum calcium may cause renal vasoconstriction, resulting in decreased renal blood flow and tubular injury, whereas hypocalcemia may reflect the severity of cardiac dysfunction and renal impairment [9]. In addition, evidence reported that calcium homeostasis was also an important factor affecting the prognosis of patients with AMI and high or low serum calcium levels were related to the increased risk of in-hospital death in patients with myocardial infarction [10, 11]. The levels of calcium were found to be the independent risk factors for developing severe AKI after their admission [12]. However, there is a lack of relevant studies to investigate the relationship between serum calcium and the risk of AKI in patients with AMI.

In our study, we planned to assess the association between serum calcium levels and the risk of AKI in AMI patients using the data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Subgroup analysis was performed in different age groups, and patients complicated with chronic kidney disease (CKD), heart failure, atrial fibrillation, or cerebral infarction or not.

Methods

Study design and population

In total, AMI patients aged ≥18 years who stayed in ICU more than 24 h were identified in MIMIC-IV database between 2012 and 2019 in this cohort study. MIMIC-IV is a database that encompasses authentic hospital admissions data for patients treated at a prominent academic medical center in Boston, MA, USA. MIMIC-IV provides comprehensive patient information during their hospitalization period, including laboratory measurements, administered medications, documented vital signs, and other pertinent details. The primary objective of this database is to facilitate diverse healthcare research endeavors. Building upon the accomplishments of its predecessor MIMIC-III, MIMIC-IV incorporates numerous enhancements [13].

Patient records were extracted from MIMIC-IV database if they met the following criteria: (1) age ≥18 years old; (2) hospitalized in the ICU at first admission; (3) diagnosed as AMI based on ICD-9 (410.0–410.9) [14] and ICD-10 (I21.0–I21.9) [15]; (4) with measurement of baseline calcium; (5) measurement for diagnosis of AKI. Patients with estimated glomerular filtration rate (eGFR) <15 at baseline (first 24 h in ICU), end-stage renal disease [ICD-9 (5856) or ICD-10 (N186)] or renal failure (ICD-9 with first three digits of 584, and 586, and ICD-10 with first three digits N17, and N19) [16] were excluded. Those who received renal replacement therapy at admission were excluded. Patients with AKI at baseline (first 24 h in ICU) were not involved in. Subjects without data on SOFA score were also excluded. Finally, the data of 1286 participants were analyzed.

Potential covariates

Age (years), gender (female or male), race (White, Black or other), weight (kg), CKD (yes or no), congestive heart failure (yes or no), arterial fibrillation (yes or no), cerebral infarction (yes or no), hypertension (yes or no), diabetes (yes or no), chronic obstructive pulmonary disease (COPD) (yes or no), heart rate (beat/min), systolic blood pressure (mmHg), diastolic blood pressure (mmHg), respiratory rate (beat/min), temperature (°C), Sequential Organ Failure Assessment (SOFA), blood urea nitrogen (BUN) (mg/dL), platelet (K/uL), white blood cell (WBC) (K/uL), red blood cell distribution width (RDW) (%) [17], hemoglobin (g/dL) [18], hematocrit (%), glucose (mg/dL), bicarbonate (mEq/L), sodium (mEq/L) [17], potassium (mEq/L), chloride (mEq/L), oxygen saturation (SpO2) (%) [19], activated partial thromboplastin time (APTT) (sec), urine output (mL), mechanical ventilation use (yes or no) [17], vasopressor use (yes or no), diuretics (yes or no), and percutaneous coronary intervention (PCI) (yes or no) were potential covariates analyzed in this study. All the data were measured within 24 h of admission to ICU.

Main and outcome variables

Serum calcium level was main variable, which was grouped according to quartiles: <6.8 mg/dL group, 6.8–8.4 mg/dL group, 8.4–8.9 mg/dL group, and ≥8.9 mg/dL group.

AKI was the outcome, which was diagnosed based on Kidney Disease: Improving Global Outcomes Clinical Practice Guidelines [20]. People with increase in SCr by ≥0.3 mg/dL (≥26.5 μmol/L) within 48 h; or increase in SCr to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or urine volume <0.5 mL/kg/h for 6 h were defined as AKI. The median follow-up time was 1.61 (1.23, 2.30) days.

Statistical analysis

The measurement data with normal distribution were described as Mean ± standard deviation (Mean ± SD), and the t-test was used to compare the differences between groups. The median and quartiles were used to describe the distribution of measurement data that did not follow the normal distribution, and the Wilcoxon rank sum test was used to compare the differences between groups. The enumeration data were presented as the number and percentage of cases, and the chi-square test was used to compare the differences between groups. Missing values were shown in Supplementary Table 1, data with missing values less than 20% were manipulated via multiple imputation, and those with missing values more than 20% were deleted. Sensitivity analysis was conducted to compare the data before and after missing values manipulation (Supplementary Table 2). Univariable logistic regression model was established to identify potential covariates. Univariate and multivariable logistic regression models were used to analyze the association between serum calcium and the risk of AKI in patients with AMI. In model 1, no variables were adjusted, and in model 2, age, congestive heart failure, arterial fibrillation, cerebral infarction, heart rate, systolic blood pressure, diastolic blood pressure, temperature, SOFA, RDW, hemoglobin, hematocrit, potassium, APTT, mechanical ventilation use, vasopressor use and diuretics were adjusted. The association between serum calcium and the risk of AKI in patients with AMI was also shown by restricted cubic spline (RCS) plot. Subgroup analysis was stratified by age, and complications including CKD, heart failure, atrial fibrillation, or cerebral infarction. Odds ratio (OR) and 95% confidence interval (CI) were calculated. Alpha was set at 0.05. Data analysis was generated using SAS 9.4. The raw data of our study were exhibited in Supplementary File.

Results

Comparisons of the characteristics of AMI patients with AKI or not

A total of 4456 AMI patients aged ≥18 years who stayed in ICU more than 24 h from MIMIC-IV were identified. Among them, participants without measuring serum calcium were not included (n = 63). People with end-stage renal disease (n = 342) or renal failure (n = 1667) were excluded. Subjects receiving renal replacement therapy were excluded (n = 3). Patients with AKI at baseline (first 24h in ICU) were not included (n = 1093). Subjects without data on SOFA were also excluded (n = 2). Finally, the data of 1286 participants were analyzed (Figure 1).

Figure 1. The screen process of the participants.

There were 436 (33.90%) participants had AKI. The mean age of all participants was 67.34 years. The percentage of subjects had congestive heart failure in the AKI group was higher than the non-AKI group (44.72% vs 31.06%). The mean serum calcium level in the AKI group was lower than the non-AKI group (7.30 mg/dL vs 7.83 mg/dL). The percentages of participants in different serum calcium levels group was statistically different (Table 1).

Table 1. The characteristics of participants with or without AKI.

Variables	Total (n = 1286)	AKI	 	
No (n = 850)	Yes (n = 436)	P	
Age (years), Mean ± SD	67.34 ± 13.42	66.06 ± 13.50	69.85 ± 12.90	<0.001	
Gender, n (%)	 	 	 	0.206	
 Female	468 (36.39)	299 (35.18)	169 (38.76)	 	
 Male	818 (63.61)	551 (64.82)	267 (61.24)	 	
Race, n (%)	 	 	 	0.457	
 White	821 (63.84)	546 (64.24)	275 (63.07)	 	
 Black	64 (4.98)	46 (5.41)	18 (4.13)	 	
 Other	401 (31.18)	258 (30.35)	143 (32.80)	 	
Weight (kg), Mean ± SD	79.34 ± 19.64	79.45 ± 19.83	79.12 ± 19.30	0.770	
CKD, n (%)	 	 	 	0.185	
 No	1139 (88.57)	760 (89.41)	379 (86.93)	 	
 Yes	147 (11.43)	90 (10.59)	57 (13.07)	 	
Congestive heart failure, n (%)	 	 	 	<0.001	
 No	827 (64.31)	586 (68.94)	241 (55.28)	 	
 Yes	459 (35.69)	264 (31.06)	195 (44.72)	 	
Arterial fibrillation, n (%)	 	 	 	<0.001	
 No	954 (74.18)	686 (80.71)	268 (61.47)	 	
 Yes	332 (25.82)	164 (19.29)	168 (38.53)	 	
Cerebral infarction, n (%)	 	 	 	0.037	
 No	1238 (96.27)	825 (97.06)	413 (94.72)	 	
 Yes	48 (3.73)	25 (2.94)	23 (5.28)	 	
Hypertension, n (%)	 	 	 	0.071	
 No	423 (32.89)	294 (34.59)	129 (29.59)	 	
 Yes	863 (67.11)	556 (65.41)	307 (70.41)	 	
Diabetes, n (%)	 	 	 	0.463	
 No	855 (66.49)	571 (67.18)	284 (65.14)	 	
 Yes	431 (33.51)	279 (32.82)	152 (34.86)	 	
COPD, n (%)	 	 	 	0.062	
 No	1208 (93.93)	806 (94.82)	402 (92.20)	 	
 Yes	78 (6.07)	44 (5.18)	34 (7.80)	 	
Heart rate (bpm), Mean ± SD	82.85 ± 16.70	82.14 ± 15.87	84.22 ± 18.16	0.044	
Systolic blood pressure (mmHg), Mean ± SD	124.11 ± 22.34	125.38 ± 22.49	121.62 ± 21.86	0.004	
Diastolic blood pressure (mmHg), Mean ± SD	69.11 ± 16.24	69.88 ± 15.61	67.63 ± 17.31	0.023	
Respiratory rate (insp/min), Mean ± SD	17.99 ± 5.33	17.90 ± 5.46	18.16 ± 5.05	0.415	
Temperature (°C), Mean ± SD	36.62 ± 0.66	36.59 ± 0.64	36.66 ± 0.71	0.086	
SOFA, M (Q1,Q3)	0.00 (0.00, 2.00)	0.00 (0.00, 1.00)	1.00 (0.00, 2.00)	<0.001	
BUN (mg/dL), M (Q1,Q3)	16.00 (13.00, 22.00)	16.00 (13.00, 22.00)	17.00 (13.00, 23.00)	0.017	
Platelet (K/uL), M (Q1,Q3)	204.00 (156.00, 254.00)	205.00 (161.00, 254.00)	197.00 (147.50, 255.50)	0.124	
WBC (K/uL), M (Q1,Q3)	11.00 (8.30, 13.80)	10.90 (8.20, 13.70)	11.40 (8.70, 14.30)	0.066	
RDW (%), Mean ± SD	14.08 ± 1.67	14.00 ± 1.60	14.22 ± 1.80	0.031	
Hemoglobin (g/dL), Mean ± SD	11.51 ± 2.35	11.63 ± 2.34	11.27 ± 2.36	0.010	
Hematocrit (%), Mean ± SD	34.43 ± 6.71	34.75 ± 6.69	33.80 ± 6.73	0.016	
Glucose (mg/dL), M (Q1,Q3)	133.00 (110.00, 168.00)	131.50 (109.00, 165.00)	134.00 (113.00, 173.50)	0.180	
Bicarbonate (mEq/L), Mean ± SD	23.54 ± 3.32	23.60 ± 3.19	23.43 ± 3.57	0.396	
Sodium (mEq/L), Mean ± SD	137.17 ± 3.95	137.09 ± 3.83	137.32 ± 4.18	0.324	
Potassium (mEq/L), Mean ± SD	4.25 ± 0.71	4.28 ± 0.75	4.19 ± 0.62	0.016	
Chloride (mEq/L), Mean ± SD	103.79 ± 4.48	103.72 ± 4.41	103.91 ± 4.62	0.471	
SpO2 (%), Mean ± SD	97.16 ± 3.25	97.26 ± 3.07	96.95 ± 3.57	0.124	
APTT (sec), M (Q1,Q3)	33.10 (27.90, 52.30)	32.60 (27.70, 50.50)	34.95 (28.20, 55.40)	0.018	
Urine output (mL), M (Q1,Q3)	2207.50 (1575.00, 2960.00)	2220.00 (1575.00, 2960.00)	2165.00 (1560.00, 2962.50)	0.755	
Mechanical ventilation use, n (%)	 	 	 	<0.001	
 No	264 (20.53)	222 (26.12)	42 (9.63)	 	
 Yes	1022 (79.47)	628 (73.88)	394 (90.37)	 	
Vasopressor use, n (%)	 	 	 	<0.001	
 No	889 (69.13)	647 (76.12)	242 (55.50)	 	
 Yes	397 (30.87)	203 (23.88)	194 (44.50)	 	
Diuretics, n (%)	 	 	 	<0.001	
 No	939 (73.02)	658 (77.41)	281 (64.45)	 	
 Yes	347 (26.98)	192 (22.59)	155 (35.55)	 	
PCI, n (%)	 	 	 	0.128	
 No	1257 (97.74)	827 (97.29)	430 (98.62)	 	
 Yes	29 (2.26)	23 (2.71)	6 (1.38)	 	
IABP, n (%)	 	 	 	0.039	
 No	1283 (99.77)	850 (100.00)	433 (99.31)	 	
 Yes	3 (0.23)	0 (0.00)	3 (0.69)	 	
Calcium (mg/dL), Mean ± SD	7.65 ± 1.78	7.83 ± 1.70	7.30 ± 1.89	<0.001	
Calcium (mg/dL), n (%)	 	 	 	<0.001	
 <6.80	321 (24.96)	179 (21.06)	142 (32.57)	 	
 6.80–8.40	286 (22.24)	180 (21.18)	106 (24.31)	 	
 8.40–8.90	346 (26.91)	247 (29.06)	99 (22.71)	 	
 ≥8.90	333 (25.89)	244 (28.71)	89 (20.41)	 	
SD: standard deviation, M: median, Q1: 1st quartile, Q3: 3st Quartile, CKD: chronic kidney disease, COPD: chronic obstructive pulmonary disease, SOFA: Sequential Organ Failure Assessment, BUN: blood urea nitrogen, WBC: white blood cell, RDW: red blood cell distribution width, SpO2: oxygen saturation, APTT: activated partial thromboplastin time, PCI: percutaneous coronary intervention, IABP: intro-aortic balloon pump.

Association between serum calcium level and the risk of AKI in patients with AMI

As exhibited in Table 2, age, congestive heart failure, arterial fibrillation, cerebral infarction, heart rate, systolic blood pressure, diastolic blood pressure, temperature, SOFA, RDW, hemoglobin, hematocrit, potassium, APTT, mechanical ventilation use, vasopressor use, and diuretics were covariates associated with AKI in patients with AMI.

Table 2. Potential covariates associated with AKI in AMI patients.

Variables	OR (95%CI)	P	
Age (years)	1.02 (1.01–1.03)	<0.001	
Gender	 	 	
 Female	Ref	 	
 Male	0.86 (0.68–1.09)	0.206	
Race	 	 	
 White	Ref	 	
 Black	0.78 (0.44–1.37)	0.380	
 Other	1.10 (0.86–1.41)	0.454	
Weight	1.00 (0.99–1.01)	0.770	
CKD	 	 	
 No	Ref	 	
 Yes	1.27 (0.89–1.81)	0.186	
Congestive heart failure	 	 	
 No	Ref	 	
 Yes	1.80 (1.42–2.28)	<0.001	
Arterial fibrillation	 	 	
 No	Ref	 	
 Yes	2.62 (2.03–3.39)	<0.001	
Cerebral infarction	 	 	
 No	Ref	 	
 Yes	1.84 (1.03–3.28)	0.039	
Hypertension	 	 	
 No	Ref	 	
 Yes	1.26 (0.98–1.62)	0.071	
Diabetes	 	 	
 No	Ref	 	
 Yes	1.10 (0.86–1.40)	0.463	
COPD	 	 	
 No	Ref	 	
 Yes	1.55 (0.97–2.46)	0.064	
Heart rate	1.01 (1.01–1.01)	0.036	
Systolic blood pressure	0.99 (0.99–0.99)	0.004	
Diastolic blood pressure	0.99 (0.98–0.99)	0.019	
Respiratory rate	1.01 (0.99–1.03)	0.415	
Temperature	1.18 (0.98–1.40)	0.075	
SOFA	1.19 (1.11–1.28)	<0.001	
BUN	1.01 (1.00–1.02)	0.102	
Platelet	1.00 (1.00–1.00)	0.204	
WBC	1.00 (0.99–1.01)	0.715	
RDW	1.08 (1.01–1.16)	0.027	
Hemoglobin	0.94 (0.89–0.98)	0.010	
Hematocrit	0.98 (0.96–0.99)	0.016	
Glucose	1.00 (1.00–1.00)	0.615	
Bicarbonate	0.98 (0.95–1.02)	0.379	
Sodium	1.02 (0.99–1.05)	0.310	
Potassium	0.82 (0.69–0.97)	0.024	
Chloride	1.01 (0.98–1.04)	0.470	
SpO2	0.97 (0.94–1.01)	0.108	
APTT	1.01 (1.01–1.01)	0.038	
urine output	1.00 (1.00–1.00)	0.521	
Mechanical ventilation use	 	 	
 No	Ref	 	
 Yes	3.32 (2.33–4.72)	<0.001	
Vasopressor use	 	 	
 No	Ref	 	
 Yes	2.55 (2.00–3.27)	<0.001	
Diuretics	 	 	
 No	Ref	 	
 Yes	1.89 (1.47–2.44)	<0.001	
PCI	 	 	
 No	Ref	 	
 Yes	0.50 (0.20–1.24)	0.136	
AKI: acute kidney injury, AMI: acute myocardial infarction, OR: odds ratio, CI: confidence interval, CKD: chronic kidney disease, COPD: chronic obstructive pulmonary disease, SOFA: Sequential Organ Failure Assessment, BUN: blood urea nitrogen, WBC: white blood cell, RDW: red blood cell distribution width, SpO2: oxygen saturation, APTT: activated partial thromboplastin time, PCI: percutaneous coronary intervention, IABP: intro-aortic balloon pump.

In the crude model, increased serum calcium level might be correlated with decreased risk of AKI in AMI patients (OR = 0.85, 95%CI: 0.80–0.90). After adjusting for covariates, elevated level of serum calcium level was related to reduced risk of AKI in AMI patients (OR = 0.88, 95%CI: 0.80–0.98). Compared with serum calcium level <6.80 mg/dL group, AMI patients with serum calcium level of 8.40–8.90 mg/dL (OR = 0.51, 95%CI: 0.37–0.70) or ≥8.90 mg/dL (OR = 0.46, 95%CI: 0.33–0.64) might be associated with decreased risk of AKI. In the adjusted model, decreased risk of AKI was found in AMI patients with serum calcium level of 8.40–8.90 mg/dL (OR = 0.54, 95%CI: 0.34–0.86) or ≥8.90 mg/dL (OR = 0.60, 95%CI: 0.37–0.99) (Table 3). The RCS plot depicted that serum calcium level was negatively correlated with the risk of AKI in patients with AMI (Figure 2). AMI patients with AKI had lower serum calcium levels compared with those without AKI (Figure 3).

Figure 2. RSC Curve showing the association between serum calcium and or of AKI in AMI patients.

Figure 3. The serum calcium level of AMI patients with or without AKI.

Table 3. Associations between serum calcium level and the risk of AKI in patients with AMI.

Variables	Model 1	Model 2	
OR (95%CI)	P	OR (95%CI)	P	
Calcium (mg/dL)	0.85 (0.80–0.90)	<0.001	0.88 (0.80–0.98)	0.018	
Calcium (mg/dL)	 	 	 	 	
 <6.80	Ref	 	Ref	 	
 6.80–8.40	0.74 (0.54–1.03)	0.073	0.66 (0.42–1.02)	0.064	
 8.40–8.90	0.51 (0.37–0.70)	<0.001	0.54 (0.34–0.86)	0.009	
 ≥8.90	0.46 (0.33–0.64)	<0.001	0.60 (0.37–0.99)	0.045	
Model 1: No covariates adjusted.

Model 2: Adjusted for age, congestive heart failure, arterial fibrillation, cerebral infarction, heart rate, systolic blood pressure, diastolic blood pressure, temperature, SOFA, RDW, hemoglobin, hematocrit, potassium, APTT, mechanical ventilation use, vasopressor use and diuretics.

AKI: acute kidney injury, AMI: acute myocardial infarction, OR: odds ratio, CI: confidence interval.

Subgroup analysis of association between serum calcium level and the risk of AKI in patients with AMI

In males, compared with serum calcium level <6.80 mg/dL group, AMI patients with serum calcium level of 6.80–8.40 mg/dL (OR = 0.51, 95%CI: 0.28–0.92), or 8.40–8.90 mg/dL (OR = 0.43, 95%CI: 0.24–0.80) were correlated with decreased risk of AKI. Serum calcium level of 8.40–8.90 mg/dL was related to reduced risk of AKI in AMI patients without CKD (OR = 0.52, 95%CI: 0.31–0.85). In AMI patients without cerebral infarction, serum calcium level of 6.80–8.40 mg/dL (OR = 0.52, 95%CI: 0.30–0.91) or 8.40–8.90 mg/dL (OR = 0.53, 95%CI: 0.30–0.93) were associated to AKI. In AMI patients complicated with arterial fibrillation, serum calcium level of 8.40–8.90 mg/dL was related to reduced risk of AMI (OR = 0.41, 95%CI: 0.17–0.95). Decreased risk of AKI was observed in AMI patients complicated with congestive heart failure with serum calcium level of 8.40–8.90 mg/dL (OR = 0.37, 95%CI: 0.17–0.82) (Figure 4).

Figure 4. Subgroup analysis of association between serum calcium level and the risk of AKI in patients with AMI.

Discussion

In the current study, the association between serum calcium levels and the risk of AKI in AMI patients was evaluated. We identified that serum calcium level was negatively correlated with the risk of AKI in patients with AMI. AMI patients with AKI had lower serum calcium levels compared with those without AKI. Serum calcium level ≥ 8.40 mg/dL was correlated with decreased risk of AKI. Subgroup analysis revealed that AMI patients with serum calcium level of 6.80–8.90 mg/dL was correlated with decreased risk of AKI. Serum calcium level of 8.40–8.90 mg/dL was related to reduced risk of AKI in AMI patients without CKD. In AMI patients without cerebral infarction, serum calcium level of 6.80–8.90 mg/dL was associated to AKI. In AMI patients complicated with arterial fibrillation, serum calcium level of 8.40–8.90 was related to reduced risk of AMI. Decreased risk of AKI was observed in AMI patients complicated with congestive heart failure with serum calcium level of 8.40–8.90 mg/dL. The findings might provide reference for the identifying AMI patients with poor prognosis.

Previously, a statistically significant reduction was found in the measured total calcium and the ionized calcium levels in blood gas in AKIN stage 3 patients who applied to the emergency department [21]. Afshinnia et al. conducted a trial network study, which revealed that ionized serum calcium played a role on the outcomes in acute kidney injury needing renal replacement therapy, and the presence of severe hypocalcemia with iCa < 1 mmol/L was found to be an independent predictor of mortality in patients with AKI requiring renal replacement therapy [22]. Hypocalcemia might reflect the severity of renal dysfunction and associated with mortality in hospitalized patients with CKD [23]. Felsenfeld et al. indicated that maintaining normal calcium homeostasis is essential for chronic kidney disease [24]. A study including 259 ICU patients revealed that patients with hypocalcemia were associated with a higher risk of renal failure as compared to the normocalcemic group [25].

In addition, calcium homeostasis disorders can cause various cardiovascular diseases, and the association between serum calcium and cardiovascular diseases were well acknowledged [26]. An 8-year study depicted that serum calcium was an independent predictor for in-hospital mortality in patients with acute ST-elevated myocardial infarction [27]. A previous study using data from population-based registry delineated that low serum calcium was associated with higher long-term mortality in myocardial infarction patients [28]. Low serum calcium levels were identified as an independent risk factor for in-hospital mortality among patients with AMI [29]. The utilization of calcium supplements in conjunction with vitamin D was correlated with a reduced risk, particularly evident among patients exhibiting a heightened cardiovascular vulnerability [30]. Helte et al. indicated that the consumption of calcium-rich drinking water may potentially reduce the incidence of stroke in postmenopausal women [31]. The evaluation of calcium was useful for the detection of irreversible ischemia and helped to diagnose very early myocardial infarction morphologically [32]. Miura and colleagues conducted a study that examined a cohort with hypocalcemia, revealing significantly elevated rates of cardiovascular and all-cause mortality, as well as indications of cardiac and renal impairment in patients with heart failure and CKD [33]. These findings provided support to results in the current study. We found that there was a positive association between serum calcium level and the risk of AKI in patients with AMI. The risk of AKI in AMI patients was decreased as the increase of serum calcium level, and serum calcium level ≥ 8.40 mg/dL was correlated with decreased risk of AKI compared to those with serum calcium level <6.80 mg/dL. Subgroup analysis indicated that serum calcium values of 6.8–8.9 mg/dL were associated to AKI in AMI patients without cerebral infarction, this might due to the limited sample size in patients with cerebral infarction (n = 48). About 96.27% patients were not complicated with cerebral infarction.

The potential mechanisms explaining the association between serum calcium level and the risk of AKI in AMI patients were still unclear. The electrophysiological characteristic of the cardiomyocyte membrane is directly correlated with serum calcium levels. Decreased serum calcium may result in delayed closure of calcium channels, thereby causing prolonged plateaus [34]. Low serum calcium levels increased the susceptibility of patients to ventricular arrhythmias and cardiac arrest [35]. The cellular function of almost every system relied on the multifaceted roles of calcium [36]. Calcium plays a pivotal role in signal transduction pathways, contributes to the establishment of cell membrane potential and nerve conduction, initiates muscle contraction, serves as a cofactor for numerous enzymes, and acts as the second messenger for various hormones that regulate metabolism and gene expression [37].

This study evaluated the association between serum calcium and the risk of AKI in patients with AMI. The serum calcium for routine surveillance indexes in AMI patients in the ICU, which is easy to obtain. The evaluation of serum calcium might help early assess the AKI risk in AMI patients. Low serum calcium should be considered in patients with AMI, and the kidney function should be checked. Early prevention should be provided for those with high risk of AKI. For patients with AMI, routinely monitoring of serum calcium and vitamin D administration might be necessary for maintaining calcium homeostasis at admission. Our study also has some potential limitations. Firstly, this was a retrospective cohort study, and causal relationship between serum calcium and the risk of AKI in patients with AMI could not be inferred. Secondly, due to the limitation of the database, the lack of data on some important biomarkers such as data on AMI-related indexed were not included and analyzed, and there might be potential for residual confounding. Thirdly, variables such as lifestyle factors affecting the prognosis of patients with AMI were not included in the database, which might affect the results. In the future, more well-designed studies were needed to verify the results in this study.

Conclusion

The present study assessed the association between serum calcium levels and the risk of AKI in AMI patients, which found that increased serum calcium level was associated with decreased risk of AKI in patients with AMI. Serum calcium level ≥ 8.40 mg/dL was correlated with decreased risk of AKI. These findings suggested the importance of routinely monitoring of serum calcium in AMI patients.

Supplementary Material

Figure 4.tiff

Supplementary Tables .docx

Figure 1.tif

Raw data.csv

Figure 2.tif

Figure 3.tiff

Disclosure statement

No potential conflict of interest was reported by the author(s).
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