Characteristics of cardiac injury complicating with acute kidney injury and mortality risk in coronavirus disease 2019 (COVID-19) patients

Hongmei Li; Hui Dai; Renjun Huang; Yalei Shang; Jianan Huang; Daxiong Zeng; Weizhong Tian; Chunfeng Hu; Yonggang Li

doi:10.4103/RID.RID_36_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 9 | Issue : 4 | Page : 111-118

Characteristics of cardiac injury complicating with acute kidney injury and mortality risk in coronavirus disease 2019 (COVID-19) patients

Hongmei Li¹, Hui Dai², Renjun Huang³, Yalei Shang³, Jianan Huang⁴, Daxiong Zeng⁴, Weizhong Tian⁵, Chunfeng Hu⁶, Yonggang Li²
¹ Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu Province, China
² Department of Radiology; Institute of Medical Imaging, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
³ Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
⁴ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
⁵ Department of Radiology, Taizhou People's Hospital Affiliated to Nantong University, Taizhou, Jiangsu Province, China
⁶ Department of Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China

Date of Submission	27-Sep-2022
Date of Decision	19-Dec-2022
Date of Acceptance	30-Dec-2022
Date of Web Publication	21-Mar-2023

Correspondence Address:
Yonggang Li
Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000
China

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/RID.RID_36_22

Abstract

Objectives: This study aimed to identify the clinical features of cardiac injury complicating with acute kidney injury (AKI) and its risk for a fatal outcome in patients infected with coronavirus disease 2019 (COVID-19) pneumonia.
Methods: Initial signs and symptoms and clinical laboratory, radiological, and treatment information were obtained from seven hospitals in China from January 23, 2020, to March 15, 2020.
Results: Of 438 patients, 36 (8.22%) displayed isolated cardiac injury, 17 (3.88%) had isolated AKI, and 17 (3.88%) displayed cardiac injury complicating with AKI. Compared with patients without cardiac injury or AKI, patients with isolated cardiac injury, isolated AKI, and cardiac injury complicating with AKI were older (55, 65, 74 vs. 48 years, P < 0.0001) and critically severe. More patients displayed fatigue, dyspnea, and comorbidities in the group with cardiac injury complicating with AKI. Moreover, the indexes reflecting myocardial, renal, liver, and coagulation dysfunctions and infection-related factors were significantly different among the four groups. After adjustment for covariates, patients with cardiac injury complicating with AKI had a higher hazard ratio for mortality (6.64; 95% confidence interval, 1.51–29.30).
Conclusion: Cardiac injury complicating with kidney injury significantly increased the risk for in-hospital mortality in COVID-19 pneumonia patients. Therefore, early detection at admission and careful monitoring of myocardial and renal injury through biomarkers during hospitalization is recommended to reduce the harm to patients.

Keywords: Acute kidney injury, cardiac injury, COVID-19, mortality risk

How to cite this article:
Li H, Dai H, Huang R, Shang Y, Huang J, Zeng D, Tian W, Hu C, Li Y. Characteristics of cardiac injury complicating with acute kidney injury and mortality risk in coronavirus disease 2019 (COVID-19) patients. Radiol Infect Dis 2022;9:111-8

How to cite this URL:
Li H, Dai H, Huang R, Shang Y, Huang J, Zeng D, Tian W, Hu C, Li Y. Characteristics of cardiac injury complicating with acute kidney injury and mortality risk in coronavirus disease 2019 (COVID-19) patients. Radiol Infect Dis [serial online] 2022 [cited 2023 Jun 3];9:111-8. Available from: http://www.ridiseases.org/text.asp?2022/9/4/111/372194

Introduction

Since its outbreak in December 2019, the coronavirus disease 2019 (COVID-19) infection, as caused by the severe acute respiratory syndrome (SARS) coronavirus 2,^[1] has spread globally. In addition to the typical respiratory manifestations of patients with COVID-19 infection, the myocardial and kidney injuries associated with viral infection require attention. It has been reported that approximately 7%–20% of patients suffered cardiac injury and 0.5%–7% of cases, and 2.9%–23% of intensive care unit (ICU) patients displayed acute kidney injury (AKI).^{[2],[3],[4],[5]}

However, the information on clinical features of cardiac injury complicating with kidney injury in mild and severe cases infected with the COVID-19 virus is limited, and the risk of a combination of cardiac and renal injury leading to mortality requires investigation. The present study aimed to explore clinical features of cardiac injury complicating with AKI and their risks for mortality in patients with COVID-19 pneumonia.

Materials and Methods

Study participants

Cases with confirmed COVID-19 in six hospitals in Jiangsu and one hospital in Wuhan from January 23, 2020, to March 15, 2020, were included in this cohort study. All cases were diagnosed by reverse transcription-polymerase chain reaction. This study was conducted in accordance with the amended Declaration of Helsinki and was approved by the institutional review board at every hospital. Written informed consent was obtained from all participants.

Data collection

Epidemic history, demographic characteristics (including age and gender), history of diseases, symptoms and signs, treatments and outcomes, and laboratory findings were obtained. Cardiac biomarkers, including high sensitivity troponin I (hs-TnI), creatine kinase (CK), CK isoenzyme-MB (CK-MB), and myoglobin, and renal biomarkers, such as serum creatinine and blood urea nitrogen, were determined at admission and during hospitalization. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation.^[6] The radiologic assessments included chest radiography and computed tomography. Not all subjects were tested for the biomarkers hs-TnI, CK, or CK-MB; thus, cardiac injury was defined as blood levels of hs-TnI over the 99^th percentile (P₉₉) upper reference limit, CK >198 U/L (P_97.5), or CK-MB >18 U/L (p_97.5), regardless of new abnormalities in electrocardiography and echocardiography.^[4],[7],[8] AKI was identified according to the Kidney Disease: Improving Global Outcomes definition.^[9] Clinical outcomes were monitored up to March 15, 2020, the final date of follow-up.

Statistical analysis

The patients were divided into four groups: patients without cardiac or AKI, with isolated cardiac injury, with isolated AKI, and with cardiac injury complicating with AKI. Descriptive statistics were obtained for all study variables. Continuous data were expressed as median (interquartile range [IQR]) and were compared using the Kruskal–Wallis rank sum test. All categorical variables were expressed as proportions and were compared using the Chi-square test or Fisher's exact test. Bonferroni corrections were used for pairwise comparisons. Survival curves were plotted using the Kaplan–Meier method and compared across the four different cardiac injury and AKI groups using the log-rank test. The Cox regression model was used to determine the risk factors for mortality during hospitalization. All P values were based on two-sided tests, and the statistical significance level was set at 0.05. All the statistical analyses were performed using SAS (version 9.4) (SAS Institute, Cary, NC, USA).

Results

Patient characteristics

In total, 438 patients hospitalized with confirmed COVID-19 pneumonia were included in the present analysis. Among all patients, 36 (8.22%) had isolated cardiac injury, 17 (3.88%) displayed isolated AKI, and 17 (3.88%) had cardiac injury complicating with AKI. The median age of all patients was 49 years (IQR: 35–60 years), and 237 (54.11%) were males. Among these participants, 53.20% had a contact history with the epidemic area of Wuhan, 7.08% were diagnosed with mild type, 67.81% were moderate, and 16.67% and 8.45% were severe and critically ill types, respectively. Fever (303 patients, 69.18%) was the most common symptom, followed by a cough, of which the proportion with a dry cough was 38.13% and with sputum production was 28.31%. The proportions of anorexia, fatigue, dyspnea and muscle soreness, sore throat, and diarrhea were 34.47%, 24.43%, 15.07%, 13.24%, and 10.73%, respectively. By contrast, headaches (33 patients, 7.53%) and nausea or vomiting (18 patients, 4.11%) were relatively rare. Hypertension (79 patients, 18.04%) and diabetes (44 patients, 10.05%) were the most common coexisting conditions. Of the total 438 patients, 18 (4.11%) had cardiovascular disease, including coronary heart disease and cardiac dysfunction and 15 (3.42%) had chronic obstructive pulmonary disease (COPD). The proportions of chronic liver disease, chronic kidney disease, and malignancy were 1.83% (eight patients), 1.37% (six patients), and 1.83% (eight patients), respectively [Table 1].

Table 1: Comparison of baseline and clinical characteristics across 4 groups of patients with different cardiac and kidney injury status

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Compared with patients without cardiac injury or AKI, patients with isolated cardiac injury, isolated kidney injury, and cardiac injury complicating with AKI were older (55, 65, 74 vs. 48 years, P < 0.0001), had higher proportions of a contact history with the epidemic area of Wuhan, were of the critically ill type, and were more likely to experience dyspnea. Furthermore, comorbidities, including hypertension, cardiovascular disease, and COPD, were more common in patients with cardiac injury complicating with AKI.

The median time from symptom onset to admission was 6 (IQR, 3–9) days for all participants, and patients with cardiac injury complicating with AKI had a longer mean time from symptom onset to admission than those without cardiac or kidney injury.

Laboratory and radiologic findings

The laboratory and radiologic findings at admission to the hospital are listed in [Table 2]. In the study, the median levels of white blood cell, neutrophil, and lymphocyte counts among patients with COVID-19 pneumonia were 4.98, 2.90, and 1.10 (×10⁹/L), respectively, and the medians of the myocardial zymogram such as troponin I, CK, CK-MB, myoglobin, and lactic dehydrogenase were 4.65 ng/ml, 60.28 U/L, 1.30 U/L, 30.00 ng/ml, and 270.65 U/L, respectively. For indexes reflecting renal function, the medians of serum creatinine, blood urea nitrogen, and eGFR were 67.06 μmol/L, 4.25 μmol/L, and 102.35 ml/min, respectively. Furthermore, the median levels of glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, glucose, prothrombin time, fibrinogen, hypersensitive C-reactive protein, and erythrocyte sedimentation rate were 27.47 U/L, 24.11 U/L, 6.63 mmol/L, 13.14 s, 2.52 g/L, 7.50 mg/L, and 26.64 mm/H, respectively. In total, 6.85% of patients had a respiratory rate >24 times/min and 11.19% had a SaO₂ <94%. The proportion of patients with bilateral pneumonia was 83.33% (365 patients) according to chest radiography and computed tomography findings [Figure 1]a and [Figure 1]b, and 90.18% of patients (n = 395) had multiple mottling and ground glass [Figure 1]c and [Figure 1]d.

Table 2: Comparison of laboratory findings on admission to hospital across 4 groups of patients with different cardiac and kidney injury status

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Figure 1: Bilateral pneumonia and multiple ground glass on the chest CT in patients with COVID-19 infection. (a and b) A 39-year-old male patient with fever, a cough, and sore throat for 6 days, a positive COVID-19 nucleic acid test, and CT showing multiple infections in both lungs with irregular dense shadows. (c and d) A 59-year-old male patient with a cough for 4 days, fever for 2 days, a positive COVID-19nucleic acid test, and CT showing multiple ground glass shadows in both lungs. CT: Computed tomography

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Compared with patients without cardiac injury or AKI, patients with isolated cardiac injury or cardiac injury complicating with AKI had elevated levels of white blood cell and neutrophil counts. In terms of the myocardial zymogram findings, patients with isolated cardiac injury or cardiac injury complicating with AKI had higher median levels of troponin I, CK, CK-MB, myoglobin, and lactic dehydrogenase. For renal function indicators on admission, patients with isolated AKI or cardiac injury complicating with AKI had higher serum creatinine and lower eGFR levels. Patients with cardiac injury complicating with AKI had higher levels of blood urea nitrogen glutamic-oxaloacetic transaminase, prothrombin time, fibrinogen, and hypersensitive C-reactive protein and higher proportions of respiratory rate >24 times/min and SaO₂ <94%. However, the proportions of patients with pulmonary bilateral density shadow and multiple mottling and ground glass across the four groups were not found to be significant.

Treatment, complications, and clinical outcome

Of all patients, most (93.61%) were treated with antiviral therapy, just over half (55.71%) were treated with antibiotic therapy, 22.37% were treated with hormones, and the percentages of using oxygen inhalation, noninvasive ventilation, and invasive mechanical ventilation (IV) were 25.34% (111 patients), 8.22% (36 patients), and 7.31% (32 patients), respectively. Moreover, 2.51% (n = 11) and 0.69% (n = 3) of patients were given continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation, respectively. In total, 37 (8.41%) patients displayed acute respiratory distress syndrome (ARDS), 27 (6.16%) had septic shock, and 17 (3.88%) displayed disseminated intravascular coagulation (DIC) during hospitalization. During follow-up, a total of 25 (5.71%) patients died, 10 (2.25%) patients remained hospitalized, and 403 patients (92.01%) were discharged.

Compared with those without cardiac or kidney injury, patients with isolated cardiac injury or isolated AKI were more likely to have received IV treatment and CRRT and displayed higher proportions of ARDS and septic shock symptoms. Patients with cardiac injury complicating with AKI needed more antibiotic treatment and hormone therapy, they required more noninvasive ventilation, IV, and CRRT treatments, and they had more complications, including ARDS, septic shock, and DIC than patients without cardiac or kidney injury. In addition, compared with patients with isolated cardiac injury, those with cardiac injury complicating with AKI required more IV treatment and CRRT and had higher proportions of ARDS as well as septic shock and DIC.

Patients with cardiac injury complicating with AKI had shorter durations from symptom onset to follow-up (median: 32, IQR: 19–48 days) than those without cardiac or kidney injury (median: 48, IQR: 44–52 days). The mortality rates were higher among patients with isolated cardiac injury (16.67%), isolated AKI (23.53%), and cardiac injury complicating with AKI (64.71%) than in those without cardiac or kidney injury (1.09%) [Table 3].

Table 3: Treatment, complications and clinical outcome among patients with acute cardiac and renal injury

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Cardiac injury complicating with kidney injury and mortality risk

[Figure 2] presents the Kaplan–Meier survival curves together with the log-rank test, which was used to describe and compare the survival condition. Patients with isolated cardiac injury and isolated AKI had lower cumulative survival rates than those without cardiac injury or AKI, and patients with cardiac injury complicating with AKI had a lower survival rate than patients with isolated cardiac injury, isolated AKI, and those without both injuries (Log-rank test, P < 0.0001).

Figure 2: Kaplan–Meier survival curves among different cardiac and kidney injury groups

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In the univariate Cox proportional-hazard regression model, patients with isolated cardiac injury, isolated AKI, and cardiac injury complicating with AKI had higher risks of mortality than those without both injuries, with hazard ratios (HRs) of 16.38 (4.62–58.09), 23.64 (5.91–94.52), and 97.33 (30.45–308.08), respectively. After adjustment for age, sex, preexisting cardiovascular diseases, hypertension, diabetes, COPD, malignancy, glutamic-pyruvic transaminase levels >40 U/L, and ARDS, patients with cardiac injury complicating with AKI still had a higher adjusted HR (6.64; 95% confidence interval [CI], 1.51–29.30) for a fatal outcome. In the multivariate Cox hazard regression model, age and ARDS were also independent risk factors for the mortality of patients infected with COVID-19 [Table 4].

Table 4: Cardiac injury complicating with acute kidney injury and mortality risk among COVID-19 patients

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Discussion

The present study investigated patients with COVID-19 pneumonia from mild-to-very severe clinical types, and found that 12.10% of these patients had a cardiac injury, 7.76% displayed AKI, and 3.88% had cardiac injury complicating with AKI. The combination of cardiac injury and AKI statistically increased the risk for in-hospital mortality.

A large clinical sample study in China^[10] reported that severe pneumonia was independently associated with admission to an ICU, mechanical ventilation, and mortality. However, it was notable that acute cardiac injury and AKI complicated with pneumonia were more common, and were possibly associated with the adverse clinical outcomes of COVID-19 patients. A report^[5] on 138 patients hospitalized with COVID-19 found that 7.2% of them developed an acute cardiac injury, and patients who received care in an ICU were more likely to have a cardiac injury (22.2%) than non-ICU patients. Another study^[11] of 416 patients demonstrated that 19.7% of them had a cardiac injury, and cardiac injury was independently associated with an increased risk for mortality from symptom onset to endpoint, with an HR of 4.26 (1.92–9.49). However, the occurrence of AKI has been reported to be inconsistent in COVID-19-infected patients. A study from Wuhan, China^[3] reported that >5.1% of patients with COVID-19 pneumonia displayed AKI, and this significantly increased the risk for in-hospital mortality, with an HR of 1.90 (0.76–4.76) at AKI stage 1, 3.51 (1.49–8.26) at stage 2, and 4.38 (2.31–8.31) at stage 3. Two studies from the United States^[12],[13] reported that 46% and 36.6% of hospitalized patients with COVID-19 developed AKI, respectively, and another study from Italy^[14] showed that 22.4% of patients with COVID-19 were diagnosed with AKI. Moreover, all the above studies indicated that AKI increased the risk for in-hospital mortality.

Of note, multiple organ involvement, including the heart, liver, and kidney, has been reported during the course of the SARS outbreak^[15] and recently in patients with COVID-19.^[16] It was reported that 6.7% of patients with SARS developed AKI, and the mortality of those with AKI was 91.7%.^[17] Another study of multiple organ dysfunctions of SARS^[18] in 135 patients found SARS could cause multiple organ dysfunctions, with the proportions of patients with dysfunction of the immune system, cardiovascular system, liver, and kidney being 92.3%, 30.8%, 38.5%, and 53.8%, respectively. In addition, the authors proposed that multiple organ injuries in SARS may be associated with the immune system and systemic inflammatory response syndrome. However, the mechanism of cardiac and kidney injuries among patients with COVID-19 remains unclear. The proposed mechanisms of myocardial and kidney injuries are direct damage by the virus, systemic inflammation, and interferon-mediated immune response, among others.^{[19],[20],[21]}

Some signs, symptoms, and clinical features are also of note in patients with cardiac and kidney injuries. Compared with patients without cardiac injury or AKI, patients with isolated cardiac injury, isolated AKI, or a combination of cardiac injury and AKI were likely to be older, presented with a more severe clinical type, and had higher proportions of fatigue and dyspnea. Moreover, they displayed higher levels of indicators of liver and coagulation dysfunctions and infection-related factors, and higher proportions required invasive and noninvasive mechanical ventilation. Furthermore, the present study found that, of patients with cardiac injury complicating with AKI, 47.06% and 17.65% had a history of hypertension and cardiovascular disease, respectively, which was more frequent than 15.76% and 3.26% among the patients without cardiac or kidney injury. Similar to Middle East respiratory syndrome,^[22] preexisting CVD, including hypertension, diabetes, and coronary heart disease, was associated with the severity and mortality of COVID-19 pneumonia.^[23] A meta-analysis^[24] demonstrated that the prevalence of hypertension, cardiac and cerebrovascular disease, and diabetes were 17.1%, 16.4%, and 9.7% among patients infected with COVID-19, respectively. In addition, in cases requiring ICU admission, the prevalence of cardiac and cerebrovascular disease was 16.7%, while it was 6.2% in non-ICU cases. Chen et al.^[25] reported that both coronary heart disease and cerebrovascular disease were risks for a fatal outcome, with an HR of 4.28 (95% CI, 1.14–16.13) and 3.10 (95% CI, 1.07–8.94), respectively.

There are some limitations in the present study. First, the clinical and imaging data of patients were from multiple centers; therefore, the data were heterogeneous, which might have affected the statistical analysis results. Second, echocardiography and electrocardiography data were lacking for the majority of patients; thus, this information could not be analyzed. Third, although the point estimates of the HR of mortality with the isolated cardiac injury and the isolated AKI were greatly above 1, they were not statistically significant because of the sample size. Studies from larger populations and multiple centers are needed to further confirm the outcomes of cardiac injury and AKI in COVID-19-infected patients.

Conclusion

Both cardiac and kidney injury, particularly cardiac injury complicating with kidney injury, are associated with a higher risk for in-hospital mortality in COVID-19 pneumonia patients, which highlights the need to consider the complications of cardiac and kidney injury in COVID-19 patient management. Therefore, strategies including early detection at admission, regular monitoring of serum myocardial zymogram and creatinine and urine output during hospitalization and the avoidance of cardiotoxic and nephrotoxic drugs are recommended to be implemented according to the guidelines for heart and kidney diseases, to improve severe and critically ill patients with COVID-19.

Ethic statement

Not appliable.

Acknowledgments

We would like to thank Liwen Bianji (Edanz) (www. liwenbianji. cn) for editing the language of a draft of this manuscript.

Financial support and sponsorship

This work was mainly supported by the National Natural Science Foundation of China (grant number 81971573, 81671743), the Clinical Key Diseases Diagnosis And Therapy Special Project of Health and Family Planning Commission of Suzhou (LCZX201801), the Project of Invigorating Health Care through Science, Technology, and Education, Jiangsu Provincial Medical Youth Talent (QNRC2016709), the High-level Health Personnel “six-one” Project of Jiangsu Province (LGY2016035), and the Program for Advanced Talents within Six Industries of Jiangsu Province (WSW-057).

Conflicts of interest

There are no conflicts of interest.

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