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ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 3  |  Page : 1192-1197

Acute kidney injury in hospitalized patients with Covid-19


1 Department of Internal Medicine, Benha Teaching Hospital, Qalubia, Menoufia, Egypt
2 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission16-May-2022
Date of Decision15-Jun-2022
Date of Acceptance19-Jun-2022
Date of Web Publication29-Oct-2022

Correspondence Address:
Shaban E E. Mohamed
Benha, Qalubia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_164_22

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  Abstract 


Objectives
To investigate the severity, risk factors, and outcomes of acute kidney injury (AKI) in hospitalized patients with coronavirus disease 2019 (COVID-19).
Background
COVID-19 has been associated with elevated incidence of AKI. More search is required to confirm the role of COVID-19 as an independent risk factor for AKI.
Patients and methods
This retrospective cohort study included data collected from medical records, patients' follow-up, and charts of 100 patients who were diagnosed with COVID-19 infection by a positive RT-PCR assay of a specimen collected via nasopharyngeal swab between the first of December 2020 and 31 May 2021 in COVID-19 isolation wards and ICU in Benha Teaching Hospital.
Results
Age and BMI were significantly higher in the AKI group, but oxygen saturation was significantly lower than in the non-AKI group (P < 0.0001). AKI was significantly associated with respiratory diseases (P = 0.003), administrating immune-suppressive drugs (P = 0.042), high sequential organ failure assessment score, critical severity, and invasive respiratory support (P < 0001). D-dimer, creatinine kinase, and creatinine were significantly higher among cases with AKI, but glomerular filtration rate was significantly lower (P < 0.001). AKI was significantly associated with high mortality (P < 0.001). The severity of disease, sequential organ failure assessment score, creatinine, glomerular filtration rate, and D-dimer were significant independent predictors for AKI.
Conclusion
AKI is a frequent serious complication in hospitalized patients with COVID-19 and is associated with a high risk of mortality, and the severity of COVID is an independent predictor for AKI.

Keywords: acute kidney injury, coronavirus disease 2019, hospitalized


How to cite this article:
Mohamed SE, Kora MA, Emara MM, Kasem HE. Acute kidney injury in hospitalized patients with Covid-19. Menoufia Med J 2022;35:1192-7

How to cite this URL:
Mohamed SE, Kora MA, Emara MM, Kasem HE. Acute kidney injury in hospitalized patients with Covid-19. Menoufia Med J [serial online] 2022 [cited 2024 Mar 29];35:1192-7. Available from: http://www.mmj.eg.net/text.asp?2022/35/3/1192/359466




  Introduction Top


Since December 2019, coronavirus disease 2019 (COVID-19) has emerged as an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently considered by the WHO to be a pandemic[1].

The rapid progression of the global pandemic caused by the novel coronavirus has resulted in an urgent need to understand the pathogenesis and variable clinical features of COVID-19. Lung involvement in the form of viral pneumonia, inflammatory infiltrates, and endothelial damage resulting in respiratory failure has been well documented and has been the focus of attention, but other organs including the kidneys are also affected by COVID-19[2],[3].

Several studies have focused attention on acute kidney injury (AKI) in critically and noncritically ill patients with COVID-19. In March 2020, Cheng et al.[4] reported a prospective cohort of 701 COVID-19 cases in Tongji Hospital, Wuhan, China, and found that 43.9% of these patients had proteinuria during hospitalization, with AKI occurring in 5.1%[4].

The incidence of COVID-19 rose across European countries and the USA, and reports showed that AKI was a more predominant feature of the condition than seen in initial reports from China[5].

COVID-19-infected patients with severe AKI had fatal outcomes; however, the mortality rate was not increased in patients with mild and moderate AKI. Among patients with AKI, those with acute respiratory distress syndrome (ARDS) or a low serum albumin level on admission had a higher incidence of severe AKI. Clinicians need to pay more attention to preventing and managing severe AKI in COVID-19-infected patients[6].

Using available evidence, a multifactorial AKI pathogenesis model including hypovolemia, cytokine storm, endothelial dysfunction, ARDS, complement activation, angiotensin II overactivity, direct viral attack of podocyte and tubules, myocardial dysfunction, and hypercoagulability has been proposed[7],[8].

In Egypt, there are few studies about the incidence of AKI in COVID-19-infected patients. Azeem et al.[9] reported that within 7 days of admission, 61 patients out of 86 developed AKI and met the Kidney Disease Improving Global Outcomes criteria. The development of AKI was associated with increased severity of illness, prolonged duration of hospitalization, and increased mortality rate. Furthermore, Refat et al.[10] in a retrospective study has reported a 5.3% incidence rate of AKI.

This study aims to investigate the incidence, severity, risk factors, and outcomes of AKI in hospitalized COVID-19-infected patients admitted to Benha Teaching Hospital.


  Patients and methods Top


The study was approved by the local ethical committee of Menoufia University Faculty of Medicine. This was a retrospective observational study that included data of 100 hospitalized patients aged more than 18 years who were diagnosed with COVID-19 infection by a positive RT-PCR assay of a specimen collected via nasopharyngeal swab. The study included data of patients admitted in the period between the first of December 2020 to the end of May 2021 in COVID-19 isolation wards and ICU in Benha Teaching Hospital. Patients who were hospitalized for less than 48 h, patients with known end-stage kidney disease, patients on maintenance hemodialysis, and/or renal transplant recipients were excluded from the study. Hospital ethical committee approval and IRB approval were attained.

All data were collected from medical records, patients' follow-up, and charts. Baseline patients' characteristics were collected, including demographics, comorbidities before hospital admission, clinical data, laboratory characteristics, and outcome data.

Kidney Disease Improving Global Outcomes criteria were used to define AKI according to both urinary output and serum creatinine[11]. Proteinuria was defined as protein creatinine ratio more than 0.5 or more on dipstick (trace counted as no proteinuria), or more than or equal to 30 mg/dl on urinalysis. Leukocyturia was defined as more than five white blood cells per high-power field. Hematuria was defined as 11 or higher on dipstick or urinalysis[12].

The primary outcome was the incidence of AKI. The secondary outcomes were in-hospital all-cause mortality, need for mechanical ventilation, ICU admission, and length of stay.

Statistical analysis

Data were analyzed using IBM SPSS 23.0 for Windows (SPSS Inc., Chicago, Illinois, USA) and NCSS 11 for Windows (NCSS LCC, Kaysville, Utah, USA). Quantitative data were expressed as mean ± SD. Qualitative data were expressed as frequency and percentage. Continuous data were checked for normality using the Shapiro–Wilk test. The following tests were used to test differences for significance: difference and association of qualitative variable by χ2 test and differences between quantitative independent groups by t test. P value was set at less than 0.05 for significant results and less than 0.001 for high significant result. The logistic regression was used to describe data and to explain the relationship between one dependent binary variable and one or more nominal, ordinal, interval, or ratio-level independent variables.


  Results Top


A total of 100 patients were included in the study with a mean age of 53.29 ± 8.32 years ranging from 28 to 71 years. There was a male predominance, as 66% of the studied cases were males. The mean BMI was 29.99 ± 4.26, and the means of systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, and oxygen saturation were 117.8 ± 16.03, 76.40 ± 9.9, 88.59 ± 7.3, 22.28 ± 2.95, and 91.29 ± 6.93, respectively. Regarding risk factors, 30.05% were smokers, 46.0% had diabetes, and 30% were hypertensive. Regarding comorbid disease rates of respiratory diseases, cardiac diseases, and immunosuppressive therapy were 16.0, 24.0, and 14.0%, respectively [Table 1].
Table 1: Demographic, clinical data, and risk factors among the studied group (n=100)

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Overall, 22% of patients developed AKI, and the patients were divided into two groups according to the presence of AKI or not. Age and BMI were significantly higher in the AKI group, but oxygen saturation was significantly lower than that in the non-AKI group, with P value less than 0.0001 [Table 2].
Table 2: Demographic data distribution between studied groups

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AKI was significantly associated with respiratory diseases (P = 0.003), administering immune-suppressive drugs (P = 0.042), high sequential organ failure assessment (SOFA) score, critical severity, and invasive respiratory support (P < 0001) [Table 3].
Table 3: Risk factors and clinical data distribution between studied groups

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Regarding laboratory data, D-dimer, creatinine kinase, and creatinine were significantly higher among cases with AKI, but glomerular filtration rate (GFR) was significantly lower (P < 0.001) [Table 4].
Table 4: Laboratory distribution between studied groups

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AKI was significantly associated with high mortality (P < 0.001) [Figure 1]. Multivariate logistic regression analysis showed that severity of disease, SOFA score, creatinine, GFR, and D-dimer were significant independent predictors for AKI [Table 5].
Figure 1: AKI cases were significantly associated with mortality. AKI, acute kidney injury.

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Table 5: Multivariate logistic regression for predictors of acute kidney injury

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  Discussion Top


COVID-19, a newly emerged infection caused by SARS-CoV-2, has become a pandemic all over the world. COVID-19-infected patients are usually accompanied by multiple organ injuries, including myocardial dysfunction, hepatic injury, and even acute renal failure[13].

The cause of AKI with SARS-CoV-2 is multifactorial and may be due to direct viral injury via its receptor (ACE2), which is highly expressed in the kidney; an imbalanced renin–angiotensin–aldosterone system; an elevation of pro-inflammatory cytokines elicited by the viral infection; and microvascular thrombosis[14].

Especially in critically ill patients, old age, and other comorbidities such as hypertension or diabetes mellitus, the severity of symptoms like fever, diarrhea, and others could lead to hypovolemia and subsequent pre-renal AKI. In addition to other associated incidences like nephrotoxic drugs and contrast nephropathy could happen. Patients with ARDS have impairment of gas exchange and severe hypoxemia. In addition, hemodynamic disturbances such as central venous pressure elevation, increased intra-thoracic pressure, and PEEP could influence urine output and glomerular filtration[15].

The mean BMI of the studied cases was 29.99 ± 4.26. This is in agreement with Zahid et al.[16], who reported mean ± SD BMI of 30.63 ± 7.73. The clinical data of our study participants were close to the results that were presented by Chan et al.[12] and Azeem et al.[9].

Risk factors and comorbidities among studied cases may increase the severity of COVID infection. Our findings were supported by many previous studies[10],[17],[18],[19],[20].

The incidence of AKI in our study was 22%. Our result was in line with Hamilton et al.[21], who reported that 20.3% of patients included in the analysis had a diagnosis of AKI. A higher incidence of AKI was reported in an American study by Zahid et al.[16] (27.3%) and in the Italian study by Fanelli et al.[22] (27.8%). Moreover, in May 2020, Hirsch et al.[23] reported even higher rates of AKI, that is, 36.6% overall in 1993 out of 5449 patients admitted with COVID-19 to 13 New York Metropolitan Area hospitals.

In contrast, lower incidences were reported by two Asian studies (5.1 and 9.2%)[4],[24], and locally in Egypt by Refat et al.[10], who reported that the incidence of AKI in hospitalized COVID cases was 5.3%.

Current evidence suggests that AKI in COVID-19-infected patients is a result of an interplay of virus-mediated injury, a dysregulated inflammatory response, angiotensin II pathway activation, hypercoagulation, and microangiopathy[8].

The increase in the cumulative incidence of AKI over time in our cohort is likely associated with concomitant clinical deterioration and less likely to represent a unique renal effect of COVID-19. We have found that age and BMI were significantly higher in the group with AKI. Moreover, AKI cases were significantly associated with respiratory diseases and administrating immune-suppressive drugs as comorbidities.

Zahid et al.[16] identified various risk factors for AKI in their study as patients with AKI were more likely to be male, have a history of hypertension, and have severe respiratory failure requiring mechanical ventilation. Moreover, higher BMI increased the likelihood of developing severe AKI. Furthermore, Xu et al.[18] analyzed the effect of sex and age on AKI at the early stage of COVID-19. They found that the levels of serum creatinine, urea nitrogen, and uric acid were higher in males and patients older than 70 years. Moreover, Azeem et al.[9] and Chan et al.[12] revealed that patients who developed incident AKI were older and were more likely to have other comorbidities.

In the current study, AKI cases were significantly associated with severity of disease, represented by high SOFA score, critical severity, and invasive respiratory support. This is in accordance with Mohamed et al.[25], who found that mechanical ventilation and shock were more common for the AKI group compared with those without AKI.

Cui et al.[19] also reported that most of the patients in the AKI group were critical (52.4%), had a higher admission SOFA score (4.5 ± 2.1), and had combined shock (47.6%), whereas in the non-AKI group, 27.4% of patients were critical, and the mean admission SOFA score was 2.8 ± 1.4, and the incidence of shock was significantly lower (25.3%). The study revealed that admission SOFA score was independently associated with the development of AKI in COVID-19-infected patients.

Regarding laboratory parameters, D-dimer, creatinine kinase, and creatinine were significantly higher among cases with AKI but GFR was significantly lower. This is in agreement with Azeem et al.[9]. Moreover, Hamilton et al.[21] reported that at baseline, patients with a higher serum sodium and creatinine were more likely to have AKI compared with those in the non-AKI cohort. There was no statistical difference in the lymphocyte count between the groups (P = 0.718) and it did not appear to be a risk factor for developing AKI, but patients in the AKI cohort had a higher baseline C-reactive protein, which was a significant risk factor for the development of AKI.

Regarding survival analysis in the current study, 20.0% of COVID cases died and 80.0% survived. This is in accordance with Hirsch et al.[23] who reported that among the 5449 patients included in the study, 888 (16.3%) died, 3280 (60.2%) were discharged to home or a rehabilitation facility, and 1281 (23.5%) were still in treatment. Moreover, Cui et al.[19] reported that 18 of 116 patients included in the study had died, with a mortality rate of 15.5%.

In contrast, Zahid et al.[16] reported a higher mortality rate as 40.1% (n = 188) of all the patients studied died during hospitalization, 54.3% (n = 255) were discharged, and 5.6% (n = 26) were transferred to the other institution. They contributed to the increased mortality rate to the high representation of ethnic minorities in the study population as the study was held in a hospital that provides medical services for an ethnic minority and a low-income population.

In our study, AKI was found to be associated with a high mortality rate, as 100% of AKI cases died, whereas only 10.8% of the COVID non-AKI patient died. Previous studies have revealed similar results as Zahid et al.[16] who reported that the in-hospital mortality was significantly higher in patients with an estimated GFR less than 60 ml/min/1.73 m2 (52.6%) than in patients with an estimated GFR equal to 60 ml/min/1.73 m2 (30.2%) at presentation. The in-hospital mortality of patients with AKI was 71.1% (91 out of 128 who developed AKI died). Moreover, Xu et al.[18] revealed that the fatality rate was obviously higher among COVID-19-infected patients with AKI than those without renal injury (33.9 vs. 4.3%, respiratory rate = 7.88, P < 0.001). In the study by Hamilton et al.[21], the overall mortality was significantly higher in the AKI group (52.4%) (n = 110) compared with 26.3% (n = 216) in the non-AKI group (P < 0.001).

Multivariate logistic regression for predictors of AKI in our study revealed that severity of infection, SOFA score, level of creatinine, GFR, and D-dimer were significant independent predictors for AKI. Other studies reported different predictors of AKI in COVID-infected patients, like the study by Xu et al.[18], who reported that male sex, older age, and comorbidity with diabetes were major predictors of AKI at the early stage of COVID-19. Moreover, Hirsch et al.[23] studied various baseline characteristics as potential predictors of AKI in COVID-19 and found that older age, male sex, diabetes mellitus, hypertension, history of cardiovascular disease, increased BMI, and use of vasopressor medications were independent predictors of AKI in COVID-19-infected patients. Hamilton et al.[21] have revealed by multiple logistic regression analyses that baseline serum sodium, C-reactive protein, male sex, and a previous diagnosis of the renal disease remain statistically significant for the development of AKI in association with COVID-19 after adjusting for variables.


  Conclusion Top


AKI is a frequent serious complication in hospitalized patients with COVID-19 and is associated with a high risk of mortality. It is more common in older patients with higher BMI and comorbidities such as respiratory diseases and immunosuppressive therapy. The severity of infection, SOFA score, GFR, creatinine, and D-dimer levels were identified as significant independent predictors for AKI in COVID-19-infected patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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