The consequences of severe acute respiratory syndrome coronavirus-2 on acute kidney injury among iraqi patients

Zahraa Faris Al-Khero; Zahra’a Abd Al-Aziz Yousif; Hamzah Abdulrahman Salman; Allaa Hatim Thanoon

doi:10.4103/bbrj.bbrj_353_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 7 | Issue : 1 | Page : 48-51

The consequences of severe acute respiratory syndrome coronavirus-2 on acute kidney injury among iraqi patients

Zahraa Faris Al-Khero¹, Zahra’a Abd Al-Aziz Yousif², Hamzah Abdulrahman Salman¹, Allaa Hatim Thanoon¹
¹ Department of Medical Laboratory Techniques, College of Medical Sciences Techniques, The University of Mashreq, Baghdad, Iraq
² Department of Microbiology, College of Medicine, Al-Nahrain University, Baghdad, Iraq

Date of Submission	06-Nov-2022
Date of Decision	24-Dec-2022
Date of Acceptance	14-Jan-2023
Date of Web Publication	14-Mar-2023

Correspondence Address:
Hamzah Abdulrahman Salman
Department of Medical Laboratory Techniques, College of Medical Sciences Techniques, The University of Mashreq, Baghdad
Iraq

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bbrj.bbrj_353_22

Abstract

Background: COVID-19 is considered one of the most infectious diseases that can spread by air droplets and can cause serious complications in the respiratory tract, also could affect many organs like the kidney and causing acute kidney injury (AKI). The study aimed to evaluate the status of the kidney function of patients who are infected with COVID-19 and how the virus is involved in AKI. Methods: The research was conducted from 15 January to 25 February 2021. One hundred patients (56% of males and 44% of females) were involved in the present study. All the samples were tested for COVID-19 using real-time reverse transcription polymerase chain reaction. Kidney function tests such as serum creatinine and blood urea, as well as COVID-19 infection severity measurements such as level of ferritin, D-dimer, and C-reactive protein (CRP) were tested for all patients. Results: All enrolled patients were positive for COVID-19. All the patients (100%) were positive for AKI (the mean of urea and creatinine were 78.87 mg/dl, and 2.16 μg/ml, respectively) and the mean age was 66.9 years. The infection severity was high as the level of ferritin (729.19 ng/ml), D-dimer (3.84 μg/ml), and CRP (71.87 mg/L) were high compared to normal values. The study revealed that AKI is probably worsened by COVID-19 infection, which is also connected to the greater severity of the disease. Conclusion: According to the results, we found a direct link between COVID-19 infection and the development of AKI. The study recommended giving critical care and attention with respect to kidney function to those who had COVID-19 infection.

Keywords: AKI, angiotensin-converting enzyme 2, D-dimer test, real-time reverse transcription-polymerase chain reaction, SARS-CoV-2

How to cite this article:
Al-Khero ZF, Yousif ZA, Salman HA, Thanoon AH. The consequences of severe acute respiratory syndrome coronavirus-2 on acute kidney injury among iraqi patients. Biomed Biotechnol Res J 2023;7:48-51

How to cite this URL:
Al-Khero ZF, Yousif ZA, Salman HA, Thanoon AH. The consequences of severe acute respiratory syndrome coronavirus-2 on acute kidney injury among iraqi patients. Biomed Biotechnol Res J [serial online] 2023 [cited 2023 Apr 1];7:48-51. Available from: https://www.bmbtrj.org/text.asp?2023/7/1/48/371697

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), member of the genus Coronavirus, order Nidovirales and family of Coronaviridae.^[1] SARA-COV-2 was documented initially in January 2020 as a pneumonia epidemic affecting the city of Wuhan.^[2] It binds to target cells using a specific receptor angiotensin-converting enzyme 2 (ACE2) that is expressed by these cells and leads to develop the infection.^[3]

The main notable signs of this disease are fever, slight dyspnea cough, pharyngitis, headache, conjunctivitis, fatigue, and gastrointestinal problems.^[4] Whereas in severe and critical cases, the main viral complication was an acute respiratory disease with interstitial and alveolar pneumonia,^[5] which also could affect many organs like the kidney and causing acute kidney injury (AKI).^[6] However, other organs can be affected, i.e., the heart, digestive tract, blood, nervous system, and respiratory system, and causes organ failure.^[7] A recent critical review reported that AKI usually obscures the progression of COVID-19 treatment and is responsible for delaying patients' stay in the hospital.^[8] The up-to-date report showed that AKI cases happened in 37% of COVID-19 patients in New York associated with the risk increased of mortality.^[9]

The precise mechanism of how the virus affects the kidney and leads to developed AKI is due to sepsis leads to cytokine storm or by direct virus cellular injury.^[10] The virus directly infects the kidney cells and makes duplicates of itself and possibly destruct these tissues.^[11] Moreover, a low oxygen ratio can cause a disturbance in kidney function.^[12] COVID-19 also causes thrombus, which can block the smallest capillaries in the renal and affect its function.^[13] The fast and precise diagnosis of the SARS-CoV-2 virus is critical in the management and prevention of COVID-19 expansion. However, real-time reverse transcription-polymerase chain reaction (RT-PCR) is the prime technique for the detection of COVID-19.^[14],[15] The current research set out to determine the consequences of the SRAS-CoV-2 on AKI among Iraqi patients.

Methods

Ethical approval

The research was conducted from 15 January to 25 February 2021. Due to the critical time in the middle of the epidemic, the research was exempt from acquiring written ethical approval. However, this study was approved by the Dar-Al Salam hospital's Ethics Board in Baghdad, Iraq. The study was explained to the patients and their companions, and a written consent form was obtained.

Sample collection

The samples were collected from 100 patients who were admitted to Dar-Al Salam hospital, Baghdad, which is specialized in COVID-19 infection. The samples were collected from adult patients (≥25 years). Blood samples (5 ml) were collected from each patient involved in this study. Two sets of tests were included: first, kidney function tests such as serum creatinine and blood urea; second, disease severity tests such as level of ferritin, D-dimer, and C-reactive protein (CRP).

Real-time reverse transcription-polymerase chain reaction

All the patients were tested for COVID-19 by RT-PCR. The RT-PCR assay was performed in accordance with the company's protocol, using a special 2019-nCoV nucleic acid detection kit (Shanghai Biogerm Medical Technology Co., Ltd.). Briefly, samples were collected from the nasopharyngeal by swabs. RNA was extracted within 2 h by RNA separation Kit (Zhongzhi, Wuhan, China). SARS-CoV-2 RNA templates were used for the RT-PCR method. The principal identification of SARS-CoV-2 was by the amplification of one or both genes: nucleocapsid protein gene and open reading frame 1ab gene. The primers and conditions of RT-PCR were obtained from Wang et al.^[16]

Determination of creatinine, urea, ferritin, D-dimer, and C-reactive protein

All the tests followed the manufacturer's protocols. Briefly, creatinine and urea tests were done using the CREA test kit (trinitrophenol) and Urea test kit (Urease-GLDH), respectively, by BIOBASE (China). While ferritin, D-dimer, and CRP tests were performed using a ferritin kit, D-dimer kit, and serum CRP kit (Roche Germany), respectively, by the Cobas^® analyzer series (Cobas, Germany).

Statistical analysis

The percentage and mean were obtained using MS Excel 2013 (Microsoft Corporation, USA).

Results

One hundred patients (56% of males and 44% of females) with severe COVID-19 infection were included in this study. All the patients were confirmed positive for COVID-19 by RT-PCR [Figure 1]. All the patients (100%) showed positive for AKI. The infection severity was high as the level of ferritin, D-dimer, and CRP was high [Table 1]. The majority of patients who had AKI, followed or during the COVID-19 infection, were elderly people, with a mean age of 66.9 years. The mean of urea, creatinine, D-dimer, ferritin, and CRP of patients is listed in [Table 1].

Figure 1: Amplification plots of the RT-PCR. The amplification of the gene started in 29 cycle. RT-PCR: Real-time reverse transcription-polymerase chain reaction

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Table 1: The mean and normal values of urea, creatinine, D-dimer, ferritin, and C-reactive protein of patients

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Discussion

All the tested samples were positive for SARS-CoV-2, which was detected by RT-PCR [Figure 1]. The RT-PCR showed high sensitivity for the detection of SARS-CoV-2, which was comparable with previous reports.^[17],[18] Moreover, Munne et al. recorded the RT-PCR as a gold-standard method for the detection of the SARS-CoV-2.^[19] The recent reports demonstrated that the specificity of RT-PCR is 95%, while the sensitivity is estimated to be 70% and 98%.^[20],[21]

The present study revealed a high frequency (100%) of AKI in hospitalized patients with COVID-19 infection; this is in agreement with the report of Hamilton et al.^[22] Therefore, we discovered a significant association between COVID-19 and AKI infection. As a result, COVID-19 patients with AKI may be more susceptible to deteriorating kidney health. The kidney is a target organ for SARS-CoV-2, which affects the endothelium, podocytes, and renal tubular epithelial cells. The main clinical signs of the kidney associated with COVID-19 vary from proteinuria and hematuria to severe AKI and abnormality of renal function.^[8]

The level of kidney function indicators (creatinine and urea) was raised than the normal values [Table 1]. Moreover, the level of D-dimer, ferritin, and CRP was higher than usual [Table 1]. Hamilton et al. stated that patients with AKI who are infected with COVID-19 are often much probable to decease than to be moved into the special intensive unit.^[22] Our results were in accordance with recent studies that stated SARS-CoV-2 infection evoked many organs injury such as liver dysfunction, myocardial damage, lymphopenia, and respiratory failure.^{[23],[24],[25],[26]}

The results showed an increase in the levels of serum creatinine and urea [Table 1], which indicates dysfunction in the kidney. Our finding was also supported by different studies that showed an increased level of creatinine and urea in severe cases of COVID-19.^[9],[27] However, the indirect mechanisms of hypovolemia, both from diarrhea loss or insensitive loss from hyperpyrexia, could lead to tubular injury. The secondary infections may lead to the development of sepsis-related AKI.^[27],[28] On the other hand, we proposed that SARS-CoV-2 may cause a direct injury to the kidney through binding to the ACE2 receptor on kidney tissue. The ACE2 receptors found on the endothelial cells, podocytes, and proximal tubular cells suggest a part of direct viral tropism in the development of AKI.^{[29],[30],[31]}

Besides mounting evidence of kidney function abnormality in critically severe cases due to viral infection there were characteristics of hyper inflammation, which are represented by raised in the serum of CRP, D-dimer, and hyperferritinemia [Table 1]. These results suggest to play a vital role of a cytokine storm in COVID-19 pathophysiology and severity on disease. This study was similar with the findings reported the elevation of D-dimer levels.^{[32],[33],[34]} Moreover, ferritin is an important mediator of the immune dysregulation that participates to the cytokine storm, particularly under the extreme hyperferritinemia.^[35] The evaluation of ferritin level was linked to death and severity of COVID-19. This might lead to a better understanding of the occurrence of secondary hemophagocytic lymphohistiocytosis (sHLH) in COVID-19.^[36] sHLH is a disorder of hyperinflammation recognized by a cytokine storm causing serious multi-organ failure.^[37] That condition is more frequently activated through viral infection, which explains the occurrence of abnormality in kidney function. However, the outcomes were parallel to the results of previous reports that showed an increased level of ferritin.^{[35],[38],[39]} On the other hand, the elevated level of CRP was generally associated with cytokine storm which can expect in the brutality of COVID-19 cases. CRP is a pro-inflammatory cytokine and a delicate marker of disease and tissue injury.^[40] However, the high level of CRP induces cytokine storms and damages many organ activities.^[41]

In our research, the results showed that there were significant associations between AKI and increased levels of CRP in severe cases of COVID-19. However, these findings were comparable with other studies that increased level of CRP is connected with the severity of COVID-19 cases.^{[27],[31],[35],[41]} Consequently, all these results of biomarker disclose that cytokine storm may include in the mechanism of SARS-CoV-2-induced renal impairment.

Conclusion

According to our results, we found a direct link between COVID-19 infection and the development of AKI. The study recommended giving critical care and attention to kidney function to those who had COVID-19, especially elderly patients. Otherwise, we cannot help many people who have no idea about their kidney function that may be weakened by the virus. The study also suggests including kidney function tests with the RT-PCR for patients who are suspected of COVID-19 during and postinfection.

Limitation of the study

The follow-up of patients after collecting the samples was the major limitation of the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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