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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 13  |  Issue : 2  |  Page : 64-67

Acute kidney injury in patients with COVID-19


1 Department of Urology, JN Medical College, KLE Academy of Higher Education and Research, JNMC Campus, Belagavi, Karnataka, India
2 Department of Urology, Urinary Biomarkers Research Centre, KLES Dr. Prabhakar Kore Hospital and M.R.C., Belagavi, Karnataka, India
3 Department of General Surgery, JN Medical College, KLE Academy of Higher Education and Research, JNMC Campus, Belagavi, Karnataka, India
4 Department of Biotechnology and Microbiology, Karnatak University, Dharwad, Pavate Nagar, Karnataka, India

Date of Submission27-Apr-2020
Date of Acceptance12-May-2020
Date of Web Publication23-Jun-2020

Correspondence Address:
Dr. R B Nerli
Department of Urology, JN Medical College, KLE Academy of Higher Education and Research (Deemed-to-be-University), JNMC Campus, Belagavi - 590 010, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kleuhsj.kleuhsj_116_20

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  Abstract 


INTRODUCTION: An outbreak of a coronavirus disease 2019 (COVID-19) was noted in December 2019, affecting Wuhan city, Hubei Province, in China. It soon spread to other areas across the world. It is well known that the diffuse alveolar damage and acute respiratory failure caused by the coronavirus remain the main features; however, the involvement of other organs is also noted. In this review, we have attempted to determine the prevalence of acute kidney injury (AKI) in patients with COVID-19.
MATERIALS AND METHODS: We conducted a literature search for relevant research papers published till April 25, 2020, using the electronic Google Scholar and PubMed database with the following terms: COVID-19, acute kidney injury, renal failure, and outcome.
RESULTS: We found 16 articles related to AKI and COVID-19 in the English language from the Google Scholar database and PubMed database. Of these, six articles from China were directly related to the AKI in patients with COVID-19. Forty-nine percent (49.7%) of the admitted patients had comorbidities. Thirty patients (2%) out of 1430 patients had chronic kidney disease before admission. A total of 139 patients (9.36%) developed AKI during hospital admission. A total of 51 patients (52%) with AKI died during the course of treatment.
CONCLUSIONS: The occurrence of AKI in patients hospitalized with COVID-19 was around 9%. Coexisting chronic kidney disease and other comorbidities were risk factors for the development of AKI. AKI was associated with a higher mortality in these patients.

Keywords: Acute kidney injury, coronavirus disease 2019, inhospital death, kidney disease


How to cite this article:
Nerli R B, Sharma M, Ghagane SC, Gupta P, Patil SD, Shubhashree M, Hiremath MB. Acute kidney injury in patients with COVID-19. Indian J Health Sci Biomed Res 2020;13:64-7

How to cite this URL:
Nerli R B, Sharma M, Ghagane SC, Gupta P, Patil SD, Shubhashree M, Hiremath MB. Acute kidney injury in patients with COVID-19. Indian J Health Sci Biomed Res [serial online] 2020 [cited 2020 Sep 29];13:64-7. Available from: http://www.ijournalhs.org/text.asp?2020/13/2/64/287409




  Introduction Top


Coronavirus disease 2019 (COVID-19) is a severe infectious disease caused by a recently discovered coronavirus. Most people infected with the COVID-19 virus experience mild-to-moderate respiratory illness and recover without requiring special treatment. However, older people and those with comorbidities such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious illnesses. Dr. Tedros Adhanom Ghebreyesus, WHO's Director-General, announced on March 12, 2020 that COVID-19 is to be characterized as a pandemic. This was due to the rapid increase in the number of cases outside China over the preceding 2 weeks that had affected a growing number of countries.[1] The updated figures as of April 27, 2020 were that 3,017,766 individuals had tested positive, and there were 207,722 deaths due to COVID-19. Over 894,464 patients had recovered from the disease.[2]

Acute respiratory distress syndrome (ARDS) is one life-threatening complication that can arise in patients hospitalized with the infection. Recent research has suggested that >40% of patients in the study hospitalized for severe and life-threatening COVID-19 developed ARDS and over 50% of those diagnosed died from the disease.[3] In a Chinese cohort[4] of 1099 patients with COVID-19, 93.6% were hospitalized, 91.1% had pneumonia, 5.3% were admitted to the intensive care unit, 3.4% had ARDS, and only 0.5% had acute kidney injury (AKI). The prevalence of AKI among patients with COVID-19 appears to be low.

The potential mechanisms of kidney involvement in these patients include three aspects, namely cytokine damage, organ crosstalk, and systemic effects. Organ crosstalk is defined as the intricate biological interaction and feedback mechanism between distant organs, which is mediated by cellular, molecular, neural, endocrine, and paracrine factors. These mechanisms are profoundly interconnected and have important implications for extracorporeal therapy.[5] Cytokine release syndrome (CRS) has been well documented since the first reports of this disease.[6],[7] AKI occurs as a result of intrarenal inflammation, increased vascular permeability, volume depletion, and cardiomyopathy, which can lead to cardiorenal syndrome type 1. Pro-inflammatory interleukin-6 (IL-6) is the most important causative cytokine in CRS, and the plasma concentration of IL-6 is increased in those with ARDS in patients with COVID-19.

There is a close relationship between alveolar and tubular damage and is known as the lung–kidney axis in ARDS.[8] Cytokine overproduction is involved in lung–kidney bidirectional damage. Injured renal tubular epithelium promotes the upregulation of IL-6, and inhuman and animal studies increased IL-6 serum concentration in AKI was associated with higher alveolar-capillary permeability and pulmonary hemorrhage.[9] Fluid expansion or systemic effects have a detrimental effect in ARDS, as it increases alveolar-capillary leakage, and in AKI, it worsens renal vein congestion, leading to renal compartment syndrome. In light of the rapidly growing incidence of COVID-19 infection and its associated morbidity and mortality, we decided to review the available data in literature. We aimed at evaluating the incidence of AKI in patients with COVID-19 infection and more precisely estimate the effect of AKI on survival and compare the outcome of AKI in other regions affected by the disease.


  Materials and Methods Top


Literature search

We conducted a literature search for relevant research articles published till April 25, 2020, using the Google Scholar and PubMed database with the following terms: “COVID-19, acute kidney injury, renal failure, and outcome”. References of the retrieved articles were also screened for earlier original studies. The inclusion criteria were as follows: patients with (a) COVID-19 infection and (b) AKI. In the first part of the review, we have included all articles with patients having AKI associated with COVID-19 infection. In the second part of our review, we have looked at the outcome of AKI in these patients.

Data extraction

We extracted the following information from each published article: author, month and year of publication, country of origin, number of patients with COVID-19, patients with AKI, treatment given, outcome, and survival.


  Results Top


We were able to retrieve 16 articles related to AKI and COVID-19 in the English language from Google Scholar and PubMed database. Of these, six articles from China were directly related to the AKI in patients with COVID-19.[10],[11],[12],[13],[14],[15] The number of patients admitted with COVID-19 infection, the median age, gender, comorbidities, serum creatinine on admission, the number of patients developing AKI, requirement of renal replacement therapy, and overall mortality and mortality in patients with AKI were tabulated [Table 1].
Table 1: Details of the patients admitted in Wuhan, China

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The median age in the abovementioned series[10],[11],[12],[13],[14],[15] ranged between 54 and 63 years. Males (55.4%) outnumbered the females (44.6%) in hospitalized patients. Forty-nine percent (49.7%) of the admitted patients had comorbidities that included hypertension, diabetes, cardiac disease, chronic obstructive pulmonary disease, and cancer. Thirty patients (2%) had chronic kidney disease before admission.[10],[11],[12],[13],[14] A total of 139 (9.36%) patients developed AKI during admission.[10],[11],[13],[14],[15] A total of 51 patients (52%) with AKI died during treatment.[11],[13],[15] Of the 381 patients, 21 (5.5%) required renal replacement therapy.[11],[14],[15]


  Discussion Top


This pandemic caused by the novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) is named COVID-19 by the World Health Organization. The primary involvement of the lung with diffuse alveolar damage and respiratory failure has been the major focus in patients with COVID-19; however, recent reports have highlighted the fact that kidney injury is also relatively common in this infection and is associated with increased morbidity and mortality.[7],[10] Involvement of other organs including the liver, gastrointestinal tract, and kidney had been reported earlier during SARS in 2003, and it seems that it is true even for patients with COVID-19.

Succeeding the lung infection, the virus is likely to enter the blood circulation and affects other organs including the kidney, wherein it damages renal tubular cells. Cheng et al.[10] reported that the RNA of COVID-19 was found in the plasma of 15% of the patients as tested by the real-time polymerase chain reaction.[7] Cheng et al.[10] reported an incidence of 5.1% of AKI occurring in their patients, and that the incidence of AKI was ominously higher in patients with elevated serum creatinine (11.9%) than in patients with normal values (4.0%). He also reported that the inhospital death occurred in 16.1% of patients. The incidence of inhospital death in the COVID-19 patients with elevated serum creatinine was 33.7%. This was significantly higher than the deaths recorded in those with normal serum creatinine (13.2%).

Using Kaplan–Meier analysis, Cheng et al.[10] noted a considerably higher inhospital death rate for patients with kidney abnormalities, including elevated serum creatinine, elevated blood urea nitrogen, proteinuria, hematuria, and AKI (P < 0.001). Univariable Cox regression analysis exhibited that age above 65 years, male sex, and severe COVID-19 disease were associated with inhospital death.

A similar data was recently confirmed by the Italian report of “Istituto Superiore di Sanitaà” describing an incidence of 27.8% of AKI in >2000 patients as updated on March 17, 2020.[16] Fanelli et al.[16] reported that the occurrence of AKI represented a lethal complication in seriously ill patients, leading to an increased risk of death. Similarly, Wilson and Calfee[17] reported that the onset of moderate-to-severe AKI was associated with a significant risk for mortality in patients with ARDS. Based on information derived from previous studies, it is known that the beta coronaviruses, SARS-CoV and the most recent SARS-CoV-2, use angiotensin-converting enzyme 2 (ACE-2) as a receptor to assist viral entry into target cells; ACE-2 is also found on the surface of renal tubular cells, and their infection may exacerbate the local inflammatory response and subsequently the incidence and the extent of AKI episodes.[18]

Key points regarding acute kidney injury in coronavirus disease 2019 patients are as follows

  1. AKI is frequently observed in patients with ARDS
  2. Respiratory distress-associated AKI occurs due to inflammatory/immune reaction, characterized by an enhanced release of circulating mediators able to interact and damage kidney-resident cells
  3. Kidney epithelial infection may worsen the local inflammatory response
  4. Associated preexisting kidney disease leads to a tendency to develop AKI episodes
  5. Identification of patients with AKI may lead to a better allocation of hospital resources
  6. Use of extracorporeal blood purification techniques and antiviral therapies may theoretically limit the systemic and local inflammatory response.



  Conclusions Top


Patients infected with COVID-19 and hospitalized have a high risk of developing AKI. Patients with preexisting comorbidities, namely hypertension, type 2 diabetes mellitus, and cardiac and pulmonary disease (chronic obstructive pulmonary disease), are at an increased risk to developing AKI. Patients with deranged serum creatinine and kidney disease are at an increased of needing renal replacement therapy as well as death.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
WHO Announces COVID-19 Outbreak a Pandemic. World Health Organization Regional Office for Europe. 12 March, 2020. Available from: http://www.euro.who.int/en/health-topics/health-emerg encies/coronavirus-covid-19/ne ws/news/2020/3/who-announces-covid-19-outbreak-a-pandemic. [Last accessed on 2020 Apr 27].  Back to cited text no. 1
    
2.
COVID-19 CORONAVIRUS PANDEMIC. Worldometer; 27 April, 2020. Available from: https://www.worldometers.info/coronavirus/. [Last accessed on 2020 Apr 27].  Back to cited text no. 2
    
3.
Leah G. ARDS Is A Common Cause Of Death In Critically Ill Coronavirus Patients. Above Whispers; 01 April, 2020. Available from: https://www.health.com/condition/infectious-diseases/co ronavirus/what-is-ards. [Last accessed on 2020 Apr 27].  Back to cited text no. 3
    
4.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708-20.  Back to cited text no. 4
    
5.
Ronco, C., Reis, T. Kidney involvement in COVID-19 and rationale for extracorporeal therapies. Nat Rev Nephrol 2020;16:308–10. Available from: https://doi.org/10.1038/s41581-020-0284-7. [Last accessed on 2020 May 27].  Back to cited text no. 5
    
6.
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020:e200994. DOI: doi:10.1001/jamainternmed.2020.0994.  Back to cited text no. 6
    
7.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020;395:497-506.  Back to cited text no. 7
    
8.
Panitchote A, Mehkri O, Hasting A, Hanane T, Demirjian S, Torbic H, et al. Factors associated with acute kidney injury in acute respiratory distress syndrome. Ann Intensive Care 2019;9:74.  Back to cited text no. 8
    
9.
Husain-Syed F, Slutsky AS, Ronco C. Lung-kidney cross-talk in the critically ill patient. Am J Respir Crit Care Med 2016;194:402-14.  Back to cited text no. 9
    
10.
Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int 2020;97:829-38.  Back to cited text no. 10
    
11.
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62.  Back to cited text no. 11
    
12.
Wang L, Li X, Chen H, Yan S, Li D, Li Y, Gong Z. Coronavirus disease 19 infection does not result in acute kidney injury: an analysis of 116 hospitalized patients from Wuhan, China. American journal of nephrology. 2020;51:343-8.  Back to cited text no. 12
    
13.
Zeng Z, Sha T, Zhang Y, Wu F, Hu H, Li H, et al. Hypertension in Patients Hospitalized with COVID-19 in Wuhan, China: A Single-Center Retrospective Observational Study. medRxiv; 2020.  Back to cited text no. 13
    
14.
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020;323:1061-9.  Back to cited text no. 14
    
15.
Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med 2020;8:475-81.  Back to cited text no. 15
    
16.
Fanelli V, Fiorentino M, Cantaluppi V, Gesualdo L, Stallone G, Ronco C, et al. Acute kidney injury in SARS-CoV-2 infected patients. Crit Care 2020;24:155.  Back to cited text no. 16
    
17.
Wilson JG, Calfee CS. ARDS subphenotypes: Understanding a heterogeneous syndrome. Crit Care 2020;24:102.  Back to cited text no. 17
    
18.
Letko MC, Munster V. Functional Assessment of Cell Entry and Receptor Usage for Lineage B β-Coronaviruses, Including 2019-nCoV. bioRxiv; 2020.  Back to cited text no. 18
    



 
 
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