[Downloaded free from http://www.ijournalhs.org on Monday, August 10, 2020, IP: 114.4.218.

74]

Review Article

Access this article online

Quick Response Code:
Acute kidney injury in patients with
COVID‑19
R. B. Nerli, Manas Sharma, Shridhar C. Ghagane1, Pulkit Gupta, Shashank D. Patil,
M. Shubhashree2, Murigendra B. Hiremath3

Website:
www.ijournalhs.org Abstract:
DOI:
INTRODUCTION: An outbreak of a  coronavirus disease 2019 (COVID‑19) was noted in December
10.4103/kleuhsj. 2019, affecting Wuhan city, Hubei Province, in China. It soon spread to other areas across the world. It
kleuhsj_116_20 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.
Departments of Urology CONCLUSIONS: The occurrence of AKI in patients hospitalized with COVID‑19 was around 9%.
and 2General Surgery, Coexisting chronic kidney disease and other comorbidities were risk factors for the development of
JN Medical College, AKI. AKI was associated with a higher mortality in these patients.
KLE Academy of
Keywords:
Higher Education and
Research, JNMC Campus, Acute kidney injury, coronavirus disease 2019, inhospital death, kidney disease
1
Department of Urology,
Urinary Biomarkers
Research Centre, KLES
Dr. Prabhakar Kore Introduction as a pandemic. This was due to the rapid
Hospital and M.R.C., increase in the number of cases outside
Belagavi, 3Department
of Biotechnology and
Microbiology, Karnatak
C oronavirus disease 2019 (COVID‑19)
is a severe infectious disease caused
by a recently discovered coronavirus.
China over the preceding 2 weeks that had
affected a growing number of countries.[1]
The updated figures as of April 27, 2020
University, Dharwad,
Pavate Nagar, Karnataka, Most people infected with the COVID‑19 were that 3,017,766 individuals had tested
India virus experience mild‑to‑moderate positive, and there were 207,722 deaths due
respiratory illness and recover without to COVID‑19. Over 894,464 patients had
requiring special treatment. However, recovered from the disease.[2]
older people and those with comorbidities
Address for such as cardiovascular disease, diabetes, Acute respiratory distress syndrome (ARDS)
correspondence: chronic respiratory disease, and cancer are is one life‑threatening complication
Dr. R. B. Nerli,
Department of Urology, more likely to develop serious illnesses. that can arise in patients hospitalized
JN Medical College, Dr. Tedros Adhanom Ghebreyesus, WHO’s with the infection. Recent research has
KLE Academy of Higher Director‑General, announced on March 12, suggested that >40% of patients in the study
Education and Research 2020 that COVID‑19 is to be characterized hospitalized for severe and life‑threatening
(Deemed‑to‑be‑University),
JNMC Campus, COVID‑19 developed ARDS and over 50%
Belagavi ‑ 590 010, This is an open access journal, and articles are of those diagnosed died from the disease.[3]
Karnataka, India. distributed under the terms of the Creative Commons
E‑mail: rbnerli@gmail.com Attribution‑NonCommercial‑ShareAlike 4.0 License, which
allows others to remix, tweak, and build upon the work How to cite this article: Nerli RB, Sharma M,
Received: 27 April 2020, non‑commercially, as long as appropriate credit is given and Ghagane SC, Gupta P, Patil SD, Shubhashree M, et al.
Revised: 04 May 2020, the new creations are licensed under the identical terms. Acute kidney injury in patients with COVID‑19. Indian J
Accepted: 12 May 2020, Health Sci Biomed Res 2020;13:64-7.
Published: 23 June 2020 Forreprintscontact:WKHLRPMedknow_reprints@wolterskluwer.com

64 © 2020 Indian Journal of Health Sciences and Biomedical Research KLEU | Published by Wolters Kluwer - Medknow
[Downloaded free from http://www.ijournalhs.org on Monday, August 10, 2020, IP: 114.4.218.74]
Nerli, et al.: Acute Kidney Injury in COVID-19 Patients
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
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
Indian Journal of Health Sciences and Biomedical Research KLEU - Volume 13, Issue 2, May-August 2020 65
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
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.[10‑15] 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].
The median age in the abovementioned series[10‑15] 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.[10‑14] A total of 139 (9.36%) patients
developed AKI during admission.[10,11,13‑15] 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
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
[Downloaded free from http://www.ijournalhs.org on Monday, August 10, 2020, IP: 114.4.218.74]

Nerli, et al.: Acute Kidney Injury in COVID-19 Patients

Table 1: Details of the patients admitted in Wuhan, China

Xiao G et al. Zhou F et al. Wang D et al. Yang X et al. Cheng Y et al. Wang L et al. Total
Number of patients 287 191 138 52 701 116 1485
Median age (years) 62 (51-70) 56 (46-67) 56 (42-68) NA 63 (50-71) 54 (38-59)
Male (%) 160 (55.7) 119 (62) 75 (54.3) 35 (67) 367 (52.4) 67 (57.8) 823 (55.4)
Females (%) 127 (44.3) 72 (38) 63 (45.7) 17 (33) 49 (42.2) 662 (44.6)
Comorbidities (%) 206 (71.7) 91 (48) 64 (46.4) 21 (40) 297 (42.5) NA 679 (49.7)
Known CKD (%) 5 (2) 2 (1) 4 (2.9) NA 14 (2) 5 (4.3) 30 (2.09)
Creatinine (>1.5 mg/dL) (%) NA 8 NA NA 101 (94.3) NA 109
AKI (%) 55 (19) 28 (15) 5 (3.6) 15 (29) 36 (5.13) NA 139 (9.36)
Renal replacement therapy NA 10 (5.23) 2 (1.44) 9 (17.3) NA NA 21 (5.5)
(%)
Total death (%) 19 (6.62) 54 (28.2) NA 32 (61.5) 113 (16.1) NA 218 (17.7)
Deaths in AKI (%) 12 (21.8) 27 (96.4) NA 12 (80) NA NA 51 (52)
CKD: Chronic kidney disease, AKI: Acute kidney injury, NA: Date not available

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 Sanità” 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
i. AKI is frequently observed in patients with ARDS
ii. 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
iii. Kidney epithelial infection may worsen the local
inflammatory response
iv. Associated preexisting kidney disease leads to a
tendency to develop AKI episodes
v. Identification of patients with AKI may lead to a better
allocation of hospital resources
vi. Use of extracorporeal blood purification techniques
and antiviral therapies may theoretically limit the
systemic and local inflammatory response.
Conclusions
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
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

66 Indian Journal of Health Sciences and Biomedical Research KLEU - Volume 13, Issue 2, May-August 2020
[Downloaded free from http://www.ijournalhs.org on Monday, August 10, 2020, IP: 114.4.218.74]
Nerli, et al.: Acute Kidney Injury in COVID-19 Patients
2020 Apr 27].
2. COVID‑19 CORONAVIRUS PANDEMIC. Worldometer;
27 April, 2020. Available from: https://www.worldometers.info/
coronavirus/. [Last accessed on 2020 Apr 27].
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].
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.
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].
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.
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.
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.
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.
10. Cheng  Y, Luo  R, Wang  K, Zhang  M, Wang  Z, Dong  L, et al.
Indian Journal of Health Sciences and Biomedical Research KLEU - Volume 13, Issue 2, May-August 2020 67
Kidney disease is associated with in‑hospital death of patients
with COVID‑19. Kidney Int 2020;97:829‑38.
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.
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.
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.
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.
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.
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.
17. Wilson JG, Calfee CS. ARDS subphenotypes: Understanding a
heterogeneous syndrome. Crit Care 2020;24:102.
18. Letko  MC, Munster  V. Functional Assessment of Cell Entry
and Receptor Usage for Lineage B β‑Coronaviruses, Including
2019‑nCoV. bioRxiv; 2020.