Acute kidney injury: Incidence, risk factors, and outcomes in severe COVID-19 patients

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Abstract

Background

COVID-19 is a multisystemic disorder that frequently causes acute kidney injury (AKI). However, the precise clinical and biochemical variables associated with AKI progression in patients with severe COVID-19 remain unclear.

Methods

We performed a retrospective study on 278 hospitalized patients who were admitted to the ward and intensive care unit (ICU) with COVID-19 between March 2020 and June 2020, at the University Hospital, São Paulo, Brazil. Patients aged ≥ 18 years with COVID-19 confirmed on RT-PCR were included. AKI was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. We evaluated the incidence of AKI, several clinical variables, medicines used, and outcomes in two sub-groups: COVID-19 patients with AKI (Cov-AKI), and COVID-19 patients without AKI (non-AKI). Univariate and multivariate analyses were performed.

Results

First, an elevated incidence of AKI (71.2%) was identified, distributed across different stages of the KDIGO criteria. We further observed higher levels of creatinine, C-reactive protein (CRP), leukocytes, neutrophils, monocytes, and neutrophil-to-lymphocyte ratio (NLR) in the Cov-AKI group than in the non-AKI group, at hospital admission. On univariate analysis, Cov-AKI was associated with older age (>62 years), hypertension, CRP, MCV, leucocytes, neutrophils, NLR, combined hydroxychloroquine and azithromycin treatment, use of mechanical ventilation, and vasoactive drugs. Multivariate analysis showed that hypertension and the use of vasoactive drugs were independently associated with a risk of higher AKI in COVID-19 patients. Finally, we preferentially found an altered erythrocyte and leukocyte cellular profile in the Cov-AKI group compared to the non-AKI group, at hospital discharge.

Conclusions

In our study, the development of AKI in patients with severe COVID-19 was related to inflammatory blood markers and therapy with hydroxychloroquine/azithromycin, with vasopressor requirement and hypertension considered potential risk factors. Thus, attention to the protocol, hypertension, and some blood markers may help assist doctors with decision-making for the management of COVID-19 patients with AKI.

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Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang, Yeming Wang, Xingwang Li … (2020)

Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.

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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Fei Zhou, Ting Yu, Ronghui Du … (2020)

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

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Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

Xiaobo Yang, Yuan Yu, Jiqian Xu … (2020)

Summary Background An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding None.

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Author and article information

Contributors

Danilo Candido de Almeida:

ORCID: https://orcid.org/0000-0003-3661-2124

Role: ConceptualizationRole: Data curationRole: Formal analysisRole: SoftwareRole: Writing – original draft

Maria do Carmo Pinho Franco: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Writing – original draft

Davi Rettori Pardo dos Santos: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: Methodology

Marina Colella Santos: Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Resources

Isabela Soucin Maltoni: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Resources

Felipe Mascotte: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: Methodology

Alexandra Aparecida de Souza: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ResourcesRole: Software

Paula Massaroni Pietrobom:

ORCID: https://orcid.org/0000-0003-0360-9922

Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Writing – original draft

Eduardo Alexandrino Medeiros: Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: ValidationRole: Writing – original draft

Paulo Roberto Abrão Ferreira: Role: ConceptualizationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – original draft

Flavia Ribeiro Machado: Role: ConceptualizationRole: Data curationRole: MethodologyRole: SupervisionRole: Writing – original draft

Miguel Angelo Goes:

ORCID: https://orcid.org/0000-0001-7687-3826

Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: Writing – original draft

Antonio Carlos Seguro: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS One

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 25 May 2021

Publication date Collection: 2021

Publication date PMC-release: 25 May 2021

Volume: 16

Issue: 5

Electronic Location Identifier: e0251048

Affiliations

[1 ] Nephrology Division, Federal University of São Paulo, São Paulo, Brazil

[2 ] Laboratory of Applied Computing (LABCOM), Federal Institute of Education, Science and Technology of São Paulo, São Paulo, Brazil

[3 ] Infectious Disease Division, Federal University of São Paulo, São Paulo, Brazil

[4 ] Intensive Care Unit Division, Federal University of São Paulo, São Paulo, Brazil

Universidade de Sao Paulo Faculdade de Medicina, BRAZIL

Author notes

Competing Interests: No authors have competing interests.

‡ DRPS, MCS, ISM, FM, AAS, PMP, EAM, PRAF, FRM and MAG also contributed equally to this work.

* E-mail: miguelpitico7@ 123456gmail.com

Author information

Danilo Candido de Almeida https://orcid.org/0000-0003-3661-2124

Paula Massaroni Pietrobom https://orcid.org/0000-0003-0360-9922

Miguel Angelo Goes https://orcid.org/0000-0001-7687-3826

Article

Publisher ID: PONE-D-21-00655

DOI: 10.1371/journal.pone.0251048

PMC ID: 8148326

PubMed ID: 34033655

SO-VID: 960bddb3-2ee5-4413-bc21-3b3d59d813bb

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 13 January 2021

Date accepted : 20 April 2021

Page count

Figures: 3, Tables: 4, Pages: 17

Funding

The author(s) received no specific funding for this work.

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Data Availability The anonymized data set used during the present study are available for sharing.

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Acute kidney injury: Incidence, risk factors, and outcomes in severe COVID-19 patients

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Abstract

Background

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Novel Coronavirus Disease COVID-19

Most cited references 54

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

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