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Yuan L, Mehmood A, Meng L. A meta-analysis of risk factors for acute kidney injury in pneumonia: Effectiveness of nursing interventions. Ther Apher Dial 2024; 28:518-533. [PMID: 38545743 DOI: 10.1111/1744-9987.14124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 01/10/2024] [Accepted: 03/01/2024] [Indexed: 07/05/2024]
Abstract
INTRODUCTION The spread of coronavirus disease 2019 (COVID-19) worldwide since November 2019 is of interest to understand its impact on various organs. COVID-19 patients experience a higher incidence of acute kidney injury (AKI) compared with non-COVID-19 patients. METHODS A systematic literature search was conducted that covered the period from November 1, 2019 to February 28, 2021. RESULTS The analysis incorporated a comprehensive review of 19 studies of 21 362 patients. The older age (mean difference [MDs] = 5.11), cardiovascular disease (CVD) (odds ratio [OR] = 1.94), male sex (OR = 1.55), chronic kidney disease (CKD) (OR = 3.82), hypertension (OR = 2.15), diabetes (OR = 1.71), cancer (OR = 1.16), and chronic obstructive pulmonary disease (COPD) (OR = 1.40), mechanical ventilation (OR = 8.66), and vasopressor (OR = 6.30), were significantly associated with risk factor for AKI (P < 0.05). CONCLUSION The analysis revealed independent risk factors for AKI.
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Affiliation(s)
- Liangjuan Yuan
- Department of Respiratory, Shandong Provincial Third Hospital, Jinan, China
| | - Arshad Mehmood
- Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Lei Meng
- Department of Nephrology, The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital), Jinan, China
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2
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Sun J, Edsfeldt A, Svensson J, Ruge T, Goncalves I, Swärd P. ADAM-17 Activity and Its Relation to ACE2: Implications for Severe COVID-19. Int J Mol Sci 2024; 25:5911. [PMID: 38892098 PMCID: PMC11172796 DOI: 10.3390/ijms25115911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/20/2024] [Accepted: 05/23/2024] [Indexed: 06/21/2024] Open
Abstract
There is a lack of studies aiming to assess cellular a disintegrin and metalloproteinase-17 (ADAM-17) activity in COVID-19 patients and the eventual associations with the shedding of membrane-bound angiotensin-converting enzyme 2 (mACE2). In addition, studies that investigate the relationship between ACE2 and ADAM-17 gene expressions in organs infected by SARS-CoV-2 are lacking. We used data from the Massachusetts general hospital COVID-19 study (306 COVID-19 patients and 78 symptomatic controls) to investigate the association between plasma levels of 33 different ADAM-17 substrates and COVID-19 severity and mortality. As a surrogate of cellular ADAM-17 activity, an ADAM-17 substrate score was calculated. The associations between soluble ACE2 (sACE2) and the ADAM-17 substrate score, renin, key inflammatory markers, and lung injury markers were investigated. Furthermore, we used data from the Genotype-Tissue Expression (GTEx) database to evaluate ADAM-17 and ACE2 gene expressions by age and sex in ages between 20-80 years. We found that increased ADAM-17 activity, as estimated by the ADAM-17 substrates score, was associated with COVID-19 severity (p = 0.001). ADAM-17 activity was also associated with increased mortality but did not reach statistical significance (p = 0.06). Soluble ACE2 showed the strongest positive correlation with the ADAM-17 substrate score, follow by renin, interleukin-6, and lung injury biomarkers. The ratio of ADAM-17 to ACE2 gene expression was highest in the lung. This study indicates that increased ADAM-17 activity is associated with severe COVID-19. Our findings also indicate that there may a bidirectional relationship between membrane-bound ACE2 shedding via increased ADAM-17 activity, dysregulated renin-angiotensin system (RAS) and immune signaling. Additionally, differences in ACE2 and ADAM-17 gene expressions between different tissues may be of importance in explaining why the lung is the organ most severely affected by COVID-19, but this requires further evaluation in prospective studies.
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Affiliation(s)
- Jiangming Sun
- Cardiovascular Research-Translational Studies, Department of Clinical Sciences Malmö, Lund University, 205 02 Malmö, Sweden; (J.S.); (A.E.); (I.G.)
| | - Andreas Edsfeldt
- Cardiovascular Research-Translational Studies, Department of Clinical Sciences Malmö, Lund University, 205 02 Malmö, Sweden; (J.S.); (A.E.); (I.G.)
- Department of Cardiology, Skåne University Hospital, 205 02 Malmö, Sweden
- Wallenberg Center for Molecular Medicine, Lund University, 221 00 Lund, Sweden
| | - Joel Svensson
- Department of Laboratory Medicine, Lund University, 221 00 Lund, Sweden;
| | - Toralph Ruge
- Department of Emergency and Internal Medicine, Skånes University Hospital, 214 28 Malmö, Sweden;
- Department of Clinical Sciences Malmö, Lund University, 214 28 Malmö, Sweden
- Department of Internal Medicine, Skåne University Hospital, 214 28 Malmö, Sweden
| | - Isabel Goncalves
- Cardiovascular Research-Translational Studies, Department of Clinical Sciences Malmö, Lund University, 205 02 Malmö, Sweden; (J.S.); (A.E.); (I.G.)
- Department of Cardiology, Skåne University Hospital, 205 02 Malmö, Sweden
| | - Per Swärd
- Clinical and Molecular Osteoporosis Research Unit, Departments of Orthopedics and Clinical Sciences, Skåne University Hospital, Lund University, 205 02 Malmö, Sweden
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Cumhur Cure M, Cure E. Why have SGLT2 Inhibitors Failed to Achieve the Desired Success in COVID-19? Curr Pharm Des 2024; 30:1149-1156. [PMID: 38566383 DOI: 10.2174/0113816128300162240322075423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 03/11/2024] [Accepted: 03/12/2024] [Indexed: 04/04/2024]
Abstract
The SARS-CoV-2 virus emerged towards the end of 2019 and caused a major worldwide pandemic lasting at least 2 years, causing a disease called COVID-19. SARS-CoV-2 caused a severe infection with direct cellular toxicity, stimulation of cytokine release, increased oxidative stress, disruption of endothelial structure, and thromboinflammation, as well as angiotensin-converting enzyme 2 (ACE2) down-regulation-mediated renin-angiotensin system (RAS) activation. In addition to glucosuria and natriuresis, sodium-glucose transport protein 2 (SGLT2) inhibitors (SGLT2i) cause weight loss, a decrease in glucose levels with an insulin-independent mechanism, an increase in erythropoietin levels and erythropoiesis, an increase in autophagy and lysosomal degradation, Na+/H+-changer inhibition, prevention of ischemia/reperfusion injury, oxidative stress and they have many positive effects such as reducing inflammation and improving vascular function. There was great anticipation for SGLT2i in treating patients with diabetes with COVID-19, but current data suggest they are not very effective. Moreover, there has been great confusion in the literature about the effects of SGLT2i on COVID-19 patients with diabetes . Various factors, including increased SGLT1 activity, lack of angiotensin receptor blocker co-administration, the potential for ketoacidosis, kidney injury, and disruptions in fluid and electrolyte levels, may have hindered SGLT2i's effectiveness against COVID-19. In addition, the duration of use of SGLT2i and their impact on erythropoiesis, blood viscosity, cholesterol levels, and vitamin D levels may also have played a role in their failure to treat the virus. This article aims to uncover the reasons for the confusion in the literature and to unravel why SGLT2i failed to succeed in COVID-19 based on some solid evidence as well as speculative and personal perspectives.
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Affiliation(s)
- Medine Cumhur Cure
- Medilab Laboratory and Imaging Center, Department of Biochemistry, Sisli, Istanbul, Turkey
| | - Erkan Cure
- Department of Internal Medicine, Beylikdüzü Medilife Hospital, Yakuplu Mh, Beylikduzu, Istanbul, Turkey
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Mackintosh L, Busby A, Farrington K, Hawkins J, Afuwape S, Bristow P, Silva-Gane MD, Hall N, Harris T, Hudson J, Norton S, Ormandy P, Pearce CJ, Santhakumaran S, Sharma S, Sridharan S, Steenkamp R, Slevin J, Wellsted D, Chilcot J. Impact of the COVID-19 pandemic on services for patients with chronic kidney disease: findings of a national survey of UK kidney centres. BMC Nephrol 2023; 24:356. [PMID: 38049710 PMCID: PMC10696738 DOI: 10.1186/s12882-023-03344-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Accepted: 09/21/2023] [Indexed: 12/06/2023] Open
Abstract
BACKGROUND Services for patients with kidney disease underwent radical adaptations in response to the COVID-19 pandemic. We undertook an online national survey of UK kidney centres to understand the nature, range, and degree of variation in these changes and to explore factors contributing to differing practice. METHODS The survey was designed by a multidisciplinary team of kidney professionals, service users and researchers. It enquired about centre services and staffing, including psychosocial provision, and changes to these in response to the COVID-19 pandemic. Links to the survey were sent to all 68 UK kidney centres and remained active from December 2021 to April 2022, and a revised version to nurses in late 2022 for additional data. Quantitative data were analysed descriptively. Content analysis on free-text responses identified common themes. RESULTS Analysable responses were received from 41 out of the 68 UK centres (60%), with partial data from an additional 7 (11%). Adaptations were system-wide and affected all aspects of service provision. Some changes were almost universal such as virtual consultations for outpatient appointments, with significant variation in others. Outpatient activity varied from fully maintained to suspended. Many centres reduced peritoneal dialysis access provision but in some this was increased. Centres considered that changes to transplant surgical services and for patients with advanced CKD approaching end-stage kidney disease had the greatest impact on patients. Few centres implemented adjustments aimed at vulnerable and underrepresented groups, including the frail elderly, people with language and communication needs, and those with mental health needs. Communication issues were attributed to rapid evolution of the pandemic, changing planning guidance and lack of resources. Staffing shortages, involving all staff groups particularly nurses, mainly due to COVID-19 infection and redeployment, were compounded by deficiencies in staffing establishments and high vacancy levels. Centres cited three main lessons influencing future service delivery, the need for service redesign, improvements in communication, and better support for staff. CONCLUSION Kidney centre responses to the pandemic involved adaptations across the whole service. Though some changes were almost universal, there was wide variation in other areas. Exploring the role of centre characteristics may help planning for potential future severe service disruptions.
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Affiliation(s)
- Lucy Mackintosh
- School of Life and Medical Sciences, University of Hertfordshire, College Lane Campus, Hatfield, AL10 9AB, UK.
| | - Amanda Busby
- School of Life and Medical Sciences, University of Hertfordshire, College Lane Campus, Hatfield, AL10 9AB, UK
| | - Ken Farrington
- School of Life and Medical Sciences, University of Hertfordshire, College Lane Campus, Hatfield, AL10 9AB, UK
- Renal Unit, Lister Hospital, Stevenage, SG1 4AB, UK
| | - Janine Hawkins
- School of Life and Medical Sciences, University of Hertfordshire, College Lane Campus, Hatfield, AL10 9AB, UK
| | - Sarah Afuwape
- Nephrology, Urology and Renal Transplant, Royal Free London NHS Foundation Trust, Royal Free Hospital, Pond Street, London, NW3 2QG, UK
- Department of Renal Medicine, UCL Medical School, Rowland Hill Street, London, NW3 2PF, UK
| | | | | | - Natalie Hall
- School of Life and Medical Sciences, University of Hertfordshire, College Lane Campus, Hatfield, AL10 9AB, UK
| | - Tess Harris
- The Polycystic Kidney Disease Charity, 91 Royal College St, London, NW1 0SE, UK
| | - Joanna Hudson
- Health Psychology Section, Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 5th Floor Bermondsey Wing, Guy's Campus, London Bridge, London, SE1 9RT, UK
| | - Sam Norton
- Health Psychology Section, Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 5th Floor Bermondsey Wing, Guy's Campus, London Bridge, London, SE1 9RT, UK
| | - Paula Ormandy
- School of Health and Society, University of Salford, Salford, M6 6PU, UK
| | - Christina J Pearce
- Health Psychology Section, Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 5th Floor Bermondsey Wing, Guy's Campus, London Bridge, London, SE1 9RT, UK
| | - Shalini Santhakumaran
- The UK Kidney Association, Brandon House, Building 20a1, Southmead Road, Bristol, BS34 7RR, UK
| | - Shivani Sharma
- School of Life and Medical Sciences, University of Hertfordshire, College Lane Campus, Hatfield, AL10 9AB, UK
| | - Sivakumar Sridharan
- School of Life and Medical Sciences, University of Hertfordshire, College Lane Campus, Hatfield, AL10 9AB, UK
- Renal Unit, Lister Hospital, Stevenage, SG1 4AB, UK
| | - Retha Steenkamp
- The UK Kidney Association, Brandon House, Building 20a1, Southmead Road, Bristol, BS34 7RR, UK
| | - Julie Slevin
- The UK Kidney Association, Brandon House, Building 20a1, Southmead Road, Bristol, BS34 7RR, UK
| | - David Wellsted
- School of Life and Medical Sciences, University of Hertfordshire, College Lane Campus, Hatfield, AL10 9AB, UK
| | - Joseph Chilcot
- Health Psychology Section, Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 5th Floor Bermondsey Wing, Guy's Campus, London Bridge, London, SE1 9RT, UK
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Basty N, Sorokin EP, Thanaj M, Srinivasan R, Whitcher B, Bell JD, Cule M, Thomas EL. Abdominal imaging associates body composition with COVID-19 severity. PLoS One 2023; 18:e0283506. [PMID: 37053189 PMCID: PMC10101472 DOI: 10.1371/journal.pone.0283506] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 03/10/2023] [Indexed: 04/14/2023] Open
Abstract
The main drivers of COVID-19 disease severity and the impact of COVID-19 on long-term health after recovery are yet to be fully understood. Medical imaging studies investigating COVID-19 to date have mostly been limited to small datasets and post-hoc analyses of severe cases. The UK Biobank recruited recovered SARS-CoV-2 positive individuals (n = 967) and matched controls (n = 913) who were extensively imaged prior to the pandemic and underwent follow-up scanning. In this study, we investigated longitudinal changes in body composition, as well as the associations of pre-pandemic image-derived phenotypes with COVID-19 severity. Our longitudinal analysis, in a population of mostly mild cases, associated a decrease in lung volume with SARS-CoV-2 positivity. We also observed that increased visceral adipose tissue and liver fat, and reduced muscle volume, prior to COVID-19, were associated with COVID-19 disease severity. Finally, we trained a machine classifier with demographic, anthropometric and imaging traits, and showed that visceral fat, liver fat and muscle volume have prognostic value for COVID-19 disease severity beyond the standard demographic and anthropometric measurements. This combination of image-derived phenotypes from abdominal MRI scans and ensemble learning to predict risk may have future clinical utility in identifying populations at-risk for a severe COVID-19 outcome.
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Affiliation(s)
- Nicolas Basty
- Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, United Kingdom
| | - Elena P. Sorokin
- Calico Life Sciences LLC, South San Francisco, California, United States of America
| | - Marjola Thanaj
- Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, United Kingdom
| | | | - Brandon Whitcher
- Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, United Kingdom
| | - Jimmy D. Bell
- Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, United Kingdom
| | - Madeleine Cule
- Calico Life Sciences LLC, South San Francisco, California, United States of America
| | - E. Louise Thomas
- Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, United Kingdom
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Brock S, Jackson DB, Soldatos TG, Hornischer K, Schäfer A, Diella F, Emmert MY, Hoerstrup SP. Whole patient knowledge modeling of COVID-19 symptomatology reveals common molecular mechanisms. FRONTIERS IN MOLECULAR MEDICINE 2023; 2:1035290. [PMID: 39086962 PMCID: PMC11285600 DOI: 10.3389/fmmed.2022.1035290] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 12/12/2022] [Indexed: 08/02/2024]
Abstract
Infection with SARS-CoV-2 coronavirus causes systemic, multi-faceted COVID-19 disease. However, knowledge connecting its intricate clinical manifestations with molecular mechanisms remains fragmented. Deciphering the molecular basis of COVID-19 at the whole-patient level is paramount to the development of effective therapeutic approaches. With this goal in mind, we followed an iterative, expert-driven process to compile data published prior to and during the early stages of the pandemic into a comprehensive COVID-19 knowledge model. Recent updates to this model have also validated multiple earlier predictions, suggesting the importance of such knowledge frameworks in hypothesis generation and testing. Overall, our findings suggest that SARS-CoV-2 perturbs several specific mechanisms, unleashing a pathogenesis spectrum, ranging from "a perfect storm" triggered by acute hyper-inflammation, to accelerated aging in protracted "long COVID-19" syndromes. In this work, we shortly report on these findings that we share with the community via 1) a synopsis of key evidence associating COVID-19 symptoms and plausible mechanisms, with details presented within 2) the accompanying "COVID-19 Explorer" webserver, developed specifically for this purpose (found at https://covid19.molecularhealth.com). We anticipate that our model will continue to facilitate clinico-molecular insights across organ systems together with hypothesis generation for the testing of potential repurposing drug candidates, new pharmacological targets and clinically relevant biomarkers. Our work suggests that whole patient knowledge models of human disease can potentially expedite the development of new therapeutic strategies and support evidence-driven clinical hypothesis generation and decision making.
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Affiliation(s)
| | | | - Theodoros G. Soldatos
- Molecular Health GmbH, Heidelberg, Germany
- SRH Hochschule, University of Applied Science, Heidelberg, Germany
| | | | | | | | - Maximilian Y. Emmert
- Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland
- Wyss Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland
- Department of Cardiothoracic and Vascular Surgery, German Heart Institute Berlin, Berlin, Germany
- Department of Cardiovascular Surgery, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Simon P. Hoerstrup
- Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland
- Wyss Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland
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Luther T, Eckerbom P, Cox E, Lipcsey M, Bülow S, Hultström M, Torrente FM, Weis J, Palm F, Francis S, Frithiof R, Liss P. Decreased renal perfusion during acute kidney injury in critical COVID-19 assessed by magnetic resonance imaging: a prospective case control study. Crit Care 2022; 26:262. [PMID: 36050748 PMCID: PMC9434518 DOI: 10.1186/s13054-022-04132-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 08/19/2022] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Renal hypoperfusion has been suggested to contribute to the development of acute kidney injury (AKI) in critical COVID-19. However, limited data exist to support this. We aim to investigate the differences in renal perfusion, oxygenation and water diffusion using multiparametric magnetic resonance imaging in critically ill COVID-19 patients with and without AKI. METHODS A prospective case-control study where patients without prior kidney disease treated in intensive care for respiratory failure due to COVID-19 were examined. Kidney Disease: Improving Global Outcomes Creatinine criteria were used for group allocation. Main comparisons were tested using Mann-Whitney U test. RESULTS Nineteen patients were examined, ten with AKI and nine without AKI. Patients with AKI were examined in median 1 [0-2] day after criteria fulfillment. Age and baseline Plasma-Creatinine were similar in both groups. Total renal blood flow was lower in patients with AKI compared with patients without (median 645 quartile range [423-753] vs. 859 [746-920] ml/min, p = 0.037). Regional perfusion was reduced in both cortex (76 [51-112] vs. 146 [123-169] ml/100 g/min, p = 0.015) and medulla (28 [18-47] vs. 47 [38-73] ml/100 g/min, p = 0.03). Renal venous saturation was similar in both groups (72% [64-75] vs. 72% [63-84], ns.), as was regional oxygenation (R2*) in cortex (17 [16-19] vs. 17 [16-18] 1/s, ns.) and medulla (29 [24-39] vs. 27 [23-29] 1/s, ns.). CONCLUSIONS In critically ill COVID-19 patients with AKI, the total, cortical and medullary renal blood flows were reduced compared with similar patients without AKI, whereas no differences in renal oxygenation were demonstrable in this setting. Trial registration ClinicalTrials ID: NCT02765191 , registered May 6 2014 and updated May 7 2020.
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Affiliation(s)
- Tomas Luther
- Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University Hospital, Uppsala University, 751 85, Uppsala, Sweden.
| | - Per Eckerbom
- Section of Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Eleanor Cox
- Sir Peter Mansfield Imaging Centre, School of Physics & Astronomy, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Miklos Lipcsey
- Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University Hospital, Uppsala University, 751 85, Uppsala, Sweden
- Hedenstierna Laboratory, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Sara Bülow
- Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University Hospital, Uppsala University, 751 85, Uppsala, Sweden
| | - Michael Hultström
- Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University Hospital, Uppsala University, 751 85, Uppsala, Sweden
- Integrative Physiology, Department Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | - Francisco Martinez Torrente
- Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University Hospital, Uppsala University, 751 85, Uppsala, Sweden
| | - Jan Weis
- Department of Medical Physics, Uppsala University Hospital, Uppsala, Sweden
| | - Fredrik Palm
- Integrative Physiology, Department Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | - Susan Francis
- Sir Peter Mansfield Imaging Centre, School of Physics & Astronomy, University of Nottingham, Nottingham, UK
- NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK
| | - Robert Frithiof
- Anaesthesiology and Intensive Care Medicine, Department of Surgical Sciences, Uppsala University Hospital, Uppsala University, 751 85, Uppsala, Sweden
| | - Per Liss
- Section of Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
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Chiao C, Faust H, Singh T. Regional citrate and systemic heparin are adequate to maintain filter half-life for COVID-19 patients on continuous renal replacement therapy. Semin Dial 2022; 35:325-329. [PMID: 35141966 PMCID: PMC9115506 DOI: 10.1111/sdi.13061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 08/23/2021] [Accepted: 01/23/2022] [Indexed: 11/29/2022]
Abstract
INTRODUCTION The aim of our study is to compare clotting of CRRT filters in patients with COVID-19-associated AKI versus septic shock-associated AKI. METHODS Retrospective study of adult ICU patients with COVID-19 compared to those with septic shock admitted to a tertiary hospital April-October 2020. Independent t test and chi-square test used to determine statistical significance of CRRT filter clotting between the two groups. Time-to-event data analyzed with Kaplan-Meier curves. Analyses performed on Microsoft Excel and MedCalc. RESULTS Twenty-seven ICU patients with AKI requiring CRRT were included, 13 with COVID-19 and 14 non-COVID-19 patients with septic shock. The mean half-life of CRRT hemofilter was similar in COVID-19 patients compared to non-COVID-19 patients (27.4 vs. 27.5 h, p = 0.79). The number of CRRT hemofilter changes per day was similar in both groups (0.6 filter changes per day, p = 0.84). However, significantly more patients with COVID-19 were on systemic heparin (69% vs. 13%, p = 0.02). CONCLUSION We found that COVID-19 patients with AKI requiring CRRT had similar CRRT hemofilter half-life compared with sepsis-associated AKI patients with use of regional citrate and systemic heparin. Further studies are needed to find which methods of anticoagulation are optimal in patients with COVID-19 infection with AKI requiring CRRT.
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Affiliation(s)
- Cassandra Chiao
- Department of MedicineUniversity of Wisconsin‐Madison School of Medicine and Public HealthMadisonWisconsinUSA
| | - Hilary Faust
- Department of MedicineUniversity of Wisconsin‐Madison School of Medicine and Public HealthMadisonWisconsinUSA
| | - Tripti Singh
- Department of MedicineUniversity of Wisconsin‐Madison School of Medicine and Public HealthMadisonWisconsinUSA
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Plasma glucose levels and diabetes are independent predictors for mortality in patients with COVID-19. Epidemiol Infect 2022; 150:e106. [PMID: 35570587 PMCID: PMC9171060 DOI: 10.1017/s095026882200022x] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
This study is performed to figure out how the presence of diabetes affects the infection, progression and prognosis of 2019 novel coronavirus disease (COVID-19), and the effective therapy that can treat the diabetes-complicated patients with COVID-19. A multicentre study was performed in four hospitals. COVID-19 patients with diabetes mellitus (DM) or hyperglycaemia were compared with those without these conditions and matched by propensity score matching for their clinical progress and outcome. Totally, 2444 confirmed COVID-19 patients were recruited, from whom 336 had DM. Compared to 1344 non-DM patients with age and sex matched, DM-COVID-19 patients had significantly higher rates of intensive care unit entrance (12.43% vs. 6.58%, P = 0.014), kidney failure (9.20% vs. 4.05%, P = 0.027) and mortality (25.00% vs. 18.15%, P < 0.001). Age and sex-stratified comparison revealed increased susceptibility to COVID-19 only from females with DM. For either non-DM or DM group, hyperglycaemia was associated with adverse outcomes, featured by higher rates of severe pneumonia and mortality, in comparison with non-hyperglycaemia. This was accompanied by significantly altered laboratory indicators including lymphocyte and neutrophil percentage, C-reactive protein and urea nitrogen level, all with correlation coefficients >0.35. Both diabetes and hyperglycaemia were independently associated with adverse prognosis of COVID-19, with hazard ratios of 10.41 and 3.58, respectively.
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10
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Sullivan MK, Lees JS, Drake TM, Docherty AB, Oates G, Hardwick HE, Russell CD, Merson L, Dunning J, Nguyen-Van-Tam JS, Openshaw P, Harrison EM, Baillie JK, Semple MG, Ho A, Mark PB. Acute kidney injury in patients hospitalized with COVID-19 from the ISARIC WHO CCP-UK Study: a prospective, multicentre cohort study. Nephrol Dial Transplant 2022; 37:271-284. [PMID: 34661677 PMCID: PMC8788218 DOI: 10.1093/ndt/gfab303] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). This study investigated adults hospitalized with COVID-19 and hypothesized that risk factors for AKI would include comorbidities and non-White race. METHODS A prospective multicentre cohort study was performed using patients admitted to 254 UK hospitals with COVID-19 between 17 January 2020 and 5 December 2020. RESULTS Of 85 687 patients, 2198 (2.6%) received acute kidney replacement therapy (KRT). Of 41 294 patients with biochemistry data, 13 000 (31.5%) had biochemical AKI: 8562 stage 1 (65.9%), 2609 stage 2 (20.1%) and 1829 stage 3 (14.1%). The main risk factors for KRT were chronic kidney disease (CKD) [adjusted odds ratio (aOR) 3.41: 95% confidence interval 3.06-3.81], male sex (aOR 2.43: 2.18-2.71) and Black race (aOR 2.17: 1.79-2.63). The main risk factors for biochemical AKI were admission respiratory rate >30 breaths per minute (aOR 1.68: 1.56-1.81), CKD (aOR 1.66: 1.57-1.76) and Black race (aOR 1.44: 1.28-1.61). There was a gradated rise in the risk of 28-day mortality by increasing severity of AKI: stage 1 aOR 1.58 (1.49-1.67), stage 2 aOR 2.41 (2.20-2.64), stage 3 aOR 3.50 (3.14-3.91) and KRT aOR 3.06 (2.75-3.39). AKI rates peaked in April 2020 and the subsequent fall in rates could not be explained by the use of dexamethasone or remdesivir. CONCLUSIONS AKI is common in adults hospitalized with COVID-19 and it is associated with a heightened risk of mortality. Although the rates of AKI have fallen from the early months of the pandemic, high-risk patients should have their kidney function and fluid status monitored closely.
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Affiliation(s)
- Michael K Sullivan
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Jennifer S Lees
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Thomas M Drake
- Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK
| | - Annemarie B Docherty
- Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK
| | - Georgia Oates
- Edinburgh Medical School, University of Edinburgh, Edinburgh, UK
| | - Hayley E Hardwick
- HPRU in Infection and Emerging Diseases, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK
| | - Clark D Russell
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
| | - Laura Merson
- ISARIC Global Support Centre, University of Oxford, Oxford, UK
| | - Jake Dunning
- Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK
| | | | - Peter Openshaw
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Ewen M Harrison
- Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, UK
| | | | - Malcolm G Semple
- HPRU in Infection and Emerging Diseases, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK
| | - Antonia Ho
- Medical Research Council-University of Glasgow Centre for Virus Research, Glasgow, UK
| | - Patrick B Mark
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
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11
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Noble RA, Selby NM. The changing nature of COVID-19-associated AKI: where are we now? Nephrol Dial Transplant 2022; 37:201-202. [PMID: 34792169 PMCID: PMC8690015 DOI: 10.1093/ndt/gfab326] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Indexed: 12/15/2022] Open
Affiliation(s)
- Rebecca A Noble
- Centre for Kidney Research and Innovation, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, UK
- Department of Renal Medicine, Royal Derby Hospital, Derby, UK
| | - Nicholas M Selby
- Centre for Kidney Research and Innovation, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, UK
- Department of Renal Medicine, Royal Derby Hospital, Derby, UK
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12
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Abdelsalam M, Abd El Wahab AM, Nassar MK, Samaan E, Eldeep A, Abdalbary M, Tawfik M, Saleh M, Shemies RS, Sabry A. Kidneys in SARS-CoV-2 Era; a challenge of multiple faces. Ther Apher Dial 2022; 26:552-565. [PMID: 34989119 DOI: 10.1111/1744-9987.13792] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 12/31/2021] [Accepted: 01/03/2022] [Indexed: 01/08/2023]
Abstract
INTRODUCTION With the evolution of SARS-CoV-2 pandemic, it was believed to be a direct respiratory virus. But, its deleterious effects were observed on different body systems, including kidneys. AIM OF WORK In this review, we tried as much as we can to summarize what has been discussed in the literature about the relation between SARS-CoV-2 infection and kidneys since December, 2019. METHODS Each part of the review was assigned to one or two authors to search for relevant articles in three databases (Pubmed, Scopus and Google scholar) and collected data were summarized and revised by two independent researchers. CONCLUSION The complexity of COVID-19 pandemic and kidney could be attributed to the direct effect of SARS-CoV-2 infection on the kidneys, different clinical presentation, difficulties confronting dialysis patients, restrictions of the organ transplant programs, poor outcomes and bad prognosis in patients with known history of kidney diseases who got infected with SARS-CoV-2. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Mostafa Abdelsalam
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | | | | | - Emad Samaan
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | - Ahmed Eldeep
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | - Mohamed Abdalbary
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt.,Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, US
| | - Mona Tawfik
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | - Marwa Saleh
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
| | | | - Alaa Sabry
- Mansoura Nephrology and Dialysis Unit, Mansoura University, Mansoura, Egypt
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13
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Chen A, Yin L, Lee K, He JC. Similarities and Differences between COVID-19-Associated Nephropathy and HIV-Associated Nephropathy. KIDNEY DISEASES (BASEL, SWITZERLAND) 2022; 8:1-12. [PMID: 35127839 PMCID: PMC8805054 DOI: 10.1159/000520235] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 09/11/2021] [Indexed: 12/13/2022]
Abstract
Kidney disease is a major complication of viral infection, which can cause both acute and chronic kidney diseases via different mechanisms such as immune-mediated injury, kidney cell injury from a direct viral infection, systemic effects, and antiviral drug-induced nephrotoxicity. HIV-associated nephropathy (HIVAN), characterized by collapsing focal segmental glomerulosclerosis (cFSGS), has been described 2 decades ago as a major complication of acquired-immunodeficiency syndrome. The pathogenesis of HIVAN has been well studied, including viral entry, host response, and genetic factors. The incidence of this disease has been dramatically dropped with current antiretroviral therapy. In the recent severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic, acute kidney injury was also found to be a major complication in patients with (coronavirus disease) COVID-19. These patients also developed glomerular disease such as cFSGS in African Americans with apolipoprotein L1 risk alleles, similar to HIVAN. Whether SARS-CoV-2 can infect kidney cells locally remains controversial, but both local infection and systemic effects are likely involved in the pathogenesis of this disease. In this review, we present a comparison of the clinical presentations, pathological findings, disease mechanisms, and potential treatments between HIVAN and COVID-19. Leveraging the knowledge in HIVAN and experimental approaches used to study HIVAN will facilitate the exploration in the pathogenesis of COVID-19-associated kidney disease and improve our management of COVID-19 patients.
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Affiliation(s)
- Anqun Chen
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China
| | - Lijun Yin
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China
| | - Kyung Lee
- Division of Nephrology, Department of Medicine, Icahn School of Medicineat Mount Sinai, New York, New York, USA
| | - John Cijiang He
- Division of Nephrology, Department of Medicine, Icahn School of Medicineat Mount Sinai, New York, New York, USA
- Renal Program, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA
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14
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Bohorquez-Rivero JD, García-Ballestas E, Janjua T, Moscote-Salazar L. Liberal Versus Conservative Fluid Therapy in COVID-19 Patients: What is the Best Strategy for the Treatment of Critically ill Patients? JOURNAL OF TRANSLATIONAL CRITICAL CARE MEDICINE 2022. [PMCID: PMC9070581 DOI: 10.4103/jtccm.jtccm_1_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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15
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Yaseen MO, Yaseen M, Khan TM, Rehman I, Suleiman AK, Baig MR, Jaber AA, Telb A, Alnafoosi FN. Pharmacotherapeutic Evaluation of Covid-19 Patients Suffering from Acute Kidney Injury. ARCHIVES OF PHARMACY PRACTICE 2022. [DOI: 10.51847/n74tsc598e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
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16
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Cai X, Wu G, Zhang J, Yang L. Risk Factors for Acute Kidney Injury in Adult Patients With COVID-19: A Systematic Review and Meta-Analysis. Front Med (Lausanne) 2021; 8:719472. [PMID: 34938742 PMCID: PMC8685316 DOI: 10.3389/fmed.2021.719472] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 09/30/2021] [Indexed: 02/05/2023] Open
Abstract
Background and Objective: Since December 2019, coronavirus disease 2019 (COVID-19) has spread rapidly around the world. Studies found that the incidence of acute kidney injury (AKI) in COVID-19 patients was more than double the incidence of AKI in non-COVID-19 patients. Some findings confirmed that AKI is a strong independent risk factor for mortality in patients with COVID-19 and is associated with a three-fold increase in the odds of in-hospital mortality. However, little information is available about AKI in COVID-19 patients. This study aimed to analyse the risk factors for AKI in adult patients with COVID-19. Methods: A systematic literature search was conducted in PubMed, EMBASE, Web of Science, the Cochrane Library, CNKI, VIP and WanFang Data from 1 December 2019 to 30 January 2021. We extracted data from eligible studies to compare the effects of age, sex, chronic diseases and potential risk factors for AKI on the prognosis of adult patients with COVID-19. Results: In total, 38 studies with 42,779 patients were included in this analysis. The meta-analysis showed that male sex (OR = 1.37), older age (MD = 5.63), smoking (OR = 1.23), obesity (OR = 1.12), hypertension (OR=1.85), diabetes (OR=1.71), pneumopathy (OR = 1.36), cardiovascular disease (OR = 1.98), cancer (OR = 1.26), chronic kidney disease (CKD) (OR = 4.56), mechanical ventilation (OR = 8.61) and the use of vasopressors (OR = 8.33) were significant risk factors for AKI (P < 0.05). Conclusions: AKI is a common and serious complication of COVID-19. Overall, male sex, age, smoking, obesity, hypertension, diabetes, pneumopathy, cardiovascular disease, cancer, CKD, mechanical ventilation and the use of vasopressors were independent risk factors for AKI in adult patients with COVID-19. Clinicians need to be aware of these risk factors to reduce the incidence of AKI. System Review Registration: PROSPERO, identifier [CRD42021282233].
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Affiliation(s)
| | | | - Jie Zhang
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Lichuan Yang
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
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17
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Sadiq S, Lipski C, Hanif UK, Arshad F, Chaudary M, Chaudhry F. Hip and distal femur fracture outcomes over three successive UK lockdown periods during the COVID-19 pandemic: what have we learnt? : a single-centre retrospective cohort study. Bone Jt Open 2021; 2:1017-1026. [PMID: 34847700 PMCID: PMC8711658 DOI: 10.1302/2633-1462.212.bjo-2021-0102.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Aims This study assessed the impact of COVID-19 on hip and distal femur fracture patient outcomes across three successive UK lockdown periods over one year. Methods A single-centre retrospective cohort study was performed at an acute NHS Trust. Hip and distal femur fracture patients admitted within the first month from each of the three starting dates of each national lockdown were included and compared to a control group in March 2019. Data were collected as per the best practice tariff outcomes including additional outcomes as required. Data collection included COVID-19 status, time to theatre, 30-day mortality, presence of acute kidney injury (AKI) and pneumonia, and do not attempt cardiopulmonary resuscitation (DNACPR) status. Data were analyzed using an independent-samples t-test or chi-squared test with Fisher’s exact test where applicable. A p-value of < 0.05 was considered statistically significant. Results A total of 95 patients during the pandemic were included and 20 were COVID-positive. Patients experienced a statistically significant increase in time to theatre in Lockdown 1 compared to 2019 (p = 0.039) with a decrease with successive lockdown periods by Lockdown 3. The 30-day mortality increased from 8.8% in 2019 to 10.0% to 14.8% in all lockdown periods. COVID-positive patient mortality was 30.0% (p = 0.063, odds ratio (OR) = 4.43 vs 2019). The rates of AKI and pneumonia experienced were higher for patients during the pandemic. The highest rates were experienced in COVID-positive patients, with 45.0% of patients with AKI versus 27.0% in 2019 (p = 0.38, OR = 1.80), and 50.0% of patients diagnosed with pneumonia versus 16.2% in 2019 (p = 0.0012, OR = 5.17). The percentage of patients with a DNACPR increased from 30.0% in 2019 to 60.7% by Lockdown 3 (p = 0.034, OR = 3.61). Conclusion COVID-positive hip and distal femur fracture patients are at a higher risk of mortality due to AKI and pneumonia. Patient outcomes have improved with successive lockdowns to pre-pandemic levels. Cite this article: Bone Jt Open 2021;2(12):1017–1026.
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18
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Jolobe OMP. Use of non-steroidal anti-inflammatory drugs as a risk factor for acute kidney injury. QJM 2021; 114:613. [PMID: 32609362 DOI: 10.1093/qjmed/hcaa211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- O M P Jolobe
- Medical Division Manchester Medical Society Simon, Building Brunswick Street, Manchester, M13 9PL, UK
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19
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Cottam D, Nadim MK, Forni LG. Management of acute kidney injury associated with Covid-19: what have we learned? Curr Opin Nephrol Hypertens 2021; 30:563-570. [PMID: 34535006 DOI: 10.1097/mnh.0000000000000742] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Although initially kidney involvement in COVID-19 infection was felt to occur relatively infrequently, this has proved not to be the case. In critically ill patients with COVID-19, multiorgan failure including acute kidney injury (AKI) is common and is associated with an increased risk of mortality and morbidity. This review focuses briefly on the epidemiology and pathophysiology of COVID-19 associated AKI as well as options for management. RECENT FINDINGS The risk factors for AKI are common to both noncovid-related AKI and COVID-19 associated AKI. Kidney injury in COVID-19 associated AKI may arise through several mechanisms, including not only direct effects on the kidney leading to tubular injury but also through the effects of treatment of multiorgan failure complicating infection. During surge conditions, the use of kidney replacement therapy has embraced all modalities including the use of peritoneal dialysis. The use of blood purification techniques has been proposed, but to date, the results are variable. SUMMARY COVID-19 associated AKI is common, affecting approximately a quarter of patients hospitalized with COVID-19. Glomerular injury can occur, but in the main tubular injury seems most likely leading to AKI, which should be managed following clinical pathways informed by accepted guidelines.
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Affiliation(s)
- Daniel Cottam
- Department of Critical Care, Royal Surrey Hospital, Surrey, UK
| | - Mitra K Nadim
- Division of Nephrology and Hypertension, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Lui G Forni
- Department of Critical Care, Royal Surrey Hospital, Surrey, UK
- Department of Clinical & Experimental Medicine, Faculty of Health Sciences, University of Surrey, Surrey, UK
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20
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Cihakova D, Streiff MB, Menez SP, Chen TK, Gilotra NA, Michos ED, Marr KA, Karaba AH, Robinson ML, Blair PW, Dioverti MV, Post WS, Cox AL, R Antar AA. High-value laboratory testing for hospitalized COVID-19 patients: a review. Future Virol 2021; 16:10.2217/fvl-2020-0316. [PMID: 34567235 PMCID: PMC8457535 DOI: 10.2217/fvl-2020-0316] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 09/03/2021] [Indexed: 01/08/2023]
Abstract
We present here an evidence-based review of the utility, timing, and indications for laboratory test use in the domains of inflammation, cardiology, hematology, nephrology and co-infection for clinicians managing the care of hospitalized COVID-19 patients. Levels of IL-6, CRP, absolute lymphocyte count, neutrophils and neutrophil-to-lymphocyte ratio obtained upon admission may help predict the severity of COVID-19. Elevated LDH, ferritin, AST, and d-dimer are associated with severe illness and mortality. Elevated cardiac troponin at hospital admission can alert clinicians to patients at risk for cardiac complications. Elevated proBNP may help distinguish a cardiac complication from noncardiac etiologies. Evaluation for co-infection is typically unnecessary in nonsevere cases but is essential in severe COVID-19, intensive care unit patients, and immunocompromised patients.
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Affiliation(s)
- Daniela Cihakova
- Department of Pathology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA
| | - Michael B Streiff
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Steven P Menez
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Teresa K Chen
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Nisha A Gilotra
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Erin D Michos
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Kieren A Marr
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Andrew H Karaba
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Matthew L Robinson
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Paul W Blair
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
- Austere environments Consortium for Enhanced Sepsis Outcomes, Henry M. Jackson Foundation, 6700 Rockledge Drive, Bethesda, MD 20817, USA
| | - Maria V Dioverti
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Wendy S Post
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Andrea L Cox
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
| | - Annukka A R Antar
- Department of Medicine, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA
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21
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Smarz-Widelska I, Grywalska E, Morawska I, Forma A, Michalski A, Mertowski S, Hrynkiewicz R, Niedźwiedzka-Rystwej P, Korona-Glowniak I, Parczewski M, Załuska W. Pathophysiology and Clinical Manifestations of COVID-19-Related Acute Kidney Injury-The Current State of Knowledge and Future Perspectives. Int J Mol Sci 2021; 22:7082. [PMID: 34209289 PMCID: PMC8268979 DOI: 10.3390/ijms22137082] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 05/26/2021] [Accepted: 06/28/2021] [Indexed: 01/08/2023] Open
Abstract
The continually evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in a vast number of either acute or chronic medical impairments of a pathophysiology that is not yet fully understood. SARS-CoV-2 tropism for the organs is associated with bilateral organ cross-talks as well as targeted dysfunctions, among which acute kidney injury (AKI) seems to be highly prevalent in infected patients. The need for efficient management of COVID-related AKI patients is an aspect that is still being investigated by nephrologists; however, another reason for concern is a disturbingly high proportion of various types of kidney dysfunctions in patients who have recovered from COVID-19. Even though the clinical picture of AKI and COVID-related AKI seems to be quite similar, it must be considered that regarding the latter, little is known about both the optimal management and long-term consequences. These discrepancies raise an urgent need for further research aimed at evaluating the molecular mechanisms associated with SARS-CoV-2-induced kidney damage as well as standardized management of COVID-related AKI patients. The following review presents a comprehensive and most-recent insight into the pathophysiology, clinical manifestations, recommended patient management, treatment strategies, and post-mortem findings in patients with COVID-related AKI.
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Affiliation(s)
- Iwona Smarz-Widelska
- Department of Nephrology, Cardinal Stefan Wyszynski Provincial Hospital in Lublin, 20-718 Lublin, Poland;
| | - Ewelina Grywalska
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, 20-093 Lublin, Poland; (I.M.); (A.M.); (S.M.)
| | - Izabela Morawska
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, 20-093 Lublin, Poland; (I.M.); (A.M.); (S.M.)
| | - Alicja Forma
- Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Adam Michalski
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, 20-093 Lublin, Poland; (I.M.); (A.M.); (S.M.)
| | - Sebastian Mertowski
- Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, 20-093 Lublin, Poland; (I.M.); (A.M.); (S.M.)
| | - Rafał Hrynkiewicz
- Institute of Biology, University of Szczecin, 71-412 Szczecin, Poland;
| | | | - Izabela Korona-Glowniak
- Department of Pharmaceutical Microbiology, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland;
| | - Miłosz Parczewski
- Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University in Szczecin, 71-455 Szczecin, Poland;
| | - Wojciech Załuska
- Department of Nephrology, Medical University of Lublin, 20-954 Lublin, Poland;
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22
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ÖZTÜRK S, TURGUTALP K, ARICI M, ÇETİNKAYA H, ALTIPARMAK MR, AYDIN Z, SOYPAÇACI Z, BORA F, KARA E, CEBECİ E, ÖZLER TE, DÖLARSLAN ME, SİPAHİ S, AYAR Y, ŞAHİN İ, BAKIRDÖĞEN S, İSLAM M, GÖRGÜLÜ N, ÖĞÜTMEN MB, ŞENGÜL E, GÜNGÖR Ö, SEYAHİ N, TOKGÖZ B, ODABAŞ AR, TONBUL HZ, SEZER S, YILDIZ A, ATEŞ K. Impact of hospital-acquired acute kidney injury on Covid-19 outcomes in patients with and without chronic kidney disease: a multicenter retrospective cohort study. Turk J Med Sci 2021; 51:947-961. [PMID: 33611868 PMCID: PMC8283512 DOI: 10.3906/sag-2011-169] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 02/21/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND/AIM Hospital-acquired acute kidney injury (HA-AKI) may commonly develop in Covid-19 patients and is expected to have higher mortality. There is little comparative data investigating the effect of HA-AKI on mortality of chronic kidney disease (CKD) patients and a control group of general population suffering from Covid-19. MATERIALS AND METHODS HA-AKI development was assessed in a group of stage 3–5 CKD patients and control group without CKD among adult patients hospitalized for Covid-19. The role of AKI development on the outcome (in-hospital mortality and admission to the intensive care unit [ICU]) of patients with and without CKD was compared. RESULTS Among 621 hospitalized patients (age 60 [IQR: 47–73]), women: 44.1%), AKI developed in 32.5% of the patients, as stage 1 in 84.2%, stage 2 in 8.4%, and stage 3 in 7.4%. AKI developed in 48.0 % of CKD patients, whereas it developed in 17.6% of patients without CKD. CKD patients with HA-AKI had the highest mortality rate of 41.1% compared to 14.3% of patients with HA-AKI but no CKD (p < 0.001). However, patients with AKI+non-CKD had similar rates of ICU admission, mechanical ventilation, and death rate to patients with CKD without AKI. Adjusted mortality risks of the AKI+non-CKD group (HR: 9.0, 95% CI: 1.9–44.2) and AKI+CKD group (HR: 7.9, 95% CI: 1.9–33.3) were significantly higher than that of the non-AKI+non-CKD group. CONCLUSION AKI frequently develops in hospitalized patients due to Covid-19 and is associated with high mortality. HA-AKI has worse outcomes whether it develops in patients with or without CKD, but the worst outcome was seen in AKI+CKD patients.
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Affiliation(s)
- Savaş ÖZTÜRK
- Department of Nephrology, University of Health Sciences, Haseki Training and Research Hospital, İstanbulTurkey
| | - Kenan TURGUTALP
- Division of Nephrology, Department of Internal Medicine, Mersin University Faculty of Medicine, Training and Research Hospital, MersinTurkey
| | - Mustafa ARICI
- Department of Nephrology, Faculty of Medicine, Hacettepe University, AnkaraTurkey
| | - Hakkı ÇETİNKAYA
- Department of Nephrology, Sultan 2. Abdulhamid Han Training and Research Hospital, University of Health Sciences, İstanbulTurkey
| | - Mehmet Rıza ALTIPARMAK
- Division of Nephrology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, İstanbul University–Cerrahpaşa, İstanbulTurkey
| | - Zeki AYDIN
- Department of Nephrology, Darıca Farabi Training and Research Hospital, KocaeliTurkey
| | - Zeki SOYPAÇACI
- Division of Nephrology, Department of Internal Medicine, İzmir Katip Çelebi University, Atatürk Training and Research Hospital, İzmirTurkey
| | - Feyza BORA
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Akdeniz University, AntalyaTurkey
| | - Ekrem KARA
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Recep Tayyip Erdoğan University, RizeTurkey
| | - Egemen CEBECİ
- Department of Nephrology, University of Health Sciences, Haseki Training and Research Hospital, İstanbulTurkey
| | - Tuba Elif ÖZLER
- Division of Nephrology, Department of Internal Medicine, Kanuni Sultan Süleyman Training and Research Hospital, University of Health Sciences, İstanbulTurkey
| | - Mürşide Esra DÖLARSLAN
- Department of Nephrology, Trabzon Kanuni Training and Research Hospital, University of Health Sciences, TrabzonTurkey
| | - Savaş SİPAHİ
- Division of Nephrology, Department of Internal Medicine, Sakarya University Training and Research Hospital, SakaryaTurkey
| | - Yavuz AYAR
- Department of Nephrology, Bursa City Hospital, BursaTurkey
| | - İdris ŞAHİN
- Division of Nephrology, Department of Internal Medicine, Turgut Özal Medical Center, İnönü University Faculty of Medicine, MalatyaTurkey
| | - Serkan BAKIRDÖĞEN
- Division of Nephrology, Department of Internal Medicine, Çanakkale Onsekiz Mart University, ÇanakkaleTurkey
| | - Mahmud İSLAM
- Department of Nephrology, Zonguldak Atatürk State Hospital, ZonguldakTurkey
| | - Numan GÖRGÜLÜ
- Division of Nephrology, Department of Internal Medicine, Bağcılar Training and Research Hospital, University of Health Sciences, İstanbulTurkey
| | - Melike Betül ÖĞÜTMEN
- Department of Nephrology, Haydarpaşa Numune Training and Research Hospital, University of Health Sciences, İstanbulTurkey
| | - Erkan ŞENGÜL
- Department of Nephrology, Kocaeli Derince Training and Research Hospital, University of Health Sciences, KocaeliTurkey
| | - Özkan GÜNGÖR
- Department of Nephrology, Faculty of Medicine, Kahramanmaraş Sütçü İmam University, KahramanmaraşTurkey
| | - Nurhan SEYAHİ
- Division of Nephrology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, İstanbul University–Cerrahpaşa, İstanbulTurkey
| | - Bülent TOKGÖZ
- Department of Nephrology, Faculty of Medicine, Erciyes University, KayseriTurkey
| | - Ali Rıza ODABAŞ
- Department of Nephrology, Sultan 2. Abdulhamid Han Training and Research Hospital, University of Health Sciences, İstanbulTurkey
| | - Halil Zeki TONBUL
- Department of Nephrology, Meram Faculty of Medicine, Necmettin Erbakan University, KonyaTurkey
| | - Siren SEZER
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Atılım University, AnkaraTurkey
| | - Alaattin YILDIZ
- Division of Nephrology, Department of Internal Medicine, İstanbul Faculty of Medicine, İstanbul University, İstanbulTurkey
| | - Kenan ATEŞ
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Ankara University, AnkaraTurkey
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23
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Parker K, Hamilton P, Hanumapura P, Castelino L, Murphy M, Challiner R, Thachil J, Ebah L. Chronic anticoagulation is not associated with a reduced risk of acute kidney injury in hospitalised Covid-19 patients. BMC Nephrol 2021; 22:224. [PMID: 34134645 PMCID: PMC8208381 DOI: 10.1186/s12882-021-02436-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 04/26/2021] [Indexed: 12/15/2022] Open
Abstract
Background Coronavirus-19 (COVID-19) has been declared a global pandemic by the World Health Organisation. Severe disease typically presents with respiratory failure but Acute Kidney Injury (AKI) and a hypercoagulable state can also occur. Early reports suggest that thrombosis may be linked with AKI. We studied the development of AKI and outcomes of patients with COVID-19 taking chronic anticoagulation therapy. Methods Electronic records were reviewed for all adult patients admitted to Manchester University Foundation Trust Hospitals between March 10 and April 302,020 with a diagnosis of COVID-19. Patients with end-stage kidney disease were excluded. AKI was classified as per KDIGO criteria. Results Of the 1032 patients with COVID-19 studied,164 (15.9%) were taking anticoagulant therapy prior to admission. There were similar rates of AKI between those on anticoagulants and those not anticoagulated (23.8% versus 19.7%) with no difference in the severity of AKI or requirement of renal replacement therapy between groups (1.2% versus 3.5%). Risk factors for AKI included hypertension, pre-existing renal disease and male sex. There was a higher mortality in those taking anticoagulant therapy (40.2% versus 30%). Patients taking anticoagulants were less likely to be admitted to the Intensive Care Unit (8.5% versus 17.4%) and to receive mechanical ventilation (42.9% versus 78.1%). Conclusion Patients on chronic anticoagulant therapy did not have a reduced incidence or severity of AKI suggesting that AKI is unlikely to be thrombotic in nature. Therapeutic anticoagulation is currently still under investigation in randomised controlled studies to determine whether it has a potential role in COVID-19 treatment. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-021-02436-5.
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Affiliation(s)
- Kathrine Parker
- Manchester Institute of Nephrology and Transplantation, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK. .,Manchester Academic Health Sciences Centre (MAHSC), Citylabs 1.0, Nelson Street, Manchester, M13 9NQ, UK.
| | - Patrick Hamilton
- Manchester Institute of Nephrology and Transplantation, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK.,Manchester Academic Health Sciences Centre (MAHSC), Citylabs 1.0, Nelson Street, Manchester, M13 9NQ, UK.,Wellcome Centre for Cell-Matrix Research, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, M13 9PL, UK
| | - Prasanna Hanumapura
- Manchester Institute of Nephrology and Transplantation, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK.,Manchester Academic Health Sciences Centre (MAHSC), Citylabs 1.0, Nelson Street, Manchester, M13 9NQ, UK
| | - Laveena Castelino
- Manchester Institute of Nephrology and Transplantation, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK
| | - Michelle Murphy
- Manchester Institute of Nephrology and Transplantation, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK
| | - Rachael Challiner
- Manchester Institute of Nephrology and Transplantation, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK.,Manchester Academic Health Sciences Centre (MAHSC), Citylabs 1.0, Nelson Street, Manchester, M13 9NQ, UK
| | - Jecko Thachil
- Department of Haematology, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK
| | - Leonard Ebah
- Manchester Institute of Nephrology and Transplantation, Manchester University NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK.,Manchester Academic Health Sciences Centre (MAHSC), Citylabs 1.0, Nelson Street, Manchester, M13 9NQ, UK.,Wellcome Centre for Cell-Matrix Research, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, M13 9PL, UK
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24
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Endothelin antagonism and sodium glucose Co-transporter 2 inhibition. A potential combination therapeutic strategy for COVID-19. Pulm Pharmacol Ther 2021; 69:102035. [PMID: 33933611 PMCID: PMC8084922 DOI: 10.1016/j.pupt.2021.102035] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 03/30/2021] [Accepted: 04/22/2021] [Indexed: 02/08/2023]
Abstract
The novel coronavirus 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global pandemic that requires a multi-faceted approach to tackle this unprecedent health crisis. Therapeutics to treat COVID-19 are an integral part of any such management strategy and there is a substantial unmet need for treatments for individuals most at risk of severe disease. This perspective review provides rationale of a combined therapeutic regimen of selective endothelin-A (ET-A) receptor antagonism and sodium glucose co-transporter-2 (SGLT-2) inhibition to treat COVID-19. Endothelin is a potent vasoconstrictor with pro-inflammatory and atherosclerotic effects. It is upregulated in a number of conditions including acute respiratory distress syndrome and cardiovascular disease. Endothelin mediates vasocontractility via endothelin (ET-A and ET-B) receptors on vascular smooth muscle cells (VSMCs). ET-B receptors regulate endothelin clearance and are present on endothelial cells, where in contrast to their role on VSMCs, mediate vasodilation. Therefore, selective endothelin-A (ET-A) receptor inhibition is likely the optimal approach to attenuate the injurious effects of endothelin and may reduce ventilation-perfusion mismatch and pulmonary inflammation, whilst improving pulmonary haemodynamics and oxygenation. SGLT-2 inhibition may dampen inflammatory cytokines, reduce hyperglycaemia if present, improve endothelial function, cardiovascular haemodynamics and cellular bioenergetics. This combination therapeutic approach may therefore have beneficial effects to mitigate both the pulmonary, metabolic and cardiorenal manifestations of COVID-19. Given these drug classes include medicines licensed to treat heart failure, diabetes and pulmonary hypertension respectively, information regarding their safety profile is established. Randomised controlled clinical trials are the best way to determine efficacy and safety of these medicines in COVID-19.
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25
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Venketasubramanian N, Anderson C, Ay H, Aybek S, Brinjikji W, de Freitas GR, Del Brutto OH, Fassbender K, Fujimura M, Goldstein LB, Haberl RL, Hankey GJ, Heiss WD, Lestro Henriques I, Kase CS, Kim JS, Koga M, Kokubo Y, Kuroda S, Lee K, Lee TH, Liebeskind DS, Lip GYH, Meairs S, Medvedev R, Mehndiratta MM, Mohr JP, Nagayama M, Pantoni L, Papanagiotou P, Parrilla G, Pastori D, Pendlebury ST, Pettigrew LC, Renjen PN, Rundek T, Schminke U, Shinohara Y, Tang WK, Toyoda K, Wartenberg KE, Wasay M, Hennerici MG. Stroke Care during the COVID-19 Pandemic: International Expert Panel Review. Cerebrovasc Dis 2021; 50:245-261. [PMID: 33756459 PMCID: PMC8089455 DOI: 10.1159/000514155] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 12/16/2020] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) has placed a tremendous strain on healthcare services. This study, prepared by a large international panel of stroke experts, assesses the rapidly growing research and personal experience with COVID-19 stroke and offers recommendations for stroke management in this challenging new setting: modifications needed for prehospital emergency rescue and hyperacute care; inpatient intensive or stroke units; posthospitalization rehabilitation; follow-up including at-risk family and community; and multispecialty departmental developments in the allied professions. SUMMARY The severe acute respiratory syndrome coronavirus 2 uses spike proteins binding to tissue angiotensin-converting enzyme (ACE)-2 receptors, most often through the respiratory system by virus inhalation and thence to other susceptible organ systems, leading to COVID-19. Clinicians facing the many etiologies for stroke have been sobered by the unusual incidence of combined etiologies and presentations, prominent among them are vasculitis, cardiomyopathy, hypercoagulable state, and endothelial dysfunction. International standards of acute stroke management remain in force, but COVID-19 adds the burdens of personal protections for the patient, rescue, and hospital staff and for some even into the postdischarge phase. For pending COVID-19 determination and also for those shown to be COVID-19 affected, strict infection control is needed at all times to reduce spread of infection and to protect healthcare staff, using the wealth of well-described methods. For COVID-19 patients with stroke, thrombolysis and thrombectomy should be continued, and the usual early management of hypertension applies, save that recent work suggests continuing ACE inhibitors and ARBs. Prothrombotic states, some acute and severe, encourage prophylactic LMWH unless bleeding risk is high. COVID-19-related cardiomyopathy adds risk of cardioembolic stroke, where heparin or warfarin may be preferable, with experience accumulating with DOACs. As ever, arteritis can prove a difficult diagnosis, especially if not obvious on the acute angiogram done for clot extraction. This field is under rapid development and may generate management recommendations which are as yet unsettled, even undiscovered. Beyond the acute management phase, COVID-19-related stroke also forces rehabilitation services to use protective precautions. As with all stroke patients, health workers should be aware of symptoms of depression, anxiety, insomnia, and/or distress developing in their patients and caregivers. Postdischarge outpatient care currently includes continued secondary prevention measures. Although hoping a COVID-19 stroke patient can be considered cured of the virus, those concerned for contact safety can take comfort in the increasing use of telemedicine, which is itself a growing source of patient-physician contacts. Many online resources are available to patients and physicians. Like prior challenges, stroke care teams will also overcome this one. Key Messages: Evidence-based stroke management should continue to be provided throughout the patient care journey, while strict infection control measures are enforced.
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Affiliation(s)
| | - Craig Anderson
- The George Institute for Global Health, Camperdown, Washington, Australia
| | - Hakan Ay
- Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard School of Medicine, Boston, Massachusetts, USA
- Takeda Pharmaceutical Co. Limited, Cambridge, Massachusetts, USA
| | - Selma Aybek
- Department of Neurology, University Hospital Inselspital, Bern University, Bern, Switzerland
| | - Waleed Brinjikji
- Department of Radiology, Vascular Center, Mayo Clinic, Rochester, Minnesota, USA
| | - Gabriel R de Freitas
- Instituto D'Or de Pesquisa e Ensino (IDOR), Rio de Janeiro, Brazil
- Department of Neurology, Universidade Federal Fluminense (UFF), Niterói, Brazil
| | - Oscar H Del Brutto
- School of Medicine, Universidad Espiritu Santo-Ecuador, Samborondón, Ecuador
| | - Klaus Fassbender
- Department of Neurology, Saarland University Medical Centre, Homburg, Germany
| | - Miki Fujimura
- Department of Neurosurgery, Kohnan Hospital, Sendai, Japan
- Division of Advanced Cerebrovascular Surgery, Tohoku University School of Medicine, Sendai, Japan
| | - Larry B Goldstein
- Department of Neurology, University of Kentucky, Lexington, Kentucky, USA
| | - Roman L Haberl
- Department of Neurology and Neurological Intensive Medicine, Munich Clinic gGmbH, Academic Teaching Hospital of the Ludwig-Maximilians-University Munich, Munich, Germany
| | - Graeme J Hankey
- Medical School, The University of Western Australia, Perth, Washington, Australia
| | | | - Isabel Lestro Henriques
- Department of Neurosciences, Neurology Service, Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal
| | - Carlos S Kase
- Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Jong S Kim
- Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Masatoshi Koga
- Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Yoshihiro Kokubo
- Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Satoshi Kuroda
- Department of Neurosurgery, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan
| | - Kiwon Lee
- Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA
| | - Tsong-Hai Lee
- Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - David S Liebeskind
- Department of Neurology, University of California, Los Angeles, Los Angeles, California, USA
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Stephen Meairs
- Department of Neurology, Universitätsmedizin Mannheim, Mannheim, Germany
| | - Roman Medvedev
- Research Center of Neurology, Moscow, Russian Federation
| | | | - Jay P Mohr
- Tananbaum Stroke Center, New York, New York, USA
| | - Masao Nagayama
- Department of Neurology, International University of Health and Welfare(IUHW), Graduate School of Medicine, Tokyo, Japan
| | - Leonardo Pantoni
- Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
| | - Panagiotis Papanagiotou
- Department of Diagnostic and Interventional Neuroradiology, Klinikum Bremen-Mitte, Germany
- Aretaieion University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Guillermo Parrilla
- Department of Neurology, Interventional Neuroradiology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
| | - Daniele Pastori
- Department of Clinical, Internal, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Sarah T Pendlebury
- Departments of Internal Medicine and Geratology, John Radcliffe Hospital, Oxford, United Kingdom
- Centre for Prevention of Stroke and Dementia, University of Oxford, Oxford, United Kingdom
| | | | | | - Tatjana Rundek
- Department of Neurology, Miller School of Medicine, University of Miami, Miami, Florida, USA
| | - Ulf Schminke
- Department of Neurology, University Medicine, Greifswald, Germany
| | | | - Wai Kwong Tang
- Department of Psychiatry, Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Kazunori Toyoda
- Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
| | | | - Mohammad Wasay
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Michael G Hennerici
- Department of Neurology, Medical Faculty, Mannheim University of Heidelberg, Mannheim, Germany
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26
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Chen S, Li J, Liu Z, Chen D, Zhou L, Hu D, Li M, Long W, Huang Y, Huang J, Wang S, Li Q, Zeng W, Guo L, Wu X. Comparing the Value of Cystatin C and Serum Creatinine for Evaluating the Renal Function and Predicting the Prognosis of COVID-19 Patients. Front Pharmacol 2021; 12:587816. [PMID: 33828483 PMCID: PMC8019901 DOI: 10.3389/fphar.2021.587816] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 01/25/2021] [Indexed: 01/14/2023] Open
Abstract
Background: Coronavirus disease- (COVID-19-) related renal function abnormality is associated with poor prognosis. However, the clinical significance of dynamic changes in renal function indicators has not been studied, and no studies have evaluated the renal function in COVID-19 patients by cystatin C. Objective: This study aimed to evaluate the effect of abnormal renal function on admission on prognosis of COVID-19 patients and the prognostic value of various renal function indicators. Methods: A total of 1,764 COVID-19 patients without a history of chronic kidney disease were categorized into two groups, an elevated cystatin C group and a normal cystatin C group, based on the results of renal function tests on admission. The clinical characteristics were compared between the two groups, and logistic or Cox regression analyses were performed to explore the associations between elevated cystatin C/serum creatinine levels and disease severity and survival. We also performed receiver operating characteristic (ROC) curve, Kaplan-Meier survival, and curve fitting analyses. Results: When adjusted for several significant clinical variables, elevated cystatin C levels on admission were independent predictors of disease severity (p < 0.001), and elevated creatinine levels were independent predictors of death (p = 0.020). Additionally, the ROC curve analysis shows that elevated cystatin C levels [area under the curve (AUC): 0.656] have a better predictive value for disease severity than elevated creatinine levels (AUC: 0.540). The survival curves of patients with elevated cystatin C/creatinine levels show a sharper decline than those of patients with normal cystatin C/creatinine levels (p < 0.001). The curve fitting analysis revealed that, compared to the flat curves of cystatin C and creatinine levels for patients who survived, the curves for patients who died kept rising, and cystatin C levels rose above the normal range earlier than creatinine. Conclusions: Elevated cystatin C, which occurs earlier than serum creatinine, is useful for the early detection of renal function abnormality and might have better predictive value for disease severity in COVID-19 patients, while elevated serum creatinine may have a better predictive value for risks of death.
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Affiliation(s)
- Sichao Chen
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jinpeng Li
- Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zeming Liu
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Danyang Chen
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Ling Zhou
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Di Hu
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Man Li
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wei Long
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yihui Huang
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jianglong Huang
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Shipei Wang
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Qianqian Li
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wen Zeng
- Department of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Liang Guo
- Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Xiaohui Wu
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
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27
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Armstrong L, Collin J, Mostafa I, Queen R, Figueiredo FC, Lako M. In the eye of the storm: SARS-CoV-2 infection and replication at the ocular surface? Stem Cells Transl Med 2021; 10:976-986. [PMID: 33710758 PMCID: PMC8235146 DOI: 10.1002/sctm.20-0543] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 01/26/2021] [Accepted: 01/30/2021] [Indexed: 01/08/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) first emerged in December 2019 and spread quickly causing the coronavirus disease 2019 (COVID‐19) pandemic. Recent single cell RNA‐Seq analyses have shown the presence of SARS‐CoV‐2 entry factors in the human corneal, limbal, and conjunctival superficial epithelium, leading to suggestions that the human ocular surface may serve as an additional entry gateway and infection hub for SARS‐CoV‐2. In this article, we review the ocular clinical presentations of COVID‐19 and the features of the ocular surface that may underline the overall low ocular SARS‐CoV‐2 infection. We critically evaluate the studies performed in nonhuman primates, ex vivo organ culture ocular models, stem cell derived eye organoids and the differences in infection efficiency observed in different parts of human ocular surface epithelium. Finally, we highlight the additional work that needs to be carried out to understand the immune response of the ocular surface to SARS‐CoV‐2 infection, which can be translated into prophylactic treatments that may be applied to other organ systems.
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Affiliation(s)
- Lyle Armstrong
- Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK
| | - Joseph Collin
- Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK
| | - Islam Mostafa
- Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK
| | - Rachel Queen
- Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK
| | - Francisco C Figueiredo
- Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK.,Department of Ophthalmology, Royal Victoria Infirmary and Newcastle University, Newcastle, UK
| | - Majlinda Lako
- Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK
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28
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COVID-19-Related Laboratory Analyte Changes and the Relationship Between SARS-CoV-2 and HIV, TB, and HbA1c in South Africa. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1321:183-197. [PMID: 33656724 DOI: 10.1007/978-3-030-59261-5_16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
We conducted a retrospective analysis on data of all adults tested for SARS-CoV-2 across our laboratory network in South Africa over a 4-month period. Out of 842,197 tests, 11.7% were positive and 88.3% negative. The prevalence of HIV was 6.25 and 6.31% in the SARS-CoV-2-positive and SARS-CoV-2-negative cohort, respectively (p = 0.444). However, the prevalence of HIV-positive individuals in the critical cohort (9.15%) was higher than in the noncritical group (6.24%) (p = 0.011). Active tuberculosis infection was approximately 50% less in SARS-CoV-2-positive than in SARS-CoV-2-negative individuals. The prevalence of uncontrolled diabetes was 3.4 times higher in SARS-CoV-2-positive cases but was not higher in the critical vs. noncritical cases (p = 0.612). The neutrophil-to-lymphocyte ratio, coagulation markers, urea, and cardiac- and liver-related analytes were significantly elevated in the critical compared to noncritical cases. Platelet count and creatinine concentration did not differ significantly between the two groups. These findings do not support increased prevalence of HIV or tuberculosis in individuals with SARS-CoV-2 infection but do suggest an association of increased disease severity with HIV-positive status. Uncontrolled diabetes was positively associated with a significantly higher prevalence of SARS-CoV-2, and our investigation into analyte changes associated with SARS-CoV-2 disease severity supported previous findings of raised inflammatory markers, coagulation markers, liver- and cardiac-related analytes, and urea but not for creatinine and platelet count.
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29
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Sanchez-Russo L, Billah M, Chancay J, Hindi J, Cravedi P. COVID-19 and the Kidney: A Worrisome Scenario of Acute and Chronic Consequences. J Clin Med 2021; 10:900. [PMID: 33668833 PMCID: PMC7956338 DOI: 10.3390/jcm10050900] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 02/13/2021] [Accepted: 02/16/2021] [Indexed: 02/07/2023] Open
Abstract
Acute kidney injury (AKI) is a common finding in patients with coronavirus disease 2019 (COVID-19) and has been associated with higher rates of death when compared to COVID-19 patients without kidney injury. Whereas the definitive pathogenesis of COVID-19-related AKI (CoV-AKI) is not clear, histopathologic evidence seems to point at multiple etiologies for the disease, including indirect and direct viral kidney injury. The high incidence of CoV-AKI, along with the aggressive clinical presentation of this entity, have increased the demands for kidney replacement therapies, rapidly overwhelming the supplies of healthcare systems even in major tertiary care centers. As a result, nephrologists have come up with alternatives to maximize the efficiency of treatments and have developed non-conventional therapeutic alternatives such as the implementation of acute peritoneal dialysis for critically ill patients. The long-term implications of CoV-AKI are yet unknown, though early studies suggest that around one third of the patients who survive will remain dependent on kidney replacement therapy. Nephrologists and healthcare workers need to be familiar with the clinical presentation and therapeutic challenges of CoV-AKI in order to develop strategies to mitigate the burden of the disease for patients, and for services providing kidney replacement therapies.
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Affiliation(s)
| | | | | | | | - Paolo Cravedi
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; (L.S.-R.); (M.B.); (J.C.); (J.H.)
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Baker SA, Kwok S, Berry GJ, Montine TJ. Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation. PLoS One 2021; 16:e0247060. [PMID: 33592054 PMCID: PMC7886150 DOI: 10.1371/journal.pone.0247060] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 01/30/2021] [Indexed: 01/08/2023] Open
Abstract
Mortality due to Covid-19 is highly associated with advanced age, owing in large part to severe lower respiratory tract infection. SARS-CoV-2 utilizes the host ACE2 receptor for infection. Whether ACE2 abundance in the lung contributes to age-associated vulnerability is currently unknown. We set out to characterize the RNA and protein expression profiles of ACE2 in aging human lung in the context of phenotypic parameters likely to affect lung physiology. Examining publicly available RNA sequencing data, we discovered that mechanical ventilation is a critical variable affecting lung ACE2 levels. Therefore, we investigated ACE2 protein abundance in patients either requiring mechanical ventilation or spontaneously breathing. ACE2 distribution and expression were determined in archival lung samples by immunohistochemistry (IHC). Tissues were selected from the specimen inventory at a large teaching hospital collected between 2010-2020. Twelve samples were chosen from patients receiving mechanical ventilation for acute hypoxic respiratory failure (AHRF). Twenty samples were selected from patients not requiring ventilation. We compared samples across age, ranging from 40-83 years old in the ventilated cohort and 14-80 years old in the non-ventilated cohort. Within the alveolated parenchyma, ACE2 expression is predominantly observed in type II pneumocytes (or alveolar type II / AT2 cells) and alveolar macrophages. All 12 samples from our ventilated cohort showed histologic features of diffuse alveolar damage including reactive, proliferating AT2 cells. In these cases, ACE2 was strongly upregulated with age when normalized to lung area (p = 0.004) or cellularity (p = 0.003), associated with prominent expression in AT2 cells. In non-ventilated individuals, AT2 cell reactive changes were not observed and ACE2 expression did not change with age when normalized to lung area (p = 0.231) or cellularity (p = 0.349). In summary, ACE2 expression increases with age in the setting of alveolar damage observed in patients on mechanical ventilation, providing a potential mechanism for higher Covid-19 mortality in the elderly.
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Affiliation(s)
- Steven Andrew Baker
- Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America
| | - Shirley Kwok
- Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America
| | - Gerald J. Berry
- Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America
| | - Thomas J. Montine
- Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America
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31
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Rudd KE, Cizmeci EA, Galli GM, Lundeg G, Schultz MJ, Papali A. Pragmatic Recommendations for the Prevention and Treatment of Acute Kidney Injury in Patients with COVID-19 in Low- and Middle-Income Countries. Am J Trop Med Hyg 2021; 104:87-98. [PMID: 33432912 PMCID: PMC7957240 DOI: 10.4269/ajtmh.20-1242] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 12/21/2020] [Indexed: 12/15/2022] Open
Abstract
Current recommendations for the management of patients with COVID-19 and acute kidney injury (AKI) are largely based on evidence from resource-rich settings, mostly located in high-income countries. It is often unpractical to apply these recommendations to resource-restricted settings. We report on a set of pragmatic recommendations for the prevention, diagnosis, and management of patients with COVID-19 and AKI in low- and middle-income countries (LMICs). For the prevention of AKI among patients with COVID-19 in LMICs, we recommend using isotonic crystalloid solutions for expansion of intravascular volume, avoiding nephrotoxic medications, and using a conservative fluid management strategy in patients with respiratory failure. For the diagnosis of AKI, we suggest that any patient with COVID-19 presenting with an elevated serum creatinine level without available historical values be considered as having AKI. If serum creatinine testing is not available, we suggest that patients with proteinuria should be considered to have possible AKI. We suggest expansion of the use of point-of-care serum creatinine and salivary urea nitrogen testing in community health settings, as funding and availability allow. For the management of patients with AKI and COVID-19 in LMICS, we recommend judicious use of intravenous fluid resuscitation. For patients requiring dialysis who do not have acute respiratory distress syndrome (ARDS), we suggest using peritoneal dialysis (PD) as first choice, where available and feasible. For patients requiring dialysis who do have ARDS, we suggest using hemodialysis, where available and feasible, to optimize fluid removal. We suggest using locally produced PD solutions when commercially produced solutions are unavailable or unaffordable.
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Affiliation(s)
- Kristina E. Rudd
- Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Elif A. Cizmeci
- Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada
| | - Gabriela M. Galli
- School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Ganbold Lundeg
- Department of Critical Care and Anaesthesia, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
| | - Marcus J. Schultz
- Department of Intensive Care, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Mahidol–Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand
- Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom
| | - Alfred Papali
- Division of Pulmonary & Critical Care Medicine, Atrium Health, Charlotte, North Carolina
| | - for the COVID-LMIC Task Force and the Mahidol-Oxford Research Unit (MORU)
- Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada
- School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Critical Care and Anaesthesia, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
- Department of Intensive Care, Amsterdam University Medical Centers, Amsterdam, The Netherlands
- Mahidol–Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand
- Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom
- Division of Pulmonary & Critical Care Medicine, Atrium Health, Charlotte, North Carolina
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32
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Phillips T, Stammers M, Leggatt G, Bonfield B, Fraser S, Armstrong K, Veighey K. Acute kidney injury in COVID‐19: Identification of risk factors and potential biomarkers of disease in a large UK cohort. Nephrology (Carlton) 2021. [DOI: 10.1111/nep.13847] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Thomas Phillips
- Specialist Medicine University Hospital Southampton Southampton UK
| | - Matthew Stammers
- Specialist Medicine University Hospital Southampton Southampton UK
| | - Gary Leggatt
- Specialist Medicine University Hospital Southampton Southampton UK
| | - Becky Bonfield
- Specialist Medicine University Hospital Southampton Southampton UK
| | - Simon Fraser
- Specialist Medicine University Hospital Southampton Southampton UK
| | | | - Kristin Veighey
- Specialist Medicine University Hospital Southampton Southampton UK
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33
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Ahmed AR, Ebad CA, Stoneman S, Satti MM, Conlon PJ. Kidney injury in COVID-19. World J Nephrol 2020; 9:18-32. [PMID: 33312899 PMCID: PMC7701935 DOI: 10.5527/wjn.v9.i2.18] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 10/03/2020] [Accepted: 10/20/2020] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) continues to affect millions of people around the globe. As data emerge, it is becoming more evident that extrapulmonary organ involvement, particularly the kidneys, highly influence mortality. The incidence of acute kidney injury has been estimated to be 30% in COVID-19 non-survivors. Current evidence suggests four broad mechanisms of renal injury: Hypovolaemia, acute respiratory distress syndrome related, cytokine storm and direct viral invasion as seen on renal autopsy findings. We look to critically assess the epidemiology, pathophysiology and management of kidney injury in COVID-19.
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Affiliation(s)
- Adeel Rafi Ahmed
- Department of Nephrology, Beaumont Hospital, Dublin D09 V2N0, Ireland
| | | | - Sinead Stoneman
- Department of Nephrology, Beaumont Hospital, Dublin D09 V2N0, Ireland
| | | | - Peter J Conlon
- Department of Nephrology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin D09 V2N0, Ireland
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Abstract
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has impacted a large portion of the world population. From a virus genetic perspective, a recent study described what genomic data revealed about the origin and emergence of SARS-CoV-2, proposing stronger action against illegal wildlife trade. In the current "big data" era, an increasing number of large-scale, multidimensional omics data sets were publicly available. Herein, we review how human genetics tells us about the transmission, pathogenesis, susceptibility, severity, and drug prioritization of COVID-19. We further drafted a genetic roadmap of COVID-19, which was also expected to be applicable to other viruses with known receptors. Our review provides insights into the way of understanding a pandemic from a human genetic perspective.
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Affiliation(s)
- Yue-Miao Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100871, China
- Institute of Nephrology, Peking University, Beijing 100871, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing 100871, China
| | - Lin Wang
- Department of Microbiology and Infectious Disease Centre, School of Basic Medical Sciences, Peking University Health Science Centre, Beijing 100871, China
| | - Xing-Zi Liu
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100871, China
- Institute of Nephrology, Peking University, Beijing 100871, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing 100871, China
| | - Hong Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100871, China
- Institute of Nephrology, Peking University, Beijing 100871, China
- Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing 100871, China
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35
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Marcilla Vázquez C, Vidal Company A, Navarro Felipe A, Alfaro Ponce B. [Thrombotic microangiopathy: A renal manifestation in SARS-CoV-2 infection (COVID-19 disease)]. An Pediatr (Barc) 2020; 93:352-353. [PMID: 32943329 PMCID: PMC7831569 DOI: 10.1016/j.anpedi.2020.06.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 06/20/2020] [Accepted: 06/30/2020] [Indexed: 11/21/2022] Open
Affiliation(s)
- Carlos Marcilla Vázquez
- Unidad de Nefrología Pediátrica, Complejo Hospitalario Universitario de Albacete, Albacete, España.
| | - Alberto Vidal Company
- Unidad de Nefrología Pediátrica, Complejo Hospitalario Universitario de Albacete, Albacete, España
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Abstract
Despite initial reports, renal involvement, including acute kidney injury, has emerged as a serious complication of COVID-19 disease, particularly in critically ill patients. The reported prevalence varies considerably, which may reflect reporting practices, although differences in pre-existing comorbidities and socioeconomic factors, and differences between ethnic groups, almost certainly contribute. Renal involvement may present as an active urinary sediment or as changes in serum creatinine levels and urine output leading to acute kidney injury. In common with acute kidney injury complicating critical illness, the cause is often multifactorial and often presents as part of a multiorgan dysfunction syndrome. Treatment is, in the main, supportive, with kidney replacement therapy required in nearly 25% of reported cases. Few data currently exist as to the long-term burden of COVID-19-associated acute kidney injury but evidence suggests that only approximately one-third of patients are discharged with recovered renal function.
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Affiliation(s)
| | | | - Lui G Forni
- Department of Clinical and Experimental Medicine, Faculty of Health Sciences, University of Surrey, Guildford, UK
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37
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Abstract
Coronavirus disease 2019 (COVID-19) not only causes pulmonary inflammation but also causes multiple organ damages, including the kidney. ACE2, as one of the receptors for SARS-CoV-2 intrusion, is widely distributed in kidney tissues. Currently, the diagnosis and treatment of SARS-CoV-2 infection in patients with chronic kidney disease (CKD) are still unclear. Here, we review the recent findings of characteristics of COVID-19 in CKD patients and highlight the possible mechanisms of kidney injury caused by SARS-CoV-2 infection. We then discuss the emerging therapeutic approaches aimed at reducing kidney damage and protecting kidney function including virus removal, immunotherapy, supporting treatment, special blood purification therapy, etc. Problems unresolved and challenges ahead are also discussed.
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38
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Braun F, Lütgehetmann M, Pfefferle S, Wong MN, Carsten A, Lindenmeyer MT, Nörz D, Heinrich F, Meißner K, Wichmann D, Kluge S, Gross O, Pueschel K, Schröder AS, Edler C, Aepfelbacher M, Puelles VG, Huber TB. SARS-CoV-2 renal tropism associates with acute kidney injury. Lancet 2020; 396:597-598. [PMID: 32818439 PMCID: PMC7431179 DOI: 10.1016/s0140-6736(20)31759-1] [Citation(s) in RCA: 234] [Impact Index Per Article: 46.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 07/28/2020] [Accepted: 07/29/2020] [Indexed: 12/24/2022]
Affiliation(s)
- Fabian Braun
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Marc Lütgehetmann
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Susanne Pfefferle
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Milagros N Wong
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Alexander Carsten
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Maja T Lindenmeyer
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Dominik Nörz
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Fabian Heinrich
- Department of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Kira Meißner
- Department of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Dominic Wichmann
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Stefan Kluge
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Oliver Gross
- Clinic of Nephrology and Rheumatology, University of Gottingen, Gottingen, Germany
| | - Klaus Pueschel
- Department of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Ann S Schröder
- Department of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Carolin Edler
- Department of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Martin Aepfelbacher
- Institute of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Victor G Puelles
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany
| | - Tobias B Huber
- Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
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39
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Bajaj JS, Garcia-Tsao G, Biggins S, Kamath PS, Wong F, McGeorge S, Shaw J, Pearson M, Chew M, Fagan A, de la Rosa Rodriguez R, Worthington J, Olofson A, Weir V, Trisolini C, Dwyer S, Reddy KR. Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort. Gut 2020; 70:531-536. [PMID: 32660964 PMCID: PMC7371484 DOI: 10.1136/gutjnl-2020-322118] [Citation(s) in RCA: 166] [Impact Index Per Article: 33.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 06/18/2020] [Accepted: 06/24/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Comorbid conditions are associated with poor prognosis in COVID-19. Registry data show that patients with cirrhosis may be at high risk. However, outcome comparisons among patients with cirrhosis+COVID-19 versus patients with COVID-19 alone and cirrhosis alone are lacking. The aim of this study was to perform these comparisons. DESIGN A multicentre study of inpatients with cirrhosis+COVID-19 compared with age/gender-matched patients with COVID-19 alone and cirrhosis alone was performed. COVID-19 and cirrhosis characteristics, development of organ failures and acute-on-chronic liver failure (ACLF) and mortality (inpatient death+hospice) were compared. RESULTS 37 patients with cirrhosis+COVID-19 were matched with 108 patients with COVID-19 and 127 patients with cirrhosis from seven sites. Race/ethnicity were similar. Patients with cirrhosis+COVID-19 had higher mortality compared with patients with COVID-19 (30% vs 13%, p=0.03) but not between patients with cirrhosis+COVID-19 and patients with cirrhosis (30% vs 20%, p=0.16). Patients with cirrhosis+COVID-19 versus patients with COVID-19 alone had equivalent respiratory symptoms, chest findings and rates of intensive care unit transfer and ventilation. However, patients with cirrhosis+COVID-19 had worse Charlson Comorbidity Index (CCI 6.5±3.1 vs 3.3±2.5, p<0.001), lower presenting GI symptoms and higher lactate. Patients with cirrhosis alone had higher cirrhosis-related complications, maximum model for end-stage liver disease (MELD) score and lower BiPAP/ventilation requirement compared with patients with cirrhosis+COVID-19, but CCI and ACLF rates were similar. In the entire group, CCI (OR 1.23, 95% CI 1.11 to 1.37, p<0.0001) was the only variable predictive of mortality on multivariable regression. CONCLUSIONS In this multicentre North American contemporaneously enrolled study, age/gender-matched patients with cirrhosis+COVID-19 had similar mortality compared with patients with cirrhosis alone but higher than patients with COVID-19 alone. CCI was the only independent mortality predictor in the entire matched cohort.
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Affiliation(s)
- Jasmohan S Bajaj
- Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University Health System, Richmond, Virginia, USA .,Department of Medicine, Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Health Care System, Richmond, Virginia, USA
| | - Guadalupe Garcia-Tsao
- Department of Medicine, Internal Medicine, Yale University, New Haven, Connecticut, USA
| | | | - Patrick S Kamath
- Department of Medicine, Gastroenterology and Hepatology, Mayo Medical School, Rochester, Minnesota, USA
| | | | - Sara McGeorge
- Department of Medicine, Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Health Care System, Richmond, Virginia, USA
| | - Jawaid Shaw
- Department of Medicine, Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Health Care System, Richmond, Virginia, USA
| | | | - Micheal Chew
- Department of Medicine, Internal Medicine, Yale University, New Haven, Connecticut, USA
| | - Andrew Fagan
- Department of Medicine, Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and Central Virginia Health Care System, Richmond, Virginia, USA
| | | | - Janelle Worthington
- Department of Medicine, Gastroenterology and Hepatology, Mayo Medical School, Rochester, Minnesota, USA
| | - Amy Olofson
- Department of Medicine, Gastroenterology and Hepatology, Mayo Medical School, Rochester, Minnesota, USA
| | - Vanessa Weir
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Calvin Trisolini
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Sarah Dwyer
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - K Rajender Reddy
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA,Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
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