RetractionWatch-Flagged.pdf
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flag high Retracted work cited Retracted work cited: 10.1016/s0140-6736(20)32656-8 expand_more
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1. Xinhua, M.A.; Xizhe, L.I.; Liang, F.; Yujin, W.A.N.; Qiang, S.H.I.; Yonghui, W.A.N.G.; Wei, G.U.O. China's CDC detects a large number of new coronaviruses in the South China seafood market in Wuhan. Xinhua 2020 , 1 , 901-915.
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2. Mishra, S.; Chand, M.; Barrett, J.C.; Johnson, R.; Geidelberg, L.; Ferguson, N.M. Assessing transmissibility of SARS-CoV-2 lineage B. 1.1. 7 in England. Nature 2021 , 13 , 266-269.
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26. Menon, G.R.; Sharma, R.K.; Sahu, D.; Wig, N.; Kumar, G.; Mukherjee, A.; National Clinical Registry for COVID-19 Team. Clinical profile of hospitalized COVID-19 patients in first & second wave of the pandemic: Insights from an Indian registry based observational study. Indian J. Med. Res. 2021 , 153 , 619.
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123. Micke, O.; Vormann, J.; Kisters, K. Magnesium and COVID-19-cardiovascular implications. Trace Elem. Electrolytes 2022 , 39 , 82-83.
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145. D'Agati, D.A.NI.E.L.A.; Drago, V.; Leonardi, G.; La Morella, M.L. Biomarkers [timp-2]*[igfbp7]: Application in clinical practice for acute kidney injury prevention. Acta Med. 2022 , 38 , 2505.
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Beyond 4 weeks after the onset of symptoms, the long-term complications of SARSCoV-2 infection are further classified as sub-acute and chronic, or post-COVID-19 syndrome [13,14].
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AKI could also be caused by direct SARS-CoV-2 infection of renal tubular epithelial cells [28,46,47], and considering the participation of additional epithelia (lung, gastrointestinal tract, etc.), it appears to be a very plausible contributing factor in AKI [48].
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Both the mRNA vaccine and the inactivated vaccine have the potential to cause new-onset and relapsing glomerular diseases; these diseases could occur after the first or second dose of vaccination [17,18].
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The majority of AKI developed within 7 days, but it was much more severe and occurred much sooner in patients with higher baseline serum creatinine levels, whereas patients with normal baseline creatinine had a later onset of AKI and recovered quickly [41].
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This type of glomerulopathy has been associated with a number of illnesses, including viral infections [55].
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Since uremia is connected to reduced leucocyte function, patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) or peritoneal dialysis (PD) may be more at risk [37].
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Cytokine storm, hypoxemia, direct viral invasion via angiotensin-converting enzyme 2 and cathepsin L, electrolyte imbalance, and fever are among the pathophysiological mechanisms underlying these clinical symptoms, which may also relate to renal injury and/or functional decline in the majority of seriously impacted patients [83,84].
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The pathophysiology of COVID-19 AKI is considered to involve endothelial damage, activation of coagulation pathways, local and systemic inflammatory and immunological responses, and the renin-angiotensin system [82].
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The national clinical management protocol stated that remdesivir is contraindicated in patients with a GFR < 30 mL/min and in patients on hemodialysis [111].
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In fact, 93% of ICU patients admitted to hospitals had hypokalemia at that time [38].
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It is further divided into two categories based on recent literature: (1) subacute or ongoing symptomatic COVID-19, which includes symptoms and abnormalities present from 4-12 weeks beyond acute COVID-19; and (2) chronic or post-COVID-19 syndrome, which includes symptoms and abnormalities persisting or present beyond 12 weeks of the onset of acute COVID-19 and not attributable to alternative diagnoses [133,136].
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At six months following the acute SARS-CoV-2 infection, 35% of patients reported a decreased estimated glomerular filtration rate (eGFR), and 13% of those patients experienced a new beginning of eGFR decline following the acute SARS-CoV-2 infection but with confirmed normal renal function [15].
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On the other hand, a number of studies point to the vaccine-induced anti-S IgG antibodies persisting for a longer time in hemodialysis patients, which would allay concerns about their rapid drop due to repeated dialysis over time [148].
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Within 90 days, 37 patients' scores returned to baseline, and six patients had no results reported [98].
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Proteinuria is common during SARS-CoV-2 infection and has been reported in 7-63% of cases [53,54].
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Depending on the series described, there were anywhere from 0.7 to 47.6% of patients with known CKD [48,71].
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ACE2 functions as an enzyme within the renin-angiotensin system, metabolizing angiotensin II by cleaving a terminal peptide to generate angiotensin (1-7) (Ang 1-7) in addition to mediating SARS-CoV-2 entrance into cells [99].
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Examples of these antibiotics are vancomycin, colistin, and aminoglycosides [109].
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The observed link between the risk of AKI and the use of vasopressors and mechanical ventilation further supports the idea that hemodynamic variables are a factor in COVID-19 AKI [117].
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Uncommon instances of acute myocarditis [113] and myocardial injury [114] have been described in patients with COVID-19, which might affect cardiac function, reduce cardiac output, congest renal veins, and compromise kidney perfusion [115].
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Early research on patients needing renal replacement therapy (RRT) revealed that between 27 and 64% were independent of dialysis by 28 days following ICU release [130,137].
Recommendations
Relevance analysis suggests additional references and improvement opportunities. Use [R#] markers to jump to the full reference list below.
To strengthen this review, the primary focus should be on integrating foundational clinical data from early 2020 outbreaks [R48, R51] to ground the introduction in established epidemiological facts. Priority 2 involves deepening the discussion on the specific mechanisms of kidney injury, particularly by incorporating more recent narrative reviews [R54, R58] that synthesize multi-organ damage. Finally, Priority 3 suggests justifying the use of older, non-COVID specific citations [R30, R31] to ensure the review remains focused on the current pandemic's unique renal challenges.
Top priorities
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Priority 1: Add early clinical data from Wuhan to provide a more robust baseline for the initial outbreak description. - Insert this after the mention of the virus being described as a coronavirus in early January.
AddThis is a foundational study that established the first clinical features of the virus.
On January 7, the virus was described as a coronavirus [1].
Supporting refs: [R48] -
Priority 2: Include specific hospitalization statistics to support the severity of pneumonia and renal involvement. - Add this when discussing the severity of illness and the impact on the kidney.
AddIt provides essential context on the scale of organ failure seen in early hospitalized patients.
the kidney is among the different organs that are significantly affected with the SARS-CoV-2 infection [2,3].
Supporting refs: [R51] -
Priority 3: Address the conflicting evidence regarding direct viral presence in renal tissue - In section 2.1, after the discussion of US autopsies
JustifyThe text presents viral particles in podocytes as fact, but other high-quality studies in the references could not distinguish definitive virions, suggesting a need for a more balanced discussion.
definitive virions could not be distinguished at the ultrastructural level [29]
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Priority 4: Integrate ICU-specific AKI incidence and mortality predictors - In section 2.2, after the mention of ICU AKI rates
AddIt provides specific clinical markers (albumin, age, comorbidities) that correlate with AKI-related mortality in the ICU.
AKI rates were significantly elevated to 14.5-50% in patients in the ICU
Supporting refs: [R43] -
Priority 5: Integrate recent epidemiological insights on kidney disease progression - At the end of the first paragraph of section 3
AddIt provides a comprehensive 2022 perspective on how COVID-19 transitions from acute injury to long-term kidney disease.
functional decline in the majority of seriously impacted patients [83,84].
Supporting refs: [R45]
Other changes by section
edit Section Insights into COVID-19 and Its Potential Implications for Kidney Dysfunction 3 actions expand_more
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Provide context for the frequency of vaccine-related renal side effects
JustifyThe mention of vaccine harms is currently anecdotal; adding context regarding the rarity of these events compared to the benefits of vaccination would provide a more balanced perspective.
Where: At the end of the sentence discussing hospitalization after vaccination.
necessitated hospitalization after receiving COVID-19 vaccinations.
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Elaborate on the specific renal pathologies mentioned
StrengthenThe list of pathologies is currently a brief enumeration and would benefit from a more detailed description of how these manifest in COVID-19 patients.
Where: In the middle of the paragraph after the mention of thrombosis complications.
acute tubular necrosis, proteinuria, hematuria, and thrombosis complications.
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Clarify the role of Cathepsin L in viral entry
AddWhile ACE2 is well-known, the specific role of Cathepsin L in the context of renal cell invasion is less commonly detailed and needs a brief explanatory phrase.
Where: Within the sentence describing pathophysiological mechanisms.
direct viral invasion via angiotensin-converting enzyme 2 and cathepsin L
edit Section 1. Introduction 3 actions expand_more
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Clarify the debate regarding direct viral invasion versus indirect injury
JustifySome early studies suggested AKI was not a common outcome, which contrasts with the 'direct invasion' theory presented later.
Where: In the second paragraph, when discussing the ACE2 pathway.
SARS-CoV-2 can directly infect kidney podocytes and proximal tubular cells
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Include pediatric renal involvement to broaden the scope of the introduction
AddThe text mentions these groups are affected but lacks the specific 28-day mortality rates (approx. 21-25%) found in large collaborations.
Where: After the discussion of chronic replacement therapies and kidney transplants.
COVID-19 also affects patients receiving chronic replacement therapies and those receiving kidney transplants [9,10].
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Synthesize the reported incidence rates of AKI to show the range of clinical observations
StrengthenThe current text mentions a 25% severity and a 28% ICU incidence, but other studies show rates as high as 43%, indicating significant variability.
Where: In the first paragraph, after the mention of ICU patients.
The contributing factors for developing AKI have been evaluated in 161 intensive care unit (ICU) patients with a 28% incidence of AKI.
edit Section 2. COVID-19 and Manifestations of Kidney Dysfunction 3 actions expand_more
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Incorporate specific risk factors for ICU mortality in AKI patients
StrengthenThe current text lists general symptoms but lacks specific clinical predictors of mortality in critically ill patients which are available in the provided literature.
Where: At the end of section 2.2
Some of the clinical symptoms of COVID-19 include a cough, shortness of breath, muscle aches, disorientation, headache, sore throat, rhinorrhea, and chest pain [19,20].
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Expand on the systemic nature of COVID-19 and its multi-organ impact
AddKidney dysfunction often occurs as part of a broader multi-organ failure syndrome which is central to the pathophysiology of severe COVID-19.
Where: In the opening paragraph of section 2
Some of the clinical symptoms of COVID-19 include a cough
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Connect coagulopathy findings to anti-phospholipid antibodies
AddThe text mentions coagulopathy and fibrin thrombi; this reference provides a potential immunological explanation.
Where: In section 2.1, after the mention of focal fibrin thrombi
focal fibrin thrombi seen in 6 of the 42 autopsies
Supporting refs: [R68]
edit Section 3. Pathophysiology of COVID-19-Induced Kidney Dysfunction 3 actions expand_more
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Clarify the debate regarding direct viral presence in kidney tissue
JustifyThe text presents direct viral damage as a primary driver, but some studies suggest systemic factors are more dominant or that viral detection in the kidney is inconsistent.
Where: In section 3.1, after the mention of nucleocapsid protein
associated with a possible direct tubular injury from the virus.
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Contextualize the clinical impact and mortality risk of AKI in COVID-19
StrengthenThe opening paragraph lists mechanisms but lacks the clinical significance and high incidence rates that justify the study of these pathways.
Where: At the beginning of section 3
The pathophysiology of COVID-19 AKI is considered to involve endothelial damage
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Incorporate the role of patient comorbidities in pathophysiology
AddHost factors like age and pre-existing conditions significantly influence the progression of kidney dysfunction and ACE2 expression levels.
Where: In the transition between general pathophysiology and direct viral damage
Thus, a direct viral infection may influence the mechanisms causing kidney damage.
edit Section 4. Limitations 3 actions expand_more
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Elaborate on the 'heterogeneity in diagnostic criteria'
JustifyDifferent definitions of Acute Kidney Injury (AKI) or chronic stages can significantly alter prevalence rates across studies.
Where: Middle of the section.
the heterogeneity in diagnostic criteria, treatment protocols, and severity classification
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Provide specific examples of confounding comorbidities
StrengthenThe mention of comorbidities is currently too abstract and needs to specify which conditions (e.g., diabetes, hypertension) most complicate the causal link to kidney dysfunction.
Where: In the second sentence of the paragraph.
due to the presence of other comorbidities and variations in patient populations.
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Address the limitation of 'long-COVID' data
AddThe text mentions insufficient follow-up but should explicitly link this to the emerging need for longitudinal data on chronic kidney disease (CKD) progression post-infection.
Where: After the mention of follow-up periods.
insufficient follow-up periods, making it difficult to draw definitive conclusions.
edit Section 5. Conclusions 3 actions expand_more
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Elaborate on the mention of vaccine-associated kidney injury
JustifyThis is a significant claim that requires more nuance to avoid overstating risks compared to the benefits of vaccination.
Where: After the mention of current vaccinations
However, some of the current vaccinations are associated with a slight increase in kidney injury.
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Remove the redundant Figure 1 captions and metadata from the text body
ReconsiderThe conclusion text is currently interrupted by repeated figure captions and author contribution metadata which should be in the back matter.
Where: End of the section
There is an association between COVID-19 and the kidney due to the high expression of ACE2 in kidney tissue.
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Synthesize the clinical implications of the identified pathways
StrengthenThe section lists pathologies but does not explicitly connect them to the 'great caution' needed in drug delivery mentioned later.
Where: Middle of the paragraph
Acute tubular injury, glomerular fibrin thrombi, pigmented tubular casts, and collapsing localized segmental glomerulosclerosis are all examples of kidney pathology.
edit Section Literature Review 3 actions expand_more
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Incorporate findings from this 2025 narrative review to provide a more modern synthesis of AKI outcomes.
StrengthenUsing a very recent review helps bridge early findings with long-term clinical observations.
Where: Use this to expand the paragraph discussing the incidence of AKI in ICU patients.
The contributing factors for developing AKI have been evaluated in 161 intensive care unit (ICU) patients with a 28% incidence of AKI.
Supporting refs: [R54] -
Use this source to detail the specific molecular pathways of COVID-associated kidney injury.
StrengthenIt offers a more comprehensive look at the pathophysiology than the earlier 2020 sources alone.
Where: Add this to the section describing the ACE2 pathway and mitochondrial dysfunction.
SARS-CoV-2 can directly infect kidney podocytes and proximal tubular cells and cause acute tubular necrosis
Supporting refs: [R58] -
Evaluate if this 2002 study on microvascular permeability is necessary given the abundance of COVID-specific vascular data.
ReconsiderThe review should prioritize recent findings that account for the specific behavior of the SARS-CoV-2 spike protein.
Where: Review the necessity of this citation in the section on coagulopathy and thrombosis.
COVID-19 patients have organ failure and coagulopathy, resulting in a higher mortality rate [8].
Supporting refs: [R31]
edit Section Future Work 1 actions expand_more
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Reference this review on Long COVID to suggest directions for studying permanent renal scarring.
AddIt provides a framework for understanding the long-term autoimmune and epidemiological aspects of the post-viral phase.
Where: Include this in the closing discussion about long-term outcomes and post-COVID syndrome.
the long-term complications of SARSCoV-2 infection are further classified as sub-acute and chronic, or post-COVID-19 syndrome [13,14].
Supporting refs: [R57]
Potential reviewers
28 suggestedDerived from citation-coupled works that cite many of your references.
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Daniel E. Platt — IBM (United States)
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Diana Kadi — Saint George Hospital
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Eid Azar — Saint George Hospital
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Gilbert Karayakoupoglou — Haykel Hospital
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Hamdan Hamdan — Khalifa University of Science and Technology
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Jad Azar — Saint George Hospital
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Moni Nader — Khalifa University of Science and Technology
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Omar Zmerli — Saint George Hospital
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Pierre Zalloua — Khalifa University of Science and Technology
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Rami Abi Tayeh — Saint George Hospital
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Salwa Hamdash — Haykel Hospital
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Youssef Sultan — Saint George Hospital
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T. Bazarbachi — Haykel Hospital
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Taha Bazarbachi — Laboratory Medicine, Haykel Hospital, Tripoli, Lebanon
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Asieh Aref — Ahvaz Jundishapur University of Medical Sciences
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Hashem Kazemi — Islamic Azad University, Dezful Branch
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Mohsen Maleknia — Ahvaz Jundishapur University of Medical Sciences
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Zohre Valizadeh — Department of Nursing and Midwifery, Dezfoul Branch, Islamic Azad Unuversity, Unit Dezfoul, Iran
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Abdelhamid Hachimi — Cadi Ayyad University
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Mohamed Merzouki — Université Sultan Moulay Slimane
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Olga Ciepiela — University Clinical Centre; Medical University of Warsaw
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Paweł Kozłowski — Medical University of Warsaw; University Clinical Centre
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Cosmin Bălan — Institutul de Urgenţă pentru Boli Cardiovasculare "Prof.Dr. C.C. Iliescu"
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Tudor Ciuhodaru — Prof. Dr. Nicolae Oblu Emergency Clinical Hospital , Iași , Romania
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Şerban-Ion Bubenek-Turconi — Institutul de Urgenţă pentru Boli Cardiovasculare "Prof.Dr. C.C. Iliescu"; Carol Davila University of Medicine and Pharm…
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Ramakrishnan Veerabathiran — Chettinad Academy of Research and Education
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В. А. Федулкина — Regional Clinical Research
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Zhanjun Shu — Infectious Diseases and Nephropathy, The Fourth Clinical College of Xinjiang Medical University, Urumqi 830000, China
Complete reference list
All deep-analysis references, alphabetized by author. Use the filter to show only references from a given group.
Groups are derived from deep-analysis reference categories.
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[R100] Adamsick, M. L., Gandhi, R. G., Bidell, M. R., Elshaboury, R. H., Bhattacharyya, R. P., et al. (2020). Remdesivir in Patients with Acute or Chronic Kidney Disease and COVID-19. Journal of the American Society of Nephrology, 31(7), 1384–1386.Source: Journal of the American Society of NephrologyAlready cited
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[R113] Adapa, S., Chenna, A., Balla, M., Merugu, G. P., Koduri, N. M., et al. (2020). COVID-19 Pandemic Causing Acute Kidney Injury and Impact on Patients With Chronic Kidney Disease and Renal Transplantation. Journal of Clinical Medicine Research, 12(6), 352–361.Source: Journal of Clinical Medicine ResearchAlready cited
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[R218] Agís‐Balboa, R. C. & Fischer, A. (2013). Generating new neurons to circumvent your fears: the role of IGF signaling.Source: Cellular and Molecular Life Sciences
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[R24] Ahmadian, E., Khatibi, S. M. H., Soofiyani, S. R., Abediazar, S., Shoja, M. M., et al. (2020). Covid‐19 and kidney injury: Pathophysiology and molecular mechanisms. Reviews in Medical Virology, 31(3), e2176.Source: Reviews in Medical VirologyAlready cited
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[R135] Ahmed, H., Patel, K., Greenwood, D. C., Halpin, S., Lewthwaite, P., et al. (2020). LONG-TERM CLINICAL OUTCOMES IN SURVIVORS OF CORONAVIRUS OUTBREAKS AFTER HOSPITALISATION OR ICU ADMISSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF FOLLOW-UP STUDIES.Already cited
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[R13] Ajaimy, M. & Melamed, M. L. (2020). COVID-19 in Patients with Kidney Disease. Clinical Journal of the American Society of Nephrology, 15(8), 1087–1089.Source: Clinical Journal of the American Society of NephrologyAlready cited
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[R107] Akalin, E., Azzi, Y. A., Bartash, R., Seethamraju, H., Parides, M. K., et al. (2020). Covid-19 and Kidney Transplantation. New England Journal of Medicine, 382(25), 2475–2477.Source: New England Journal of MedicineAlready cited
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[R90] Akilesh, S., Nast, C. C., Yamashita, M., Henriksen, K., Charu, V., et al. (2020). Multicenter Clinicopathologic Correlation of Kidney Biopsies Performed in COVID-19 Patients Presenting With Acute Kidney Injury or Proteinuria. American Journal of Kidney Diseases, 77(1), 82–93.e1.Source: American Journal of Kidney DiseasesAlready cited
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[R149] Alberici, F., Delbarba, E., Manenti, C., Econimo, L., Valerio, F., et al. (2020). A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia. Kidney International, 97(6), 1083–1088.Source: Kidney InternationalAlready cited
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[R70] Anandh, U., Noorin, A., Kazmi, S. K. S., Bannur, S., Shah, S. S. A., et al. (2022). Acute kidney injury in critically ill COVID-19 infected patients requiring dialysis: experience from India and Pakistan. BMC Nephrology, 23(1), 308.Source: BMC NephrologyAlready cited
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[R145] Anderegg, M., Liu, M., Saganas, C., Montani, M., Vogt, B., et al. (2021). De novo vasculitis after mRNA-1273 (Moderna) vaccination. Kidney International, 100(2), 474–476.Source: Kidney InternationalAlready cited
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[R186] Anderson, R. M., Fraser, C., Ghani, A. C., Donnelly, C. A., Riley, S., et al. (2004). Epidemiology, transmission dynamics and control of SARS: the 2002–2003 epidemic.Source: Philosophical Transactions of the Royal Society B Biological Sciences
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[R253] Angus, D. C., Linde‐Zwirble, W. T., Lidicker, J., Clermont, G., Carcillo, J. A., & Pinsky, M. R. (2001). Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care.Source: Critical Care Medicine
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[R46] Ansems, K., Grundeis, F., Dahms, K., Mikołajewska, A., Thieme, V., et al. (2021). Remdesivir for the treatment of COVID-19. Cochrane Database of Systematic Reviews, 2021(8), CD014962.Source: Cochrane Database of Systematic ReviewsAlready cited
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