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1.
Clin J Am Soc Nephrol ; 16(11): 1755-1765, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526737

ABSTRACT

Despite evidence of multiorgan tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19), direct viral kidney invasion has been difficult to demonstrate. The question of whether SARS-CoV2 can directly infect the kidney is relevant to the understanding of pathogenesis of AKI and collapsing glomerulopathy in patients with COVID-19. Methodologies to document SARS-CoV-2 infection that have been used include immunohistochemistry, immunofluorescence, RT-PCR, in situ hybridization, and electron microscopy. In our review of studies to date, we found that SARS-CoV-2 in the kidneys of patients with COVID-19 was detected in 18 of 94 (19%) by immunohistochemistry, 71 of 144 (49%) by RT-PCR, and 11 of 84 (13%) by in situ hybridization. In a smaller number of patients with COVID-19 examined by immunofluorescence, SARS-CoV-2 was detected in 10 of 13 (77%). In total, in kidneys from 102 of 235 patients (43%), the presence of SARS-CoV-2 was suggested by at least one of the methods used. Despite these positive findings, caution is needed because many other studies have been negative for SARS-CoV-2 and it should be noted that when detected, it was only in kidneys obtained at autopsy. There is a clear need for studies from kidney biopsies, including those performed at early stages of the COVID-19-associated kidney disease. Development of tests to detect kidney viral infection in urine samples would be more practical as a noninvasive way to evaluate SARS-CoV-2 infection during the evolution of COVID-19-associated kidney disease.


Subject(s)
COVID-19/virology , Kidney Diseases/virology , Kidney/virology , SARS-CoV-2/pathogenicity , Animals , Biopsy , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , COVID-19 Testing , Host-Pathogen Interactions , Humans , Kidney Diseases/diagnosis , Kidney Diseases/mortality , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors
2.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166289, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1466061

ABSTRACT

To explore the recovery of renal function in severely ill coronavirus disease (COVID-19) survivors and determine the plasma metabolomic profile of patients with different renal outcomes 3 months after discharge, we included 89 severe COVID-19 survivors who had been discharged from Wuhan Union Hospital for 3 months. All patients had no underlying kidney disease before admission. At patient recruitment, renal function assessment, laboratory examination, chest computed tomography (CT) were performed. Liquid chromatography-mass spectrometry was used to detect metabolites in the plasma. We analyzed the longitudinally change in the estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin-c levels using the CKD-EPI equation and explored the metabolomic differences in patients with different eGFR change patterns from hospitalization to 3 months after discharge. Lung CT showed good recovery; however, the median eGFR significantly decreased at the 3-month follow-up. Among the 89 severely ill COVID-19 patients, 69 (77.5%) showed abnormal eGFR (<90 mL/min per 1.73 m2) at 3 months after discharge. Age (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.08-1.47, p = 0.003), body mass index (OR = 1.97, 95% CI = 1.20-3.22, p = 0.007), and cystatin-c level (OR = 1.22, 95% CI = 1.07-1.39, p = 0.003) at discharge were independent risk factors for post-discharge abnormal eGFR. Plasma metabolomics at the 3-months follow-up revealed that ß-pseudouridine, uridine, and 2-(dimethylamino) guanosine levels gradually increased with an abnormal degree of eGFR. Moreover, the kynurenine pathway in tryptophan metabolism, vitamin B6 metabolism, cysteine and methionine metabolism, and arginine biosynthesis were also perturbed in survivors with abnormal eGFR.


Subject(s)
COVID-19/complications , COVID-19/virology , Energy Metabolism , Glomerular Filtration Rate , Kidney Diseases/etiology , Kidney Diseases/metabolism , SARS-CoV-2 , Aged , COVID-19/diagnosis , Comorbidity , Female , Humans , Kidney Diseases/diagnosis , Kidney Function Tests , Male , Metabolic Networks and Pathways , Metabolome , Metabolomics/methods , Middle Aged , Odds Ratio , Patient Discharge , Severity of Illness Index , Symptom Assessment
5.
J Am Soc Nephrol ; 32(11): 2851-2862, 2021 11.
Article in English | MEDLINE | ID: covidwho-1394649

ABSTRACT

BACKGROUND: COVID-19 is associated with increased risk of post-acute sequelae involving pulmonary and extrapulmonary organ systems-referred to as long COVID. However, a detailed assessment of kidney outcomes in long COVID is not yet available. METHODS: We built a cohort of 1,726,683 US Veterans identified from March 1, 2020 to March 15, 2021, including 89,216 patients who were 30-day survivors of COVID-19 and 1,637,467 non-infected controls. We examined risks of AKI, eGFR decline, ESKD, and major adverse kidney events (MAKE). MAKE was defined as eGFR decline ≥50%, ESKD, or all-cause mortality. We used inverse probability-weighted survival regression, adjusting for predefined demographic and health characteristics, and algorithmically selected high-dimensional covariates, including diagnoses, medications, and laboratory tests. Linear mixed models characterized intra-individual eGFR trajectory. RESULTS: Beyond the acute illness, 30-day survivors of COVID-19 exhibited a higher risk of AKI (aHR, 1.94; 95% CI, 1.86 to 2.04), eGFR decline ≥30% (aHR, 1.25; 95% CI, 1.14 to 1.37), eGFR decline ≥40% (aHR, 1.44; 95% CI, 1.37 to 1.51), eGFR decline ≥50% (aHR, 1.62; 95% CI, 1.51 to 1.74), ESKD (aHR, 2.96; 95% CI, 2.49 to 3.51), and MAKE (aHR, 1.66; 95% CI, 1.58 to 1.74). Increase in risks of post-acute kidney outcomes was graded according to the severity of the acute infection (whether patients were non-hospitalized, hospitalized, or admitted to intensive care). Compared with non-infected controls, 30-day survivors of COVID-19 exhibited excess eGFR decline (95% CI) of -3.26 (-3.58 to -2.94), -5.20 (-6.24 to -4.16), and -7.69 (-8.27 to -7.12) ml/min per 1.73 m2 per year, respectively, in non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of COVID-19 infection. CONCLUSIONS: Patients who survived COVID-19 exhibited increased risk of kidney outcomes in the post-acute phase of the disease. Post-acute COVID-19 care should include attention to kidney disease.


Subject(s)
COVID-19/complications , Kidney Diseases/epidemiology , Kidney Diseases/virology , Veterans/statistics & numerical data , Aged , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Case-Control Studies , Cohort Studies , Critical Care , Female , Glomerular Filtration Rate , Hospitalization , Humans , Kidney Diseases/diagnosis , Male , Middle Aged , United States
6.
Clin J Am Soc Nephrol ; 16(11): 1755-1765, 2021 11.
Article in English | MEDLINE | ID: covidwho-1269953

ABSTRACT

Despite evidence of multiorgan tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with coronavirus disease 2019 (COVID-19), direct viral kidney invasion has been difficult to demonstrate. The question of whether SARS-CoV2 can directly infect the kidney is relevant to the understanding of pathogenesis of AKI and collapsing glomerulopathy in patients with COVID-19. Methodologies to document SARS-CoV-2 infection that have been used include immunohistochemistry, immunofluorescence, RT-PCR, in situ hybridization, and electron microscopy. In our review of studies to date, we found that SARS-CoV-2 in the kidneys of patients with COVID-19 was detected in 18 of 94 (19%) by immunohistochemistry, 71 of 144 (49%) by RT-PCR, and 11 of 84 (13%) by in situ hybridization. In a smaller number of patients with COVID-19 examined by immunofluorescence, SARS-CoV-2 was detected in 10 of 13 (77%). In total, in kidneys from 102 of 235 patients (43%), the presence of SARS-CoV-2 was suggested by at least one of the methods used. Despite these positive findings, caution is needed because many other studies have been negative for SARS-CoV-2 and it should be noted that when detected, it was only in kidneys obtained at autopsy. There is a clear need for studies from kidney biopsies, including those performed at early stages of the COVID-19-associated kidney disease. Development of tests to detect kidney viral infection in urine samples would be more practical as a noninvasive way to evaluate SARS-CoV-2 infection during the evolution of COVID-19-associated kidney disease.


Subject(s)
COVID-19/virology , Kidney Diseases/virology , Kidney/virology , SARS-CoV-2/pathogenicity , Animals , Biopsy , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , COVID-19 Testing , Host-Pathogen Interactions , Humans , Kidney Diseases/diagnosis , Kidney Diseases/mortality , Predictive Value of Tests , Prognosis , Risk Assessment , Risk Factors
8.
Drugs R D ; 21(1): 9-27, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-986820

ABSTRACT

INTRODUCTION: In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy. The aim of this paper is to review the pharmacokinetics and available study data for the experimental COVID-19 therapies in patients with any degree of renal or hepatic impairment to make recommendations for dosing. METHODS: COVID-19 agents included in these recommendations were listed as primaries on the University of Liverpool COVID-19 drug interaction website ( www.covid19-druginteractions.org ), initially identified from Clinicialtrials.gov and ChicCTR.org.cn. A literature search was performed using PubMed and EMBASE as well as product licences and pharmacokinetic databases. FINDINGS: Remdesivir, dexamethasone, azithromycin, favipiravir, lopinavir/ritonavir, atazanavir, hydroxychloroquine, interferon beta, ribavirin, tocilizumab, anakinra and sarilumab were identified as experimental drugs being used in COVID-19 trials as of November 2020. Limited study data was found for these drugs in patients with renal or hepatic impairment for COVID-19 or other indications. Recommendations were made based on available data, consideration of pharmacokinetic properties (including variability), the dosing and anticipated treatment duration of each regimen in COVID-19 and known toxicities. CONCLUSION: Dosing of drugs used to treat COVID-19 in patients with renal or hepatic impairment is complex. These recommendations were produced to provide guidance to clinicians worldwide who are treating patients with COVID-19, many of whom will have some degree of acute or chronic renal or hepatic impairment.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , Drug Repositioning/methods , Kidney Diseases/drug therapy , Liver Diseases/drug therapy , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/analogs & derivatives , Alanine/administration & dosage , Alanine/analogs & derivatives , COVID-19/diagnosis , COVID-19/epidemiology , Clinical Trials as Topic/methods , Dexamethasone/administration & dosage , Dose-Response Relationship, Drug , Humans , Hydroxychloroquine/administration & dosage , Kidney Diseases/diagnosis , Kidney Diseases/epidemiology , Liver Diseases/diagnosis , Liver Diseases/epidemiology
9.
Nephrology (Carlton) ; 25(11): 822-828, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-913640

ABSTRACT

AIM: The COVID-19 pandemic poses unprecedented operational challenges to nephrology divisions in every country as they cope with COVID-19-related kidney disease in addition to regular patient care. Although general approaches have been proposed, there is a lack of practical guidance for nephrology division response in a hospital facing a surge of cases. Here, we describe the specific measures that our division has taken in the hope that our experience in Singapore may be helpful to others. METHODS: Descriptive narrative. RESULTS: A compilation of operational responses to the COVID-19 pandemic taken by a nephrology division at a Singapore university hospital. CONCLUSION: Nephrology operational readiness for COVID-19 requires a clinical mindset shift from usual standard of care to a crisis exigency model that targets best outcomes for available resources. Rapid multi-disciplinary efforts that evolve flexibly with the local dynamics of the outbreak are required.


Subject(s)
Civil Defense , Coronavirus Infections , Critical Pathways/trends , Group Practice , Kidney Diseases , Pandemics , Pneumonia, Viral , Renal Insufficiency, Chronic , Betacoronavirus , COVID-19 , Civil Defense/standards , Civil Defense/statistics & numerical data , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Group Practice/organization & administration , Group Practice/trends , Hospitals, University , Humans , Interdisciplinary Communication , Kidney Diseases/diagnosis , Kidney Diseases/epidemiology , Kidney Diseases/virology , Nephrology/trends , Organizational Innovation , Patient Care Management/methods , Patient Care Management/organization & administration , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , SARS-CoV-2 , Singapore/epidemiology
10.
Am J Clin Pathol ; 155(3): 333-342, 2021 02 11.
Article in English | MEDLINE | ID: covidwho-892069

ABSTRACT

OBJECTIVES: Laboratory testing and the measurement of appropriate biomarkers play a critical role in managing patients with coronavirus disease 2019 (COVID-19), allowing for disease diagnosis, monitoring progression, prognostication, prediction of treatment response, and risk stratification. We sought to characterize these effects on a more detailed, mechanistic level. METHODS: We reviewed the literature and identified a multitude of reports that describe the unique effects of this virus and its devastating consequences to multiple organ systems in COVID-19 patients. RESULTS: There are specific alterations in biomarkers related to coagulation, depopulation of T-cell subtypes, the cytokine storm and inflammation, and kidney and cardiac dysfunction. CONCLUSIONS: Laboratory measurement of specific parameters and the use of appropriate prognostic, predictive, and monitoring biomarkers afford clinicians the ability to make informed medical decisions and guide therapy for patients afflicted with this dreaded disease.


Subject(s)
Biomarkers/analysis , COVID-19/complications , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/virology , COVID-19/immunology , COVID-19/pathology , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/virology , Heart Diseases/diagnosis , Heart Diseases/virology , Humans , Immunity, Cellular/immunology , Inflammation/diagnosis , Inflammation/virology , Kidney Diseases/diagnosis , Kidney Diseases/virology
11.
Infection ; 49(1): 63-73, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-812468

ABSTRACT

PURPOSE: Knowledge regarding patients' clinical condition at severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is sparse. Data in the international, multicenter Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort study may enhance the understanding of COVID-19. METHODS: Sociodemographic and clinical characteristics of SARS-CoV-2-infected patients, enrolled in the LEOSS cohort study between March 16, 2020, and May 14, 2020, were analyzed. Associations between baseline characteristics and clinical stages at diagnosis (uncomplicated vs. complicated) were assessed using logistic regression models. RESULTS: We included 2155 patients, 59.7% (1,287/2,155) were male; the most common age category was 66-85 years (39.6%; 500/2,155). The primary COVID-19 diagnosis was made in 35.0% (755/2,155) during complicated clinical stages. A significant univariate association between age; sex; body mass index; smoking; diabetes; cardiovascular, pulmonary, neurological, and kidney diseases; ACE inhibitor therapy; statin intake and an increased risk for complicated clinical stages of COVID-19 at diagnosis was found. Multivariable analysis revealed that advanced age [46-65 years: adjusted odds ratio (aOR): 1.73, 95% CI 1.25-2.42, p = 0.001; 66-85 years: aOR 1.93, 95% CI 1.36-2.74, p < 0.001; > 85 years: aOR 2.38, 95% CI 1.49-3.81, p < 0.001 vs. individuals aged 26-45 years], male sex (aOR 1.23, 95% CI 1.01-1.50, p = 0.040), cardiovascular disease (aOR 1.37, 95% CI 1.09-1.72, p = 0.007), and diabetes (aOR 1.33, 95% CI 1.04-1.69, p = 0.023) were associated with complicated stages of COVID-19 at diagnosis. CONCLUSION: The LEOSS cohort identified age, cardiovascular disease, diabetes and male sex as risk factors for complicated disease stages at SARS-CoV-2 diagnosis, thus confirming previous data. Further data regarding outcomes of the natural course of COVID-19 and the influence of treatment are required.


Subject(s)
COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Diabetes Mellitus/epidemiology , Kidney Diseases/epidemiology , Lung Diseases/epidemiology , Pandemics , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Body Mass Index , COVID-19/diagnosis , COVID-19/physiopathology , COVID-19/virology , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/physiopathology , Cardiovascular Diseases/virology , Cohort Studies , Comorbidity , Diabetes Mellitus/diagnosis , Diabetes Mellitus/physiopathology , Diabetes Mellitus/virology , Europe/epidemiology , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Kidney Diseases/diagnosis , Kidney Diseases/physiopathology , Kidney Diseases/virology , Logistic Models , Lung Diseases/diagnosis , Lung Diseases/physiopathology , Lung Diseases/virology , Male , Middle Aged , SARS-CoV-2/pathogenicity , Severity of Illness Index , Sex Factors
13.
Clin J Am Soc Nephrol ; 16(3): 479-486, 2021 03 08.
Article in English | MEDLINE | ID: covidwho-653686

ABSTRACT

Preprint servers, such as arXiv and bioRxiv, have disrupted the scientific communication landscape by providing rapid access to research before peer review. medRxiv was launched as a free online repository for preprints in the medical, clinical, and related health sciences in 2019. In this review, we present the uptake of preprint server use in nephrology and discuss specific considerations regarding preprint server use in medicine. Distribution of kidney-related research on preprint servers is rising at an exponential rate. Survey of nephrology journals identified that 15 of 17 (88%) are publishing original research accepted submissions that have been uploaded to preprint servers. After reviewing 52 clinically impactful trials in nephrology discussed in the online Nephrology Journal Club (NephJC), an average lag of 300 days was found between study completion and publication, indicating an opportunity for faster research dissemination. Rapid review of papers discussing benefits and risks of preprint server use from the researcher, publisher, or end user perspective identified 53 papers that met criteria. Potential benefits of biomedical preprint servers included rapid dissemination, improved transparency of the peer review process, greater visibility and recognition, and collaboration. However, these benefits come at the risk of rapid spread of results not yet subjected to the rigors of peer review. Preprint servers shift the burden of critical appraisal to the reader. Media may be especially at risk due to their focus on "late-breaking" information. Preprint servers have played an even larger role when late-breaking research results are of special interest, such as during the global coronavirus disease 2019 pandemic. Coronavirus disease 2019 has brought both the benefits and risks of preprint servers to the forefront. Given the prominent online presence of the nephrology community, it is poised to lead the medicine community in appropriate use of preprint servers.


Subject(s)
Access to Information , Biomedical Research , Information Dissemination , Internet , Kidney Diseases , Nephrology , Peer Review, Research , Preprints as Topic , Animals , Humans , Kidney Diseases/diagnosis , Kidney Diseases/physiopathology , Kidney Diseases/therapy , Periodicals as Topic , Time Factors
15.
J Vasc Access ; 21(4): 536-538, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-232756

ABSTRACT

The recommendations recently proposed by the European and American Vascular Societies in this new 'Covid-19' era regarding the triage of various vascular operations into urgent, emergent and programmed based on the nature of their pathology aim at reserving health care expenses and hospital staff towards managing the current unexpected worldwide pandemic to the highest possible degree. The suggestion for implementation of these changes into real-world practice, however, does not come without a cost. In particular, the recommendation for deferral of access creation in pre-dialysis patients, ethical, socio-economic and medico-legal issues arise which should be seriously taken into consideration. At the end of the day, vascular access creation is the lifeline of haemodialysis patients and the indication for surgery warrants patient-specific clinical judgement rather than 'group labelling'.


Subject(s)
Arteriovenous Shunt, Surgical , Betacoronavirus/pathogenicity , Catheterization, Central Venous , Coronavirus Infections/prevention & control , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Infectious Disease Transmission, Professional-to-Patient/prevention & control , Kidney Diseases/therapy , Occupational Exposure/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Renal Dialysis , Arteriovenous Shunt, Surgical/adverse effects , COVID-19 , Catheterization, Central Venous/adverse effects , Clinical Decision-Making , Coronavirus Infections/diagnosis , Coronavirus Infections/transmission , Coronavirus Infections/virology , Humans , Kidney Diseases/diagnosis , Occupational Exposure/adverse effects , Occupational Health , Patient Safety , Patient Selection , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Renal Dialysis/adverse effects , Risk Assessment , Risk Factors , SARS-CoV-2 , Time-to-Treatment , Virulence
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