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24-h proteinuria was 5&#46;8<span class="elsevierStyleHsp" style=""></span>g&#47;day&#46; Echocardiography revealed normal left ventricular functions with an ejection fraction of 66&#37; and pulmonary hypertension &#40;pulmonary artery pressure&#58; 60<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">A non-contrast chest CT revealed alveolar hemorrhage and a suspicion of pneumonia&#46; Nasopharyngeal swap for respiratory pathogens and PCR for COVID-19 was sent but there was no positivity&#46; ANA&#44; ANCA were negative&#44; C3 and C4 levels were normal&#46; However&#44; testing for anti-GBM antibody was reported as positive&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Renal biopsy revealed a focal necrotizing extra-capillary proliferative glomerulonephritis and acute tubulointerstitial nephritis&#46; Immunofluorescence microscopy showed presence of linear IgG along the glomerular basement membrane&#46; A diagnosis of anti-GBM disease with a comment about supervening possible drug reaction was made &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">500<span class="elsevierStyleHsp" style=""></span>mg intravenous metylprednisolone &#40;mps&#41; for three days and 500<span class="elsevierStyleHsp" style=""></span>mg once a week cyclophosphamide treatment was started&#46; She was discharged on oral mps treatment since there was no fever and progression in the infiltrations in the control CT imaging&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Three days after discharge&#44; patient presented to the emergency service with tachypnea and hemoptysis&#46; She was admitted to intensive care unit&#46; A control chest CT showed similar findings with the previous ones &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Considering her hospitalization history during COVID-19 outbreak and CT findings&#44; a control PCR for COVID-19 was sent which was reported as positives&#46; She had leukocytosis with lymphopenia and high level of acute phase reactants&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Combination treatment of hydroxychloroquine and azithromycin was started&#46; In the fifth day of treatment she had to be intubated and vasopressor treatment was started&#46; Favipravir and intravenous immunoglobulin were added because of resistant COVID-19 infection&#46; Patient underwent continuous renal replacement therapy due to severe oliguric acute kidney injury and died on the 14th day of hospitalization&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">This case report demonstrates a patient with anti-GBM disease who died in a short period of time after acquiring COVID-19 infection under immunosuppressive treatment&#46; Although immunosuppressive treatment may theoretically complicate the course of an infectious disease&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> there is no firm evidence of increased complication for COVID-19 infections in patients under immunosuppressive treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#8211;6</span></a> However&#44; it is impossible to completely exclude any detrimental effect of immunosuppression for specific disorders such as anti-GBM disease on COVID-19 infection&#46; The unfavorable clinical course of this patient may be related either to the immunosuppression or the primary disease affecting the lungs&#44; as it is well known that patients with lung diseases are at increased risk&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The PCR test for COVID-19 is far from perfect as approximately 30&#37; of the patients have an initial false-negative result&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> This creates a dilemma for the clinicians when encountering a patient who has or may have an alternative diagnosis requiring immunosuppression but also has some features of COVID-19 infection&#46; In this particular patient&#44; since the initial PCR for COVID-19 was negative&#44; a prompt response to antibacterial treatment was observed and there was no progression in the control CT imaging we excluded COVID-19 during the initial hospitalization&#46; However&#44; when the patient presented with a more severe condition in the second admission&#44; considering her previous hospitalization history in the same ward with COVID-19 positive patients and her severe lymphopenia a repeat PCR test for COVID-19 was ordered which was found positive&#46; The patient was therefore considered as new onset COVID-19 infection under immunosuppressive treatment&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Another point that should be considered however is the potential direct pathogenetic effect of the COVID-19 infection on the kidneys&#46; Anti-GBM disease is known to be associated with infectious triggers and to present as mini-epidemics concurrent with influenza outbreaks&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#8211;9</span></a> Considering reports of false negativity of patients at initial PCR testing there is thus the possibility that COVID-19 can be the causative factor of the anti-GBM disease&#46; A Chinese study that examined post mortem renal biopsy findings in 26 COVID-19 infection cases however did not mention any cases with necrotizing extracapillary proliferative glomerulonephritis that could suggest possibility of anti-GBM renal disease&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Thus to date there is no known case of anti-GBM glomerulonephritis in a covid19 patient&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical approval</span><p id="par0060" class="elsevierStylePara elsevierViewall">The article does not contain any studies with human participants or animals performed by any of the authors&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Informed consent</span><p id="par0065" class="elsevierStylePara elsevierViewall">Since the patient that is described in the case report was died&#44; her daughter has given consent for publication</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Funding</span><p id="par0070" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public&#44; commercial&#44; or not-for-profit sectors&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflict of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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Letter to the Editor
A patient with COVID-19 and anti-glomerular basement membrane disease
Un paciente con Covid-19 y enfermedad de la membrana basal anti glomerular
Neriman Sila Koca,
Autor para correspondencia
silacank@hotmail.com

Corresponding author.
, Tolga Yildirima, Arzu Saglamb, Mustafa Aricia, Yunus Erdema
a Hacettepe Univercity Faculty of Medicine, Department of Nephrology, 06230, Altındag, Ankara, Turkey
b Hacettepe Univercity Faculty of Medicine, Department of Pathology, 06230, Altındag, Ankara, Turkey
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Elderly patients and patients with co-morbidities such as hypertension&#44; diabetes and heart disease are under risk of COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Anti-glomerular basement membrane &#40;anti-GBM&#41; disease is an autoimmune disease presenting with features of rapidly progressive glomerulonephritis and alveolar hemorrhage&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> It requires an aggressive immunosuppressive treatment&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 80-year-old female patient with anti-GBM disease who had a fatal course after acquiring a severe COVID-19 infection under immunosuppressive treatment&#46; She had well-controlled hypertension and presented with fever&#44; dyspnea&#44; hemoptysis and hematuria for the last five days&#46; Her laboratory values were as follows&#58; Creatinine &#40;Cre&#41;&#58; 6&#46;0<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; blood urea nitrogen &#40;BUN&#41;&#58; 86&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; sodium &#40;Na&#41;&#58; 139 mEq&#47;L&#44; potassium &#40;K&#41;&#58; 3&#46;6<span class="elsevierStyleHsp" style=""></span>mEq&#47;L&#44; uric acid &#40;Ua&#41;&#58; 12&#46;6<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; albumin &#40;alb&#41;&#58; 3&#46;1<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#44; erythrocyte sedimentation rate &#40;ESR&#41;&#58; 64<span class="elsevierStyleHsp" style=""></span>mm&#47;h&#44; CRP&#58; 14&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; BNP&#58; 403<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#44; procalcitonin&#58; 1&#46;14<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46; Urinalysis revealed 1226 erythrocytes&#47;HPF and 86 leucocytes&#47;HPF&#46; 24-h proteinuria was 5&#46;8<span class="elsevierStyleHsp" style=""></span>g&#47;day&#46; Echocardiography revealed normal left ventricular functions with an ejection fraction of 66&#37; and pulmonary hypertension &#40;pulmonary artery pressure&#58; 60<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">A non-contrast chest CT revealed alveolar hemorrhage and a suspicion of pneumonia&#46; Nasopharyngeal swap for respiratory pathogens and PCR for COVID-19 was sent but there was no positivity&#46; ANA&#44; ANCA were negative&#44; C3 and C4 levels were normal&#46; However&#44; testing for anti-GBM antibody was reported as positive&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Renal biopsy revealed a focal necrotizing extra-capillary proliferative glomerulonephritis and acute tubulointerstitial nephritis&#46; Immunofluorescence microscopy showed presence of linear IgG along the glomerular basement membrane&#46; A diagnosis of anti-GBM disease with a comment about supervening possible drug reaction was made &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">500<span class="elsevierStyleHsp" style=""></span>mg intravenous metylprednisolone &#40;mps&#41; for three days and 500<span class="elsevierStyleHsp" style=""></span>mg once a week cyclophosphamide treatment was started&#46; She was discharged on oral mps treatment since there was no fever and progression in the infiltrations in the control CT imaging&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Three days after discharge&#44; patient presented to the emergency service with tachypnea and hemoptysis&#46; She was admitted to intensive care unit&#46; A control chest CT showed similar findings with the previous ones &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Considering her hospitalization history during COVID-19 outbreak and CT findings&#44; a control PCR for COVID-19 was sent which was reported as positives&#46; She had leukocytosis with lymphopenia and high level of acute phase reactants&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Combination treatment of hydroxychloroquine and azithromycin was started&#46; In the fifth day of treatment she had to be intubated and vasopressor treatment was started&#46; Favipravir and intravenous immunoglobulin were added because of resistant COVID-19 infection&#46; Patient underwent continuous renal replacement therapy due to severe oliguric acute kidney injury and died on the 14th day of hospitalization&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">This case report demonstrates a patient with anti-GBM disease who died in a short period of time after acquiring COVID-19 infection under immunosuppressive treatment&#46; Although immunosuppressive treatment may theoretically complicate the course of an infectious disease&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> there is no firm evidence of increased complication for COVID-19 infections in patients under immunosuppressive treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4&#8211;6</span></a> However&#44; it is impossible to completely exclude any detrimental effect of immunosuppression for specific disorders such as anti-GBM disease on COVID-19 infection&#46; The unfavorable clinical course of this patient may be related either to the immunosuppression or the primary disease affecting the lungs&#44; as it is well known that patients with lung diseases are at increased risk&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The PCR test for COVID-19 is far from perfect as approximately 30&#37; of the patients have an initial false-negative result&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> This creates a dilemma for the clinicians when encountering a patient who has or may have an alternative diagnosis requiring immunosuppression but also has some features of COVID-19 infection&#46; In this particular patient&#44; since the initial PCR for COVID-19 was negative&#44; a prompt response to antibacterial treatment was observed and there was no progression in the control CT imaging we excluded COVID-19 during the initial hospitalization&#46; However&#44; when the patient presented with a more severe condition in the second admission&#44; considering her previous hospitalization history in the same ward with COVID-19 positive patients and her severe lymphopenia a repeat PCR test for COVID-19 was ordered which was found positive&#46; The patient was therefore considered as new onset COVID-19 infection under immunosuppressive treatment&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Another point that should be considered however is the potential direct pathogenetic effect of the COVID-19 infection on the kidneys&#46; Anti-GBM disease is known to be associated with infectious triggers and to present as mini-epidemics concurrent with influenza outbreaks&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#8211;9</span></a> Considering reports of false negativity of patients at initial PCR testing there is thus the possibility that COVID-19 can be the causative factor of the anti-GBM disease&#46; A Chinese study that examined post mortem renal biopsy findings in 26 COVID-19 infection cases however did not mention any cases with necrotizing extracapillary proliferative glomerulonephritis that could suggest possibility of anti-GBM renal disease&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Thus to date there is no known case of anti-GBM glomerulonephritis in a covid19 patient&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical approval</span><p id="par0060" class="elsevierStylePara elsevierViewall">The article does not contain any studies with human participants or animals performed by any of the authors&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Informed consent</span><p id="par0065" class="elsevierStylePara elsevierViewall">Since the patient that is described in the case report was died&#44; her daughter has given consent for publication</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Funding</span><p id="par0070" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public&#44; commercial&#44; or not-for-profit sectors&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflict of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Glomerulus with focal fibrinoid necrosis &#40;A&#44; hematoxylin-eosin&#41;&#44; another glomerulus with fibrinoid necrosis&#44; which can be seen as the pink argyrophobic area in the silver stain &#40;B&#44; Jones methenamine silver&#41;&#46; Glomerulus with partial cellular crescent formation &#40;C&#44; hematoxylin&#8211;eosin stain&#41;&#44; another glomerulus with extensive extracapillary proliferation filling the Bowman space and part of a tubule filled with a red blood cell cast &#40;D&#44; hematoxylin&#8211;eosin stain&#41;&#46; Accompanying interstitial inflammation with abundance of eosinophils &#40;E&#44; hematoxylin&#8211;eosin stain&#41;&#46; Immunofluorescence microscopy showing lineer IgG along the glomerular basement membrane &#40;F&#41;&#46;</p>"
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