Letter to the Editor
Acute kidney failure and nephrotic syndrome secondary to COVID-19-associated focal segmental glomerulosclerosis
Fracaso renal agudo y síndrome nefrótico secundario a glomerulosclerosis segmentaria y focal asociada a COVID-19
Amir Shabakaa,
, Sofía Rovirosa-Bigotb, Carmen Guerrero Márquezc, Marina Alonso Riañod, Gema Fernández-Juáreza
Corresponding author
a Servicio de Nefrología, Hospital Universitario Fundación Alcorcón, Madrid, Spain
b Servicio de Medicina Intensiva, Hospital Universitario Fundación Alcorcón, Madrid, Spain
c Servicio de Anatomía Patológica, Hospital Universitario Fundación Alcorcón, Madrid, Spain
d Servicio de Anatomía Patológica, Hospital 12 Octubre, Madrid, Spain
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class="elsevierStyleSimplePara elsevierViewall">Aortic thrombosis.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Axial computed tomography of the abdomen following administration of arterial-phase intravenous contrast, showing a 32<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>27-mm dilation of the infrarenal aorta, with a small 6-mm-thick intramural thrombus on the posterior left aspect (arrow).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Esther Sirvent, Giomar Urzola-Rodríguez, Alicia Lorenzo, Ramiro Callejas-Martínez, Ana Saiz, Leonardo Calle-García, Álvaro Molina-Ordás, Astrid Rodríguez-Gómez, Carmen Martin-Varas, María José Fernández-Reyes-Luis" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Ana Esther" "apellidos" => "Sirvent" ] 1 => array:2 [ "nombre" => "Giomar" "apellidos" => "Urzola-Rodríguez" ] 2 => array:2 [ "nombre" => "Alicia" "apellidos" => "Lorenzo" ] 3 => array:2 [ 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class="elsevierStyleSimplePara elsevierViewall">(A) Glomerulus with solidified appearance, with loss of or reduction in capillary lumen, some capillary walls are thickened and there are hyaline segments (arrows) that may correspond to segments with irreversible damage and protein exudates or to intracapillary thrombi (haematoxylin-eosin, X400). (B) Glomerulus with ischaemic retraction, compaction and hyaline segments (short arrows), and a recent intracapillary thrombus (long arrow) (Masson trichrome, X400). (C) Intracapillary accumulations of hyaline or proteinaceous material (short arrows) that may correspond to segments of hyalinosis or to organising thrombi; a double contour is observed (long arrow) and the capillary lumen are narrow (methenamine silver, X400). (D) Diffuse podocyte injury with loss of pedicles, marked subendothelial oedema with loss of fenestrations (arrow); in other capillaries, double contours are detected, without electron-dense deposits (transmission electron microscopy, original magnification, X2.100).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "John Fredy Nieto-Ríos, Camilo Andrés García-Prada, Arbey Aristizabal-Alzate, Gustavo Zuluaga-Valencia, Dahyana Cadavid-Aljure, Lina Maria Serna-Higuita, Luis F. 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The basement membranes present their usual thickness and no parietal or mesangial deposits are observed. The endothelial cells present no alterations.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The incidence of acute kidney failure in patients with respiratory distress syndrome caused by coronavirus 2019 (COVID-19) ranges from 8% to 17% of hospitalised patients according to the different international series, rises to 14%–35% in critical patients and is associated with increased mortality.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In the series of kidney biopsies performed in patients with COVID 19-associated acute kidney failure, the most frequent diagnosis was acute tubular necrosis.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 52-year-old woman from the Dominican Republic, with no medical background of interest nor of taking nephrotoxic medication or substances who came to the Emergency Department (ED) with symptoms of progressive dyspnoea, rhinorrhoea and oedema coursing for three days. On arrival at the ED, she presented severe hypoxaemia and tachypnoea of 40<span class="elsevierStyleHsp" style=""></span>rpm, requiring oxygen therapy with reservoir. A chest radiography showed the presence of bilateral pulmonary infiltrates and a nasopharyngeal exudate sample tested positive for SARS-CoV-2 by PCR. The analysis highlighted a thrombocytosis of 1.4 million platelets/μL, leucocytosis with lymphopenia, serum creatinine of 2<span class="elsevierStyleHsp" style=""></span>mg/dL, microcytic anaemia of 9<span class="elsevierStyleHsp" style=""></span>g/dL, hypoalbuminaemia and marked elevation of acute-phase reactants, proteinuria in the nephrotic range (4<span class="elsevierStyleHsp" style=""></span>g/L) and mild microhaematuria. The peripheral blood smear showed platelets with dysplasia with megaloblastic forms. A JAK2, CALR, MPL and BCR/ABL clonal marker study was performed, proving to be negative. The patient presented a rapid leucocytosis and thrombocytosis correction, clearly pointing to a reactive condition. She progressively presented respiratory impairment, requiring admission to the Intensive Care Unit (ICU) with orotracheal intubation and invasive mechanical ventilation. She was treated with ceftriaxone, azithromycin, hydroxychloroquine, lopinavir/ritonavir, steroids and prophylactic anticoagulation, with a poor initial evolution, severe hypoxaemia with respiratory acidosis and oliguria and acute kidney failure, requiring continuous venovenous haemodiafiltration. After seven weeks in the ICU, the patient was extubated, she presented a gradual respiratory improvement and was transferred to the Nephrology ward. The patient recovered her renal function gradually and achieved stabilisation with serum creatinine of 1.5–1.7<span class="elsevierStyleHsp" style=""></span>mg/dL, nephrotic proteinuria of up to 5.8<span class="elsevierStyleHsp" style=""></span>g/24<span class="elsevierStyleHsp" style=""></span>h, hypoalbuminaemia of 2.6<span class="elsevierStyleHsp" style=""></span>g/dL, oedemas and severe arterial hypertension. The serological, immunological and electrophoretic studies were normal. A kidney biopsy was performed, with a diagnosis of focal segmental glomerulosclerosis, NOS category, according to the Columbia classification, as well as changes consistent with regenerative-phase acute tubular necrosis. The immunohistochemistry study for CoV-2 was negative. The electronic microscopy identified diffuse foot process fusion affecting more than 80% of the capillary surface, together with images of podocyte microvillus transformation (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). No viral inclusions were found. Subsequently, and parallel to the respiratory improvement and in inflammatory markers, the patient presented a gradual remission in proteinuria to 0.4<span class="elsevierStyleHsp" style=""></span>g/24<span class="elsevierStyleHsp" style=""></span>h, with full remission of the nephrotic syndrome at discharge.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Several viral infections are known to possibly cause different glomerular diseases. HIV, CMV, EBV or B-19 parvovirus may induce focal segmental glomerulosclerosis by producing podocyte involvement, either through direct infection or through the release of inflammatory cytokines that bind to the podocyte receptors.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> There have been recent reports of some cases of acute kidney failure associated with COVID-19 with a diagnosis of collapsing focal segmental glomerulosclerosis, two of them with a kidney transplantation.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–10</span></a> All the patients were black and most of them were carriers of risk variants of the APOL1 gene. All the cases initially required kidney replacement therapy, and less than half of the patients presented partial recovery of renal function with persistence of severe proteinuria. Two patients were given high doses of steroids, one remained on haemodialysis and the other achieved partial kidney function recovery and a partial improvement in proteinuria. In the two kidney graft patients, the treatment with mycophenolate was suspended provisionally and the tacrolimus and steroids were maintained, leading to graft loss in one case and the persistence of advanced kidney disease in the other.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The exact mechanism through which COVID-19-associated glomerulopathy occurs is still unknown, although the histopathology of some patients has shown the presence of viral particles in podocyte cytoplasm, which could indicate that it is due to a direct viral invasion of the podocyte.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Moreover, the possibility of the cytokine release syndrome in COVID-19 patients giving rise to an inflammation-induced podocyte lesion cannot be ruled out.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In conclusion, COVID-19-associated glomerulopathy has emerged as a specific entity associated with SARS-COV-2 infection with a preference for black patients and carriers of APOL1 risk variants, presenting an aggressive course with poor renal prognosis. In our case, the patient recovered renal function and the kidney replacement therapy was discontinued, which is the first case of complete remission of nephrotic syndrome following recovery from COVID 19-induced inflammatory syndrome.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2188 "Ancho" => 2182 "Tamanyo" => 776040 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Electronic microscopy study showing diffuse foot process fusion affecting more than 80% of the capillary surface, together with images of podocyte microvillus transformation. 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