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elsevierViewall">Evolución del filtrado glomerular estimado (línea discontinua) y el cociente proteína/creatinina (línea continua).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Francisco José de la Prada Álvarez, Melissa Cintra Cabrera, Marina Almenara Tejederas, Javier Burgos Martin, Fabiola Alonso García, Mercedes Salgueira Lazo" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Francisco José" "apellidos" => "de la Prada Álvarez" ] 1 => array:2 [ "nombre" => "Melissa" "apellidos" => "Cintra Cabrera" ] 2 => array:2 [ "nombre" => "Marina" "apellidos" => "Almenara Tejederas" ] 3 => array:2 [ "nombre" => "Javier" "apellidos" => "Burgos Martin" ] 4 => array:2 [ "nombre" => "Fabiola" "apellidos" => "Alonso García" ] 5 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Salgueira Lazo" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2013251424000622" "doi" => "10.1016/j.nefroe.2024.03.004" "estado" => "S300" "subdocumento" => 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"<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "A renal failure related to the feline world" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "308" "paginaFinal" => "310" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Un fracaso renal relacionado con el mundo felino" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 639 "Ancho" => 2533 "Tamanyo" => 346424 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Haematoxylin-eosin and Periodic Acid-Schiff (PAS) positive sample from a renal cast seen under an optical microscope. In the image on the left, two renal glomeruli can be seen, showing a large extracellular growth containing numerous nuclei (cellular crescent) (red arrows), reducing the renal tuft (green arrow). The central image shows a glomerulus with a cellular crescent. The image on the left shows positive IgM immunofluorescence.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Adriana M. Cavada-Bustamante, Clara Sanz García, Natalia Menéndez García, María Gago Fraile, Blanca Vivanco Allende, Joaquín Bande Fernández" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Adriana M." 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José de la Prada Álvarez, Melissa Cintra Cabrera, Marina Almenara Tejederas, Javier Burgos Martin, Fabiola Alonso García, Mercedes Salgueira Lazo" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Francisco José" "apellidos" => "de la Prada Álvarez" "email" => array:1 [ 0 => "fdelaprada@senefro.org" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Melissa" "apellidos" => "Cintra Cabrera" ] 2 => array:2 [ "nombre" => "Marina" "apellidos" => "Almenara Tejederas" ] 3 => array:2 [ "nombre" => "Javier" "apellidos" => "Burgos Martin" ] 4 => array:2 [ "nombre" => "Fabiola" "apellidos" => "Alonso García" ] 5 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Salgueira Lazo" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Nephrology Service, Hospital Universitario Virgen Macarena, Sevilla, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Obinutuzumab en el tratamiento de glomerulonefritis membranosa PLA2R positiva resistente a tratamiento" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1490 "Ancho" => 2508 "Tamanyo" => 234401 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0140" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evolution of the estimated glomerular filtration rate (dashed line) and the protein/creatinine ratio (solid line).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The recognition of certain autoantibodies in the pathogenesis of membranous glomerulonephritis has enabled the use of anti-CD20 therapies. Some 70–80% of patients have serum autoantibodies to phospholipase A2 receptor (PLA2R). Treatment with rituximab has been shown to be at least as effective as cyclophosphamide; however, its use is associated with recurrences (27%), requiring repeated doses, and there is a lack of response in 35–45% of cases, necessitating treatments that are associated with short- and long-term toxicity.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 44-year-old male who in November 2017 had severe nephrotic syndrome (total protein 4.9<span class="elsevierStyleHsp" style=""></span>g/dl [6.0–8.0], albumin 2.5<span class="elsevierStyleHsp" style=""></span>g/dl [3.5–5.0], urine protein/creatinine ratio 10.243.42<span class="elsevierStyleHsp" style=""></span>mg/g), with normal renal function (urea 31<span class="elsevierStyleHsp" style=""></span>mg/dl, creatinine 0.66<span class="elsevierStyleHsp" style=""></span>mg/dl, estimated glomerular filtration rate CKD-EPI [eGFR] 117.6<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>), and was diagnosed with membranous glomerulonephritis by renal biopsy, with presence of serum anti-PLA2R antibodies (positive 109.44 UR/ml). The secondary study of potential causes was negative.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Treatment was started with rituximab (induction 1000<span class="elsevierStyleHsp" style=""></span>mg/15 days, 2 doses) and oral tacrolimus (with control of serum level), requiring rituximab bolus at the sixth month. At the ninth month of evolution, due to progressive deterioration of renal function and persistence of nephrotic syndrome, we withdrew tacrolimus and initiated treatment with cyclophosphamide in monthly boluses (6 boluses). We continued treatment with semiannual rituximab until 18 months of treatment (a total of 5 boluses), with persistence of renal function deterioration (urea 42<span class="elsevierStyleHsp" style=""></span>mg/dl, creatinine 1.86<span class="elsevierStyleHsp" style=""></span>mg/dl, GFR 42<span class="elsevierStyleHsp" style=""></span>ml/min/1.73 m<span class="elsevierStyleSup">2</span>), nephrotic syndrome (albumin 2.0<span class="elsevierStyleHsp" style=""></span>g/dl, total protein 3.5<span class="elsevierStyleHsp" style=""></span>g/dl, urine protein/creatinine 5660.65<span class="elsevierStyleHsp" style=""></span>mg/g) and anti-PLA2R positivity (positive: 109.44 UR/ml).</p><p id="par0020" class="elsevierStylePara elsevierViewall">In February 2022, we decided to treat the patient with obinutuzumab (100<span class="elsevierStyleHsp" style=""></span>mg, 900<span class="elsevierStyleHsp" style=""></span>mg on consecutive days, and 1<span class="elsevierStyleHsp" style=""></span>g after 14 days), and observed a partial response in the sixth month (albumin 2.8<span class="elsevierStyleHsp" style=""></span>g/dl, total protein 4.7<span class="elsevierStyleHsp" style=""></span>g/dl, protein/creatinine 2510.46<span class="elsevierStyleHsp" style=""></span>mg/g, urea 71<span class="elsevierStyleHsp" style=""></span>mg/dl, creatinine 1.99<span class="elsevierStyleHsp" style=""></span>mg/dl, GFR 38<span class="elsevierStyleHsp" style=""></span>ml/min/1.73 m<span class="elsevierStyleSup">2</span>), that was confirmed at the ninth month (albumin 3.1<span class="elsevierStyleHsp" style=""></span>g/dl, total proteins 5.0<span class="elsevierStyleHsp" style=""></span>g/dl, protein/creatinine 1643.19<span class="elsevierStyleHsp" style=""></span>mg/g), with improvement of renal function (urea 46<span class="elsevierStyleHsp" style=""></span>mg/dl, creatinine 1.59<span class="elsevierStyleHsp" style=""></span>mg/dl, GFR 50<span class="elsevierStyleHsp" style=""></span>ml/min/1.73 m<span class="elsevierStyleSup">2</span>) and negativity of PLA2R antibodies. The patient had no infusion-related adverse effects or infectious complications after treatment (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Rituximab is a chimeric anti-CD20 type 1 monoclonal antibody that upon binding to the CD20 receptor internalizes and degrades it, resulting in reduced macrophage recruitment and phagocytosis, with reduced B-cell elimination and increased antibody requirement.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Obinutuzumab is a humanized anti-CD20 type 2 monoclonal antibody with greater cytotoxicity than rituximab against B cells <span class="elsevierStyleItalic">in vitro</span>. It binds to a CD20 epitope different from rituximab, preventing internalization of the CD20/antibody complex. Due to a modification in its carbohydrate, it has a higher affinity for the Fcγ RIIIa of B cells, which translates into greater ability to recruit effector cells, greater direct cytotoxicity, with less reliance on complement-dependent cytotoxicity compared to rituximab. In addition, it induces direct lysosome-mediated cell death and less dependence on high levels of B-cell activating factor, which contributes to greater depletion of memory B cells, which are more resistant to the action of rituximab.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The clinical experience of obinutuzumab in membranous glomerulonephritis is limited to:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall">Three patients with anti-PLA2R-positive membranous glomerulonephritis treated with rituximab, without clinical and immunological remission, and in whom, after treatment with obinutuzumab, complete immunological remission was achieved in all three patients, followed by improvement in proteinuria and normalization of serum albumin.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0045" class="elsevierStylePara elsevierViewall">A sample of 10 patients with rituximab-resistant membranous glomerulonephritis, in whom, after treatment with obinutuzumab, complete remission was achieved in 40% and partial remission in 50%, with immunological remission in all cases and response maintained at 24 months.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">Two patients with anti-PLA2R-positive membranous glomerulonephritis resistant to prednisone, cyclosporine, cyclophosphamide and rituximab, with immunological remission 12 months after treatment with obinutuzumab, with normalization of serum albumin, improvement of proteinuria and stable renal function.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">A patient with membranous glomerulonephritis secondary to IgG4-related disease, with anaphylactic reaction to rituximab, with complete remission and normalization of IgG4 levels after treatment with obinutuzumab.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></li></ul></p><p id="par0060" class="elsevierStylePara elsevierViewall">In conclusion, obinutuzumab is a therapeutic alternative in patients with membranous glomerulonephritis in whom immunologic and clinical remission is not achieved with rituximab and avoids the need for treatments with greater toxicity. Currently there is a phase <span class="elsevierStyleSmallCaps">iii</span> clinical trial to evaluate the efficacy and safety of obinutuzumab compared to tacrolimus in patients with primary membranous glomerulonephritis (ClinicalTrials.gov Identifier: <a href="ctgov:NCT04629248">NCT04629248</a>).</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Consent to publication</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that the patient presented in this article has given consent to use his or her medical information for this publication.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0070" class="elsevierStylePara elsevierViewall">This research has not received specific support from public sector agencies, commercial sector or non-profit entities.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Consent to publication" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1490 "Ancho" => 2508 "Tamanyo" => 234401 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0140" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evolution of the estimated glomerular filtration rate (dashed line) and the protein/creatinine ratio (solid line).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rituximab in idiopathic membranous nephropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. 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