Scientific Letter
Levamisole in the treatment of nephrotic syndrome
Experiencia con levamisole en el tratamiento del síndrome nefrótico primario corticodependiente
Laura García Soto, Patricia Miranda Romera, Juan Esteban Vintimilla Andrade, María Amelia Gómez Llorente, Pablo de Diego Fernández
Corresponding author
Hospital Materno-Infantil del H.U. Virgen de las Nieves. Avda. de las Fuerzas Armadas nº 2, 18014, Granada, Spain
Read
9407
Timeswas read the article
1831
Total PDF
7576
Total HTML
Share statistics
array:24 [ "pii" => "S2341287920300168" "issn" => "23412879" "doi" => "10.1016/j.anpede.2019.04.015" "estado" => "S300" "fechaPublicacion" => "2020-03-01" "aid" => "2651" "copyrightAnyo" => "2020" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "An Pediatr (Barc). 2020;92:168-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S169540331930178X" "issn" => "16954033" "doi" => "10.1016/j.anpedi.2019.04.010" "estado" => "S300" "fechaPublicacion" => "2020-03-01" "aid" => "2651" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "An Pediatr (Barc). 2020;92:168-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2562 "formatos" => array:3 [ "EPUB" => 35 "HTML" => 2197 "PDF" => 330 ] ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta científica</span>" "titulo" => "Levamisol en el tratamiento del síndrome nefrótico" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "168" "paginaFinal" => "169" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Levamisole in the treatment of nephrotic syndrome" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 834 "Ancho" => 2500 "Tamanyo" => 125550 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Diagrama de flujo sobre la respuesta al levamisol, y relación con la utilización previa o no de la ciclofosfamida.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">*SNCD: síndrome nefrótico corticodependiente. **CFM: ciclofosfamida.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Laura García Soto, Patricia Miranda Romera, Juan Esteban Vintimilla Andrade, María Amelia Gómez Llorente, Pablo de Diego Fernández" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Laura" "apellidos" => "García Soto" ] 1 => array:2 [ "nombre" => "Patricia" "apellidos" => "Miranda Romera" ] 2 => array:2 [ "nombre" => "Juan Esteban" "apellidos" => "Vintimilla Andrade" ] 3 => array:2 [ "nombre" => "María Amelia" "apellidos" => "Gómez Llorente" ] 4 => array:2 [ "nombre" => "Pablo" "apellidos" => "de Diego Fernández" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2341287920300168" "doi" => "10.1016/j.anpede.2019.04.015" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287920300168?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S169540331930178X?idApp=UINPBA00005H" "url" => "/16954033/0000009200000003/v1_202003070647/S169540331930178X/v1_202003070647/es/main.assets" ] ] "itemSiguiente" => array:18 [ "pii" => "S2341287920300193" "issn" => "23412879" "doi" => "10.1016/j.anpede.2019.03.007" "estado" => "S300" "fechaPublicacion" => "2020-03-01" "aid" => "2640" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "An Pediatr (Barc). 2020;92:169-71" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "First Spanish case of syndromic intellectual disability with dysmorphic facies, seizures, and distal limb anomalies caused by biallelic mutations in the <span class="elsevierStyleItalic">OTUD6B</span> gene" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "169" "paginaFinal" => "171" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Primer caso español de discapacidad intelectual sindrónica con dismorfia facial, crisis y anomalías de extremidades por mutaciones bialélicas en el gen <span class="elsevierStyleItalic">OTUD</span>6<span class="elsevierStyleItalic">B</span>" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "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" => 1348 "Ancho" => 1500 "Tamanyo" => 135881 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evolution of the phenotype.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "María José Sánchez-Soler, Ana Teresa Serrano-Antón, Vanesa López-González, María Juliana Ballesta Martínez, Encarna Guillén-Navarro" "autores" => array:5 [ 0 => array:2 [ "nombre" => "María José" "apellidos" => "Sánchez-Soler" ] 1 => array:2 [ "nombre" => "Ana Teresa" "apellidos" => "Serrano-Antón" ] 2 => array:2 [ "nombre" => "Vanesa" "apellidos" => "López-González" ] 3 => array:2 [ "nombre" => "María Juliana" "apellidos" => "Ballesta Martínez" ] 4 => array:2 [ "nombre" => "Encarna" "apellidos" => "Guillén-Navarro" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287920300193?idApp=UINPBA00005H" "url" => "/23412879/0000009200000003/v1_202003140714/S2341287920300193/v1_202003140714/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S234128792030017X" "issn" => "23412879" "doi" => "10.1016/j.anpede.2019.04.016" "estado" => "S300" "fechaPublicacion" => "2020-03-01" "aid" => "2657" "copyright" => "Asociación Española de Pediatría" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "An Pediatr (Barc). 2020;92:167-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Vitamin D and its receptor: Reflections on the unusual tendency to create supposed diseases" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "167" "paginaFinal" => "168" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La vitamina D y su receptor. Reflexiones sobre la inusitada tendencia a crear supuestas enfermedades" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Víctor García-Nieto, M. Cristina Ontoria Betancort, Pedro Carballo Martin, Mónica Ruiz Pons" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Víctor" "apellidos" => "García-Nieto" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Cristina Ontoria Betancort" ] 2 => array:2 [ "nombre" => "Pedro Carballo" "apellidos" => "Martin" ] 3 => array:2 [ "nombre" => "Mónica Ruiz" "apellidos" => "Pons" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1695403319301845" "doi" => "10.1016/j.anpedi.2019.04.016" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403319301845?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S234128792030017X?idApp=UINPBA00005H" "url" => "/23412879/0000009200000003/v1_202003140714/S234128792030017X/v1_202003140714/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Levamisole in the treatment of nephrotic syndrome" "tieneTextoCompleto" => true "saludo" => "To the Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "168" "paginaFinal" => "169" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Laura García Soto, Patricia Miranda Romera, Juan Esteban Vintimilla Andrade, María Amelia Gómez Llorente, Pablo de Diego Fernández" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Laura García" "apellidos" => "Soto" ] 1 => array:2 [ "nombre" => "Patricia Miranda" "apellidos" => "Romera" ] 2 => array:2 [ "nombre" => "Juan Esteban Vintimilla" "apellidos" => "Andrade" ] 3 => array:2 [ "nombre" => "María Amelia Gómez" "apellidos" => "Llorente" ] 4 => array:4 [ "nombre" => "Pablo de Diego" "apellidos" => "Fernández" "email" => array:1 [ 0 => "pdediego@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Hospital Materno-Infantil del H.U. Virgen de las Nieves. Avda. de las Fuerzas Armadas nº 2, 18014, Granada, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Experiencia con levamisole en el tratamiento del síndrome nefrótico primario corticodependiente" ] ] "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" => 858 "Ancho" => 2505 "Tamanyo" => 109139 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Flowchart representing the response to levamisole and its association with the previous use of cyclophosphamide.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">CFM, cyclophosphamide; SDNS, steroid-dependent nephrotic syndrome.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The use of levamisole in the management of nephrotic syndrome started soon after the authorisation of steroid therapy.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is an antihelminthic agent with immunomodulatory properties that are not well understood, and without immunosuppressive effects, unlike the rest of the drugs used in these patients.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> On the other hand, it is the least toxic and least expensive drug.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In 2004, it was withdrawn from commercial markets due to the lack of clear indications and its infrequent use in humans.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> It has proven effective in some patients with steroid-dependent primary nephrotic syndrome as a steroid-sparing agent.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We conducted a retrospective descriptive study on the population of patients with nephrotic syndrome and high-dose steroid dependency given levamisole at the paediatric nephrology unit of our hospital between January 1, 2000 and December 31, 2017. Of the 104 cases of nephrotic syndrome we reviewed, we excluded 38% due to missing data. Levamisole was given to patients with steroid-dependent nephrotic syndrome treated with high-dose prednisone (> 0.5 mg/kg/48 h). In some cases, this followed treatment with oral cyclophosphamide and in others it preceded administration of cyclophosphamide (second step treatment). A histopathological examination was not performed, as this diagnostic test is performed prior to initiation of the third step of treatment. We classified patient response to levamisole into 2 categories: “complete” when patients experienced no recurrences over at least 2 years of treatment, and “partial” when patients experienced 2 or fewer recurrences in 1 year, allowing discontinuation of steroid therapy. The drug was compounded in the prescribed dose in gel cap form at the hospital’s pharmacy. All patients received the standard dose of 2.5 mg/kg of body weight every 48 h, administered orally.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A total of 18 patients received levamisole, 10 girls and 8 boys, aged 2–6 years. Of these 18 patients, 12 (66.6%) responded to the treatment: 5 exhibited complete remission (27.7%) and 7 (38.8%) partial remission (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Treatment was discontinued after 2 years in patients that responded, but it had to be reintroduced in 7 out of the 12 due to recurrence. The mean duration of treatment was 4.3 years. One patient with levamisole dependence continued treatment through his transition to adult care. As for adverse reactions, only 2 patients developed transient urticaria attributable to levamisole that did not require discontinuation of the drug.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">In recent years, few studies have assessed the efficacy of levamisole. Furthermore, it is inexplicably absent from most guidelines and clinical management protocols, except in France, and thus not assigned a specific timing in the stepwise management of nephrotic syndrome, unlike the rest of the treatment options.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The few studies that have been published had study periods of at most 1 year, and usually did not have a prospective design, except for an interesting multicentre clinical trial published in 2018 with a 1-year follow-up.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> In this trial, 26% of patients treated with levamisole had not experience recurrences at 1 year, a percentage similar to the one found in our sample at 2 years (27.7%). Another study involved administration of higher doses (double) when patients did not respond to the standard dose, which had positive results.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">When it comes to adverse reactions, in addition to urticaria, there have been reports of mild to moderate neutropenia, which did not occur in any of the patients in our sample.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In Spain, levamisole is available under the regulation applied to foreign drugs. At present, authorised drugs that are used off-label are requested according to this protocol and do not require express authorization from the Agencia Española de Medicamentos y Productos Sanitarios (Spanish Agency of Medicines and Medical Devices) (Royal Decree 1015/2009 of June 19).</p><p id="par0035" class="elsevierStylePara elsevierViewall">Levamisole is a valid therapeutic option whose efficacy has not been properly evaluated and that is frequently overlooked in nephrotic syndrome treatment protocols. For this reason, we propose performance of clinical trials of levamisole with longer durations of follow-up to assess its performance and thus establish the place that this drug deserves, in our opinion, in treatment protocols.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-01-30" "fechaAceptado" => "2019-04-23" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Soto LG, Romera PM, Andrade JEV, Llorente MAG, Fernández PdD. Experiencia con levamisole en el tratamiento del síndrome nefrótico primario corticodependiente. An Pediatr (Barc). 2020;92:168–169.</p>" ] ] "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" => 858 "Ancho" => 2505 "Tamanyo" => 109139 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Flowchart representing the response to levamisole and its association with the previous use of cyclophosphamide.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">CFM, cyclophosphamide; SDNS, steroid-dependent nephrotic syndrome.</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" => "The primary nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney disease in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "ISKDC" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Kidney Int." "fecha" => "1978" "volumen" => "13" "paginaInicial" => "159" "paginaFinal" => "165" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Levamisole induces interleukin 18 and shifts THI/TH2 balance" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.C. Szeto" 1 => "K.M. Gillespie" 2 => "P.W. Mathieeson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1046/j.1365-2567.2000.00042.x" "Revista" => array:6 [ "tituloSerie" => "Immunology." "fecha" => "2000" "volumen" => "100" "paginaInicial" => "217" "paginaFinal" => "222" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10886398" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Levamisol in steroid nephrotic syndrome of childhood: the lost Paradise?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.C. Davin" 1 => "M.P. Merkus" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Pediatr Nephrol." "fecha" => "2005" "volumen" => "20" "paginaInicial" => "10" "paginaFinal" => "14" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Síndrome nefrótico pediátrico" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "E. Román Ortiz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Protoc diagn ter pediatr" "fecha" => "2014" "volumen" => "1" "paginaInicial" => "283" "paginaFinal" => "301" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A randomized clinical trial indicates thet levamisole increases the time to relapse in children with steroid-sensitive idiopathic nephrotic syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:5 [ 0 => "M.P. Gruppen" 1 => "A.H. Bouts" 2 => "Jansen van der Weide MC" 3 => "M.P. Merkus" 4 => "A. Zurowska" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Kidney Int." "fecha" => "2018" "volumen" => "93" "numero" => "2" "paginaInicial" => "510" "paginaFinal" => "518" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of higher-dose levamisole in maintaining remission in steroid-dependant nephritic syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.S. Abeyagunawardena" 1 => "U. Karunadasa" 2 => "H. Jayaweera" 3 => "S. Thalgahagoda" 4 => "S. Tennakoon" 5 => "S. Abeyagunawardena" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00467-017-3616-5" "Revista" => array:6 [ "tituloSerie" => "Pediatric Nephrology." "fecha" => "2017" "volumen" => "32" "paginaInicial" => "1363" "paginaFinal" => "1367" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28299461" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000009200000003/v1_202003140714/S2341287920300168/v1_202003140714/en/main.assets" "Apartado" => array:4 [ "identificador" => "38181" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000009200000003/v1_202003140714/S2341287920300168/v1_202003140714/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287920300168?idApp=UINPBA00005H" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 11 | 10 | 21 |
| 2024 October | 109 | 53 | 162 |
| 2024 September | 124 | 49 | 173 |
| 2024 August | 157 | 68 | 225 |
| 2024 July | 232 | 44 | 276 |
| 2024 June | 164 | 37 | 201 |
| 2024 May | 191 | 42 | 233 |
| 2024 April | 138 | 39 | 177 |
| 2024 March | 124 | 35 | 159 |
| 2024 February | 131 | 36 | 167 |
| 2024 January | 197 | 21 | 218 |
| 2023 December | 188 | 24 | 212 |
| 2023 November | 202 | 40 | 242 |
| 2023 October | 174 | 30 | 204 |
| 2023 September | 155 | 21 | 176 |
| 2023 August | 161 | 17 | 178 |
| 2023 July | 170 | 29 | 199 |
| 2023 June | 218 | 29 | 247 |
| 2023 May | 182 | 25 | 207 |
| 2023 April | 130 | 14 | 144 |
| 2023 March | 191 | 25 | 216 |
| 2023 February | 153 | 19 | 172 |
| 2023 January | 138 | 22 | 160 |
| 2022 December | 133 | 26 | 159 |
| 2022 November | 144 | 26 | 170 |
| 2022 October | 154 | 41 | 195 |
| 2022 September | 149 | 22 | 171 |
| 2022 August | 127 | 47 | 174 |
| 2022 July | 94 | 45 | 139 |
| 2022 June | 64 | 28 | 92 |
| 2022 May | 88 | 42 | 130 |
| 2022 April | 90 | 30 | 120 |
| 2022 March | 142 | 45 | 187 |
| 2022 February | 127 | 20 | 147 |
| 2022 January | 112 | 29 | 141 |
| 2021 December | 86 | 41 | 127 |
| 2021 November | 99 | 31 | 130 |
| 2021 October | 104 | 56 | 160 |
| 2021 September | 81 | 34 | 115 |
| 2021 August | 71 | 34 | 105 |
| 2021 July | 74 | 28 | 102 |
| 2021 June | 115 | 38 | 153 |
| 2021 May | 143 | 25 | 168 |
| 2021 April | 259 | 71 | 330 |
| 2021 March | 154 | 41 | 195 |
| 2021 February | 86 | 36 | 122 |
| 2021 January | 192 | 27 | 219 |
| 2020 December | 159 | 19 | 178 |
| 2020 November | 131 | 27 | 158 |
| 2020 October | 86 | 15 | 101 |
| 2020 September | 93 | 29 | 122 |
| 2020 August | 112 | 22 | 134 |
| 2020 July | 136 | 21 | 157 |
| 2020 June | 98 | 26 | 124 |
| 2020 May | 74 | 28 | 102 |
| 2020 April | 76 | 13 | 89 |
| 2020 March | 65 | 23 | 88 |
| 2020 February | 18 | 16 | 34 |
Show all
