Recommendations for the management of renal involvement in tuberous sclerosis complex

array:24 ["pii" => "S2013251420300407" "issn" => "20132514" "doi" => "10.1016/j.nefroe.2020.03.009" "estado" => "S300" "fechaPublicacion" => "2020-03-01" "aid" => "654" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2020;40:142-51" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0211699519301560" "issn" => "02116995" "doi" => "10.1016/j.nefro.2019.07.002" "estado" => "S300" "fechaPublicacion" => "2020-03-01" "aid" => "654" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Nefrologia. 2020;40:142-51" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 612 "formatos" => array:3 [ "EPUB" => 63 "HTML" => 332 "PDF" => 217 ] ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "Artículo especial" "titulo" => "Recomendaciones de manejo de la afectación renal en el complejo esclerosis tuberosa" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "142" "paginaFinal" => "151" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Recommendations for the management of renal involvement in the tuberous sclerosis complex" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Gema Ariceta, María José Buj, Mónica Furlano, Víctor Martínez, Anna Matamala, Montserrat Morales, Nicolás Roberto Robles, Laia Sans, Felipe Villacampa, Roser Torra" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Gema" "apellidos" => "Ariceta" ] 1 => array:2 [ "nombre" => "María José" "apellidos" => "Buj" ] 2 => array:2 [ "nombre" => "Mónica" "apellidos" => "Furlano" ] 3 => array:2 [ "nombre" => "Víctor" "apellidos" => "Martínez" ] 4 => array:2 [ "nombre" => "Anna" "apellidos" => "Matamala" ] 5 => array:2 [ "nombre" => "Montserrat" "apellidos" => "Morales" ] 6 => array:2 [ "nombre" => "Nicolás Roberto" "apellidos" => "Robles" ] 7 => array:2 [ "nombre" => "Laia" "apellidos" => "Sans" ] 8 => array:2 [ "nombre" => "Felipe" "apellidos" => "Villacampa" ] 9 => array:2 [ "nombre" => "Roser" "apellidos" => "Torra" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2013251420300407" "doi" => "10.1016/j.nefroe.2020.03.009" "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/S2013251420300407?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699519301560?idApp=UINPBA000064" "url" => "/02116995/0000004000000002/v1_202002280639/S0211699519301560/v1_202002280639/es/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S2013251420300365" "issn" => "20132514" "doi" => "10.1016/j.nefroe.2020.03.006" "estado" => "S300" "fechaPublicacion" => "2020-03-01" "aid" => "637" "copyright" => "Sociedad Española de Nefrología" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2020;40:152-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Renal potassium management in chronic kidney disease: Differences between patients with or without hyperkalemia" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "152" "paginaFinal" => "159" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Manejo renal del potasio en la enfermedad renal crónica avanzada: diferencias entre pacientes con o sin hipercaliemia" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1261 "Ancho" => 1577 "Tamanyo" => 107883 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Partial linear regressions between the fractional excretion of potassium and the potassium load relative to renal function in male and female patients." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Fernando Caravaca-Fontán, Julian Valladares, Rosa Díaz-Campillejo, Sergio Barroso, Enrique Luna, Francisco Caravaca" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Fernando" "apellidos" => "Caravaca-Fontán" ] 1 => array:2 [ "nombre" => "Julian" "apellidos" => "Valladares" ] 2 => array:2 [ "nombre" => "Rosa" "apellidos" => "Díaz-Campillejo" ] 3 => array:2 [ "nombre" => "Sergio" "apellidos" => "Barroso" ] 4 => array:2 [ "nombre" => "Enrique" "apellidos" => "Luna" ] 5 => array:2 [ "nombre" => "Francisco" "apellidos" => "Caravaca" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0211699519301213" "doi" => "10.1016/j.nefro.2019.04.011" "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/S0211699519301213?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251420300365?idApp=UINPBA000064" "url" => "/20132514/0000004000000002/v1_202005210712/S2013251420300365/v1_202005210712/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S201325142030047X" "issn" => "20132514" "doi" => "10.1016/j.nefroe.2020.03.016" "estado" => "S300" "fechaPublicacion" => "2020-03-01" "aid" => "681" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2020;40:133-41" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Special article" "titulo" => "Kidney Health for Everyone Everywhere – From prevention to detection and equitable access to care" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "133" "paginaFinal" => "141" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1900 "Ancho" => 2500 "Tamanyo" => 424533 ] ] "descripcion" => array:1 [ "en" => "Overview of the preventive measures in chronic kidney disease (CKD) to highlight the similarities and distinctions pertaining to primary, secondary, and tertiary preventive measures and their intended goals." ] ] ] "autores" => array:2 [ 0 => array:2 [ "autoresLista" => "Philip Kam-Tao Li, Guillermo Garcia-Garcia, Siu-Fai Lui, Sharon Andreoli, Winston Wing-Shing Fung, Anne Hradsky, Latha Kumaraswami, Vassilios Liakopoulos, Ziyoda Rakhimova, Gamal Saadi, Luisa Strani, Ifeoma Ulasi, Kamyar Kalantar-Zadeh" "autores" => array:14 [ 0 => array:2 [ "nombre" => "Philip Kam-Tao" "apellidos" => "Li" ] 1 => array:2 [ "nombre" => "Guillermo" "apellidos" => "Garcia-Garcia" ] 2 => array:2 [ "nombre" => "Siu-Fai" "apellidos" => "Lui" ] 3 => array:2 [ "nombre" => "Sharon" "apellidos" => "Andreoli" ] 4 => array:2 [ "nombre" => "Winston Wing-Shing" "apellidos" => "Fung" ] 5 => array:2 [ "nombre" => "Anne" "apellidos" => "Hradsky" ] 6 => array:2 [ "nombre" => "Latha" "apellidos" => "Kumaraswami" ] 7 => array:2 [ "nombre" => "Vassilios" "apellidos" => "Liakopoulos" ] 8 => array:2 [ "nombre" => "Ziyoda" "apellidos" => "Rakhimova" ] 9 => array:2 [ "nombre" => "Gamal" "apellidos" => "Saadi" ] 10 => array:2 [ "nombre" => "Luisa" "apellidos" => "Strani" ] 11 => array:2 [ "nombre" => "Ifeoma" "apellidos" => "Ulasi" ] 12 => array:2 [ "nombre" => "Kamyar" "apellidos" => "Kalantar-Zadeh" ] 13 => array:1 [ "colaborador" => "for the World Kidney Day Steering Committee" ] ] ] 1 => array:2 [ "autoresLista" => "" "autores" => array:1 [ 0 => array:1 [ "colaborador" => "Members of the World Kidney Day Steering Committee" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S201325142030047X?idApp=UINPBA000064" "url" => "/20132514/0000004000000002/v1_202005210712/S201325142030047X/v1_202005210712/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Special article" "titulo" => "Recommendations for the management of renal involvement in tuberous sclerosis complex" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "142" "paginaFinal" => "151" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Gema Ariceta, María José Buj, Mónica Furlano, Víctor Martínez, Anna Matamala, Montserrat Morales, Nicolás Roberto Robles, Laia Sans, Felipe Villacampa, Roser Torra" "autores" => array:10 [ 0 => array:3 [ "nombre" => "Gema" "apellidos" => "Ariceta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "María José" "apellidos" => "Buj" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Mónica" "apellidos" => "Furlano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Víctor" "apellidos" => "Martínez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Anna" "apellidos" => "Matamala" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "Montserrat" "apellidos" => "Morales" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] 6 => array:3 [ "nombre" => "Nicolás Roberto" "apellidos" => "Robles" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "g" "identificador" => "aff0035" ] ] ] 7 => array:3 [ "nombre" => "Laia" "apellidos" => "Sans" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "h" "identificador" => "aff0040" ] ] ] 8 => array:3 [ "nombre" => "Felipe" "apellidos" => "Villacampa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "i" "identificador" => "aff0045" ] ] ] 9 => array:4 [ "nombre" => "Roser" "apellidos" => "Torra" "email" => array:1 [ 0 => "rtorra@fundacio-puigvert.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:9 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología Pediátrica, Hospital Valle Hebrón, REDINREN, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Radiología, Hospital 12 de Octubre, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Enfermedades Renales Hereditarias, Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, Universitat Autónoma de Barcelona, REDINREN, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Virgen de la Arrixaca, Murcia, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Departamento de Enfermería, Fundació Puigvert, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Medicina Interna, Hospital 12 de Octubre, Madrid, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario de Badajoz, REDINREN, Badajoz, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital del Mar, REDINREN, Barcelona, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Servicio de Urología, Clínica Universitaria de Navarra, Madrid, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recomendaciones de manejo de la afectación renal en el complejo esclerosis tuberosa" ] ] "textoCompleto" => "IntroductionTuberous sclerosis complex (TSC) (ORPHA 805) is a rare (1/6,000-8,000), hereditary, multisystemic disease with a broad phenotypic spectrum.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> It is caused by mutations in the TSC1 and TSC2 genes (OMIM #191100, #613254). Adequate diagnostic/therapeutic management of TSC requires coordination between multiple paediatric and adult specialities: obstetrics, genetics, neurology, nephrology, urology, cardiology, ophthalmology, internal medicine, psychiatry, dermatology, dentistry, respiratory medicine and radiology. There are various management recommendations which take into account the systemic effects of the disease, but none focuses on managing renal involvement.<a class="elsevierStyleCrossRefs" href="#bib0010">2–4</a> The recommendations we present here are a response to the need for guidelines to improve both understanding and the diagnostic/therapeutic management of renal involvement of TSC, through a rational use of investigations and the correct use of available treatments. They are based on consensus from the hereditary kidney disease working group of the Sociedad Española de Nefrología/Red de Investigación Renal (SEN/REDINREN) [Spanish Society of Nephrology/Renal Research Network]. We also benefited from the participation of non-nephrology specialists in TSC, that helped to broaden the vision of the disease, but without diverting the focus from the renal aspects. Levels of evidence are specified according to the methodology of the Centre for Evidence-Based Medicine (University of Oxford) (<a href="http://www.cebm.net/?o=1025">http://www.cebm.net/?o=1025</a>). The authors are listed in alphabetic order.AngiomyolipomasIntroductionAngiomyolipomas (AML) are benign tumours derived from endothelial cells (perivascular epithelioid cells; PEComas).<a class="elsevierStyleCrossRef" href="#bib0025">5</a> They are composed of adipose tissue, smooth muscle and blood vessels.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> AML are the most common renal lesions in patients with TSC (prevalence of 55–80%).<a class="elsevierStyleCrossRef" href="#bib0035">7</a> In the general population, 80% of AML are sporadic and have differential characteristics with the AML associated with TSC<a class="elsevierStyleCrossRef" href="#bib0035">7</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>They increase both in size and in number with age.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> They are less common, but not unheard of, in children. They are the leading cause of morbidity and mortality in adults with TSC.<a class="elsevierStyleCrossRefs" href="#bib0045">9,10</a> AML grow faster in women on oestrogen treatment and pre-pubertal girls, suggesting that their development may be affected to some extent by hormones.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> The main complication is bleeding, which occurs mainly in lesions >4cm or in microaneurysms >5mm,<a class="elsevierStyleCrossRefs" href="#bib0055">11,12</a> and the risk may increase during pregnancy. The AML associated with TSC have a rupture and haemorrhage rate ranging from 21% to 100%, according to the published series.There are two histological types of AML: classic (fat-rich) and, in up to a third of cases, atypical (fat-poor). The epithelioid variant is an atypical AML with more than 10% epithelioid cells (cells with abundant eosinophilic and granular cytoplasm), which can undergo malignant transformation<a class="elsevierStyleCrossRef" href="#bib0065">13</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>DiagnosisDiagnosis is made from imaging tests: ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI). Ultrasound is fast and accessible, and useful as a first approach in TSC. However, it is not very accurate in small and exophytic AML, which can be confused with perirenal fat. It is also observer-dependent. A hyperechogenic lesion with suspected AML in a patient with TSC must be confirmed with CT or MRI.<a class="elsevierStyleCrossRef" href="#bib0070">14</a>On CT, the tissue has reduced density with negative attenuation coefficient values. CT has high precision to detect small amounts of fat, with slices as thin as 1.5mm.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> In clinical practice, the ellipsoid method can be used to measure the volume.<a class="elsevierStyleCrossRef" href="#bib0070">14</a>CT or MRI angiogram with vascular reconstruction is the method of choice to obtain vascular mapping of the lesion as a preventive measure in AML>3cm or after active bleeding to locate the bleeding point. In these cases, CT is more accurate than MRI.MRI is the technique of choice for initial diagnosis and follow-up. Fat appears as a hypersignal in T1 and less in T2, with hypointensity in fat-saturated T2-weighted sequences.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> In children, it is usually performed with sedation and in conjunction with brain MRI.<a class="elsevierStyleCrossRef" href="#bib0070">14</a>Differential diagnosisThe differential diagnosis of AML is made with retroperitoneal tumours and malignant renal tumours<a class="elsevierStyleCrossRefs" href="#bib0085">17,18</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). It is particularly complicated in AML where intra-tumour fat is not detected. IN case of doubts, a biopsy of the lesion should be obtained.<a class="elsevierStyleCrossRefs" href="#bib0070">14,19</a>Follow-upAML require radiological follow-up due to the risk of retroperitoneal bleeding and malignancy (very rare).In asymptomatic AML<3cm, follow-up, preferably with annual MRI scans, is recommended. If the lesion remains stable, follow-up intervals can be extended to 1–3 years. Ultrasound can be alternated with MRI for follow-up.<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a>Monitoring every six months with MRI is recommended in atypical, fast-growing lesions or in women who start oestrogen therapy.Recommendations<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0075">1Perform MRI on diagnosis of TSC to identify AML that could go unnoticed on ultrasound (B).</li><li class="elsevierStyleListItem" id="lsti0080">2Subsequently, follow-up every 1–3 years with MRI/ultrasound according to patient characteristics. MRI is recommended for greater accuracy, but in stable lesions it can be alternated with ultrasound (C). Try to avoid CT due to cumulative radiation, especially in paediatric patients (B).</li><li class="elsevierStyleListItem" id="lsti0085">3CT angiogram is reserved for vascular mapping in AML>3cm to rule out microaneurysms (D) or acute bleeding to locate the bleeding point (C).</li><li class="elsevierStyleListItem" id="lsti0090">4If in doubt of the benign nature of atypical AML, diagnostic fine-needle aspiration biopsy is recommended (C).</li></ul>Initial assessment of a patient with tuberous sclerosis complex consulting because of angiomyolipomasTSC is a disease with great phenotypic variability and multisystemic involvement. The organs most commonly affected are brain, kidney, skin, lung and eyes. The clinical manifestations are progressive and change with age. Some of the complications are life-threatening, so it is essential a protocol of clinical follow-up.All patients with tuberous sclerosis should have protocolised monitorization of the most commonly affected organs to limit the onset of complications, according to the following recommendations.<a class="elsevierStyleCrossRefs" href="#bib0015">3,4,20</a>Recommendations<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0095">1Annual monitoring of blood pressure (BP), full lab analyses with renal function and proteinuria/microalbuminuria (B).</li><li class="elsevierStyleListItem" id="lsti0100">2Neurological check-up: baseline brain MRI. Patients under the age of 25, those with symptoms (epilepsy, intellectual retardation or psychiatric disorders) or complications on MRI (subependymal giant cell astrocytoma [SEGA], hydrocephalus) should be referred to neurology (A).</li><li class="elsevierStyleListItem" id="lsti0105">3Respiratory check-up: high-resolution chest CT scan for all patients with respiratory symptoms and for women over the age of 18 regardless of being asymptomatic. Refer patients with lesions or symptoms to the neumology service (A).</li><li class="elsevierStyleListItem" id="lsti0110">4Annual dermatology and dental revisions. Early action on symptomatic lesions (A).</li><li class="elsevierStyleListItem" id="lsti0115">5Heart: annual electrocardiogram and baseline echocardiogram. In cases with symptoms or abnormalities in the complementary tests, refer to cardiology (A).</li><li class="elsevierStyleListItem" id="lsti0120">6Baseline ophthalmology examination; if lesions are detected, annual follow-up is recommended (B).</li><li class="elsevierStyleListItem" id="lsti0125">7Genetics: family counselling in all cases; in individuals of reproductive age and if there are doubts about diagnosis, perform genetic testing (A).</li><li class="elsevierStyleListItem" id="lsti0130">8There is no evidence to support other routine tests, unless there are specific symptoms (C).</li></ul>Radiological follow-up of renal involvement in tuberous sclerosis complexRecommendations<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0135">1Investigations to be used:</li><li class="elsevierStyleListItem" id="lsti0140">2In children, ultrasound and MRI are recommended, with CT only as an exception (A).</li><li class="elsevierStyleListItem" id="lsti0145">3In adults, the recommendation is essentially MRI/ultrasound, according to the characteristics of the lesions and the patient (A).</li><li class="elsevierStyleListItem" id="lsti0150">4CT is much more sensitive than MRI for detecting microaneurysms and more accurate in measuring them (motion artefacts in MRI).</li><li class="elsevierStyleListItem" id="lsti0155">5If the lesions are stable, try to keep CT scans to a minimum to avoid radiation.</li><li class="elsevierStyleListItem" id="lsti0160">6Perform MRI whenever possible (absence of microaneurysms to assess, no contraindications for MRI) (D).</li><li class="elsevierStyleListItem" id="lsti0165">7Perform CT scan instead of MRI if the patient: has apnoea and cannot cooperate; has claustrophobia; or is contraindicated due to wearing devices not compatible with MRI.</li><li class="elsevierStyleListItem" id="lsti0170">8If there are symptoms that suggest bleeding (acute/active or chronic): CT without contrast, followed by biphasic CT with contrast (arterial and venous phases) (B).</li><li class="elsevierStyleListItem" id="lsti0175">9If there are microaneurysms, alternate MR angiography and biphasic CT (arterial and venous), as they are often not visible in MR angiography. If MRI shows significant growth of AML, do CT angiography to assess microaneurysms (D).</li><li class="elsevierStyleListItem" id="lsti0180">10If it is necessary to administer iodinated contrast in the CT scan and the patient has a GFR≤30mL/min/1.73m2, applying a nephroprotection protocol is recommended (B).</li><li class="elsevierStyleListItem" id="lsti0185">11It is recommended not to perform MRI with gadolinium if GFR≤30mL/min/1.73m2.</li><li class="elsevierStyleListItem" id="lsti0190">12Cysts do not require specific follow-up, but whenever AML check-ups are performed, the presence of cysts should be assessed, and whether they are simple or complicated with bleeding, infection or neoplasm. If the patient only has cysts, perform an ultrasound scan and, if a complicated one is detected, investigate preferably by MRI to avoid CT radiation (A).</li><li class="elsevierStyleListItem" id="lsti0195">13If there is an excessive number of lesions (cysts or AML), measuring the overall renal volume for monitoring purposes is recommended (C).</li><li class="elsevierStyleListItem" id="lsti0200">14If there is radiological suspicion of possible malignancy (minimal-fat AML), take a biopsy and then continue with the usual follow-up. If no biopsy is performed but it is decided to monitor, follow-up every six months (D).</li><li class="elsevierStyleListItem" id="lsti0205">15The trend in the radiological management of AML in which response to treatment has been demonstrated should be to minimise the frequency of radiological examinations as far as possible to avoid long-term effects of contrasts and radiation (B).</li></ul>Treatment of angiomyolipomasAML associated with TSC have a high rate of rupture and haemorrhage and are frequently associated with a high morbidity in these patients.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> The greatest risk of bleeding is with a size larger than 4cm or microaneurysms >5mm, so patients with these characteristics need to have treatment.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>In view of the chronic and recurrent nature of these tumours, all treatment will aim to preserve renal function as far as possible.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>Emergency treatmentIn acute haemorrhage, the treatment of choice is transarterial embolization,<a class="elsevierStyleCrossRef" href="#bib0105">21</a> which has an efficacy of 93%.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> This treatment is associated with the onset of post-embolisation syndrome (nausea, pyrexia and pain for 72h) in 35% of patients.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Although both nephrectomy and embolisation will resolve the condition, the risk of renal failure is seven times higher with nephrectomy.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>Due to the risk of renal failure, nephrectomy should be avoided provided the emergency permits and vascular radiology techniques are available.<a class="elsevierStyleCrossRefs" href="#bib0020">4,21</a>In acute rupture associated with pregnancy, the treatment of choice remains embolisation. In certain cases, one option is emergency caesarean section and subsequent embolisation.<a class="elsevierStyleCrossRefs" href="#bib0120">24,25</a>Non-emergency treatmentSelective embolisationScheduled embolisation of AML was the treatment of choice for years, but has now been replaced by mTOR inhibitors.<a class="elsevierStyleCrossRefs" href="#bib0020">4,21</a> The success rate of embolisation is very high,<a class="elsevierStyleCrossRef" href="#bib0110">22</a> achieving a decrease in size, pain and the associated symptoms (approximately 50%<a class="elsevierStyleCrossRef" href="#bib0120">24</a>). Renal function is usually maintained, and only in 3.3% of patients is it associated with a deterioration.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> However, AML regrowth is possible, with a second AML embolisation being required in 20%–80% of cases.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>The more embolisations, the greater the risk of renal failure.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>As far as the material used is concerned, particles larger than 150μm are preferred due to their efficiency and the lower risk of distant emboli.<a class="elsevierStyleCrossRef" href="#bib0135">27</a>CryoablationThe use of ablation by freezing derives from its use in renal tumours of less than 4cm in size, although it has been used occasionally for larger tumours.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> For the treatment of AML, efficacy of up to 100% has been reported, with the possibility of hospital discharge the next day, but there is insufficient information about complications.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> It is an attractive alternative, but details are still lacking to place it above embolisation.Radio-frequency or microwaveThe use of these types of energy has also been studied and published in limited series, with efficacy rates above 78%,<a class="elsevierStyleCrossRefs" href="#bib0145">29,30</a> but associated with significant side effects such as bleeding, nerve damage and hollow viscera fistulas. For this reason, this treatment is also kept as an alternative to embolisation.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>SurgeryCurrently, 13% of patients with TSC and AML have surgery, either radical (5%) or partial (8%) nephrectomy.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> Because of the high associated rate of renal failure, both partial and radical nephrectomies have been replaced by selective embolisation.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>Partial nephrectomy in these patients is more common than radical, following the objective of preserving renal function, but almost 45% of them need a second partial,<a class="elsevierStyleCrossRef" href="#bib0145">29</a> or even a subsequent radical, nephrectomy.Active surveillanceIn all the published series, the risk of bleeding is minimal when the AML is less than 3cm in size, so surveillance is the norm in these cases, with ultrasound or MRI every two years.<a class="elsevierStyleCrossRef" href="#bib0070">14</a>When the tumour is larger than 3cm in size, 50% may become symptomatic, with risk factors being the presence of microaneurysms >5mm or rapid growth (>0.25cm/year),<a class="elsevierStyleCrossRef" href="#bib0060">12</a> so starting treatment is recommended.<a class="elsevierStyleCrossRefs" href="#bib0020">4,21</a>Recommendations<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0210">1Emergency treatment.</li><li class="elsevierStyleListItem" id="lsti0215">2The treatment of choice is transarterial embolisation (B).</li><li class="elsevierStyleListItem" id="lsti0220">3An alternative to embolisation is radical or partial nephrectomy (B).</li><li class="elsevierStyleListItem" id="lsti0225">4Non-emergency invasive treatment.</li><li class="elsevierStyleListItem" id="lsti0230">5Selective embolisation.</li><li class="elsevierStyleListItem" id="lsti0235">lowerRoman6Second-line option of choice after treatment with mTOR (B).</li><li class="elsevierStyleListItem" id="lsti0240">lowerRoman7Material >150μm should be used to prevent migrations (C).</li><li class="elsevierStyleListItem" id="lsti0245">8Cryoablation</li><li class="elsevierStyleListItem" id="lsti0250">lowerRoman9Alternative to the traditional options (D).</li><li class="elsevierStyleListItem" id="lsti0255">10Radio-frequency or microwave</li><li class="elsevierStyleListItem" id="lsti0260">lowerRoman11Alternative to the traditional options (D).</li><li class="elsevierStyleListItem" id="lsti0265">12Surgery.</li><li class="elsevierStyleListItem" id="lsti0270">lowerRoman13Surgery is the alternative only when minimally invasive options fail due to its aggressiveness and loss of renal parenchyma (B).</li><li class="elsevierStyleListItem" id="lsti0275">14Follow-up.</li><li class="elsevierStyleListItem" id="lsti0280">lowerRoman15AML less than 3cm in size associated with tuberous sclerosis should be monitored (B).</li><li class="elsevierStyleListItem" id="lsti0285">lowerRoman16If there is growth of more than 0.25cm/year or AML larger than 3cm in size, active treatment should be offered (C).</li></ul>Long-term treatment: mTOR inhibitors<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0290">•Indication. Everolimus is indicated for the treatment of adult patients with AML associated with TSC who are at risk of complications (based on factors such as tumour size or the presence of multiple or bilateral tumours) but who do not require immediate surgery. It is usually prescribed in lesions larger than 3cm in size. The evidence is based on the analysis of the change in the sum of the volume of the AML, where a permanent reduction in the size of the lesions has been demonstrated.<a class="elsevierStyleCrossRefs" href="#bib0155">31,32</a></li><li class="elsevierStyleListItem" id="lsti0295">•Dose. The recommended dose is 10mg of everolimus once a day according to the data sheet, although it seems reasonable to adjust the dose according to plasma levels. Treatment should continue as long as there is clinical benefit or until unacceptable toxicity occurs. If the patient forgets to take a dose, they should not take an additional dose, but take the next dose according to the prescribed schedule. Management of suspected serious or intolerable adverse reactions may require a dose reduction and/or a temporary discontinuation of the treatment with everolimus. For mild adverse reactions no dose adjustment is usually required. If a dose reduction is required, the recommended dose is approximately 50% lower than the daily dose previously administered. For dose reductions below the lowest available dose, dose administration should be considered every other day (<a href="http://www.emea.europa.eu/ema">http://www.emea.europa.eu/ema</a>).</li><li class="elsevierStyleListItem" id="lsti0300">•Monitoring</li><li class="elsevierStyleListItem" id="lsti0305">a)Imaging. The most usual procedure is to assess the treatment by taking scheduled volumetric measurements of the largest renal lesions and the total size of the kidney using MRI or CT, depending on availability.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Annual monitoring by MRI is recommended, allowing longer intervals when stability is achieved.</li><li class="elsevierStyleListItem" id="lsti0310">b)Laboratory tests. Use of everolimus does not cause any change in the usual clinical parameters which help to assess its effectiveness. However, it can cause some biochemical alterations which need to be monitored (albuminuria, dyslipidaemia, hypophosphataemia, increased LDH). These will be discussed in the following section. In clinical trials aimed specifically at the treatment of AML, plasma levels of everolimus were not monitored or used to guide treatment. However, the Spanish Guidelines for the Management and Treatment of Tuberous Sclerosis recommend that levels should be checked.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> This would be essential, at least at the beginning of treatment, because very low levels can be found due to concomitant treatment with inducers or inhibitors of CYP3A4 or antiepileptic drugs, and after a change in liver status (Child-Pugh).</li><li class="elsevierStyleListItem" id="lsti0315">•Adverse effects: description and management</li><li class="elsevierStyleListItem" id="lsti0320">c)Stomatitis is the most common complication, but not serious, and is usually recurrent, but gradually decreasing in intensity. Treatment is symptomatic with normal saline or alcohol-free rinses (with hyaluronic acid; e.g. Aloclair®). Topical analgesics and corticosteroids may be used, but antifungals are not recommended.</li><li class="elsevierStyleListItem" id="lsti0325">d)Infections. Take a full medical history and ask for viral markers prior to treatment. Management will depend on each case, but if there is systemic fungal invasion, treatment should be discontinued immediately. In cases of active hepatitis B or C treatment should be agreed with the hepatologist.<a class="elsevierStyleCrossRef" href="#bib0165">33</a></li><li class="elsevierStyleListItem" id="lsti0330">e)Dyslipidaemia. Treatment according to standard consensus guidelines, including: control of risk factors, dietary treatment and physical exercise, and pharmacological treatment with statins, if indicated. There are no pharmacological interactions between everolimus and statins or fibrates.</li><li class="elsevierStyleListItem" id="lsti0335">f)Hypophosphataemia. Treat mild hypophosphataemia (<2.5mg/dl) with oral phosphate: 30−100mg/kg/day in three or four divided doses, according to response. Hypophosphataemia <1mg/dl requires hospitalisation, intravenous phosphate and discontinuation of the treatment.<a class="elsevierStyleCrossRef" href="#bib0165">33</a></li><li class="elsevierStyleListItem" id="lsti0340">g)Proteinuria and renal failure. Albuminuria and renal function need to be monitored. If a patient develops albuminuria, they may be treated with angiotensin receptor antagonists. In severe proteinuria, treatment should be discontinued. The effect on renal function has not been fully assessed in the long term.<a class="elsevierStyleCrossRef" href="#bib0170">34</a></li><li class="elsevierStyleListItem" id="lsti0345">h)Use of everolimus is often accompanied by microcytic anaemia, thrombocytopenia and progressive lymphopenia, but only rarely do they lead to the medication being discontinued.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> Haematological toxicity is concentration-dependent; should it occur, it may indicate an interaction or failure to take medication. It is advisable to determine the concentration at which the toxicity appeared, in order to restart a new regimen in therapeutic range (Cmin ∼ 5ng/mL). Management is similar to any other cytopenia.<a class="elsevierStyleCrossRef" href="#bib0180">36</a></li><li class="elsevierStyleListItem" id="lsti0350">i)Amenorrhoea. It seems that amenorrhoea can be caused by mTOR inhibition, which may play an important role in controlling the onset of puberty. It is important to monitor for defects or dysfunctions in growth, development or sexual maturation. Most cases are transient, manageable and do not lead to interruption of treatment. Patients should be referred to gynaecology to rule out other causes.</li><li class="elsevierStyleListItem" id="lsti0355">j)Non-infectious pneumonitis is accompanied by nonspecific respiratory signs and symptoms such as cough, dyspnoea, hypoxaemia and pleural effusion, and a more thorough follow-up with the necessary pulmonary function tests is recommended, according to the patient's condition. Confirm the diagnosis of non-infectious pneumonitis with sputum and blood cultures in symptomatic cases. Asymptomatic cases do not require interruption of treatment. Adjust the dose of everolimus in mildly symptomatic cases. In more severe cases, discontinuation of treatment and use of corticosteroids is indicated.<a class="elsevierStyleCrossRef" href="#bib0185">37</a></li><li class="elsevierStyleListItem" id="lsti0360">k)Everolimus can alter the wound healing process. Discontinuing the drug is therefore recommended in the peri-operative period, especially in older patients and patients with diabetes, malnutrition or high body mass index (BMI). Additionally, caution should be taken in patients receiving concomitant treatment with corticosteroids and/or anticoagulants.</li><li class="elsevierStyleListItem" id="lsti0365">l)CYP3A4 or PgP inducers can lower everolimus blood concentrations. Concomitant treatment with potent CYP3A4 inhibitors such as ketoconazole and other azoles, clarithromycin, telithromycin, nefazodone or HIV protease inhibitors is not recommended.<a class="elsevierStyleCrossRef" href="#bib0190">38</a></li></ul>Recommendations<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0370">1Treatment with everolimus is recommended for adult patients with renal AML associated with TSC who are at risk of complications (AML>3cm) at an initial dose of 10mg/day (A).</li><li class="elsevierStyleListItem" id="lsti0375">2It is suggested that the effects of the treatment be monitored with yearly/two-yearly imaging tests (B).</li><li class="elsevierStyleListItem" id="lsti0380">3It is suggested that levels of the drug be determined at the beginning of treatment, after any change of dose due to concomitant treatment with inducers or inhibitors of CYP3A4 or antiepileptic drugs, and after a change in liver status (Child-Pugh) (C).</li><li class="elsevierStyleListItem" id="lsti0385">4It is suggested that everolimus plasma levels be maintained in the range of 4–10ng/mL (D).</li><li class="elsevierStyleListItem" id="lsti0390">5It is suggested treating stomatitis symptomatically (D).</li><li class="elsevierStyleListItem" id="lsti0395">6In the case of patients with active hepatitis B or C, it is suggested discussing the treatment with a hepatologist (C).</li><li class="elsevierStyleListItem" id="lsti0400">7In all cases of symptomatic infection it is recommend stopping everolimus and restarting treatment with half the dose (C).</li><li class="elsevierStyleListItem" id="lsti0405">8It is suggested treating dyslipidaemia according to standard consensus guidelines (D).</li><li class="elsevierStyleListItem" id="lsti0410">9It is suggested treating hypophosphataemia with oral or intravenous phosphorus supplements according to the severity (D).</li><li class="elsevierStyleListItem" id="lsti0415">10It is recommend monitoring albuminuria and renal function (B).</li><li class="elsevierStyleListItem" id="lsti0420">11It is suggested managing any type of cytopenia with the standard treatments (C).</li><li class="elsevierStyleListItem" id="lsti0425">12It is recommend determining the concentration at which the haematological toxicity appeared, in order to restart a new regimen in therapeutic range (B).</li><li class="elsevierStyleListItem" id="lsti0430">13It is suggested referring cases of amenorrhoea to gynaecology to rule out adjuvant causes (D).</li><li class="elsevierStyleListItem" id="lsti0435">14An immediate X-ray is recommended whenever there are respiratory symptoms. After a first episode of pneumonitis, we recommend chest X-rays every six weeks for the first six months after restarting the treatment (D).</li><li class="elsevierStyleListItem" id="lsti0440">15It is recommend discontinuing everolimus and treating with corticosteroids in severe cases of correctly diagnosed non-infectious pneumonitis (B).</li><li class="elsevierStyleListItem" id="lsti0445">16It is recommend discontinuing the drug in the peri-operative period until complete healing has taken place (B).</li><li class="elsevierStyleListItem" id="lsti0450">17It is suggested that everolimus should be used with caution in patients on concomitant treatment with corticosteroids and/or anticoagulants (D).</li><li class="elsevierStyleListItem" id="lsti0455">18Concomitant treatment with potent CYP3A4 inhibitors, such as ketoconazole and other azoles, clarithromycin, telithromycin, nefazodone or HIV protease inhibitors, is not recommended (B).</li></ul>Renal cystsRenal cysts in TSC are considered a minor criterion and are the second most common renal manifestation after AML.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> The incidence is around 50% of patients.<a class="elsevierStyleCrossRefs" href="#bib0040">8,39</a> They are more common in patients with mutation in the TSC2 gene than in TSC1, especially if the TSC2 mutation is truncated.<a class="elsevierStyleCrossRefs" href="#bib0035">7,39</a> They can present as glomerulocystic disease, single or multiple simple cortical cysts or with cystic nephromegaly associated with autosomal dominant polycystic kidney disease. They are usually asymptomatic, but occasionally, if large, they can rupture and bleed.DiagnosisDiagnosis is made by ultrasound scan. MRI or CT can be useful in the case of uncertainty.<a class="elsevierStyleCrossRefs" href="#bib0015">3,14</a>Differential diagnosis of complicated cysts<ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0460">•Hamartomatous renal polyps.</li><li class="elsevierStyleListItem" id="lsti0465">•Renal cell carcinoma.</li><li class="elsevierStyleListItem" id="lsti0470">•Atypical renal AML.</li></ul>Follow-up and treatmentUncomplicated cystic lesions do not require strict monitoring. They will be checked in the AML follow-up imaging test. They do not require specific treatment, have little clinical impact and do not usually need complex management.<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a>Recommendations<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0475">1We suggest the renal cysts be monitored radiologically in the imaging tests performed for follow-up of the AML (C).</li><li class="elsevierStyleListItem" id="lsti0480">2The renal cysts in TSC do not require specific treatment (C).</li></ul>Contiguous gene syndrome TSC2/PKD1A minority (∼ 2%) of patients with TSC have what is known as TSC2/PKD1 contiguous gene syndrome (autosomal dominant polycystic kidney disease [ADPKD] type 1 with tuberous sclerosis, OMIM: 600273; ORPHA: 88924) caused by large deletions which affect the TSC2 and PKD1 genes, located next to each other on chromosome 16. The deletion of both genes is expressed with a characteristic phenotype of severe and early onset ADPKD, associated with clinical manifestations suggestive of TSC.<a class="elsevierStyleCrossRef" href="#bib0200">40</a>The estimated prevalence of this condition is <1/1,000,000, and it is inherited with a theoretical autosomal dominant transmission pattern, although it is uncommon for affected individuals to reproduce.DiagnosisThe suspected diagnosis is based on detection before birth, at birth or during the first months of life of enlarged kidneys, with multiple cortical cysts of variable sizes, suggestive of a very early and severe ADPKD.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> Patients usually have difficult-to-control hypertension and/or a reduced glomerular filtration rate, along with symptoms or signs suggestive of TSC, usually neurological, given their early age.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> The renal phenotype is more severe than usual in patients with TSC, with the presence of multiple cysts on ultrasound, increasing nephromegaly and progression to advanced chronic kidney disease (CKD) in the young adult.<a class="elsevierStyleCrossRef" href="#bib0205">41</a>Typically, the lack of a family history of ADPKD, the progression and severity of the ADPKD, and the clinical signs and symptoms of TSC, lead to the conclusion of TSC2/PKD1 contiguous gene syndrome. The definitive diagnosis is established by genetic testing with the finding of a deletion that affects the two genes described.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>Differential diagnosisOther conditions which involve renal cysts, such as autosomal recessive polycystic kidney disease and cystic dysplasia due to mutations of the HNF1b gene need to be excluded.<a class="elsevierStyleCrossRef" href="#bib0210">42</a>Follow-upPatients with TSC should be managed according to the expert recommendations,<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a> with the symptomatic treatment required by the severity and progression of the associated ADPKD.Recommendations<ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0485">1Patients with TSC2/PKD1 contiguous gene syndrome should be followed up by the paediatric nephrologist (A).</li><li class="elsevierStyleListItem" id="lsti0490">2Strict monitoring of BP is recommended (B).</li><li class="elsevierStyleListItem" id="lsti0495">3The management of CKD is similar to that for other aetiologies. The assessment for renal replacement therapy should include the patient's neurocognitive status and be made on an individual basis (D).</li><li class="elsevierStyleListItem" id="lsti0500">4We recommend that patients are monitored by paediatric neurology and later by neurology (B).</li></ul>Hypertension in tuberous sclerosis complexThe prevalence of hypertension (HTN) in patients with TSC under the age of 25 is up to 25%. It is more common in patients with mutations in the TSC2 gene and in patients with more lesions in the kidneys,<a class="elsevierStyleCrossRef" href="#bib0215">43</a> especially those with TSC2/PKD1 contiguous gene syndrome.BP should be measured in the initial assessment of a patient diagnosed with TSC, and subsequently monitored annually.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> The target BP in monitoring should be the same as in the hypertensive population with kidney disease (<140/90mmHg in the clinic and <135/85mmHg by self-measured BP monitoring at home or BP below the adjusted 90th percentile for size and gender in a paediatric patient).<a class="elsevierStyleCrossRefs" href="#bib0220">44,45</a> Monitoring of BP is essential to prevent the progression of CKD.The renin-angiotensin system inhibitors are the first-choice antihypertensive drugs.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> In addition, the presence of type 1 angiotensin II receptors has been demonstrated in AML and, experimentally, blocking of angiotensin II potentially seems to have a therapeutic effect in this area.<a class="elsevierStyleCrossRef" href="#bib0230">46</a> In patients treated with everolimus, given the higher incidence of angioedema in association with ACE inhibitors, treatment with ARB should be given.<a class="elsevierStyleCrossRefs" href="#bib0235">47,48</a> In children with infantile spasms, treatment with corticotropin may induce HTN; in this context, initial diuretic treatment may be sufficient.Recommendations<ul class="elsevierStyleList" id="lis0075"><li class="elsevierStyleListItem" id="lsti0505">1BP should be assessed at diagnosis and subsequently, at least annually (B).</li><li class="elsevierStyleListItem" id="lsti0510">2Target BP in the clinic should be <140/90mmHg and by self-measurement, <135/85mmHg (D), or <90th percentile for size and gender in the case of children and adolescents.</li><li class="elsevierStyleListItem" id="lsti0515">3The renin-angiotensin system inhibitors are the first-choice antihypertensive drugs (C).</li></ul>Chronic renal failure in tuberous sclerosis complexThe destruction of the renal parenchyma due to the presence of AML and cysts in the renal tissue, combined with the invasive treatments of AML (embolisation and partial and total nephrectomies), are the main determinants in the development of CKD. Among patients with TSC, 40% have CKD stage 3 (or more advanced) by the age of 45-54.<a class="elsevierStyleCrossRefs" href="#bib0045">9,21</a> Kidney disease is more prevalent in patients with TSC2 mutations, and especially in patients with TSC2-PKD1contiguous gene syndrome, who usually progress towards advanced renal failure during their teenage years.<a class="elsevierStyleCrossRef" href="#bib0215">43</a>Renal function should be assessed at diagnosis and then annually in adult patients. The management of CKD-related complications should be the same as for other causes of kidney disease (<a href="https://kdigo.org/guidelines/anemia-in-ckd/;https://kdigo.org/guidelines/ckd-evaluation-and-management/">https://kdigo.org/guidelines/anemia-in-ckd/;https://kdigo.org/guidelines/ckd-evaluation-and-management/</a>; <a href="https://kdigo.org/guidelines/ckd-mbd/">https://kdigo.org/guidelines/ckd-mbd/</a>; <a href="https://kdigo.org/guidelines/lipids-in-ckd/">https://kdigo.org/guidelines/lipids-in-ckd/</a>).There are no formal contraindications in relation to the choice of renal replacement technique. In transplanted patients it seems reasonable to include mTOR inhibitors in their immunosuppressive therapy, in view of their benefits in relation to the manifestations of the disease.Recommendations<ul class="elsevierStyleList" id="lis0080"><li class="elsevierStyleListItem" id="lsti0520">1Renal function should be assessed at diagnosis and subsequently at least annually in adults (B).</li><li class="elsevierStyleListItem" id="lsti0525">2The management of CKD-related complications should be the same as for other causes of CKD (D).</li><li class="elsevierStyleListItem" id="lsti0530">3There are no formal contraindications in terms of choosing the type of renal replacement therapy (D). In transplanted patients, we recommend including mTOR inhibitors in their immunosuppressive therapy (D).</li></ul>Multidisciplinary follow-upBecause of the multisystemic nature of the disease, TSC requires coordination among all the healthcare professionals involved. The healthcare professionals need to set up a Committee specialised in TSC and meet periodically to discuss and agree on consensual actions for the different cases being monitored by the team.Patient follow-up is based on the recommendations described above. To properly coordinate the follow-up, the figure of the nurse case manager is very useful. The manager of clinical cases is responsible for ensuring correct planning of the diagnostic and follow-up tests, and the appointments with the team's different specialists according to protocol. The case manager also sets up the communication network between the healthcare professionals to help ensure smooth and efficient monitoring. Their role is fundamental in the transition from paediatrics and they are the first filter for the doubts and concerns of the patient and their relatives.Recommendations<ul class="elsevierStyleList" id="lis0085"><li class="elsevierStyleListItem" id="lsti0535">1We recommend the creation of multidisciplinary TSC teams (B).</li><li class="elsevierStyleListItem" id="lsti0540">2We suggest the need for a manager of clinical cases (B).</li></ul>FundingThis work was partially funded by ISCIII (Instituto de Salud Carlos III [Carlos III Health Institute]): RETIC REDINREN RD16/0009 FIS FEDER FUNDS (PI15/01824, PI18/00362) and (AGAUR2014/SGR-1441).Conflicts of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres1337897" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1231798" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1337896" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1231797" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Angiomyolipomas" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Diagnosis" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Differential diagnosis" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Follow-up" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Recommendations" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Initial assessment of a patient with tuberous sclerosis complex consulting because of angiomyolipomas" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Recommendations" ] ] ] 7 => array:3 [ "identificador" => "sec0050" "titulo" => "Radiological follow-up of renal involvement in tuberous sclerosis complex" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Recommendations" ] ] ] 8 => array:3 [ "identificador" => "sec0060" "titulo" => "Treatment of angiomyolipomas" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Emergency treatment" ] 1 => array:3 [ "identificador" => "sec0070" "titulo" => "Non-emergency treatment" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Selective embolisation" ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Cryoablation" ] 2 => array:2 [ "identificador" => "sec0085" "titulo" => "Radio-frequency or microwave" ] 3 => array:2 [ "identificador" => "sec0090" "titulo" => "Surgery" ] 4 => array:2 [ "identificador" => "sec0095" "titulo" => "Active surveillance" ] ] ] 2 => array:2 [ "identificador" => "sec0100" "titulo" => "Recommendations" ] 3 => array:2 [ "identificador" => "sec0105" "titulo" => "Long-term treatment: mTOR inhibitors" ] 4 => array:2 [ "identificador" => "sec0110" "titulo" => "Recommendations" ] ] ] 9 => array:3 [ "identificador" => "sec0115" "titulo" => "Renal cysts" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0120" "titulo" => "Diagnosis" ] 1 => array:2 [ "identificador" => "sec0125" "titulo" => "Differential diagnosis of complicated cysts" ] 2 => array:2 [ "identificador" => "sec0130" "titulo" => "Follow-up and treatment" ] 3 => array:2 [ "identificador" => "sec0135" "titulo" => "Recommendations" ] ] ] 10 => array:3 [ "identificador" => "sec0140" "titulo" => "Contiguous gene syndrome TSC2/PKD1" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0145" "titulo" => "Diagnosis" ] 1 => array:2 [ "identificador" => "sec0150" "titulo" => "Differential diagnosis" ] 2 => array:2 [ "identificador" => "sec0155" "titulo" => "Follow-up" ] 3 => array:2 [ "identificador" => "sec0160" "titulo" => "Recommendations" ] ] ] 11 => array:3 [ "identificador" => "sec0165" "titulo" => "Hypertension in tuberous sclerosis complex" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0170" "titulo" => "Recommendations" ] ] ] 12 => array:3 [ "identificador" => "sec0175" "titulo" => "Chronic renal failure in tuberous sclerosis complex" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0180" "titulo" => "Recommendations" ] 1 => array:2 [ "identificador" => "sec0185" "titulo" => "Multidisciplinary follow-up" ] 2 => array:2 [ "identificador" => "sec0190" "titulo" => "Recommendations" ] ] ] 13 => array:2 [ "identificador" => "sec0195" "titulo" => "Funding" ] 14 => array:2 [ "identificador" => "sec0200" "titulo" => "Conflicts of interest" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-04-23" "fechaAceptado" => "2019-07-15" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1231798" "palabras" => array:6 [ 0 => "Angiomyolipomas" 1 => "Tuberous sclerosis" 2 => "Polycystic kidney disease" 3 => "Contiguous gene syndrome" 4 => "Cysts" 5 => "mTOR protein" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1231797" "palabras" => array:6 [ 0 => "Angiomiolipomas" 1 => "Esclerosis tuberosa" 2 => "Enfermedad renal poliquística" 3 => "Síndrome del gen contiguo" 4 => "Quistes" 5 => "Proteína mTOR" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Tuberous sclerosis complex (TSC) is a rare, hereditary, multisystemic disease with a broad phenotypic spectrum. Its management requires the collaboration of multiple specialists. Just as in the paediatric age, the paediatric neurologist takes on special importance; in adulthood, renal involvement is the cause of the greatest morbidity and mortality. There are several recommendations on the general management of patients with TSC but none that focuses on renal involvement. These recommendations respond to the need to provide guidelines to facilitate a better knowledge and diagnostic-therapeutic management of the renal involvement of TSC through a rational use of complementary tests and the correct use of available treatments. Their elaboration has been based on consensus within the hereditary renal diseases working group of the S.E.N./REDINREN (Spanish Society of Nephrology/Kidney Research Network). It has also counted on the participation of non-nephrologist specialists in TSC in order to expand the vision of the disease." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El complejo esclerosis tuberosa (CET) es una enfermedad rara, hereditaria, multisistémica y con un amplio espectro fenotípico. Su manejo requiere de la colaboración de múltiples especialistas. Así como en la edad pediátrica cobra un especial relieve el neurólogo pediatra, en la edad adulta la afectación renal es la causante de la mayor morbimortalidad. Existen diversas recomendaciones sobre el manejo general del paciente con CET pero ninguna que se centre en la afectación renal. Las presentes recomendaciones responden a la necesidad de proporcionar pautas para facilitar un mejor conocimiento y manejo diagnóstico-terapéutico de la afectación renal del CET mediante un uso racional de las pruebas complementarias y el empleo correcto de los tratamientos disponibles. Su elaboración se ha basado en el consenso dentro del grupo de trabajo de enfermedades renales hereditarias de la S.E.N./REDINREN. Ha contado con la participación de especialistas en CET no nefrólogos también con el fin de ampliar la visión de la enfermedad." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Ariceta G, Buj MJ, Furlano M, Martínez V, Matamala A, Morales M, et al. Recomendaciones de manejo de la afectación renal en el complejo esclerosis tuberosa. Nefrologia. 2020;40:142–151." ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0220" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sporadic AML (80%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AML associated with TSC (20%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age of onset \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4th-5th decade of life \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2nd–3rd decade (even in the first year of life) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gender \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">More common in females (2:1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Male and female (slight predominance in females) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Characteristics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Solitary and unilateral. Smaller \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Multiple and bilateral. Larger \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Growth \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Slow \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rapid \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Likelihood of bleeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High (especially if >4cm or microaneurysms >5mm) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Malignant transformation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Very rare \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rare (happens in epithelioid AML) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2294125.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Differential characteristics between sporadic AML and AML associated with TSC." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0225" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Adapted from Buj Pradilla et al., 2017.<a class="elsevierStyleCrossRef" href="#bib0070">14</a>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TIPO de AML</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">DIAGNÓSTICO DIFERENCIAL \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AML Clásico(rico en grasa)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-Carcinoma renal de células claras (puede presentar: calcio, halo hipoecoico y quistes intratumorales; mientras que AML en ecografía: hiperecogénico y con sombra acústica)</li><li class="elsevierStyleListItem" id="lsti0010">-Lipomas y Liposarcomas retroperitoneales (se diferencian porque son masas no dependientes del riñón, por tanto puede ser útil identificar origen de la arteria nutricia).</li><li class="elsevierStyleListItem" id="lsti0015">-Otros: Tumor de Wilms, Teratoma</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="middle">AML Atípico (pobre en grasa).RMN: en T2 es hipointenso</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AML Hiperatenuante(mayor componente muscular)TAC hiperatenuante \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020">-Tumores renales papilares</li><li class="elsevierStyleListItem" id="lsti0025">-Oncocitoma</li><li class="elsevierStyleListItem" id="lsti0030">-Metástasis</li><li class="elsevierStyleListItem" id="lsti0035">-Otros: linfoma, adenoma metanéfrico, leiomioma</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AML IsoatenuanteTAC: isoatenuante \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0040">-Tumor renal papilar (es de realce tardío, mientras que AML de realce precoz)</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AML con Quistes epiteliales(grasa inexistente)TAC: hiperdenso \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0045">-Cáncer renal multiquístico</li><li class="elsevierStyleListItem" id="lsti0050">-Quiste multiloculado</li><li class="elsevierStyleListItem" id="lsti0055">-Nefroma quístico</li><li class="elsevierStyleListItem" id="lsti0060">-Tumor mixto epitelial y estromal</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AML Epiteloide(puede malignizarse) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0065">-Tumor sarcomatoide</li><li class="elsevierStyleListItem" id="lsti0070">-Carcinoma de células claras de alto grado</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2294126.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Types of AML and differential diagnosis." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:48 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberous sclerosis complex. GeneReviews®" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "H. Northrup" 1 => "M.K. Koenig" 2 => "D.A. Pearson" 3 => "K.S. Au" ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "1993" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://www.ncbi.nlm.nih.gov/pubmed/20301399" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H. Northrup" 1 => "D.A. Krueger" 2 => "International Tuberous Sclerosis Complex Consensus Group" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pediatrneurol.2013.08.001" "Revista" => array:6 [ "tituloSerie" => "Pediatr Neurol." "fecha" => "2013" "volumen" => "49" "paginaInicial" => "243" "paginaFinal" => "254" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24053982" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.A. Krueger" 1 => "H. Northrup" 2 => "International Tuberous Sclerosis Complex Consensus Group" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pediatrneurol.2013.08.002" "Revista" => array:6 [ "tituloSerie" => "Pediatr Neurol." "fecha" => "2013" "volumen" => "49" "paginaInicial" => "255" "paginaFinal" => "265" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24053983" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recommendations for the multidisciplinary management of tuberous sclerosis complex" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Macaya" 1 => "R. Torra" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)." "fecha" => "2016" "volumen" => "147" "paginaInicial" => "211" "paginaFinal" => "216" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PEComas: the past, the present and the future" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "G. Martignoni" 1 => "M. Pea" 2 => "D. Reghellin" 3 => "G. Zamboni" 4 => "F. Bonetti" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00428-007-0509-1" "Revista" => array:6 [ "tituloSerie" => "Virchows Arch." "fecha" => "2008" "volumen" => "452" "paginaInicial" => "119" "paginaFinal" => "132" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18080139" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal manifestation of tuberous sclerosis complex" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.J. Bissler" 1 => "J. Christopher Kingswood" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajmg.c.31654" "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet C Semin Med Genet." "fecha" => "2018" "volumen" => "178" "paginaInicial" => "338" "paginaFinal" => "347" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30307110" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal manifestations of tuberous sclerosis complex: incidence, prognosis, and predictive factors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S.K. Rakowski" 1 => "E.B. Winterkorn" 2 => "E. Paul" 3 => "D.J.R. Steele" 4 => "E.F. Halpern" 5 => "E.A. Thiele" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.ki.5001853" "Revista" => array:6 [ "tituloSerie" => "Kidney Int." "fecha" => "2006" "volumen" => "70" "paginaInicial" => "1777" "paginaFinal" => "1782" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17003820" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal angiomyolipomata" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.J. Bissler" 1 => "J.C. Kingswood" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1523-1755.2004.00838.x" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2004" "volumen" => "66" "paginaInicial" => "924" "paginaFinal" => "934" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15327383" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term clinical morbidity in patients with renal angiomyolipoma associated with tuberous sclerosis complex" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Bissler" 1 => "K. Cappell" 2 => "H. Charles" 3 => "X. Song" 4 => "Z. Liu" 5 => "J. Prestifilippo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.urology.2016.04.027" "Revista" => array:6 [ "tituloSerie" => "Urology." "fecha" => "2016" "volumen" => "95" "paginaInicial" => "80" "paginaFinal" => "87" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27132503" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term follow-up assessing renal angiomyolipoma treatment patterns, morbidity, and mortality: an observational study in tuberous sclerosis complex patients in the Netherlands" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.J.C. Eijkemans" 1 => "W. van der Wal" 2 => "L.J. Reijnders" 3 => "K.C.B. Roes" 4 => "S.B. van Waalwijk van Doorn-Khosrovani" 5 => "C. Pelletier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.ajkd.2015.05.016" "Revista" => array:6 [ "tituloSerie" => "Am J Kidney Dis." "fecha" => "2015" "volumen" => "66" "paginaInicial" => "638" "paginaFinal" => "645" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26165440" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Natural history of patients with tuberous sclerosis complex related renal angiomyolipoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "X. Song" 1 => "Z. Liu" 2 => "K. Cappell" 3 => "C. Gregory" 4 => "Q. Said" 5 => "J. Prestifilippo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/03007995.2017.1313726" "Revista" => array:6 [ "tituloSerie" => "Curr Med Res Opin." "fecha" => "2017" "volumen" => "33" "paginaInicial" => "1277" "paginaFinal" => "1282" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28358266" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Natural history of renal angiomyolipoma (AML): most patients with large AMLs >4 cm can be offered active surveillance as an initial management strategy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.R. Bhatt" 1 => "P.O. Richard" 2 => "N.S. Kim" 3 => "A. Finelli" 4 => "K. Manickavachagam" 5 => "L. Legere" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.eururo.2016.01.048" "Revista" => array:6 [ "tituloSerie" => "Eur Urol." "fecha" => "2016" "volumen" => "70" "paginaInicial" => "85" "paginaFinal" => "90" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26873836" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal angiomyolipoma: clinicopathologic study of 194 cases with emphasis on the epithelioid histology and tuberous sclerosis association" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Aydin" 1 => "C. Magi-Galluzzi" 2 => "B.R. Lane" 3 => "L. Sercia" 4 => "J.I. Lopez" 5 => "B.I. Rini" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/PAS.0b013e31817ed7a6" "Revista" => array:6 [ "tituloSerie" => "Am J Surg Pathol." "fecha" => "2009" "volumen" => "33" "paginaInicial" => "289" "paginaFinal" => "297" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18852677" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recommendations for imaging-based diagnosis and management of renal angiomyolipoma associated with tuberous sclerosis complex" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.J. Buj Pradilla" 1 => "T. Marti Balleste" 2 => "R. Torra" 3 => "F. Villacampa Auba" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ckj/sfx094" "Revista" => array:6 [ "tituloSerie" => "Clin Kidney J." "fecha" => "2017" "volumen" => "10" "paginaInicial" => "728" "paginaFinal" => "737" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29225800" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CT and MR imaging for evaluation of cystic renal lesions and diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.G. Wood 3rd" 1 => "L.J. Stromberg 3rd" 2 => "C.B. Harmath" 3 => "J.M. Horowitz" 4 => "C. Feng" 5 => "N.A. Hammond" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1148/rg.351130016" "Revista" => array:6 [ "tituloSerie" => "Radiographics." "fecha" => "2015" "volumen" => "35" "paginaInicial" => "125" "paginaFinal" => "141" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25590393" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of T2-weighted MRI with and without fat suppression for differentiating renal angiomyolipomas without visible fat from other renal tumors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.S. Chung" 1 => "H.J. Choi" 2 => "M.-H. Kim" 3 => "K.-S. Cho" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2214/AJR.13.11058" "Revista" => array:6 [ "tituloSerie" => "AJR Am J Roentgenol." "fecha" => "2014" "volumen" => "202" "paginaInicial" => "765" "paginaFinal" => "771" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24660704" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Angiomyolipoma with minimal fat: can it be differentiated from clear cell renal cell carcinoma by using standard mr techniques?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Hindman" 1 => "L. Ngo" 2 => "E.M. Genega" 3 => "J. Melamed" 4 => "J. Wei" 5 => "J.M. Braza" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1148/radiol.12112087" "Revista" => array:6 [ "tituloSerie" => "Radiology" "fecha" => "2012" "volumen" => "265" "paginaInicial" => "468" "paginaFinal" => "477" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23012463" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberose sclerosis complex: analysis of growth rates aids differentiation of renal cell carcinoma from atypical or minimal-fat-containing angiomyolipoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "U. Patel" 1 => "E. Simpson" 2 => "J.C. Kingswood" 3 => "A.K. Saggar-Malik" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.crad.2005.01.009" "Revista" => array:6 [ "tituloSerie" => "Clin Radiol." "fecha" => "2005" "volumen" => "60" "paginaInicial" => "665" "paginaFinal" => "673" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16038693" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal masses in the adult patient: the role of percutaneous biopsy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.G. Silverman" 1 => "Y.U. Gan" 2 => "K.J. Mortele" 3 => "K. Tuncali" 4 => "E.S. Cibas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1148/radiol.2401050061" "Revista" => array:6 [ "tituloSerie" => "Radiology." "fecha" => "2006" "volumen" => "240" "paginaInicial" => "6" "paginaFinal" => "22" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16709793" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Annual review of children with tuberous sclerosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K.H. Ng" 1 => "S.M. Ng" 2 => "A. Parker" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/archdischild-2013-304948" "Revista" => array:6 [ "tituloSerie" => "Arch Dis Child - Educ Pract Ed." "fecha" => "2015" "volumen" => "100" "paginaInicial" => "114" "paginaFinal" => "121" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25112285" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Review of the tuberous sclerosis renal guidelines from the 2012 consensus conference: current data and future study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.C. Kingswood" 1 => "J.J. Bissler" 2 => "K. Budde" 3 => "J. Hulbert" 4 => "L. Guay-Woodford" 5 => "J.R. Sampson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000448293" "Revista" => array:6 [ "tituloSerie" => "Nephron" "fecha" => "2016" "volumen" => "134" "paginaInicial" => "51" "paginaFinal" => "58" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27504842" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transarterial embolization of angiomyolipoma: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T.E. Murray" 1 => "F. Doyle" 2 => "M. Lee" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.juro.2015.04.081" "Revista" => array:6 [ "tituloSerie" => "J Urol." "fecha" => "2015" "volumen" => "194" "paginaInicial" => "635" "paginaFinal" => "639" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25916674" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcomes of angioembolization and nephrectomy for renal angiomyolipoma associated with tuberous sclerosis complex: a real-world US national study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. Sun" 1 => "J. Liu" 2 => "H. Charles" 3 => "J. Hulbert" 4 => "J. Bissler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/03007995.2017.1286307" "Revista" => array:6 [ "tituloSerie" => "Curr Med Res Opin." "fecha" => "2017" "volumen" => "33" "paginaInicial" => "821" "paginaFinal" => "827" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28112545" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of interventional radiology techniques in the management of renal angiomyolipomas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.M. Kiefer" 1 => "S.W. Stavropoulos" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11934-017-0687-6" "Revista" => array:5 [ "tituloSerie" => "Curr Urol Rep." "fecha" => "2017" "volumen" => "18" "paginaInicial" => "36" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28299630" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal angiomyolipoma and lymphangioleiomyomatosis in pregnancy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C. Iruloh" 1 => "R. Keriakos" 2 => "D.J. Smith" 3 => "T. Cleveland" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Obstet Gynaecol (Lahore)." "fecha" => "2013" "volumen" => "33" "paginaInicial" => "542" "paginaFinal" => "546" ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characterization of Fabry disease in 352 pediatric patients in the Fabry Registry" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.J. Hopkin" 1 => "J. Bissler" 2 => "M. Banikazemi" 3 => "L. Clarke" 4 => "C.M. Eng" 5 => "D.P. Germain" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1203/PDR.0b013e318183f132" "Revista" => array:6 [ "tituloSerie" => "Pediatr Res." "fecha" => "2008" "volumen" => "64" "paginaInicial" => "550" "paginaFinal" => "555" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18596579" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Selective arterial embolization of angiomyolipomas: a comparison of smaller and larger embolic agents" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.D. Villalta" 1 => "M.D. Sorensen" 2 => "J.C. Durack" 3 => "R.K. Kerlan" 4 => "M.L. Stoller" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.juro.2011.04.082" "Revista" => array:6 [ "tituloSerie" => "J Urol." "fecha" => "2011" "volumen" => "186" "paginaInicial" => "921" "paginaFinal" => "927" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21791345" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Percutaneous renal cryoablation of angiomyolipomas in patients with solitary kidneys" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.C. Johnson" 1 => "S. Graham" 2 => "H. D’Agostino" 3 => "D.A. Elmajian" 4 => "W.B. Shingleton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.urology.2008.09.005" "Revista" => array:6 [ "tituloSerie" => "Urology." "fecha" => "2009" "volumen" => "74" "paginaInicial" => "1246" "paginaFinal" => "1249" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19815260" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rates of interventional procedures in patients with tuberous sclerosis complex-related renal angiomyolipoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Bissler" 1 => "K. Cappell" 2 => "H. Charles" 3 => "X. Song" 4 => "Z. Liu" 5 => "J. Prestifilippo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1185/03007995.2015.1060212" "Revista" => array:6 [ "tituloSerie" => "Curr Med Res Opin." "fecha" => "2015" "volumen" => "31" "paginaInicial" => "1501" "paginaFinal" => "1507" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26073843" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ultrasound-guided percutaneous microwave ablation of sporadic renal angiomyolipoma: preliminary results" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Z. Han" 1 => "P. Liang" 2 => "X. Yu" 3 => "Z. Cheng" 4 => "F. Liu" 5 => "J. Yu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0284185113519357" "Revista" => array:6 [ "tituloSerie" => "Acta Radiol." "fecha" => "2015" "volumen" => "56" "paginaInicial" => "56" "paginaFinal" => "62" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24526757" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: extension of a randomized controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.J. Bissler" 1 => "J.C. Kingswood" 2 => "E. Radzikowska" 3 => "B.A. Zonnenberg" 4 => "M. Frost" 5 => "E. Belousova" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ndt/gfv249" "Revista" => array:6 [ "tituloSerie" => "Nephrol Dial Transplant." "fecha" => "2016" "volumen" => "31" "paginaInicial" => "111" "paginaFinal" => "119" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26156073" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST-2 study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.J. Bissler" 1 => "J.C. Kingswood" 2 => "E. Radzikowska" 3 => "B.A. Zonnenberg" 4 => "E. Belousova" 5 => "M.D. Frost" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "PLoS One" "fecha" => "2017" "volumen" => "12" "paginaInicial" => "1" "paginaFinal" => "16" ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety considerations of mammalian target of rapamycin inhibitors in tuberous sclerosis complex and renal transplantation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.J.G. Somers" 1 => "E. Paul" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jcph.428" "Revista" => array:6 [ "tituloSerie" => "J Clin Pharmacol." "fecha" => "2015" "volumen" => "55" "paginaInicial" => "368" "paginaFinal" => "376" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25402866" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of everolimus on renal function in patients with tuberous sclerosis complex: evidence from EXIST-1 and EXIST-2" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.J. Bissler" 1 => "K. Budde" 2 => "M. Sauter" 3 => "D.N. Franz" 4 => "B.A. Zonnenberg" 5 => "M.D. Frost" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ndt/gfy132" "Revista" => array:6 [ "tituloSerie" => "Nephrol Dial Transplant." "fecha" => "2019" "volumen" => "34" "paginaInicial" => "1000" "paginaFinal" => "1008" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30053159" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Everolimus-induced hematologic changes in patients with metastatic breast cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Chen" 1 => "L. Chen" 2 => "A. Al-Qaisi" 3 => "E. Romond" 4 => "M. Awasthi" 5 => "V. Kadamyan-Melkumyan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.clbc.2014.07.002" "Revista" => array:6 [ "tituloSerie" => "Clin Breast Cancer." "fecha" => "2015" "volumen" => "15" "paginaInicial" => "48" "paginaFinal" => "53" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25199576" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Strategies for the management of adverse events associated with mTOR inhibitors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "B. Kaplan" 1 => "Y. Qazi" 2 => "J.R. Wellen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Transplant Rev." "fecha" => "2014" "volumen" => "28" "paginaInicial" => "126" "paginaFinal" => "133" ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Practical management of everolimus-related toxicities in patients with advanced solid tumors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Grünwald" 1 => "S. Weikert" 2 => "M.E. Pavel" 3 => "D. Hörsch" 4 => "D. Lüftner" 5 => "W. Janni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000350625" "Revista" => array:6 [ "tituloSerie" => "Onkologie." "fecha" => "2013" "volumen" => "36" "paginaInicial" => "295" "paginaFinal" => "302" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23689226" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets: a randomized, open-label, two-way crossover study of healthy volunteers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K. Thudium" 1 => "J. Gallo" 2 => "E. Bouillaud" 3 => "C. Sachs" 4 => "S. Eddy" 5 => "W. Cheung" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/CPAA.S73472" "Revista" => array:6 [ "tituloSerie" => "Clin Pharmacol." "fecha" => "2015" "volumen" => "7" "paginaInicial" => "11" "paginaFinal" => "17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25653564" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.L. Dabora" 1 => "S. Jozwiak" 2 => "D.N. Franz" 3 => "P.S. Roberts" 4 => "A. Nieto" 5 => "J. Chung" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/316951" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet." "fecha" => "2001" "volumen" => "68" "paginaInicial" => "64" "paginaFinal" => "80" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11112665" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease–a contiguous gene syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.T. Brook-Carter" 1 => "B. Peral" 2 => "C.J. Ward" 3 => "P. Thompson" 4 => "J. Hughes" 5 => "M.M. Maheshwar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng1294-328" "Revista" => array:6 [ "tituloSerie" => "Nat Genet." "fecha" => "1994" "volumen" => "8" "paginaInicial" => "328" "paginaFinal" => "332" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7894481" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.J. Back" 1 => "S. Andronikou" 2 => "T. Kilborn" 3 => "B.S. Kaplan" 4 => "K. Darge" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00247-014-3147-1" "Revista" => array:6 [ "tituloSerie" => "Pediatr Radiol." "fecha" => "2015" "volumen" => "45" "paginaInicial" => "386" "paginaFinal" => "395" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25355409" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imaging of kidney cysts and cystic kidney diseases in children: an international working group consensus statement" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Gimpel" 1 => "E.F. Avni" 2 => "L. Breysem" 3 => "K. Burgmaier" 4 => "A. Caroli" 5 => "M. Cetiner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1148/radiol.2018181243" "Revista" => array:6 [ "tituloSerie" => "Radiology." "fecha" => "2019" "volumen" => "290" "paginaInicial" => "769" "paginaFinal" => "782" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30599104" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early manifestations of renal disease in patients with tuberous sclerosis complex" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Malaga-Dieguez" 1 => "R. Spencer" 2 => "L.J. Pehrson" 3 => "S. Vento" 4 => "K. Menzer" 5 => "O. Devinsky" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Int J Nephrol Renovasc Dis." "fecha" => "2017" "paginaInicial" => "91" "paginaFinal" => "95" ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2013 ESH/ESC Practice guidelines for the management of arterial hypertension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Mancia" 1 => "R. Fagard" 2 => "K. Narkiewicz" 3 => "J. Redon" 4 => "A. Zanchetti" 5 => "M. Böhm" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/08037051.2014.868629" "Revista" => array:6 [ "tituloSerie" => "Blood Press" "fecha" => "2014" "volumen" => "23" "paginaInicial" => "3" "paginaFinal" => "16" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24359485" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical practice guideline for screening and management of high blood pressure in children and adolescents" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.T. Flynn" 1 => "D.C. Kaelber" 2 => "C.M. Baker-Smith" 3 => "D. Blowey" 4 => "A.E. Carroll" 5 => "S.R. Daniels" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1542/peds.2017-0685" "Revista" => array:4 [ "tituloSerie" => "Pediatrics." "fecha" => "2017" "volumen" => "140" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28924060" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.J. Siroky" 1 => "H. Yin" 2 => "B.P. Dixon" 3 => "R.J. Reichert" 4 => "A.R. Hellmann" 5 => "T. Ramkumar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajprenal.00569.2013" "Revista" => array:6 [ "tituloSerie" => "Am J Physiol Renal Physiol." "fecha" => "2014" "volumen" => "307" "paginaInicial" => "F560" "paginaFinal" => "70" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24920756" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased incidence of angioedema with ACE inhibitors in combination with mTOR inhibitors in kidney transplant recipients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Duerr" 1 => "P. Glander" 2 => "F. Diekmann" 3 => "D. Dragun" 4 => "H.H. Neumayer" 5 => "K. Budde" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2215/CJN.07371009" "Revista" => array:6 [ "tituloSerie" => "Clin J Am Soc Nephrol." "fecha" => "2010" "volumen" => "5" "paginaInicial" => "703" "paginaFinal" => "708" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20093343" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Angioedema induced by angiotensin converting enzyme inhibitors, potentiated by m-TOR inhibitors: successful treatment with icatibant" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Charmillon" 1 => "J. Deibener" 2 => "P. Kaminsky" 3 => "G. Louis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-014-3290-z" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med." "fecha" => "2014" "volumen" => "40" "paginaInicial" => "893" "paginaFinal" => "894" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24737261" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000004000000002/v1_202005210712/S2013251420300407/v1_202005210712/en/main.assets" "Apartado" => array:4 [ "identificador" => "42660" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000004000000002/v1_202005210712/S2013251420300407/v1_202005210712/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251420300407?idApp=UINPBA000064"]

Statistics

Special article

Recomendaciones de manejo de la afectación renal en el complejo esclerosis tuberosa

Gema Aricetaa, María José Bujb, Mónica Furlanoc, Víctor Martínezd, Anna Matamalae, Montserrat Moralesf, Nicolás Roberto Roblesg, Laia Sansh, Felipe Villacampai, Roser Torrac,

Corresponding author

rtorra@fundacio-puigvert.es

Corresponding author.

a Servicio de Nefrología Pediátrica, Hospital Valle Hebrón, REDINREN, Barcelona, Spain

b Servicio de Radiología, Hospital 12 de Octubre, Madrid, Spain

c Enfermedades Renales Hereditarias, Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, Universitat Autónoma de Barcelona, REDINREN, Barcelona, Spain

d Servicio de Nefrología, Hospital Virgen de la Arrixaca, Murcia, Spain

e Departamento de Enfermería, Fundació Puigvert, Barcelona, Spain

f Servicio de Medicina Interna, Hospital 12 de Octubre, Madrid, Spain

g Servicio de Nefrología, Hospital Universitario de Badajoz, REDINREN, Badajoz, Spain

h Servicio de Nefrología, Hospital del Mar, REDINREN, Barcelona, Spain

i Servicio de Urología, Clínica Universitaria de Navarra, Madrid, Spain

Read

7264

Times
was read the article

2631

Total PDF

4633

Total HTML

Share statistics

 array:24 [
  "pii" => "S2013251420300407"
  "issn" => "20132514"
  "doi" => "10.1016/j.nefroe.2020.03.009"
  "estado" => "S300"
  "fechaPublicacion" => "2020-03-01"
  "aid" => "654"
  "copyrightAnyo" => "2020"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "fla"
  "cita" => "Nefrologia &#40;English Version&#41;. 2020;40:142-51"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0211699519301560"
      "issn" => "02116995"
      "doi" => "10.1016/j.nefro.2019.07.002"
      "estado" => "S300"
      "fechaPublicacion" => "2020-03-01"
      "aid" => "654"
      "documento" => "article"
      "crossmark" => 0
      "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
      "subdocumento" => "fla"
      "cita" => "Nefrologia. 2020;40:142-51"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:2 [
        "total" => 612
        "formatos" => array:3 [
          "EPUB" => 63
          "HTML" => 332
          "PDF" => 217
        ]
      ]
      "es" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Art&#237;culo especial</span>"
        "titulo" => "Recomendaciones de manejo de la afectaci&#243;n renal en el complejo esclerosis tuberosa"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "142"
            "paginaFinal" => "151"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Recommendations for the management of renal involvement in the tuberous sclerosis complex"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Gema Ariceta, Mar&#237;a Jos&#233; Buj, M&#243;nica Furlano, V&#237;ctor Mart&#237;nez, Anna Matamala, Montserrat Morales, Nicol&#225;s Roberto Robles, Laia Sans, Felipe Villacampa, Roser Torra"
            "autores" => array:10 [
              0 => array:2 [
                "nombre" => "Gema"
                "apellidos" => "Ariceta"
              ]
              1 => array:2 [
                "nombre" => "Mar&#237;a Jos&#233;"
                "apellidos" => "Buj"
              ]
              2 => array:2 [
                "nombre" => "M&#243;nica"
                "apellidos" => "Furlano"
              ]
              3 => array:2 [
                "nombre" => "V&#237;ctor"
                "apellidos" => "Mart&#237;nez"
              ]
              4 => array:2 [
                "nombre" => "Anna"
                "apellidos" => "Matamala"
              ]
              5 => array:2 [
                "nombre" => "Montserrat"
                "apellidos" => "Morales"
              ]
              6 => array:2 [
                "nombre" => "Nicol&#225;s Roberto"
                "apellidos" => "Robles"
              ]
              7 => array:2 [
                "nombre" => "Laia"
                "apellidos" => "Sans"
              ]
              8 => array:2 [
                "nombre" => "Felipe"
                "apellidos" => "Villacampa"
              ]
              9 => array:2 [
                "nombre" => "Roser"
                "apellidos" => "Torra"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2013251420300407"
          "doi" => "10.1016/j.nefroe.2020.03.009"
          "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/S2013251420300407?idApp=UINPBA000064"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699519301560?idApp=UINPBA000064"
      "url" => "/02116995/0000004000000002/v1_202002280639/S0211699519301560/v1_202002280639/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:20 [
    "pii" => "S2013251420300365"
    "issn" => "20132514"
    "doi" => "10.1016/j.nefroe.2020.03.006"
    "estado" => "S300"
    "fechaPublicacion" => "2020-03-01"
    "aid" => "637"
    "copyright" => "Sociedad Espa&#241;ola de Nefrolog&#237;a"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Nefrologia &#40;English Version&#41;. 2020;40:152-9"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Renal potassium management in chronic kidney disease&#58; Differences between patients with or without hyperkalemia"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "152"
          "paginaFinal" => "159"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Manejo renal del potasio en la enfermedad renal cr&#243;nica avanzada&#58; diferencias entre pacientes con o sin hipercaliemia"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0020"
          "etiqueta" => "Fig&#46; 4"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr4.jpeg"
              "Alto" => 1261
              "Ancho" => 1577
              "Tamanyo" => 107883
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "at0020"
              "detalle" => "Fig&#46; "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Partial linear regressions between the fractional excretion of potassium and the potassium load relative to renal function in male and female patients&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Fernando Caravaca-Font&#225;n, Julian Valladares, Rosa D&#237;az-Campillejo, Sergio Barroso, Enrique Luna, Francisco Caravaca"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Fernando"
              "apellidos" => "Caravaca-Font&#225;n"
            ]
            1 => array:2 [
              "nombre" => "Julian"
              "apellidos" => "Valladares"
            ]
            2 => array:2 [
              "nombre" => "Rosa"
              "apellidos" => "D&#237;az-Campillejo"
            ]
            3 => array:2 [
              "nombre" => "Sergio"
              "apellidos" => "Barroso"
            ]
            4 => array:2 [
              "nombre" => "Enrique"
              "apellidos" => "Luna"
            ]
            5 => array:2 [
              "nombre" => "Francisco"
              "apellidos" => "Caravaca"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0211699519301213"
        "doi" => "10.1016/j.nefro.2019.04.011"
        "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/S0211699519301213?idApp=UINPBA000064"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251420300365?idApp=UINPBA000064"
    "url" => "/20132514/0000004000000002/v1_202005210712/S2013251420300365/v1_202005210712/en/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S201325142030047X"
    "issn" => "20132514"
    "doi" => "10.1016/j.nefroe.2020.03.016"
    "estado" => "S300"
    "fechaPublicacion" => "2020-03-01"
    "aid" => "681"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Nefrologia &#40;English Version&#41;. 2020;40:133-41"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>"
      "titulo" => "Kidney Health for Everyone Everywhere &#8211; From prevention to detection and equitable access to care"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "133"
          "paginaFinal" => "141"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Fig&#46; 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1900
              "Ancho" => 2500
              "Tamanyo" => 424533
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Overview of the preventive measures in chronic kidney disease &#40;CKD&#41; to highlight the similarities and distinctions pertaining to primary&#44; secondary&#44; and tertiary preventive measures and their intended goals&#46;</p>"
          ]
        ]
      ]
      "autores" => array:2 [
        0 => array:2 [
          "autoresLista" => "Philip Kam-Tao Li, Guillermo Garcia-Garcia, Siu-Fai Lui, Sharon Andreoli, Winston Wing-Shing Fung, Anne Hradsky, Latha Kumaraswami, Vassilios Liakopoulos, Ziyoda Rakhimova, Gamal Saadi, Luisa Strani, Ifeoma Ulasi, Kamyar Kalantar-Zadeh"
          "autores" => array:14 [
            0 => array:2 [
              "nombre" => "Philip Kam-Tao"
              "apellidos" => "Li"
            ]
            1 => array:2 [
              "nombre" => "Guillermo"
              "apellidos" => "Garcia-Garcia"
            ]
            2 => array:2 [
              "nombre" => "Siu-Fai"
              "apellidos" => "Lui"
            ]
            3 => array:2 [
              "nombre" => "Sharon"
              "apellidos" => "Andreoli"
            ]
            4 => array:2 [
              "nombre" => "Winston Wing-Shing"
              "apellidos" => "Fung"
            ]
            5 => array:2 [
              "nombre" => "Anne"
              "apellidos" => "Hradsky"
            ]
            6 => array:2 [
              "nombre" => "Latha"
              "apellidos" => "Kumaraswami"
            ]
            7 => array:2 [
              "nombre" => "Vassilios"
              "apellidos" => "Liakopoulos"
            ]
            8 => array:2 [
              "nombre" => "Ziyoda"
              "apellidos" => "Rakhimova"
            ]
            9 => array:2 [
              "nombre" => "Gamal"
              "apellidos" => "Saadi"
            ]
            10 => array:2 [
              "nombre" => "Luisa"
              "apellidos" => "Strani"
            ]
            11 => array:2 [
              "nombre" => "Ifeoma"
              "apellidos" => "Ulasi"
            ]
            12 => array:2 [
              "nombre" => "Kamyar"
              "apellidos" => "Kalantar-Zadeh"
            ]
            13 => array:1 [
              "colaborador" => "for the World Kidney Day Steering Committee"
            ]
          ]
        ]
        1 => array:2 [
          "autoresLista" => ""
          "autores" => array:1 [
            0 => array:1 [
              "colaborador" => "Members of the World Kidney Day Steering Committee"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S201325142030047X?idApp=UINPBA000064"
    "url" => "/20132514/0000004000000002/v1_202005210712/S201325142030047X/v1_202005210712/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>"
    "titulo" => "Recommendations for the management of renal involvement in tuberous sclerosis complex"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "142"
        "paginaFinal" => "151"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Gema Ariceta, Mar&#237;a Jos&#233; Buj, M&#243;nica Furlano, V&#237;ctor Mart&#237;nez, Anna Matamala, Montserrat Morales, Nicol&#225;s Roberto Robles, Laia Sans, Felipe Villacampa, Roser Torra"
        "autores" => array:10 [
          0 => array:3 [
            "nombre" => "Gema"
            "apellidos" => "Ariceta"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Mar&#237;a Jos&#233;"
            "apellidos" => "Buj"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "M&#243;nica"
            "apellidos" => "Furlano"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "V&#237;ctor"
            "apellidos" => "Mart&#237;nez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Anna"
            "apellidos" => "Matamala"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Montserrat"
            "apellidos" => "Morales"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">f</span>"
                "identificador" => "aff0030"
              ]
            ]
          ]
          6 => array:3 [
            "nombre" => "Nicol&#225;s Roberto"
            "apellidos" => "Robles"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">g</span>"
                "identificador" => "aff0035"
              ]
            ]
          ]
          7 => array:3 [
            "nombre" => "Laia"
            "apellidos" => "Sans"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">h</span>"
                "identificador" => "aff0040"
              ]
            ]
          ]
          8 => array:3 [
            "nombre" => "Felipe"
            "apellidos" => "Villacampa"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">i</span>"
                "identificador" => "aff0045"
              ]
            ]
          ]
          9 => array:4 [
            "nombre" => "Roser"
            "apellidos" => "Torra"
            "email" => array:1 [
              0 => "rtorra@fundacio-puigvert.es"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              1 => array:2 [
                "etiqueta" => "&#42;"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:9 [
          0 => array:3 [
            "entidad" => "Servicio de Nefrolog&#237;a Pedi&#225;trica&#44; Hospital Valle Hebr&#243;n&#44; REDINREN&#44; Barcelona&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Servicio de Radiolog&#237;a&#44; Hospital 12 de Octubre&#44; Madrid&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Enfermedades Renales Hereditarias&#44; Servicio de Nefrolog&#237;a&#44; Fundaci&#243; Puigvert&#44; IIB Sant Pau&#44; Universitat Aut&#243;noma de Barcelona&#44; REDINREN&#44; Barcelona&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Servicio de Nefrolog&#237;a&#44; Hospital Virgen de la Arrixaca&#44; Murcia&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Departamento de Enfermer&#237;a&#44; Fundaci&#243; Puigvert&#44; Barcelona&#44; Spain"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
          5 => array:3 [
            "entidad" => "Servicio de Medicina Interna&#44; Hospital 12 de Octubre&#44; Madrid&#44; Spain"
            "etiqueta" => "f"
            "identificador" => "aff0030"
          ]
          6 => array:3 [
            "entidad" => "Servicio de Nefrolog&#237;a&#44; Hospital Universitario de Badajoz&#44; REDINREN&#44; Badajoz&#44; Spain"
            "etiqueta" => "g"
            "identificador" => "aff0035"
          ]
          7 => array:3 [
            "entidad" => "Servicio de Nefrolog&#237;a&#44; Hospital del Mar&#44; REDINREN&#44; Barcelona&#44; Spain"
            "etiqueta" => "h"
            "identificador" => "aff0040"
          ]
          8 => array:3 [
            "entidad" => "Servicio de Urolog&#237;a&#44; Cl&#237;nica Universitaria de Navarra&#44; Madrid&#44; Spain"
            "etiqueta" => "i"
            "identificador" => "aff0045"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Recomendaciones de manejo de la afectaci&#243;n renal en el complejo esclerosis tuberosa"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0075" class="elsevierStylePara elsevierViewall">Tuberous sclerosis complex &#40;TSC&#41; &#40;ORPHA 805&#41; is a rare &#40;1&#47;6&#44;000-8&#44;000&#41;&#44; hereditary&#44; multisystemic disease with a broad phenotypic spectrum&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is caused by mutations in the <span class="elsevierStyleItalic">TSC1</span> and <span class="elsevierStyleItalic">TSC2</span> genes &#40;OMIM &#35;191100&#44; &#35;613254&#41;&#46; Adequate diagnostic&#47;therapeutic management of TSC requires coordination between multiple paediatric and adult specialities&#58; obstetrics&#44; genetics&#44; neurology&#44; nephrology&#44; urology&#44; cardiology&#44; ophthalmology&#44; internal medicine&#44; psychiatry&#44; dermatology&#44; dentistry&#44; respiratory medicine and radiology&#46; There are various management recommendations which take into account the systemic effects of the disease&#44; but none focuses on managing renal involvement&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a> The recommendations we present here are a response to the need for guidelines to improve both understanding and the diagnostic&#47;therapeutic management of renal involvement of TSC&#44; through a rational use of investigations and the correct use of available treatments&#46; They are based on consensus from the hereditary kidney disease working group of the Sociedad Espa&#241;ola de Nefrolog&#237;a&#47;Red de Investigaci&#243;n Renal &#40;SEN&#47;REDINREN&#41; &#91;Spanish Society of Nephrology&#47;Renal Research Network&#93;&#46; We also benefited from the participation of non-nephrology specialists in TSC&#44; that helped to broaden the vision of the disease&#44; but without diverting the focus from the renal aspects&#46; Levels of evidence are specified according to the methodology of the Centre for Evidence-Based Medicine &#40;University of Oxford&#41; &#40;<a href="http://www.cebm.net/?o=1025">http&#58;&#47;&#47;www&#46;cebm&#46;net&#47;&#63;o&#61;1025</a>&#41;&#46; The authors are listed in alphabetic order&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Angiomyolipomas</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0080" class="elsevierStylePara elsevierViewall">Angiomyolipomas &#40;AML&#41; are benign tumours derived from endothelial cells &#40;perivascular epithelioid cells&#59; PEComas&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> They are composed of adipose tissue&#44; smooth muscle and blood vessels&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> AML are the most common renal lesions in patients with TSC &#40;prevalence of 55&#8211;80&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In the general population&#44; 80&#37; of AML are sporadic and have differential characteristics with the AML associated with TSC<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">They increase both in size and in number with age&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> They are less common&#44; but not unheard of&#44; in children&#46; They are the leading cause of morbidity and mortality in adults with TSC&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> AML grow faster in women on oestrogen treatment and pre-pubertal girls&#44; suggesting that their development may be affected to some extent by hormones&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The main complication is bleeding&#44; which occurs mainly in lesions &#62;4<span class="elsevierStyleHsp" style=""></span>cm or in microaneurysms &#62;5<span class="elsevierStyleHsp" style=""></span>mm&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;12</span></a> and the risk may increase during pregnancy&#46; The AML associated with TSC have a rupture and haemorrhage rate ranging from 21&#37; to 100&#37;&#44; according to the published series&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">There are two histological types of AML&#58; classic &#40;fat-rich&#41; and&#44; in up to a third of cases&#44; atypical &#40;fat-poor&#41;&#46; The epithelioid variant is an atypical AML with more than 10&#37; epithelioid cells &#40;cells with abundant eosinophilic and granular cytoplasm&#41;&#44; which can undergo malignant transformation<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Diagnosis</span><p id="par0095" class="elsevierStylePara elsevierViewall">Diagnosis is made from imaging tests&#58; ultrasound&#44; computed tomography &#40;CT&#41; or magnetic resonance imaging &#40;MRI&#41;&#46; Ultrasound is fast and accessible&#44; and useful as a first approach in TSC&#46; However&#44; it is not very accurate in small and exophytic AML&#44; which can be confused with perirenal fat&#46; It is also observer-dependent&#46; A hyperechogenic lesion with suspected AML in a patient with TSC must be confirmed with CT or MRI&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">On CT&#44; the tissue has reduced density with negative attenuation coefficient values&#46; CT has high precision to detect small amounts of fat&#44; with slices as thin as 1&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In clinical practice&#44; the ellipsoid method can be used to measure the volume&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">CT or MRI angiogram with vascular reconstruction is the method of choice to obtain vascular mapping of the lesion as a preventive measure in AML<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>cm or after active bleeding to locate the bleeding point&#46; In these cases&#44; CT is more accurate than MRI&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">MRI is the technique of choice for initial diagnosis and follow-up&#46; Fat appears as a hypersignal in T1 and less in T2&#44; with hypointensity in fat-saturated T2-weighted sequences&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> In children&#44; it is usually performed with sedation and in conjunction with brain MRI&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Differential diagnosis</span><p id="par0115" class="elsevierStylePara elsevierViewall">The differential diagnosis of AML is made with retroperitoneal tumours and malignant renal tumours<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; It is particularly complicated in AML where intra-tumour fat is not detected&#46; IN case of doubts&#44; a biopsy of the lesion should be obtained&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;19</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Follow-up</span><p id="par0120" class="elsevierStylePara elsevierViewall">AML require radiological follow-up due to the risk of retroperitoneal bleeding and malignancy &#40;very rare&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In asymptomatic AML<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>cm&#44; follow-up&#44; preferably with annual MRI scans&#44; is recommended&#46; If the lesion remains stable&#44; follow-up intervals can be extended to 1&#8211;3 years&#46; Ultrasound can be alternated with MRI for follow-up&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Monitoring every six months with MRI is recommended in atypical&#44; fast-growing lesions or in women who start oestrogen therapy&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Recommendations</span><p id="par0780" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">1</span><p id="par0135" class="elsevierStylePara elsevierViewall">Perform MRI on diagnosis of TSC to identify AML that could go unnoticed on ultrasound &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">2</span><p id="par0140" class="elsevierStylePara elsevierViewall">Subsequently&#44; follow-up every 1&#8211;3 years with MRI&#47;ultrasound according to patient characteristics&#46; MRI is recommended for greater accuracy&#44; but in stable lesions it can be alternated with ultrasound &#40;C&#41;&#46; Try to avoid CT due to cumulative radiation&#44; especially in paediatric patients &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">3</span><p id="par0145" class="elsevierStylePara elsevierViewall">CT angiogram is reserved for vascular mapping in AML<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>cm to rule out microaneurysms &#40;D&#41; or acute bleeding to locate the bleeding point &#40;C&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">4</span><p id="par0150" class="elsevierStylePara elsevierViewall">If in doubt of the benign nature of atypical AML&#44; diagnostic fine-needle aspiration biopsy is recommended &#40;C&#41;&#46;</p></li></ul></p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Initial assessment of a patient with tuberous sclerosis complex consulting because of angiomyolipomas</span><p id="par0155" class="elsevierStylePara elsevierViewall">TSC is a disease with great phenotypic variability and multisystemic involvement&#46; The organs most commonly affected are brain&#44; kidney&#44; skin&#44; lung and eyes&#46; The clinical manifestations are progressive and change with age&#46; Some of the complications are life-threatening&#44; so it is essential a protocol of clinical follow-up&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">All patients with tuberous sclerosis should have protocolised monitorization of the most commonly affected organs to limit the onset of complications&#44; according to the following recommendations&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4&#44;20</span></a></p><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Recommendations</span><p id="par0785" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">1</span><p id="par0165" class="elsevierStylePara elsevierViewall">Annual monitoring of blood pressure &#40;BP&#41;&#44; full lab analyses with renal function and proteinuria&#47;microalbuminuria &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">2</span><p id="par0170" class="elsevierStylePara elsevierViewall">Neurological check-up&#58; baseline brain MRI&#46; Patients under the age of 25&#44; those with symptoms &#40;epilepsy&#44; intellectual retardation or psychiatric disorders&#41; or complications on MRI &#40;subependymal giant cell astrocytoma &#91;SEGA&#93;&#44; hydrocephalus&#41; should be referred to neurology &#40;A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">3</span><p id="par0175" class="elsevierStylePara elsevierViewall">Respiratory check-up&#58; high-resolution chest CT scan for all patients with respiratory symptoms and for women over the age of 18 regardless of being asymptomatic&#46; Refer patients with lesions or symptoms to the neumology service &#40;A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">4</span><p id="par0180" class="elsevierStylePara elsevierViewall">Annual dermatology and dental revisions&#46; Early action on symptomatic lesions &#40;A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">5</span><p id="par0185" class="elsevierStylePara elsevierViewall">Heart&#58; annual electrocardiogram and baseline echocardiogram&#46; In cases with symptoms or abnormalities in the complementary tests&#44; refer to cardiology &#40;A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">6</span><p id="par0190" class="elsevierStylePara elsevierViewall">Baseline ophthalmology examination&#59; if lesions are detected&#44; annual follow-up is recommended &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">7</span><p id="par0195" class="elsevierStylePara elsevierViewall">Genetics&#58; family counselling in all cases&#59; in individuals of reproductive age and if there are doubts about diagnosis&#44; perform genetic testing &#40;A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">8</span><p id="par0200" class="elsevierStylePara elsevierViewall">There is no evidence to support other routine tests&#44; unless there are specific symptoms &#40;C&#41;&#46;</p></li></ul></p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Radiological follow-up of renal involvement in tuberous sclerosis complex</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Recommendations</span><p id="par0790" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">1</span><p id="par0205" class="elsevierStylePara elsevierViewall">Investigations to be used&#58;</p></li><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">2</span><p id="par0210" class="elsevierStylePara elsevierViewall">In children&#44; ultrasound and MRI are recommended&#44; with CT only as an exception &#40;A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">3</span><p id="par0215" class="elsevierStylePara elsevierViewall">In adults&#44; the recommendation is essentially MRI&#47;ultrasound&#44; according to the characteristics of the lesions and the patient &#40;A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">4</span><p id="par0220" class="elsevierStylePara elsevierViewall">CT is much more sensitive than MRI for detecting microaneurysms and more accurate in measuring them &#40;motion artefacts in MRI&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">5</span><p id="par0225" class="elsevierStylePara elsevierViewall">If the lesions are stable&#44; try to keep CT scans to a minimum to avoid radiation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">6</span><p id="par0230" class="elsevierStylePara elsevierViewall">Perform MRI whenever possible &#40;absence of microaneurysms to assess&#44; no contraindications for MRI&#41; &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0165"><span class="elsevierStyleLabel">7</span><p id="par0235" class="elsevierStylePara elsevierViewall">Perform CT scan instead of MRI if the patient&#58; has apnoea and cannot cooperate&#59; has claustrophobia&#59; or is contraindicated due to wearing devices not compatible with MRI&#46;</p></li><li class="elsevierStyleListItem" id="lsti0170"><span class="elsevierStyleLabel">8</span><p id="par0240" class="elsevierStylePara elsevierViewall">If there are symptoms that suggest bleeding &#40;acute&#47;active or chronic&#41;&#58; CT without contrast&#44; followed by biphasic CT with contrast &#40;arterial and venous phases&#41; &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0175"><span class="elsevierStyleLabel">9</span><p id="par0245" class="elsevierStylePara elsevierViewall">If there are microaneurysms&#44; alternate MR angiography and biphasic CT &#40;arterial and venous&#41;&#44; as they are often not visible in MR angiography&#46; If MRI shows significant growth of AML&#44; do CT angiography to assess microaneurysms &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0180"><span class="elsevierStyleLabel">10</span><p id="par0250" class="elsevierStylePara elsevierViewall">If it is necessary to administer iodinated contrast in the CT scan and the patient has a GFR<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#44; applying a nephroprotection protocol is recommended &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0185"><span class="elsevierStyleLabel">11</span><p id="par0255" class="elsevierStylePara elsevierViewall">It is recommended not to perform MRI with gadolinium if GFR<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0190"><span class="elsevierStyleLabel">12</span><p id="par0260" class="elsevierStylePara elsevierViewall">Cysts do not require specific follow-up&#44; but whenever AML check-ups are performed&#44; the presence of cysts should be assessed&#44; and whether they are simple or complicated with bleeding&#44; infection or neoplasm&#46; If the patient only has cysts&#44; perform an ultrasound scan and&#44; if a complicated one is detected&#44; investigate preferably by MRI to avoid CT radiation &#40;A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0195"><span class="elsevierStyleLabel">13</span><p id="par0265" class="elsevierStylePara elsevierViewall">If there is an excessive number of lesions &#40;cysts or AML&#41;&#44; measuring the overall renal volume for monitoring purposes is recommended &#40;C&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0200"><span class="elsevierStyleLabel">14</span><p id="par0270" class="elsevierStylePara elsevierViewall">If there is radiological suspicion of possible malignancy &#40;minimal-fat AML&#41;&#44; take a biopsy and then continue with the usual follow-up&#46; If no biopsy is performed but it is decided to monitor&#44; follow-up every six months &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0205"><span class="elsevierStyleLabel">15</span><p id="par0275" class="elsevierStylePara elsevierViewall">The trend in the radiological management of AML in which response to treatment has been demonstrated should be to minimise the frequency of radiological examinations as far as possible to avoid long-term effects of contrasts and radiation &#40;B&#41;&#46;</p></li></ul></p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Treatment of angiomyolipomas</span><p id="par0280" class="elsevierStylePara elsevierViewall">AML associated with TSC have a high rate of rupture and haemorrhage and are frequently associated with a high morbidity in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The greatest risk of bleeding is with a size larger than 4<span class="elsevierStyleHsp" style=""></span>cm or microaneurysms &#62;5<span class="elsevierStyleHsp" style=""></span>mm&#44; so patients with these characteristics need to have treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">In view of the chronic and recurrent nature of these tumours&#44; all treatment will aim to preserve renal function as far as possible&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Emergency treatment</span><p id="par0290" class="elsevierStylePara elsevierViewall">In acute haemorrhage&#44; the treatment of choice is transarterial embolization&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> which has an efficacy of 93&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> This treatment is associated with the onset of post-embolisation syndrome &#40;nausea&#44; pyrexia and pain for 72<span class="elsevierStyleHsp" style=""></span>h&#41; in 35&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Although both nephrectomy and embolisation will resolve the condition&#44; the risk of renal failure is seven times higher with nephrectomy&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0295" class="elsevierStylePara elsevierViewall">Due to the risk of renal failure&#44; nephrectomy should be avoided provided the emergency permits and vascular radiology techniques are available&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;21</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">In acute rupture associated with pregnancy&#44; the treatment of choice remains embolisation&#46; In certain cases&#44; one option is emergency caesarean section and subsequent embolisation&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Non-emergency treatment</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Selective embolisation</span><p id="par0305" class="elsevierStylePara elsevierViewall">Scheduled embolisation of AML was the treatment of choice for years&#44; but has now been replaced by mTOR inhibitors&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;21</span></a> The success rate of embolisation is very high&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> achieving a decrease in size&#44; pain and the associated symptoms &#40;approximately 50&#37;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#41;&#46; Renal function is usually maintained&#44; and only in 3&#46;3&#37; of patients is it associated with a deterioration&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> However&#44; AML regrowth is possible&#44; with a second AML embolisation being required in 20&#37;&#8211;80&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">The more embolisations&#44; the greater the risk of renal failure&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0315" class="elsevierStylePara elsevierViewall">As far as the material used is concerned&#44; particles larger than 150<span class="elsevierStyleHsp" style=""></span>&#956;m are preferred due to their efficiency and the lower risk of distant emboli&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Cryoablation</span><p id="par0320" class="elsevierStylePara elsevierViewall">The use of ablation by freezing derives from its use in renal tumours of less than 4<span class="elsevierStyleHsp" style=""></span>cm in size&#44; although it has been used occasionally for larger tumours&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> For the treatment of AML&#44; efficacy of up to 100&#37; has been reported&#44; with the possibility of hospital discharge the next day&#44; but there is insufficient information about complications&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> It is an attractive alternative&#44; but details are still lacking to place it above embolisation&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Radio-frequency or microwave</span><p id="par0325" class="elsevierStylePara elsevierViewall">The use of these types of energy has also been studied and published in limited series&#44; with efficacy rates above 78&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;30</span></a> but associated with significant side effects such as bleeding&#44; nerve damage and hollow viscera fistulas&#46; For this reason&#44; this treatment is also kept as an alternative to embolisation&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Surgery</span><p id="par0330" class="elsevierStylePara elsevierViewall">Currently&#44; 13&#37; of patients with TSC and AML have surgery&#44; either radical &#40;5&#37;&#41; or partial &#40;8&#37;&#41; nephrectomy&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Because of the high associated rate of renal failure&#44; both partial and radical nephrectomies have been replaced by selective embolisation&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0335" class="elsevierStylePara elsevierViewall">Partial nephrectomy in these patients is more common than radical&#44; following the objective of preserving renal function&#44; but almost 45&#37; of them need a second partial&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> or even a subsequent radical&#44; nephrectomy&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Active surveillance</span><p id="par0340" class="elsevierStylePara elsevierViewall">In all the published series&#44; the risk of bleeding is minimal when the AML is less than 3<span class="elsevierStyleHsp" style=""></span>cm in size&#44; so surveillance is the norm in these cases&#44; with ultrasound or MRI every two years&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0345" class="elsevierStylePara elsevierViewall">When the tumour is larger than 3<span class="elsevierStyleHsp" style=""></span>cm in size&#44; 50&#37; may become symptomatic&#44; with risk factors being the presence of microaneurysms &#62;5<span class="elsevierStyleHsp" style=""></span>mm or rapid growth &#40;&#62;0&#46;25<span class="elsevierStyleHsp" style=""></span>cm&#47;year&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> so starting treatment is recommended&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;21</span></a></p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Recommendations</span><p id="par0795" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0210"><span class="elsevierStyleLabel">1</span><p id="par0350" class="elsevierStylePara elsevierViewall">Emergency treatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0215"><span class="elsevierStyleLabel">2</span><p id="par0355" class="elsevierStylePara elsevierViewall">The treatment of choice is transarterial embolisation &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0220"><span class="elsevierStyleLabel">3</span><p id="par0360" class="elsevierStylePara elsevierViewall">An alternative to embolisation is radical or partial nephrectomy &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0225"><span class="elsevierStyleLabel">4</span><p id="par0365" class="elsevierStylePara elsevierViewall">Non-emergency invasive treatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0230"><span class="elsevierStyleLabel">5</span><p id="par0370" class="elsevierStylePara elsevierViewall">Selective embolisation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0235"><span class="elsevierStyleLabel">lowerRoman6</span><p id="par0375" class="elsevierStylePara elsevierViewall">Second-line option of choice after treatment with mTOR &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0240"><span class="elsevierStyleLabel">lowerRoman7</span><p id="par0380" class="elsevierStylePara elsevierViewall">Material &#62;150<span class="elsevierStyleHsp" style=""></span>&#956;m should be used to prevent migrations &#40;C&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0245"><span class="elsevierStyleLabel">8</span><p id="par0385" class="elsevierStylePara elsevierViewall">Cryoablation</p></li><li class="elsevierStyleListItem" id="lsti0250"><span class="elsevierStyleLabel">lowerRoman9</span><p id="par0390" class="elsevierStylePara elsevierViewall">Alternative to the traditional options &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0255"><span class="elsevierStyleLabel">10</span><p id="par0395" class="elsevierStylePara elsevierViewall">Radio-frequency or microwave</p></li><li class="elsevierStyleListItem" id="lsti0260"><span class="elsevierStyleLabel">lowerRoman11</span><p id="par0400" class="elsevierStylePara elsevierViewall">Alternative to the traditional options &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0265"><span class="elsevierStyleLabel">12</span><p id="par0405" class="elsevierStylePara elsevierViewall">Surgery&#46;</p></li><li class="elsevierStyleListItem" id="lsti0270"><span class="elsevierStyleLabel">lowerRoman13</span><p id="par0410" class="elsevierStylePara elsevierViewall">Surgery is the alternative only when minimally invasive options fail due to its aggressiveness and loss of renal parenchyma &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0275"><span class="elsevierStyleLabel">14</span><p id="par0415" class="elsevierStylePara elsevierViewall">Follow-up&#46;</p></li><li class="elsevierStyleListItem" id="lsti0280"><span class="elsevierStyleLabel">lowerRoman15</span><p id="par0420" class="elsevierStylePara elsevierViewall">AML less than 3<span class="elsevierStyleHsp" style=""></span>cm in size associated with tuberous sclerosis should be monitored &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0285"><span class="elsevierStyleLabel">lowerRoman16</span><p id="par0425" class="elsevierStylePara elsevierViewall">If there is growth of more than 0&#46;25<span class="elsevierStyleHsp" style=""></span>cm&#47;year or AML larger than 3<span class="elsevierStyleHsp" style=""></span>cm in size&#44; active treatment should be offered &#40;C&#41;&#46;</p></li></ul></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Long-term treatment&#58; mTOR inhibitors</span><p id="par0800" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0290"><span class="elsevierStyleLabel">&#8226;</span><p id="par0430" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Indication&#46;</span> Everolimus is indicated for the treatment of adult patients with AML associated with TSC who are at risk of complications &#40;based on factors such as tumour size or the presence of multiple or bilateral tumours&#41; but who do not require immediate surgery&#46; It is usually prescribed in lesions larger than 3<span class="elsevierStyleHsp" style=""></span>cm in size&#46; The evidence is based on the analysis of the change in the sum of the volume of the AML&#44; where a permanent reduction in the size of the lesions has been demonstrated&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#44;32</span></a></p></li><li class="elsevierStyleListItem" id="lsti0295"><span class="elsevierStyleLabel">&#8226;</span><p id="par0435" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Dose&#46;</span> The recommended dose is 10<span class="elsevierStyleHsp" style=""></span>mg of everolimus once a day according to the data sheet&#44; although it seems reasonable to adjust the dose according to plasma levels&#46; Treatment should continue as long as there is clinical benefit or until unacceptable toxicity occurs&#46; If the patient forgets to take a dose&#44; they should not take an additional dose&#44; but take the next dose according to the prescribed schedule&#46; Management of suspected serious or intolerable adverse reactions may require a dose reduction and&#47;or a temporary discontinuation of the treatment with everolimus&#46; For mild adverse reactions no dose adjustment is usually required&#46; If a dose reduction is required&#44; the recommended dose is approximately 50&#37; lower than the daily dose previously administered&#46; For dose reductions below the lowest available dose&#44; dose administration should be considered every other day &#40;<a href="http://www.emea.europa.eu/ema">http&#58;&#47;&#47;www&#46;emea&#46;europa&#46;eu&#47;ema</a>&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0300"><span class="elsevierStyleLabel">&#8226;</span><p id="par0440" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Monitoring</span></p></li><li class="elsevierStyleListItem" id="lsti0305"><span class="elsevierStyleLabel">a&#41;</span><p id="par0445" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Imaging&#46;</span> The most usual procedure is to assess the treatment by taking scheduled volumetric measurements of the largest renal lesions and the total size of the kidney using MRI or CT&#44; depending on availability&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Annual monitoring by MRI is recommended&#44; allowing longer intervals when stability is achieved&#46;</p></li><li class="elsevierStyleListItem" id="lsti0310"><span class="elsevierStyleLabel">b&#41;</span><p id="par0450" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Laboratory tests&#46;</span> Use of everolimus does not cause any change in the usual clinical parameters which help to assess its effectiveness&#46; However&#44; it can cause some biochemical alterations which need to be monitored &#40;albuminuria&#44; dyslipidaemia&#44; hypophosphataemia&#44; increased LDH&#41;&#46; These will be discussed in the following section&#46; In clinical trials aimed specifically at the treatment of AML&#44; plasma levels of everolimus were not monitored or used to guide treatment&#46; However&#44; the Spanish Guidelines for the Management and Treatment of Tuberous Sclerosis recommend that levels should be checked&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This would be essential&#44; at least at the beginning of treatment&#44; because very low levels can be found due to concomitant treatment with inducers or inhibitors of CYP3A4 or antiepileptic drugs&#44; and after a change in liver status &#40;Child-Pugh&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0315"><span class="elsevierStyleLabel">&#8226;</span><p id="par0455" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Adverse effects&#58; description and management</span></p></li><li class="elsevierStyleListItem" id="lsti0320"><span class="elsevierStyleLabel">c&#41;</span><p id="par0460" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Stomatitis</span> is the most common complication&#44; but not serious&#44; and is usually recurrent&#44; but gradually decreasing in intensity&#46; Treatment is symptomatic with normal saline or alcohol-free rinses &#40;with hyaluronic acid&#59; e&#46;g&#46; Aloclair&#174;&#41;&#46; Topical analgesics and corticosteroids may be used&#44; but antifungals are not recommended&#46;</p></li><li class="elsevierStyleListItem" id="lsti0325"><span class="elsevierStyleLabel">d&#41;</span><p id="par0465" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Infections&#46;</span> Take a full medical history and ask for viral markers prior to treatment&#46; Management will depend on each case&#44; but if there is systemic fungal invasion&#44; treatment should be discontinued immediately&#46; In cases of active hepatitis B or C treatment should be agreed with the hepatologist&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p></li><li class="elsevierStyleListItem" id="lsti0330"><span class="elsevierStyleLabel">e&#41;</span><p id="par0470" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Dyslipidaemia&#46;</span> Treatment according to standard consensus guidelines&#44; including&#58; control of risk factors&#44; dietary treatment and physical exercise&#44; and pharmacological treatment with statins&#44; if indicated&#46; There are no pharmacological interactions between everolimus and statins or fibrates&#46;</p></li><li class="elsevierStyleListItem" id="lsti0335"><span class="elsevierStyleLabel">f&#41;</span><p id="par0475" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Hypophosphataemia&#46;</span> Treat mild hypophosphataemia &#40;&#60;2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41; with oral phosphate&#58; 30&#8722;100<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day in three or four divided doses&#44; according to response&#46; Hypophosphataemia &#60;1<span class="elsevierStyleHsp" style=""></span>mg&#47;dl requires hospitalisation&#44; intravenous phosphate and discontinuation of the treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p></li><li class="elsevierStyleListItem" id="lsti0340"><span class="elsevierStyleLabel">g&#41;</span><p id="par0480" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Proteinuria and renal failure&#46;</span> Albuminuria and renal function need to be monitored&#46; If a patient develops albuminuria&#44; they may be treated with angiotensin receptor antagonists&#46; In severe proteinuria&#44; treatment should be discontinued&#46; The effect on renal function has not been fully assessed in the long term&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p></li><li class="elsevierStyleListItem" id="lsti0345"><span class="elsevierStyleLabel">h&#41;</span><p id="par0485" class="elsevierStylePara elsevierViewall">Use of everolimus is often accompanied by <span class="elsevierStyleItalic">microcytic anaemia</span>&#44; <span class="elsevierStyleItalic">thrombocytopenia</span> and progressive <span class="elsevierStyleItalic">lymphopenia</span>&#44; but only rarely do they lead to the medication being discontinued&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> Haematological toxicity is concentration-dependent&#59; should it occur&#44; it may indicate an interaction or failure to take medication&#46; It is advisable to determine the concentration at which the toxicity appeared&#44; in order to restart a new regimen in therapeutic range &#40;Cmin &#8764; 5<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#46; Management is similar to any other cytopenia&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p></li><li class="elsevierStyleListItem" id="lsti0350"><span class="elsevierStyleLabel">i&#41;</span><p id="par0490" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Amenorrhoea&#46;</span> It seems that amenorrhoea can be caused by mTOR inhibition&#44; which may play an important role in controlling the onset of puberty&#46; It is important to monitor for defects or dysfunctions in growth&#44; development or sexual maturation&#46; Most cases are transient&#44; manageable and do not lead to interruption of treatment&#46; Patients should be referred to gynaecology to rule out other causes&#46;</p></li><li class="elsevierStyleListItem" id="lsti0355"><span class="elsevierStyleLabel">j&#41;</span><p id="par0495" class="elsevierStylePara elsevierViewall">Non-infectious pneumonitis is accompanied by nonspecific respiratory signs and symptoms such as cough&#44; dyspnoea&#44; hypoxaemia and pleural effusion&#44; and a more thorough follow-up with the necessary pulmonary function tests is recommended&#44; according to the patient&#39;s condition&#46; Confirm the diagnosis of non-infectious pneumonitis with sputum and blood cultures in symptomatic cases&#46; Asymptomatic cases do not require interruption of treatment&#46; Adjust the dose of everolimus in mildly symptomatic cases&#46; In more severe cases&#44; discontinuation of treatment and use of corticosteroids is indicated&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p></li><li class="elsevierStyleListItem" id="lsti0360"><span class="elsevierStyleLabel">k&#41;</span><p id="par0500" class="elsevierStylePara elsevierViewall">Everolimus can alter the wound healing process&#46; Discontinuing the drug is therefore recommended in the peri-operative period&#44; especially in older patients and patients with diabetes&#44; malnutrition or high body mass index &#40;BMI&#41;&#46; Additionally&#44; caution should be taken in patients receiving concomitant treatment with corticosteroids and&#47;or anticoagulants&#46;</p></li><li class="elsevierStyleListItem" id="lsti0365"><span class="elsevierStyleLabel">l&#41;</span><p id="par0505" class="elsevierStylePara elsevierViewall">CYP3A4 or PgP inducers can lower everolimus blood concentrations&#46; Concomitant treatment with potent CYP3A4 inhibitors such as ketoconazole and other azoles&#44; clarithromycin&#44; telithromycin&#44; nefazodone or HIV protease inhibitors is not recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a></p></li></ul></p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Recommendations</span><p id="par0805" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0370"><span class="elsevierStyleLabel">1</span><p id="par0510" class="elsevierStylePara elsevierViewall">Treatment with everolimus is recommended for adult patients with renal AML associated with TSC who are at risk of complications &#40;AML<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>cm&#41; at an initial dose of 10<span class="elsevierStyleHsp" style=""></span>mg&#47;day &#40;A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0375"><span class="elsevierStyleLabel">2</span><p id="par0515" class="elsevierStylePara elsevierViewall">It is suggested that the effects of the treatment be monitored with yearly&#47;two-yearly imaging tests &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0380"><span class="elsevierStyleLabel">3</span><p id="par0520" class="elsevierStylePara elsevierViewall">It is suggested that levels of the drug be determined at the beginning of treatment&#44; after any change of dose due to concomitant treatment with inducers or inhibitors of CYP3A4 or antiepileptic drugs&#44; and after a change in liver status &#40;Child-Pugh&#41; &#40;C&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0385"><span class="elsevierStyleLabel">4</span><p id="par0525" class="elsevierStylePara elsevierViewall">It is suggested that everolimus plasma levels be maintained in the range of 4&#8211;10<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0390"><span class="elsevierStyleLabel">5</span><p id="par0530" class="elsevierStylePara elsevierViewall">It is suggested treating stomatitis symptomatically &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0395"><span class="elsevierStyleLabel">6</span><p id="par0535" class="elsevierStylePara elsevierViewall">In the case of patients with active hepatitis B or C&#44; it is suggested discussing the treatment with a hepatologist &#40;C&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0400"><span class="elsevierStyleLabel">7</span><p id="par0540" class="elsevierStylePara elsevierViewall">In all cases of symptomatic infection it is recommend stopping everolimus and restarting treatment with half the dose &#40;C&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0405"><span class="elsevierStyleLabel">8</span><p id="par0545" class="elsevierStylePara elsevierViewall">It is suggested treating dyslipidaemia according to standard consensus guidelines &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0410"><span class="elsevierStyleLabel">9</span><p id="par0550" class="elsevierStylePara elsevierViewall">It is suggested treating hypophosphataemia with oral or intravenous phosphorus supplements according to the severity &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0415"><span class="elsevierStyleLabel">10</span><p id="par0555" class="elsevierStylePara elsevierViewall">It is recommend monitoring albuminuria and renal function &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0420"><span class="elsevierStyleLabel">11</span><p id="par0560" class="elsevierStylePara elsevierViewall">It is suggested managing any type of cytopenia with the standard treatments &#40;C&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0425"><span class="elsevierStyleLabel">12</span><p id="par0565" class="elsevierStylePara elsevierViewall">It is recommend determining the concentration at which the haematological toxicity appeared&#44; in order to restart a new regimen in therapeutic range &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0430"><span class="elsevierStyleLabel">13</span><p id="par0570" class="elsevierStylePara elsevierViewall">It is suggested referring cases of amenorrhoea to gynaecology to rule out adjuvant causes &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0435"><span class="elsevierStyleLabel">14</span><p id="par0575" class="elsevierStylePara elsevierViewall">An immediate X-ray is recommended whenever there are respiratory symptoms&#46; After a first episode of pneumonitis&#44; we recommend chest X-rays every six weeks for the first six months after restarting the treatment &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0440"><span class="elsevierStyleLabel">15</span><p id="par0580" class="elsevierStylePara elsevierViewall">It is recommend discontinuing everolimus and treating with corticosteroids in severe cases of correctly diagnosed non-infectious pneumonitis &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0445"><span class="elsevierStyleLabel">16</span><p id="par0585" class="elsevierStylePara elsevierViewall">It is recommend discontinuing the drug in the peri-operative period until complete healing has taken place &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0450"><span class="elsevierStyleLabel">17</span><p id="par0590" class="elsevierStylePara elsevierViewall">It is suggested that everolimus should be used with caution in patients on concomitant treatment with corticosteroids and&#47;or anticoagulants &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0455"><span class="elsevierStyleLabel">18</span><p id="par0595" class="elsevierStylePara elsevierViewall">Concomitant treatment with potent CYP3A4 inhibitors&#44; such as ketoconazole and other azoles&#44; clarithromycin&#44; telithromycin&#44; nefazodone or HIV protease inhibitors&#44; is not recommended &#40;B&#41;&#46;</p></li></ul></p></span></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Renal cysts</span><p id="par0600" class="elsevierStylePara elsevierViewall">Renal cysts in TSC are considered a minor criterion and are the second most common renal manifestation after AML&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The incidence is around 50&#37; of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;39</span></a> They are more common in patients with mutation in the <span class="elsevierStyleItalic">TSC2</span> gene than in <span class="elsevierStyleItalic">TSC1</span>&#44; especially if the <span class="elsevierStyleItalic">TSC2</span> mutation is truncated&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;39</span></a> They can present as glomerulocystic disease&#44; single or multiple simple cortical cysts or with cystic nephromegaly associated with autosomal dominant polycystic kidney disease&#46; They are usually asymptomatic&#44; but occasionally&#44; if large&#44; they can rupture and bleed&#46;</p><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Diagnosis</span><p id="par0605" class="elsevierStylePara elsevierViewall">Diagnosis is made by ultrasound scan&#46; MRI or CT can be useful in the case of uncertainty&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;14</span></a></p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Differential diagnosis of complicated cysts</span><p id="par0810" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0460"><span class="elsevierStyleLabel">&#8226;</span><p id="par0610" class="elsevierStylePara elsevierViewall">Hamartomatous renal polyps&#46;</p></li><li class="elsevierStyleListItem" id="lsti0465"><span class="elsevierStyleLabel">&#8226;</span><p id="par0615" class="elsevierStylePara elsevierViewall">Renal cell carcinoma&#46;</p></li><li class="elsevierStyleListItem" id="lsti0470"><span class="elsevierStyleLabel">&#8226;</span><p id="par0620" class="elsevierStylePara elsevierViewall">Atypical renal AML&#46;</p></li></ul></p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Follow-up and treatment</span><p id="par0625" class="elsevierStylePara elsevierViewall">Uncomplicated cystic lesions do not require strict monitoring&#46; They will be checked in the AML follow-up imaging test&#46; They do not require specific treatment&#44; have little clinical impact and do not usually need complex management&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a></p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Recommendations</span><p id="par0815" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0475"><span class="elsevierStyleLabel">1</span><p id="par0630" class="elsevierStylePara elsevierViewall">We suggest the renal cysts be monitored radiologically in the imaging tests performed for follow-up of the AML &#40;C&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0480"><span class="elsevierStyleLabel">2</span><p id="par0635" class="elsevierStylePara elsevierViewall">The renal cysts in TSC do not require specific treatment &#40;C&#41;&#46;</p></li></ul></p></span></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Contiguous gene syndrome <span class="elsevierStyleItalic">TSC2&#47;PKD1</span></span><p id="par0640" class="elsevierStylePara elsevierViewall">A minority &#40;&#8764; 2&#37;&#41; of patients with TSC have what is known as <span class="elsevierStyleItalic">TSC2&#47;PKD1</span> contiguous gene syndrome &#40;autosomal dominant polycystic kidney disease &#91;ADPKD&#93; type 1 with tuberous sclerosis&#44; OMIM&#58; 600273&#59; ORPHA&#58; 88924&#41; caused by large deletions which affect the <span class="elsevierStyleItalic">TSC2</span> and <span class="elsevierStyleItalic">PKD1</span> genes&#44; located next to each other on chromosome 16&#46; The deletion of both genes is expressed with a characteristic phenotype of severe and early onset ADPKD&#44; associated with clinical manifestations suggestive of TSC&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0645" class="elsevierStylePara elsevierViewall">The estimated prevalence of this condition is &#60;1&#47;1&#44;000&#44;000&#44; and it is inherited with a theoretical autosomal dominant transmission pattern&#44; although it is uncommon for affected individuals to reproduce&#46;</p><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Diagnosis</span><p id="par0650" class="elsevierStylePara elsevierViewall">The suspected diagnosis is based on detection before birth&#44; at birth or during the first months of life of enlarged kidneys&#44; with multiple cortical cysts of variable sizes&#44; suggestive of a very early and severe ADPKD&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> Patients usually have difficult-to-control hypertension and&#47;or a reduced glomerular filtration rate&#44; along with symptoms or signs suggestive of TSC&#44; usually neurological&#44; given their early age&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The renal phenotype is more severe than usual in patients with TSC&#44; with the presence of multiple cysts on ultrasound&#44; increasing nephromegaly and progression to advanced chronic kidney disease &#40;CKD&#41; in the young adult&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p><p id="par0655" class="elsevierStylePara elsevierViewall">Typically&#44; the lack of a family history of ADPKD&#44; the progression and severity of the ADPKD&#44; and the clinical signs and symptoms of TSC&#44; lead to the conclusion of <span class="elsevierStyleItalic">TSC2&#47;PKD1</span> contiguous gene syndrome&#46; The definitive diagnosis is established by genetic testing with the finding of a deletion that affects the two genes described&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Differential diagnosis</span><p id="par0660" class="elsevierStylePara elsevierViewall">Other conditions which involve renal cysts&#44; such as autosomal recessive polycystic kidney disease and cystic dysplasia due to mutations of the <span class="elsevierStyleItalic">HNF1b</span> gene need to be excluded&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a></p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Follow-up</span><p id="par0665" class="elsevierStylePara elsevierViewall">Patients with TSC should be managed according to the expert recommendations&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> with the symptomatic treatment required by the severity and progression of the associated ADPKD&#46;</p></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Recommendations</span><p id="par0820" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0485"><span class="elsevierStyleLabel">1</span><p id="par0670" class="elsevierStylePara elsevierViewall">Patients with <span class="elsevierStyleItalic">TSC2&#47;PKD1</span> contiguous gene syndrome should be followed up by the paediatric nephrologist &#40;A&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0490"><span class="elsevierStyleLabel">2</span><p id="par0675" class="elsevierStylePara elsevierViewall">Strict monitoring of BP is recommended &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0495"><span class="elsevierStyleLabel">3</span><p id="par0680" class="elsevierStylePara elsevierViewall">The management of CKD is similar to that for other aetiologies&#46; The assessment for renal replacement therapy should include the patient&#39;s neurocognitive status and be made on an individual basis &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0500"><span class="elsevierStyleLabel">4</span><p id="par0685" class="elsevierStylePara elsevierViewall">We recommend that patients are monitored by paediatric neurology and later by neurology &#40;B&#41;&#46;</p></li></ul></p></span></span><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Hypertension in tuberous sclerosis complex</span><p id="par0690" class="elsevierStylePara elsevierViewall">The prevalence of hypertension &#40;HTN&#41; in patients with TSC under the age of 25 is up to 25&#37;&#46; It is more common in patients with mutations in the <span class="elsevierStyleItalic">TSC2</span> gene and in patients with more lesions in the kidneys&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> especially those with <span class="elsevierStyleItalic">TSC2&#47;PKD1</span> contiguous gene syndrome&#46;</p><p id="par0695" class="elsevierStylePara elsevierViewall">BP should be measured in the initial assessment of a patient diagnosed with TSC&#44; and subsequently monitored annually&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The target BP in monitoring should be the same as in the hypertensive population with kidney disease &#40;&#60;140&#47;90<span class="elsevierStyleHsp" style=""></span>mmHg in the clinic and &#60;135&#47;85<span class="elsevierStyleHsp" style=""></span>mmHg by self-measured BP monitoring at home or BP below the adjusted 90th percentile for size and gender in a paediatric patient&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">44&#44;45</span></a> Monitoring of BP is essential to prevent the progression of CKD&#46;</p><p id="par0700" class="elsevierStylePara elsevierViewall">The renin-angiotensin system inhibitors are the first-choice antihypertensive drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> In addition&#44; the presence of type 1 angiotensin II receptors has been demonstrated in AML and&#44; experimentally&#44; blocking of angiotensin II potentially seems to have a therapeutic effect in this area&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> In patients treated with everolimus&#44; given the higher incidence of angioedema in association with ACE inhibitors&#44; treatment with ARB should be given&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#44;48</span></a> In children with infantile spasms&#44; treatment with corticotropin may induce HTN&#59; in this context&#44; initial diuretic treatment may be sufficient&#46;</p><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Recommendations</span><p id="par0825" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0075"><li class="elsevierStyleListItem" id="lsti0505"><span class="elsevierStyleLabel">1</span><p id="par0705" class="elsevierStylePara elsevierViewall">BP should be assessed at diagnosis and subsequently&#44; at least annually &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0510"><span class="elsevierStyleLabel">2</span><p id="par0710" class="elsevierStylePara elsevierViewall">Target BP in the clinic should be &#60;140&#47;90<span class="elsevierStyleHsp" style=""></span>mmHg and by self-measurement&#44; &#60;135&#47;85<span class="elsevierStyleHsp" style=""></span>mmHg &#40;D&#41;&#44; or &#60;90th percentile for size and gender in the case of children and adolescents&#46;</p></li><li class="elsevierStyleListItem" id="lsti0515"><span class="elsevierStyleLabel">3</span><p id="par0715" class="elsevierStylePara elsevierViewall">The renin-angiotensin system inhibitors are the first-choice antihypertensive drugs &#40;C&#41;&#46;</p></li></ul></p></span></span><span id="sec0175" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Chronic renal failure in tuberous sclerosis complex</span><p id="par0720" class="elsevierStylePara elsevierViewall">The destruction of the renal parenchyma due to the presence of AML and cysts in the renal tissue&#44; combined with the invasive treatments of AML &#40;embolisation and partial and total nephrectomies&#41;&#44; are the main determinants in the development of CKD&#46; Among patients with TSC&#44; 40&#37; have CKD stage 3 &#40;or more advanced&#41; by the age of 45-54&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;21</span></a> Kidney disease is more prevalent in patients with <span class="elsevierStyleItalic">TSC2</span> mutations&#44; and especially in patients with <span class="elsevierStyleItalic">TSC2-PKD1</span>contiguous gene syndrome&#44; who usually progress towards advanced renal failure during their teenage years&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a></p><p id="par0725" class="elsevierStylePara elsevierViewall">Renal function should be assessed at diagnosis and then annually in adult patients&#46; The management of CKD-related complications should be the same as for other causes of kidney disease &#40;<a href="https://kdigo.org/guidelines/anemia-in-ckd/;https://kdigo.org/guidelines/ckd-evaluation-and-management/">https&#58;&#47;&#47;kdigo&#46;org&#47;guidelines&#47;anemia-in-ckd&#47;&#59;https&#58;&#47;&#47;kdigo&#46;org&#47;guidelines&#47;ckd-evaluation-and-management&#47;</a>&#59; <a href="https://kdigo.org/guidelines/ckd-mbd/">https&#58;&#47;&#47;kdigo&#46;org&#47;guidelines&#47;ckd-mbd&#47;</a>&#59; <a href="https://kdigo.org/guidelines/lipids-in-ckd/">https&#58;&#47;&#47;kdigo&#46;org&#47;guidelines&#47;lipids-in-ckd&#47;</a>&#41;&#46;</p><p id="par0730" class="elsevierStylePara elsevierViewall">There are no formal contraindications in relation to the choice of renal replacement technique&#46; In transplanted patients it seems reasonable to include mTOR inhibitors in their immunosuppressive therapy&#44; in view of their benefits in relation to the manifestations of the disease&#46;</p><span id="sec0180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Recommendations</span><p id="par0830" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0080"><li class="elsevierStyleListItem" id="lsti0520"><span class="elsevierStyleLabel">1</span><p id="par0735" class="elsevierStylePara elsevierViewall">Renal function should be assessed at diagnosis and subsequently at least annually in adults &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0525"><span class="elsevierStyleLabel">2</span><p id="par0740" class="elsevierStylePara elsevierViewall">The management of CKD-related complications should be the same as for other causes of CKD &#40;D&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0530"><span class="elsevierStyleLabel">3</span><p id="par0745" class="elsevierStylePara elsevierViewall">There are no formal contraindications in terms of choosing the type of renal replacement therapy &#40;D&#41;&#46; In transplanted patients&#44; we recommend including mTOR inhibitors in their immunosuppressive therapy &#40;D&#41;&#46;</p></li></ul></p></span><span id="sec0185" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Multidisciplinary follow-up</span><p id="par0750" class="elsevierStylePara elsevierViewall">Because of the multisystemic nature of the disease&#44; TSC requires coordination among all the healthcare professionals involved&#46; The healthcare professionals need to set up a Committee specialised in TSC and meet periodically to discuss and agree on consensual actions for the different cases being monitored by the team&#46;</p><p id="par0755" class="elsevierStylePara elsevierViewall">Patient follow-up is based on the recommendations described above&#46; To properly coordinate the follow-up&#44; the figure of the nurse case manager is very useful&#46; The manager of clinical cases is responsible for ensuring correct planning of the diagnostic and follow-up tests&#44; and the appointments with the team&#39;s different specialists according to protocol&#46; The case manager also sets up the communication network between the healthcare professionals to help ensure smooth and efficient monitoring&#46; Their role is fundamental in the transition from paediatrics and they are the first filter for the doubts and concerns of the patient and their relatives&#46;</p></span><span id="sec0190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210">Recommendations</span><p id="par0835" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0085"><li class="elsevierStyleListItem" id="lsti0535"><span class="elsevierStyleLabel">1</span><p id="par0760" class="elsevierStylePara elsevierViewall">We recommend the creation of multidisciplinary TSC teams &#40;B&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0540"><span class="elsevierStyleLabel">2</span><p id="par0765" class="elsevierStylePara elsevierViewall">We suggest the need for a manager of clinical cases &#40;B&#41;&#46;</p></li></ul></p></span></span><span id="sec0195" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0215">Funding</span><p id="par0770" class="elsevierStylePara elsevierViewall">This work was partially funded by <span class="elsevierStyleGrantSponsor" id="gs0005">ISCIII</span> &#40;Instituto de Salud Carlos III &#91;Carlos III Health Institute&#93;&#41;&#58; RETIC REDINREN RD16&#47;0009 FIS <span class="elsevierStyleGrantSponsor" id="gs0010">FEDER FUNDS</span> &#40;<span class="elsevierStyleGrantNumber" refid="gs0010">PI15&#47;01824</span>&#44; <span class="elsevierStyleGrantNumber" refid="gs0010">PI18&#47;00362</span>&#41; and &#40;<span class="elsevierStyleGrantSponsor" id="gs0015">AGAUR</span><span class="elsevierStyleGrantNumber" refid="gs0015">2014&#47;SGR-1441</span>&#41;&#46;</p></span><span id="sec0200" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0220">Conflicts of interest</span><p id="par0775" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:16 [
        0 => array:3 [
          "identificador" => "xres1337897"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1231798"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1337896"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1231797"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Angiomyolipomas"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Introduction"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Diagnosis"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Differential diagnosis"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Follow-up"
            ]
            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Initial assessment of a patient with tuberous sclerosis complex consulting because of angiomyolipomas"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        7 => array:3 [
          "identificador" => "sec0050"
          "titulo" => "Radiological follow-up of renal involvement in tuberous sclerosis complex"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        8 => array:3 [
          "identificador" => "sec0060"
          "titulo" => "Treatment of angiomyolipomas"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Emergency treatment"
            ]
            1 => array:3 [
              "identificador" => "sec0070"
              "titulo" => "Non-emergency treatment"
              "secciones" => array:5 [
                0 => array:2 [
                  "identificador" => "sec0075"
                  "titulo" => "Selective embolisation"
                ]
                1 => array:2 [
                  "identificador" => "sec0080"
                  "titulo" => "Cryoablation"
                ]
                2 => array:2 [
                  "identificador" => "sec0085"
                  "titulo" => "Radio-frequency or microwave"
                ]
                3 => array:2 [
                  "identificador" => "sec0090"
                  "titulo" => "Surgery"
                ]
                4 => array:2 [
                  "identificador" => "sec0095"
                  "titulo" => "Active surveillance"
                ]
              ]
            ]
            2 => array:2 [
              "identificador" => "sec0100"
              "titulo" => "Recommendations"
            ]
            3 => array:2 [
              "identificador" => "sec0105"
              "titulo" => "Long-term treatment&#58; mTOR inhibitors"
            ]
            4 => array:2 [
              "identificador" => "sec0110"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        9 => array:3 [
          "identificador" => "sec0115"
          "titulo" => "Renal cysts"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0120"
              "titulo" => "Diagnosis"
            ]
            1 => array:2 [
              "identificador" => "sec0125"
              "titulo" => "Differential diagnosis of complicated cysts"
            ]
            2 => array:2 [
              "identificador" => "sec0130"
              "titulo" => "Follow-up and treatment"
            ]
            3 => array:2 [
              "identificador" => "sec0135"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        10 => array:3 [
          "identificador" => "sec0140"
          "titulo" => "Contiguous gene syndrome TSC2&#47;PKD1"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0145"
              "titulo" => "Diagnosis"
            ]
            1 => array:2 [
              "identificador" => "sec0150"
              "titulo" => "Differential diagnosis"
            ]
            2 => array:2 [
              "identificador" => "sec0155"
              "titulo" => "Follow-up"
            ]
            3 => array:2 [
              "identificador" => "sec0160"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        11 => array:3 [
          "identificador" => "sec0165"
          "titulo" => "Hypertension in tuberous sclerosis complex"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0170"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        12 => array:3 [
          "identificador" => "sec0175"
          "titulo" => "Chronic renal failure in tuberous sclerosis complex"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0180"
              "titulo" => "Recommendations"
            ]
            1 => array:2 [
              "identificador" => "sec0185"
              "titulo" => "Multidisciplinary follow-up"
            ]
            2 => array:2 [
              "identificador" => "sec0190"
              "titulo" => "Recommendations"
            ]
          ]
        ]
        13 => array:2 [
          "identificador" => "sec0195"
          "titulo" => "Funding"
        ]
        14 => array:2 [
          "identificador" => "sec0200"
          "titulo" => "Conflicts of interest"
        ]
        15 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-04-23"
    "fechaAceptado" => "2019-07-15"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1231798"
          "palabras" => array:6 [
            0 => "Angiomyolipomas"
            1 => "Tuberous sclerosis"
            2 => "Polycystic kidney disease"
            3 => "Contiguous gene syndrome"
            4 => "Cysts"
            5 => "mTOR protein"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1231797"
          "palabras" => array:6 [
            0 => "Angiomiolipomas"
            1 => "Esclerosis tuberosa"
            2 => "Enfermedad renal poliqu&#237;stica"
            3 => "S&#237;ndrome del gen contiguo"
            4 => "Quistes"
            5 => "Prote&#237;na mTOR"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Tuberous sclerosis complex &#40;TSC&#41; is a rare&#44; hereditary&#44; multisystemic disease with a broad phenotypic spectrum&#46; Its management requires the collaboration of multiple specialists&#46; Just as in the paediatric age&#44; the paediatric neurologist takes on special importance&#59; in adulthood&#44; renal involvement is the cause of the greatest morbidity and mortality&#46; There are several recommendations on the general management of patients with TSC but none that focuses on renal involvement&#46; These recommendations respond to the need to provide guidelines to facilitate a better knowledge and diagnostic-therapeutic management of the renal involvement of TSC through a rational use of complementary tests and the correct use of available treatments&#46; Their elaboration has been based on consensus within the hereditary renal diseases working group of the S&#46;E&#46;N&#46;&#47;REDINREN &#40;Spanish Society of Nephrology&#47;Kidney Research Network&#41;&#46; It has also counted on the participation of non-nephrologist specialists in TSC in order to expand the vision of the disease&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El complejo esclerosis tuberosa &#40;CET&#41; es una enfermedad rara&#44; hereditaria&#44; multisist&#233;mica y con un amplio espectro fenot&#237;pico&#46; Su manejo requiere de la colaboraci&#243;n de m&#250;ltiples especialistas&#46; As&#237; como en la edad pedi&#225;trica cobra un especial relieve el neur&#243;logo pediatra&#44; en la edad adulta la afectaci&#243;n renal es la causante de la mayor morbimortalidad&#46; Existen diversas recomendaciones sobre el manejo general del paciente con CET pero ninguna que se centre en la afectaci&#243;n renal&#46; Las presentes recomendaciones responden a la necesidad de proporcionar pautas para facilitar un mejor conocimiento y manejo diagn&#243;stico-terap&#233;utico de la afectaci&#243;n renal del CET mediante un uso racional de las pruebas complementarias y el empleo correcto de los tratamientos disponibles&#46; Su elaboraci&#243;n se ha basado en el consenso dentro del grupo de trabajo de enfermedades renales hereditarias de la S&#46;E&#46;N&#46;&#47;REDINREN&#46; Ha contado con la participaci&#243;n de especialistas en CET no nefr&#243;logos tambi&#233;n con el fin de ampliar la visi&#243;n de la enfermedad&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Ariceta G&#44; Buj MJ&#44; Furlano M&#44; Mart&#237;nez V&#44; Matamala A&#44; Morales M&#44; et al&#46; Recomendaciones de manejo de la afectaci&#243;n renal en el complejo esclerosis tuberosa&#46; Nefrologia&#46; 2020&#59;40&#58;142&#8211;151&#46;</p>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0220"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sporadic AML &#40;80&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AML associated with TSC &#40;20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age of onset&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4th-5th decade of life&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2nd&#8211;3rd decade &#40;even in the first year of life&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gender&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">More common in females &#40;2&#58;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Male and female &#40;slight predominance in females&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Solitary and unilateral&#46; Smaller&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Multiple and bilateral&#46; Larger&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Growth&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Slow&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rapid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Likelihood of bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Low&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">High &#40;especially if &#62;4<span class="elsevierStyleHsp" style=""></span>cm or microaneurysms &#62;5<span class="elsevierStyleHsp" style=""></span>mm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Malignant transformation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Very rare&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rare &#40;happens in epithelioid AML&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2294125.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Differential characteristics between sporadic AML and AML associated with TSC&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0225"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Adapted from Buj Pradilla et al&#46;&#44; 2017&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">TIPO de AML</span></th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleBold">DIAGN&#211;STICO DIFERENCIAL</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AML Cl&#225;sico&#40;rico en grasa&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0005" class="elsevierStylePara elsevierViewall">Carcinoma renal de c&#233;lulas claras &#40;puede presentar&#58; calcio&#44; halo hipoecoico y quistes intratumorales&#59; mientras que AML en ecograf&#237;a&#58; hiperecog&#233;nico y con sombra ac&#250;stica&#41;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0010" class="elsevierStylePara elsevierViewall">Lipomas y Liposarcomas retroperitoneales &#40;se diferencian porque son masas no dependientes del ri&#241;&#243;n&#44; por tanto puede ser &#250;til identificar origen de la arteria nutricia&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0015" class="elsevierStylePara elsevierViewall">Otros&#58; Tumor de Wilms&#44; Teratoma</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="4" align="left" valign="middle"><span class="elsevierStyleBold">AML At&#237;pico &#40;pobre en grasa&#41;&#46;</span>RMN&#58; en T2 es hipointenso</td><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AML Hiperatenuante</span>&#40;mayor componente muscular&#41;<span class="elsevierStyleItalic">TAC hiperatenuante</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0020" class="elsevierStylePara elsevierViewall">Tumores renales papilares</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0025" class="elsevierStylePara elsevierViewall">Oncocitoma</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0030" class="elsevierStylePara elsevierViewall">Met&#225;stasis</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0035" class="elsevierStylePara elsevierViewall">Otros&#58; linfoma&#44; adenoma metan&#233;frico&#44; leiomioma</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AML Isoatenuante</span><span class="elsevierStyleItalic">TAC&#58; isoatenuante</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall">Tumor renal papilar &#40;es de realce tard&#237;o&#44; mientras que AML de realce precoz&#41;</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AML con Quistes epiteliales</span>&#40;grasa inexistente&#41;<span class="elsevierStyleItalic">TAC&#58; hiperdenso</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0045" class="elsevierStylePara elsevierViewall">C&#225;ncer renal multiqu&#237;stico</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">Quiste multiloculado</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Nefroma qu&#237;stico</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Tumor mixto epitelial y estromal</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">AML Epiteloide</span>&#40;puede malignizarse&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">Tumor sarcomatoide</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">Carcinoma de c&#233;lulas claras de alto grado</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2294126.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Types of AML and differential diagnosis&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:48 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tuberous sclerosis complex&#46; GeneReviews&#174;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "H&#46; Northrup"
                            1 => "M&#46;K&#46; Koenig"
                            2 => "D&#46;A&#46; Pearson"
                            3 => "K&#46;S&#46; Au"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "1993"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;www&#46;ncbi&#46;nlm&#46;nih&#46;gov&#47;pubmed&#47;20301399"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tuberous sclerosis complex diagnostic criteria update&#58; recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H&#46; Northrup"
                            1 => "D&#46;A&#46; Krueger"
                            2 => "International Tuberous Sclerosis Complex Consensus Group"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pediatrneurol.2013.08.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Neurol&#46;"
                        "fecha" => "2013"
                        "volumen" => "49"
                        "paginaInicial" => "243"
                        "paginaFinal" => "254"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24053982"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tuberous sclerosis complex surveillance and management&#58; recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "D&#46;A&#46; Krueger"
                            1 => "H&#46; Northrup"
                            2 => "International Tuberous Sclerosis Complex Consensus Group"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pediatrneurol.2013.08.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Neurol&#46;"
                        "fecha" => "2013"
                        "volumen" => "49"
                        "paginaInicial" => "255"
                        "paginaFinal" => "265"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24053983"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recommendations for the multidisciplinary management of tuberous sclerosis complex"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Macaya"
                            1 => "R&#46; Torra"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Med Clin &#40;Barc&#41;&#46;"
                        "fecha" => "2016"
                        "volumen" => "147"
                        "paginaInicial" => "211"
                        "paginaFinal" => "216"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PEComas&#58; the past&#44; the present and the future"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "G&#46; Martignoni"
                            1 => "M&#46; Pea"
                            2 => "D&#46; Reghellin"
                            3 => "G&#46; Zamboni"
                            4 => "F&#46; Bonetti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00428-007-0509-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Virchows Arch&#46;"
                        "fecha" => "2008"
                        "volumen" => "452"
                        "paginaInicial" => "119"
                        "paginaFinal" => "132"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18080139"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal manifestation of tuberous sclerosis complex"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;J&#46; Bissler"
                            1 => "J&#46; Christopher Kingswood"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ajmg.c.31654"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med Genet C Semin Med Genet&#46;"
                        "fecha" => "2018"
                        "volumen" => "178"
                        "paginaInicial" => "338"
                        "paginaFinal" => "347"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30307110"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal manifestations of tuberous sclerosis complex&#58; incidence&#44; prognosis&#44; and predictive factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46;K&#46; Rakowski"
                            1 => "E&#46;B&#46; Winterkorn"
                            2 => "E&#46; Paul"
                            3 => "D&#46;J&#46;R&#46; Steele"
                            4 => "E&#46;F&#46; Halpern"
                            5 => "E&#46;A&#46; Thiele"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/sj.ki.5001853"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int&#46;"
                        "fecha" => "2006"
                        "volumen" => "70"
                        "paginaInicial" => "1777"
                        "paginaFinal" => "1782"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17003820"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal angiomyolipomata"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;J&#46; Bissler"
                            1 => "J&#46;C&#46; Kingswood"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1523-1755.2004.00838.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2004"
                        "volumen" => "66"
                        "paginaInicial" => "924"
                        "paginaFinal" => "934"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15327383"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term clinical morbidity in patients with renal angiomyolipoma associated with tuberous sclerosis complex"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Bissler"
                            1 => "K&#46; Cappell"
                            2 => "H&#46; Charles"
                            3 => "X&#46; Song"
                            4 => "Z&#46; Liu"
                            5 => "J&#46; Prestifilippo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.urology.2016.04.027"
                      "Revista" => array:6 [
                        "tituloSerie" => "Urology&#46;"
                        "fecha" => "2016"
                        "volumen" => "95"
                        "paginaInicial" => "80"
                        "paginaFinal" => "87"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27132503"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term follow-up assessing renal angiomyolipoma treatment patterns&#44; morbidity&#44; and mortality&#58; an observational study in tuberous sclerosis complex patients in the Netherlands"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;J&#46;C&#46; Eijkemans"
                            1 => "W&#46; van der Wal"
                            2 => "L&#46;J&#46; Reijnders"
                            3 => "K&#46;C&#46;B&#46; Roes"
                            4 => "S&#46;B&#46; van Waalwijk van Doorn-Khosrovani"
                            5 => "C&#46; Pelletier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.ajkd.2015.05.016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Kidney Dis&#46;"
                        "fecha" => "2015"
                        "volumen" => "66"
                        "paginaInicial" => "638"
                        "paginaFinal" => "645"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26165440"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Natural history of patients with tuberous sclerosis complex related renal angiomyolipoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "X&#46; Song"
                            1 => "Z&#46; Liu"
                            2 => "K&#46; Cappell"
                            3 => "C&#46; Gregory"
                            4 => "Q&#46; Said"
                            5 => "J&#46; Prestifilippo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/03007995.2017.1313726"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Med Res Opin&#46;"
                        "fecha" => "2017"
                        "volumen" => "33"
                        "paginaInicial" => "1277"
                        "paginaFinal" => "1282"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28358266"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Natural history of renal angiomyolipoma &#40;AML&#41;&#58; most patients with large AMLs &#62;4 cm can be offered active surveillance as an initial management strategy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;R&#46; Bhatt"
                            1 => "P&#46;O&#46; Richard"
                            2 => "N&#46;S&#46; Kim"
                            3 => "A&#46; Finelli"
                            4 => "K&#46; Manickavachagam"
                            5 => "L&#46; Legere"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.eururo.2016.01.048"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Urol&#46;"
                        "fecha" => "2016"
                        "volumen" => "70"
                        "paginaInicial" => "85"
                        "paginaFinal" => "90"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26873836"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal angiomyolipoma&#58; clinicopathologic study of 194 cases with emphasis on the epithelioid histology and tuberous sclerosis association"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46; Aydin"
                            1 => "C&#46; Magi-Galluzzi"
                            2 => "B&#46;R&#46; Lane"
                            3 => "L&#46; Sercia"
                            4 => "J&#46;I&#46; Lopez"
                            5 => "B&#46;I&#46; Rini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/PAS.0b013e31817ed7a6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Surg Pathol&#46;"
                        "fecha" => "2009"
                        "volumen" => "33"
                        "paginaInicial" => "289"
                        "paginaFinal" => "297"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18852677"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recommendations for imaging-based diagnosis and management of renal angiomyolipoma associated with tuberous sclerosis complex"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;J&#46; Buj Pradilla"
                            1 => "T&#46; Marti Balleste"
                            2 => "R&#46; Torra"
                            3 => "F&#46; Villacampa Auba"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ckj/sfx094"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Kidney J&#46;"
                        "fecha" => "2017"
                        "volumen" => "10"
                        "paginaInicial" => "728"
                        "paginaFinal" => "737"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29225800"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CT and MR imaging for evaluation of cystic renal lesions and diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;G&#46; Wood 3rd"
                            1 => "L&#46;J&#46; Stromberg 3rd"
                            2 => "C&#46;B&#46; Harmath"
                            3 => "J&#46;M&#46; Horowitz"
                            4 => "C&#46; Feng"
                            5 => "N&#46;A&#46; Hammond"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1148/rg.351130016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Radiographics&#46;"
                        "fecha" => "2015"
                        "volumen" => "35"
                        "paginaInicial" => "125"
                        "paginaFinal" => "141"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25590393"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of T2-weighted MRI with and without fat suppression for differentiating renal angiomyolipomas without visible fat from other renal tumors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;S&#46; Chung"
                            1 => "H&#46;J&#46; Choi"
                            2 => "M&#46;-H&#46; Kim"
                            3 => "K&#46;-S&#46; Cho"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2214/AJR.13.11058"
                      "Revista" => array:6 [
                        "tituloSerie" => "AJR Am J Roentgenol&#46;"
                        "fecha" => "2014"
                        "volumen" => "202"
                        "paginaInicial" => "765"
                        "paginaFinal" => "771"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24660704"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Angiomyolipoma with minimal fat&#58; can it be differentiated from clear cell renal cell carcinoma by using standard mr techniques&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Hindman"
                            1 => "L&#46; Ngo"
                            2 => "E&#46;M&#46; Genega"
                            3 => "J&#46; Melamed"
                            4 => "J&#46; Wei"
                            5 => "J&#46;M&#46; Braza"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1148/radiol.12112087"
                      "Revista" => array:6 [
                        "tituloSerie" => "Radiology"
                        "fecha" => "2012"
                        "volumen" => "265"
                        "paginaInicial" => "468"
                        "paginaFinal" => "477"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23012463"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tuberose sclerosis complex&#58; analysis of growth rates aids differentiation of renal cell carcinoma from atypical or minimal-fat-containing angiomyolipoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "U&#46; Patel"
                            1 => "E&#46; Simpson"
                            2 => "J&#46;C&#46; Kingswood"
                            3 => "A&#46;K&#46; Saggar-Malik"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.crad.2005.01.009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Radiol&#46;"
                        "fecha" => "2005"
                        "volumen" => "60"
                        "paginaInicial" => "665"
                        "paginaFinal" => "673"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16038693"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal masses in the adult patient&#58; the role of percutaneous biopsy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46;G&#46; Silverman"
                            1 => "Y&#46;U&#46; Gan"
                            2 => "K&#46;J&#46; Mortele"
                            3 => "K&#46; Tuncali"
                            4 => "E&#46;S&#46; Cibas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1148/radiol.2401050061"
                      "Revista" => array:6 [
                        "tituloSerie" => "Radiology&#46;"
                        "fecha" => "2006"
                        "volumen" => "240"
                        "paginaInicial" => "6"
                        "paginaFinal" => "22"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16709793"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Annual review of children with tuberous sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "K&#46;H&#46; Ng"
                            1 => "S&#46;M&#46; Ng"
                            2 => "A&#46; Parker"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/archdischild-2013-304948"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Dis Child - Educ Pract Ed&#46;"
                        "fecha" => "2015"
                        "volumen" => "100"
                        "paginaInicial" => "114"
                        "paginaFinal" => "121"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25112285"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Review of the tuberous sclerosis renal guidelines from the 2012 consensus conference&#58; current data and future study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;C&#46; Kingswood"
                            1 => "J&#46;J&#46; Bissler"
                            2 => "K&#46; Budde"
                            3 => "J&#46; Hulbert"
                            4 => "L&#46; Guay-Woodford"
                            5 => "J&#46;R&#46; Sampson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000448293"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephron"
                        "fecha" => "2016"
                        "volumen" => "134"
                        "paginaInicial" => "51"
                        "paginaFinal" => "58"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27504842"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Transarterial embolization of angiomyolipoma&#58; a systematic review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T&#46;E&#46; Murray"
                            1 => "F&#46; Doyle"
                            2 => "M&#46; Lee"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.juro.2015.04.081"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Urol&#46;"
                        "fecha" => "2015"
                        "volumen" => "194"
                        "paginaInicial" => "635"
                        "paginaFinal" => "639"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25916674"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcomes of angioembolization and nephrectomy for renal angiomyolipoma associated with tuberous sclerosis complex&#58; a real-world US national study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; Sun"
                            1 => "J&#46; Liu"
                            2 => "H&#46; Charles"
                            3 => "J&#46; Hulbert"
                            4 => "J&#46; Bissler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/03007995.2017.1286307"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Med Res Opin&#46;"
                        "fecha" => "2017"
                        "volumen" => "33"
                        "paginaInicial" => "821"
                        "paginaFinal" => "827"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28112545"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of interventional radiology techniques in the management of renal angiomyolipomas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46;M&#46; Kiefer"
                            1 => "S&#46;W&#46; Stavropoulos"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s11934-017-0687-6"
                      "Revista" => array:5 [
                        "tituloSerie" => "Curr Urol Rep&#46;"
                        "fecha" => "2017"
                        "volumen" => "18"
                        "paginaInicial" => "36"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28299630"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal angiomyolipoma and lymphangioleiomyomatosis in pregnancy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; Iruloh"
                            1 => "R&#46; Keriakos"
                            2 => "D&#46;J&#46; Smith"
                            3 => "T&#46; Cleveland"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Obstet Gynaecol &#40;Lahore&#41;&#46;"
                        "fecha" => "2013"
                        "volumen" => "33"
                        "paginaInicial" => "542"
                        "paginaFinal" => "546"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characterization of Fabry disease in 352 pediatric patients in the Fabry Registry"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;J&#46; Hopkin"
                            1 => "J&#46; Bissler"
                            2 => "M&#46; Banikazemi"
                            3 => "L&#46; Clarke"
                            4 => "C&#46;M&#46; Eng"
                            5 => "D&#46;P&#46; Germain"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1203/PDR.0b013e318183f132"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Res&#46;"
                        "fecha" => "2008"
                        "volumen" => "64"
                        "paginaInicial" => "550"
                        "paginaFinal" => "555"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18596579"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Selective arterial embolization of angiomyolipomas&#58; a comparison of smaller and larger embolic agents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;D&#46; Villalta"
                            1 => "M&#46;D&#46; Sorensen"
                            2 => "J&#46;C&#46; Durack"
                            3 => "R&#46;K&#46; Kerlan"
                            4 => "M&#46;L&#46; Stoller"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.juro.2011.04.082"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Urol&#46;"
                        "fecha" => "2011"
                        "volumen" => "186"
                        "paginaInicial" => "921"
                        "paginaFinal" => "927"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21791345"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Percutaneous renal cryoablation of angiomyolipomas in patients with solitary kidneys"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46;C&#46; Johnson"
                            1 => "S&#46; Graham"
                            2 => "H&#46; D&#8217;Agostino"
                            3 => "D&#46;A&#46; Elmajian"
                            4 => "W&#46;B&#46; Shingleton"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.urology.2008.09.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Urology&#46;"
                        "fecha" => "2009"
                        "volumen" => "74"
                        "paginaInicial" => "1246"
                        "paginaFinal" => "1249"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19815260"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rates of interventional procedures in patients with tuberous sclerosis complex-related renal angiomyolipoma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Bissler"
                            1 => "K&#46; Cappell"
                            2 => "H&#46; Charles"
                            3 => "X&#46; Song"
                            4 => "Z&#46; Liu"
                            5 => "J&#46; Prestifilippo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1185/03007995.2015.1060212"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Med Res Opin&#46;"
                        "fecha" => "2015"
                        "volumen" => "31"
                        "paginaInicial" => "1501"
                        "paginaFinal" => "1507"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26073843"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ultrasound-guided percutaneous microwave ablation of sporadic renal angiomyolipoma&#58; preliminary results"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "Z&#46; Han"
                            1 => "P&#46; Liang"
                            2 => "X&#46; Yu"
                            3 => "Z&#46; Cheng"
                            4 => "F&#46; Liu"
                            5 => "J&#46; Yu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/0284185113519357"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Radiol&#46;"
                        "fecha" => "2015"
                        "volumen" => "56"
                        "paginaInicial" => "56"
                        "paginaFinal" => "62"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24526757"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis&#58; extension of a randomized controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;J&#46; Bissler"
                            1 => "J&#46;C&#46; Kingswood"
                            2 => "E&#46; Radzikowska"
                            3 => "B&#46;A&#46; Zonnenberg"
                            4 => "M&#46; Frost"
                            5 => "E&#46; Belousova"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfv249"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant&#46;"
                        "fecha" => "2016"
                        "volumen" => "31"
                        "paginaInicial" => "111"
                        "paginaFinal" => "119"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26156073"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Everolimus long-term use in patients with tuberous sclerosis complex&#58; Four-year update of the EXIST-2 study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;J&#46; Bissler"
                            1 => "J&#46;C&#46; Kingswood"
                            2 => "E&#46; Radzikowska"
                            3 => "B&#46;A&#46; Zonnenberg"
                            4 => "E&#46; Belousova"
                            5 => "M&#46;D&#46; Frost"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One"
                        "fecha" => "2017"
                        "volumen" => "12"
                        "paginaInicial" => "1"
                        "paginaFinal" => "16"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety considerations of mammalian target of rapamycin inhibitors in tuberous sclerosis complex and renal transplantation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;J&#46;G&#46; Somers"
                            1 => "E&#46; Paul"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jcph.428"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Pharmacol&#46;"
                        "fecha" => "2015"
                        "volumen" => "55"
                        "paginaInicial" => "368"
                        "paginaFinal" => "376"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25402866"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of everolimus on renal function in patients with tuberous sclerosis complex&#58; evidence from EXIST-1 and EXIST-2"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;J&#46; Bissler"
                            1 => "K&#46; Budde"
                            2 => "M&#46; Sauter"
                            3 => "D&#46;N&#46; Franz"
                            4 => "B&#46;A&#46; Zonnenberg"
                            5 => "M&#46;D&#46; Frost"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfy132"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant&#46;"
                        "fecha" => "2019"
                        "volumen" => "34"
                        "paginaInicial" => "1000"
                        "paginaFinal" => "1008"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30053159"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Everolimus-induced hematologic changes in patients with metastatic breast cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Chen"
                            1 => "L&#46; Chen"
                            2 => "A&#46; Al-Qaisi"
                            3 => "E&#46; Romond"
                            4 => "M&#46; Awasthi"
                            5 => "V&#46; Kadamyan-Melkumyan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clbc.2014.07.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Breast Cancer&#46;"
                        "fecha" => "2015"
                        "volumen" => "15"
                        "paginaInicial" => "48"
                        "paginaFinal" => "53"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25199576"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Strategies for the management of adverse events associated with mTOR inhibitors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "B&#46; Kaplan"
                            1 => "Y&#46; Qazi"
                            2 => "J&#46;R&#46; Wellen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Transplant Rev&#46;"
                        "fecha" => "2014"
                        "volumen" => "28"
                        "paginaInicial" => "126"
                        "paginaFinal" => "133"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Practical management of everolimus-related toxicities in patients with advanced solid tumors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46; Gr&#252;nwald"
                            1 => "S&#46; Weikert"
                            2 => "M&#46;E&#46; Pavel"
                            3 => "D&#46; H&#246;rsch"
                            4 => "D&#46; L&#252;ftner"
                            5 => "W&#46; Janni"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000350625"
                      "Revista" => array:6 [
                        "tituloSerie" => "Onkologie&#46;"
                        "fecha" => "2013"
                        "volumen" => "36"
                        "paginaInicial" => "295"
                        "paginaFinal" => "302"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23689226"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 mg tablets&#58; a randomized&#44; open-label&#44; two-way crossover study of healthy volunteers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "K&#46; Thudium"
                            1 => "J&#46; Gallo"
                            2 => "E&#46; Bouillaud"
                            3 => "C&#46; Sachs"
                            4 => "S&#46; Eddy"
                            5 => "W&#46; Cheung"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2147/CPAA.S73472"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Pharmacol&#46;"
                        "fecha" => "2015"
                        "volumen" => "7"
                        "paginaInicial" => "11"
                        "paginaFinal" => "17"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25653564"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2&#44; compared with TSC1&#44; disease in multiple organs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46;L&#46; Dabora"
                            1 => "S&#46; Jozwiak"
                            2 => "D&#46;N&#46; Franz"
                            3 => "P&#46;S&#46; Roberts"
                            4 => "A&#46; Nieto"
                            5 => "J&#46; Chung"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/316951"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hum Genet&#46;"
                        "fecha" => "2001"
                        "volumen" => "68"
                        "paginaInicial" => "64"
                        "paginaFinal" => "80"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11112665"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease&#8211;a contiguous gene syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;T&#46; Brook-Carter"
                            1 => "B&#46; Peral"
                            2 => "C&#46;J&#46; Ward"
                            3 => "P&#46; Thompson"
                            4 => "J&#46; Hughes"
                            5 => "M&#46;M&#46; Maheshwar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ng1294-328"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Genet&#46;"
                        "fecha" => "1994"
                        "volumen" => "8"
                        "paginaInicial" => "328"
                        "paginaFinal" => "332"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7894481"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease&#58; a contiguous gene syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46;J&#46; Back"
                            1 => "S&#46; Andronikou"
                            2 => "T&#46; Kilborn"
                            3 => "B&#46;S&#46; Kaplan"
                            4 => "K&#46; Darge"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00247-014-3147-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Radiol&#46;"
                        "fecha" => "2015"
                        "volumen" => "45"
                        "paginaInicial" => "386"
                        "paginaFinal" => "395"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25355409"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Imaging of kidney cysts and cystic kidney diseases in children&#58; an international working group consensus statement"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Gimpel"
                            1 => "E&#46;F&#46; Avni"
                            2 => "L&#46; Breysem"
                            3 => "K&#46; Burgmaier"
                            4 => "A&#46; Caroli"
                            5 => "M&#46; Cetiner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1148/radiol.2018181243"
                      "Revista" => array:6 [
                        "tituloSerie" => "Radiology&#46;"
                        "fecha" => "2019"
                        "volumen" => "290"
                        "paginaInicial" => "769"
                        "paginaFinal" => "782"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30599104"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early manifestations of renal disease in patients with tuberous sclerosis complex"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Malaga-Dieguez"
                            1 => "R&#46; Spencer"
                            2 => "L&#46;J&#46; Pehrson"
                            3 => "S&#46; Vento"
                            4 => "K&#46; Menzer"
                            5 => "O&#46; Devinsky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Int J Nephrol Renovasc Dis&#46;"
                        "fecha" => "2017"
                        "paginaInicial" => "91"
                        "paginaFinal" => "95"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2013 ESH&#47;ESC Practice guidelines for the management of arterial hypertension"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Mancia"
                            1 => "R&#46; Fagard"
                            2 => "K&#46; Narkiewicz"
                            3 => "J&#46; Redon"
                            4 => "A&#46; Zanchetti"
                            5 => "M&#46; B&#246;hm"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3109/08037051.2014.868629"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood Press"
                        "fecha" => "2014"
                        "volumen" => "23"
                        "paginaInicial" => "3"
                        "paginaFinal" => "16"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24359485"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical practice guideline for screening and management of high blood pressure in children and adolescents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;T&#46; Flynn"
                            1 => "D&#46;C&#46; Kaelber"
                            2 => "C&#46;M&#46; Baker-Smith"
                            3 => "D&#46; Blowey"
                            4 => "A&#46;E&#46; Carroll"
                            5 => "S&#46;R&#46; Daniels"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1542/peds.2017-0685"
                      "Revista" => array:4 [
                        "tituloSerie" => "Pediatrics&#46;"
                        "fecha" => "2017"
                        "volumen" => "140"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28924060"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evidence for pericyte origin of TSC-associated renal angiomyolipomas and implications for angiotensin receptor inhibition therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;J&#46; Siroky"
                            1 => "H&#46; Yin"
                            2 => "B&#46;P&#46; Dixon"
                            3 => "R&#46;J&#46; Reichert"
                            4 => "A&#46;R&#46; Hellmann"
                            5 => "T&#46; Ramkumar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajprenal.00569.2013"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Renal Physiol&#46;"
                        "fecha" => "2014"
                        "volumen" => "307"
                        "paginaInicial" => "F560"
                        "paginaFinal" => "70"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24920756"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased incidence of angioedema with ACE inhibitors in combination with mTOR inhibitors in kidney transplant recipients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Duerr"
                            1 => "P&#46; Glander"
                            2 => "F&#46; Diekmann"
                            3 => "D&#46; Dragun"
                            4 => "H&#46;H&#46; Neumayer"
                            5 => "K&#46; Budde"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2215/CJN.07371009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin J Am Soc Nephrol&#46;"
                        "fecha" => "2010"
                        "volumen" => "5"
                        "paginaInicial" => "703"
                        "paginaFinal" => "708"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20093343"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Angioedema induced by angiotensin converting enzyme inhibitors&#44; potentiated by m-TOR inhibitors&#58; successful treatment with icatibant"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46; Charmillon"
                            1 => "J&#46; Deibener"
                            2 => "P&#46; Kaminsky"
                            3 => "G&#46; Louis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-014-3290-z"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med&#46;"
                        "fecha" => "2014"
                        "volumen" => "40"
                        "paginaInicial" => "893"
                        "paginaFinal" => "894"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24737261"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/20132514/0000004000000002/v1_202005210712/S2013251420300407/v1_202005210712/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "42660"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/20132514/0000004000000002/v1_202005210712/S2013251420300407/v1_202005210712/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251420300407?idApp=UINPBA000064"
]

Article information

ISSN: 20132514
Original language: English

DOI:10.1016/j.nefroe.2020.03.009

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	14	13	27
2024 October	63	67	130
2024 September	52	43	95
2024 August	59	85	144
2024 July	47	42	89
2024 June	64	57	121
2024 May	65	64	129
2024 April	51	45	96
2024 March	54	38	92
2024 February	46	40	86
2024 January	39	32	71
2023 December	43	42	85
2023 November	95	58	153
2023 October	138	62	200
2023 September	166	38	204
2023 August	52	28	80
2023 July	68	61	129
2023 June	65	32	97
2023 May	80	55	135
2023 April	55	41	96
2023 March	61	29	90
2023 February	59	22	81
2023 January	39	39	78
2022 December	88	36	124
2022 November	62	48	110
2022 October	85	60	145
2022 September	50	69	119
2022 August	53	39	92
2022 July	45	45	90
2022 June	61	56	117
2022 May	57	48	105
2022 April	68	51	119
2022 March	75	72	147
2022 February	143	59	202
2022 January	111	56	167
2021 December	65	53	118
2021 November	118	57	175
2021 October	142	76	218
2021 September	369	64	433
2021 August	120	64	184
2021 July	137	55	192
2021 June	71	30	101
2021 May	75	70	145
2021 April	450	96	546
2021 March	136	68	204
2021 February	58	37	95
2021 January	80	40	120
2020 December	78	25	103
2020 November	40	28	68
2020 October	40	22	62
2020 September	36	25	61
2020 August	73	29	102
2020 July	43	27	70
2020 June	34	26	60
2020 May	44	27	71
2020 April	51	40	91

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter