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La extensi&#243;n de las lesiones glomerulares e intersticiales tiene valor pron&#243;stico en enfermos no tratados&#44; pero no en enfermos que han recibido tratamiento con glucocorticoides u otros inmunomoduladores<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">6</span></a>&#46; En la actualidad&#44; se acepta que&#44; tras el dep&#243;sito mesangial de IgA&#44; la lesi&#243;n renal se inicia a trav&#233;s de la activaci&#243;n del complemento por la v&#237;a alternativa&#44; por la v&#237;a de las lectinas o por ambas<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a>&#46; Este proceso resulta en la generaci&#243;n de diversas citocinas y factores de crecimiento que act&#250;an como mediadores del da&#241;o renal&#44; estimulando la proliferaci&#243;n celular y el aumento en la producci&#243;n de la matriz mesangial<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">7&#44;8</span></a>&#46; Hay tambi&#233;n datos que indican que las citocinas producidas por la c&#233;lula mesangial pueden inducir alteraciones en la estructura y funci&#243;n de los podocitos y de las c&#233;lulas del t&#250;bulo proximal&#44; que se relacionan con la aparici&#243;n de lesiones de glomeruloesclerosis y de fibrosis intersticial<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">9&#8211;11</span></a>&#46; De las diferentes mol&#233;culas potencialmente implicadas&#44; la interleucina-6 &#40;IL-6&#41;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">12&#8211;15</span></a>&#44; el factor de crecimiento epid&#233;rmico &#40;EGF&#41;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">16&#8211;18</span></a>&#44; la prote&#237;na quimioatractante de monocitos de tipo 1 &#40;MCP-1&#41;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">19&#8211;23</span></a> y el factor de crecimiento transformante &#946;1 &#40;TGF&#946;1&#41;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a> han sido objeto de estudios detallados&#46; Los datos disponibles demuestran una correlaci&#243;n significativa entre la excreci&#243;n urinaria y la expresi&#243;n renal de IL-6<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">15</span></a> y de EGF<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">15</span></a> y de una correlaci&#243;n significativa entre los niveles urinarios de IL-6<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">15&#44;16</span></a>&#44; EGF<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">15&#44;17&#44;18</span></a>&#44; MCP-1<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">22&#44;23</span></a> y TGF&#946;1<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a> y la extensi&#243;n de las lesiones de fibrosis intersticial y atrofia tubular&#46; Estos datos se&#241;alan que el nivel urinario de estas citocinas y factores de crecimiento podr&#237;a proporcionar informaci&#243;n funcional sobre la patogenia de la lesi&#243;n renal o ser biomarcadores indirectos de la extensi&#243;n de la fibrosis glomerular e intersticial&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Tres estudios independientes han demostrado que la medici&#243;n de la excreci&#243;n urinaria de algunas de estas mol&#233;culas podr&#237;a tener valor pron&#243;stico en la nefropat&#237;a IgA<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">15&#44;17&#44;18</span></a>&#46; En concreto&#44; se ha descrito que el cociente IL-6&#47;EGF<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">15</span></a> podr&#237;a ser un indicador de la progresi&#243;n hacia la fibrosis renal y que la relaci&#243;n MCP-1&#47;EGF identificar&#237;a&#44; en el momento del diagn&#243;stico&#44; a los pacientes con mayor riesgo de progresi&#243;n a la insuficiencia cr&#243;nica renal&#44; con independencia de la funci&#243;n renal y de la proteinuria inicial<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">17&#44;18</span></a>&#46; Por otra parte&#44; el potencial valor pron&#243;stico de la excreci&#243;n urinaria de EGF tambi&#233;n se ha puesto de manifiesto en un reciente estudio que la identific&#243; como predictor de progresi&#243;n independiente en 3<span class="elsevierStyleHsp" style=""></span>cohortes de enfermos con enfermedades glomerulares<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">25</span></a>&#46; Estos datos indican que la medici&#243;n de la excreci&#243;n urinaria de uno o varios de estos biomarcadores podr&#237;a tener utilidad en la pr&#225;ctica cl&#237;nica&#46; Sin embargo&#44; hasta la fecha&#44; no se ha realizado ning&#250;n estudio comparativo para analizar cu&#225;l de ellos es el que se correlaciona mejor con las lesiones de fibrosis renal&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">El objetivo del presente estudio fue analizar las asociaciones entre el nivel urinario de IL-6&#44; EGF&#44; MCP-1 y TGF&#946;1 y las caracter&#237;sticas cl&#237;nicas&#44; bioqu&#237;micas y anatomopatol&#243;gicas en enfermos con nefropat&#237;a IgA primaria&#44; y cu&#225;les de estas mol&#233;culas permiten una estimaci&#243;n m&#225;s precisa de la extensi&#243;n de las lesiones de fibrosis glomerular o intersticial&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes y m&#233;todos</span><p id="par0020" class="elsevierStylePara elsevierViewall">Se estudi&#243; un total de 58 pacientes con nefropat&#237;a IgA idiop&#225;tica diagnosticada por biopsia renal&#46; En el momento de la biopsia renal y antes de iniciar cualquier tratamiento&#44; se registraron las variables demogr&#225;ficas y cl&#237;nicas&#44; se realizaron determinaciones de creatinina s&#233;rica&#44; filtrado glomerular estimado &#40;FGe&#41; mediante la ecuaci&#243;n CKD-EPI<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a>&#44; excreci&#243;n urinaria de sodio y cociente proteinuria&#47;creatinina y se obtuvieron muestras de orina de la segunda micci&#243;n de la ma&#241;ana para medir los niveles de IL-6&#44; EGF&#44; MCP-1 y TGF&#946;1&#46; En las muestras de orina&#44; se descart&#243; la presencia de piuria mediante estudio del sedimento urinario&#46; Las muestras de orina se centrifugaron a 1&#46;500<span class="elsevierStyleHsp" style=""></span>g durante 10&#160;min y se almacenaron a &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C hasta su procesamiento&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">En el momento de obtener las muestras de orina&#44; ning&#250;n paciente recib&#237;a tratamiento con bloqueadores de los receptores de la angiotensina II&#44; inhibidores de la ECA&#44; combinaciones de ambos ni con antagonistas de la aldosterona&#46; Ning&#250;n paciente fue tratado con esteroides ni otros medicamentos inmunosupresores y ning&#250;n paciente recibi&#243; paricalcitol&#46; La adecuaci&#243;n de la colecci&#243;n de 24<span class="elsevierStyleHsp" style=""></span>h se evalu&#243; mediante la comparaci&#243;n de la creatinina total en la muestra con la creatinina predicha&#58; 28<span class="elsevierStyleHsp" style=""></span>-<span class="elsevierStyleHsp" style=""></span> &#40;0&#44;2<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>edad&#41;<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>kg en hombres y 23&#44;8<span class="elsevierStyleHsp" style=""></span>-<span class="elsevierStyleHsp" style=""></span> &#40;0&#44;17<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>edad&#41;<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>kg en mujeres en mg&#47;d&#237;a<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">27</span></a>&#46; Los valores de creatinina se obtuvieron utilizando un compensado IDMS trazable &#40;Hitachi Modular P-800 Roche Diagnostics&#44; Berl&#237;n&#44; Alemania&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Los niveles de a EGF&#44; IL-6&#44; MCP-1 y TGF&#946;1 en orina se midieron mediante an&#225;lisis ELISA comerciales &#40;Quantikine R &#38; D Systems&#44; Minneapolis&#44; EE&#46;&#160;UU&#46;&#41; siguiendo las instrucciones del fabricante&#46; Para medir el TGF&#946;1 total &#40;latente<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>activo&#41;&#44; las muestras de orina se diluyeron con 4<span class="elsevierStyleHsp" style=""></span>vol&#250;menes de soluci&#243;n salina tamponada con fosfato y se a&#241;adi&#243; HCl hasta obtener un pH de 2&#44;5 a 2&#44;0&#46; Despu&#233;s de 30<span class="elsevierStyleHsp" style=""></span>min a temperatura ambiente&#44; el pH se reajust&#243; a 7&#44;4 con NaOH<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">28</span></a>&#46; Todos los an&#225;lisis se realizaron por duplicado y fueron calibrados con est&#225;ndares purificados y sueros de referencia de los fabricantes&#46; La precisi&#243;n intraan&#225;lisis se calcul&#243; realizando 10 determinaciones en la misma placa de 3 muestras con concentraciones conocidas y fueron &#60;5&#37; para todas las mol&#233;culas&#44; tanto a baja como a alta concentraci&#243;n&#46; La precisi&#243;n interan&#225;lisis se estudi&#243; con 10 determinaciones en distintas placas de 3 muestras con concentraciones conocidas&#44; que fueron &#60;6&#44;8&#37; para todas las mol&#233;culas&#44; tanto a bajas como a altas concentraciones&#46; Las concentraciones urinarias se ajustaron por concentraci&#243;n de creatinina y se expresaron en pg&#47;mg creatinina &#40;IL-6&#41; o ng&#47;mg de creatinina &#40;EGF&#44; MCP-1 y TGF&#223;1&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">El estudio se realiz&#243; siguiendo las normas de Helsinki&#44; fue aprobado por el Comit&#233; de &#201;tica del hospital y todos los pacientes firmaron un consentimiento informado&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Estudio anatomopatol&#243;gico de las biopsias renales</span><p id="par0040" class="elsevierStylePara elsevierViewall">El tejido renal se fij&#243; en parafina&#44; y se realizaron cortes de 4<span class="elsevierStyleHsp" style=""></span>&#956;m&#44; que se ti&#241;eron con hematoxilina-eosina&#44; tricr&#243;mico de Masson&#44; &#225;cido peri&#243;dico de Schiff y metenamina de Jones&#46; Los estudios de inmunofluorescencia se realizaron en muestras de tejido congeladas&#44; utilizando anticuerpos contra las inmunoglobulinas A&#44; G y M&#44; fibrin&#243;geno y C3&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">En las biopsias renales&#44; se contabiliz&#243; la proporci&#243;n de glom&#233;rulos con lesiones de proliferaci&#243;n mesangial y esclerosis segmentaria&#44; la presencia de proliferaci&#243;n intra- y extracapilar y la extensi&#243;n de la fibrosis intersticial mediante morfometr&#237;a cuantitativa&#44; utilizando un autoanalizador Olympus WCE2&#46; Las biopsias renales fueron&#44; adem&#225;s&#44; clasificadas siguiendo el documento de consenso internacional de Oxford 2009<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">29</span></a>&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">An&#225;lisis estad&#237;stico</span><p id="par0050" class="elsevierStylePara elsevierViewall">La comparaci&#243;n de 2<span class="elsevierStyleHsp" style=""></span>medias se realiz&#243; mediante la t de Student para datos independientes&#46; La comparaci&#243;n de proporciones se realiz&#243; mediante la prueba de chi cuadrado o el test exacto de Fischer&#46; Para el an&#225;lisis de correlaciones entre variables cuantitativas se utiliz&#243; el coeficiente de correlaci&#243;n de Pearson&#46; Con objeto de analizar la relaci&#243;n entre cada una de las mol&#233;culas estudiadas y la extensi&#243;n de las lesiones de la fibrosis glomerular e intersticial&#44; se realiz&#243; un an&#225;lisis univariado&#44; seguido de un an&#225;lisis de regresi&#243;n m&#250;ltiple paso a paso&#44; tomando la superficie de fibrosis como variable dependiente tras transformaci&#243;n logar&#237;tmica y tras comprobar de la normalidad de su distribuci&#243;n&#46; Asimismo&#44; se clasific&#243; a los pacientes en 2<span class="elsevierStyleHsp" style=""></span>grupos en funci&#243;n de la presencia &#40;T1<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>T2&#41; o la ausencia &#40;T0&#41; de lesiones de fibrosis intersticial en la clasificaci&#243;n de Oxford y&#44; tras un an&#225;lisis univariado de selecci&#243;n de variables&#44; se realiz&#243; un an&#225;lisis de regresi&#243;n log&#237;stica paso a paso&#44; con un m&#233;todo de introducci&#243;n manual&#44; basado en el cambio de &#8211;LR&#44; para identificar las variables independientemente asociadas a la presencia de fibrosis intersticial&#46; La calibraci&#243;n del modelo por categor&#237;as de riesgo se realiz&#243; mediante la prueba de Hosmer-Lemeshow<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">30</span></a>&#46; En todos los casos se consider&#243; estad&#237;sticamente significativo un valor de p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46; Para el an&#225;lisis estad&#237;stico se utiliz&#243; el programa SPSS versi&#243;n 20&#46;0&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><p id="par0055" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se resumen las caracter&#237;sticas cl&#237;nicas y anatomopatol&#243;gicas de la muestra de enfermos incluida en el estudio&#46; En la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a> se resume la matriz de correlaciones entre las variables analizadas en el estudio&#46; En lo que respecta a la relaci&#243;n con las variables histol&#243;gicas&#44; se apreci&#243; una asociaci&#243;n estad&#237;sticamente significativa entre los niveles de IL-6&#44; MCP-1 y TGF&#946;1 y la extensi&#243;n de la glomeruloesclerosis focal&#44; pero no con la presencia de proliferaci&#243;n intra- o extracapilar&#46; Asimismo&#44; se apreci&#243; una correlaci&#243;n positiva entre la extensi&#243;n de las lesiones de fibrosis intersticial y el nivel urinario de IL-6&#44; MCP-1 y TGF&#946;1 y negativa entre las lesiones de fibrosis intersticial y el nivel urinario de EGF&#46; Al categorizar a los enfermos seg&#250;n la clasificaci&#243;n de Oxford &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#44; no se apreciaron diferencias significativas en ninguna de las mol&#233;culas estudiadas en funci&#243;n de los criterios M&#44; E o S&#46; Los enfermos con <span class="elsevierStyleItalic">scores</span> de fibrosis intersticial T1 y T2 presentaron niveles significativamente superiores de IL-6&#44; MCP-1 y TGF&#946;1&#44; y niveles de EGF significativamente inferiores que los enfermos T0&#44; pero no se apreciaron diferencias significativas entre T1 y T2&#46; Se apreci&#243; una correlaci&#243;n significativa entre niveles urinarios de IL-6&#44; MCP-1&#44; TGF&#946;1 y proteinuria&#46; Los niveles de EGF solo tuvieron asociaci&#243;n con el grado de esclerosis intersticial y con el filtrado glomerular&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> se resumen los predictores independientes de la excreci&#243;n urinaria de cada una de las mol&#233;culas estudiadas en los an&#225;lisis de regresi&#243;n m&#250;ltiple y el porcentaje de la variabilidad de cada una de ellas explicada por el conjunto de variables independientes&#46; En todos los casos se aprecian asociaciones independientes y significativas con la superficie de fibrosis intersticial&#46; En el caso de la IL-6 y del TGF&#946;1&#44; se aprecian tambi&#233;n asociaciones significativas con la esclerosis glomerular y&#44; en el de la IL-6 y MCP-1&#44; con la proteinuria&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">En los an&#225;lisis de regresi&#243;n m&#250;ltiple para predecir la extensi&#243;n de las lesiones de fibrosis intersticial&#44; la mayor capacidad predictiva se apreci&#243; con los modelos que incluyeron la edad&#44; el FGe&#44; la MCP-1 y&#44; o bien la el EGF o bien la IL-6&#44; pero no ambos a la vez&#44; ya que entre ellos se detect&#243; colinealidad &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Al clasificar a los enfermos en 2<span class="elsevierStyleHsp" style=""></span>categor&#237;as en funci&#243;n de la presencia &#40;T1<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>T2&#41; o ausencia &#40;T0&#41; de fibrosis en las biopsias seg&#250;n la clasificaci&#243;n de Oxford&#44; en el an&#225;lisis de regresi&#243;n log&#237;stica se apreci&#243; que los predictores independientes de fibrosis fueron la edad&#44; el FGe&#44; la MCP-1 y el EGF &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">tabla 6</a>&#41;&#46; El modelo tuvo una buena capacidad predictiva con un &#225;rea bajo la curva de 0&#44;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;07 &#40;p&#58; 0&#44;0001&#41; y una buena calibraci&#243;n para todas las categor&#237;as de riesgo &#40;<a class="elsevierStyleCrossRef" href="#tbl0035">tabla 7</a>&#41;&#46; Los niveles de TGF&#946;1&#44; adem&#225;s de asociarse con la esclerosis glomerular y con la fibrosis intersticial&#44; tuvieron una asociaci&#243;n muy significativa con los de IL-6 y MCP-1&#46; La introducci&#243;n del nivel de TGF&#946;1 en los modelos&#44; manteniendo MCP-1 e IL-6&#44; caus&#243; colinealidad y&#44; al introducir el nivel de TGF&#946;1 en lugar del de MCP-1 o el de IL-6&#44; en los modelos tanto el de regresi&#243;n m&#250;ltiple como el de regresi&#243;n log&#237;stica perdieron capacidad predictiva de forma significativa&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="tbl0035"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discusi&#243;n</span><p id="par0075" class="elsevierStylePara elsevierViewall">Los resultados de nuestro estudio indican que&#44; en enfermos con nefropat&#237;a IgA&#44; el nivel urinario de IL-6&#44; EGF&#44; MCP-1 y TFG&#946;1 se correlaciona de forma significativa con el grado de esclerosis glomerular e intersticial observado en las biopsias renales&#44; pero no con las lesiones proliferativas intra- o extracapilares ni con el grado de proliferaci&#243;n mesangial&#46; Los niveles de dichas mol&#233;culas no permitieron diferenciar entre subgrupos de la clasificaci&#243;n de Oxford en cuanto al grado de proliferaci&#243;n mesangial&#44; proliferaci&#243;n intracapilar o esclerosis focal&#44; pero fueron significativamente distintos en los enfermos con estadios de fibrosis T1 y T2 con relaci&#243;n a T0&#46; En los modelos multivariados&#44; el mejor predictor de la superficie de fibrosis intersticial fue el filtrado glomerular&#44; pero los modelos que incluyeron FGe&#44; edad&#44; MCP-1 y EGF o IL-6 tuvieron capacidad predictiva significativamente superior&#44; por lo que aportan una informaci&#243;n adicional y m&#225;s precisa sobre la superficie de fibrosis intersticial&#46; Por otra parte&#44; en los modelos de regresi&#243;n log&#237;stica&#44; estas mismas variables tuvieron capacidad para identificar a los enfermos que presentaron niveles de fibrosis T1-T2 en las biopsias&#44; con alto poder predictivo y con buena discriminaci&#243;n para cualquier categor&#237;a de riesgo&#46; En conjunto&#44; estos datos indican que la informaci&#243;n que proporciona la medici&#243;n de la excreci&#243;n del nivel urinario de IL-6&#44; MCP-1 y EGF permite la estimaci&#243;n de la superficie de fibrosis de forma m&#225;s precisa que el filtrado glomerular de forma aislada y&#44; en consecuencia&#44; pueden aportar datos relevantes en la pr&#225;ctica cl&#237;nica&#46; Estudios previos&#44; combinando t&#233;cnicas de hibridaci&#243;n <span class="elsevierStyleItalic">in situ</span> e inmunohistoquimia&#44; han demostrado que&#44; en la nefropat&#237;a IgA&#44; la s&#237;ntesis de IL-6 est&#225; incrementada tanto en las c&#233;lulas mesangiales como en las c&#233;lulas del t&#250;bulo proximal y de las c&#233;lulas del infiltrado intersticial<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">13&#8211;15</span></a>&#46; El aumento en la expresi&#243;n de IL-6 se ha correlacionado con la extensi&#243;n de la fibrosis glomerular y con la de la fibrosis intersticial&#44; con o sin lesi&#243;n proliferativa mesangial<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">13&#8211;15</span></a>&#46; Los niveles de IL-6 urinarios observados en nuestros enfermos y su correlaci&#243;n con las lesiones de fibrosis intersticial concuerdan con los datos previamente publicados<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">12&#8211;15</span></a> y&#44; por tanto&#44; corroboran la idea de que su determinaci&#243;n podr&#237;a ser &#250;til como indicador de la severidad de las lesiones renales&#46; MCP-1<span class="elsevierStyleHsp" style=""></span>ha sido identificada como una de las mol&#233;culas directamente implicadas en el reclutamiento de c&#233;lulas inflamatorias al intersticio renal tanto en modelos experimentales como en diversas enfermedades glomerulares&#44; incluyendo la nefropat&#237;a IgA<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">20&#44;22</span></a>&#46; En nuestros enfermos&#44; MCP-1 se correlaciona con el filtrado glomerular y con la extensi&#243;n de la fibrosis e infiltrado intersticial y&#44; en menor grado&#44; con la proteinuria&#44; lo que coincide con los datos descritos en estudios previos<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">19&#8211;23</span></a>&#46; El TFG&#946;1 es considerado como uno de los moduladores claves en la reparaci&#243;n tras la lesi&#243;n&#46; Sin embargo&#44; un exceso de producci&#243;n se ha asociado a dep&#243;sito de col&#225;geno y cicatrizaci&#243;n<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">31&#44;32</span></a>&#46; En diversas glomerulopat&#237;as cr&#243;nicas&#44; se ha demostrado que la expresi&#243;n renal de TFG&#946;1 se encuentra incrementada y que los niveles urinarios de TFG&#946;1 reflejan su producci&#243;n local a nivel renal<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">24&#44;31</span></a>&#46; Los datos de nuestros enfermos coinciden con los previamente publicados en la nefropat&#237;a IgA&#44; en hallar una correlaci&#243;n entre los niveles urinarios de de TFG&#946;1 y en la severidad de las lesiones de esclerosis glomerular e intersticial&#46; En los enfermos estudiados&#44; los niveles de IL-6&#44; MCP-1 y TFG&#946;1&#44; adem&#225;s de estar correlacionados con la fibrosis glomerular e intersticial&#44; est&#225;n altamente correlacionados entre s&#237;&#44; lo que indica que probablemente reflejan aspectos de un proceso patog&#233;nico com&#250;n&#46; La elevada correlaci&#243;n entre el nivel de TFG&#946;1 y el de MCP-1 motiva que&#44; en los modelos predictivos&#44; la introducci&#243;n de ambas variables resulte en colinealidad y&#44; por ello&#44; no sea posible introducir m&#225;s que una de ellas&#46; Los diferentes modelos analizados tienen mayor poder predictivo y mejor calibraci&#243;n al introducir el nivel de MCP-1 que el de TFG&#946;1&#46; El EGF est&#225; considerado como un factor tr&#243;fico para las c&#233;lulas tubulares renales<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">33&#44;34</span></a>&#46; Diversos estudios indican que su excreci&#243;n urinaria se halla reducida en presencia de lesiones tubulares cr&#243;nicas que implican reducci&#243;n del n&#250;mero de c&#233;lulas tubulares<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">17&#44;18</span></a> y recientemente se ha identificado como un predictor pron&#243;stico independiente en enfermos con diversas glomerulopat&#237;as<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">25</span></a>&#46; En nuestros enfermos&#44; los niveles urinarios de EGF se correlacionaron con el filtrado glomerular y con la extensi&#243;n de las lesiones de fibrosis intersticial y atrofia tubular&#44; lo que concuerda con la evidencia previa e indica que podr&#237;an tambi&#233;n ser un estimador indirecto de la extensi&#243;n de las lesiones de fibrosis intersticial y de atrofia tubular&#46; Nuestros datos&#44; adem&#225;s&#44; indican que la mejora en la predicci&#243;n de la superficie de fibrosis puede tambi&#233;n obtenerse mediante la determinaci&#243;n de la excreci&#243;n de MCP-1 o de IL-6&#46; Los niveles de MCP-1 contribuyen de forma significativa ya que&#44; en los modelos multivariados&#44; tras ajustar por edad y filtrado glomerular&#44; o bien complementan la informaci&#243;n que proporciona el nivel de EGF&#44; o bien aparecen como predictor independiente&#44; en asociaci&#243;n con IL-6&#44; sin tener en cuenta los valores de EGF&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Los datos de nuestro estudio tienen la limitaci&#243;n de carecer de estudios preanal&#237;ticos que permitan definir con exactitud el tipo de muestras y la metodolog&#237;a m&#225;s adecuada para su procesamiento&#44; de haber utilizado una &#250;nica t&#233;cnica de medici&#243;n y de no haber sido validados de forma independiente en otras cohortes de enfermos&#46; Por ello&#44; los modelos predictivos descritos solo pueden considerarse v&#225;lidos para las condiciones en las que se han realizado las mediciones y para el grupo de enfermos estudiado&#46; Hacer extensivos estos resultados a otros grupos de enfermos con nefropat&#237;a IgA requerir&#237;a previamente estandarizar los aspectos t&#233;cnicos relacionados con las mediciones y analizar&#44; de forma independiente&#44; su reproductibilidad&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">En resumen&#44; nuestros datos indican que en la nefropat&#237;a IgA&#44; la concentraci&#243;n urinaria de IL-6&#44; EGF&#44; MCP-1 y TFG&#946;1 no permite estimar adecuadamente la extensi&#243;n de las lesiones de proliferaci&#243;n mesangial&#44; intracapilar o extracapilar ni el grado de esclerosis glomerular&#44; pero proporciona una informaci&#243;n adicional&#44; no invasiva&#44; que complementa la que aporta el filtrado glomerular&#44; tras ajustar por la edad&#44; y mejora de forma significativa la estimaci&#243;n de la superficie de fibrosis intersticial&#46; Entre los biomarcadores estudiados&#44; la combinaci&#243;n de EGF y MCP-1 o de IL-6 y MCP-1 tiene un valor predictivo similar sobre la superficie de fibrosis y parecen las m&#225;s adecuadas para realizar estudios en la pr&#225;ctica cl&#237;nica&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Financiaci&#243;n</span><p id="par0090" class="elsevierStylePara elsevierViewall">El presente estudio ha sido financiado mediante una ayuda del Fondo de Investigaciones Sanitarias FISS n&#46;&#176; de expediente&#58; PI14&#47;01831&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicto de intereses</span><p id="par0095" class="elsevierStylePara elsevierViewall">Ninguno de los autores declara tener conflictos de inter&#233;s&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
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          "titulo" => "Resumen"
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            0 => array:2 [
              "identificador" => "abst0005"
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            1 => array:2 [
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              "titulo" => "Pacientes y m&#233;todos"
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              "titulo" => "Resultados"
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              "titulo" => "Conclusi&#243;n"
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          "titulo" => "Palabras clave"
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        2 => array:3 [
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          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Objective"
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            1 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Patients and methods"
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            2 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Results"
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            3 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "Conclusion"
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          "titulo" => "Keywords"
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        4 => array:2 [
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          "titulo" => "Introducci&#243;n"
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          "titulo" => "Pacientes y m&#233;todos"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Estudio anatomopatol&#243;gico de las biopsias renales"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "An&#225;lisis estad&#237;stico"
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        6 => array:2 [
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          "titulo" => "Resultados"
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        7 => array:2 [
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          "titulo" => "Discusi&#243;n"
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          "titulo" => "Financiaci&#243;n"
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          "identificador" => "sec0040"
          "titulo" => "Conflicto de intereses"
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          "titulo" => "Bibliograf&#237;a"
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    "fechaRecibido" => "2016-03-14"
    "fechaAceptado" => "2016-11-17"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec887011"
          "palabras" => array:7 [
            0 => "Biomarcadores"
            1 => "Interleucina 6"
            2 => "Factor de crecimiento epid&#233;rmico"
            3 => "Prote&#237;na quimioatractante de monocitos de tipo 1"
            4 => "Factor de crecimiento transformante &#946;1"
            5 => "Fibrosis intersticial"
            6 => "Nefropat&#237;a IgA"
          ]
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      ]
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec887010"
          "palabras" => array:7 [
            0 => "Biomarkers"
            1 => "Interleukin-6"
            2 => "Epidermal growth factor"
            3 => "Monocyte chemoattractant protein type1"
            4 => "Transforming growth factor &#946;1"
            5 => "Interstitial fibrosis"
            6 => "IgA nephropathy"
          ]
        ]
      ]
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    "resumen" => array:2 [
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Analizar las asociaciones entre el nivel urinario de IL-6&#44; EGF&#44; MCP-1 y TGF&#946;1 y las caracter&#237;sticas cl&#237;nicas&#44; bioqu&#237;micas y anatomopatol&#243;gicas en enfermos con nefropat&#237;a IgA primaria y determinar su capacidad para realizar una estimaci&#243;n de la extensi&#243;n de las lesiones de esclerosis glomerular e intersticial&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Pacientes y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se estudi&#243; a 58 enfermos con nefropat&#237;a IgA&#46; Se determinaron los niveles urinarios de IL-6&#44; EGF&#44; MCP-1 y TGF&#946;1 en el momento del diagn&#243;stico&#46; Tras realizar un an&#225;lisis de la extensi&#243;n de las lesiones renales mediante morfometr&#237;a cuantitativa y mediante los criterios de Oxford&#44; se analiz&#243; la capacidad de dichas mol&#233;culas para estimar la extensi&#243;n de las lesiones glomerulares e intersticiales de fibrosis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La IL-6&#44; MCP-1 y TGF-&#946;1 se asociaron a glomeruloesclerosis focal y a la extensi&#243;n de la fibrosis intersticial&#44; pero no a la presencia de proliferaci&#243;n mesangial&#44; intracapilar o extracapilar&#46; EGF present&#243; una asociaci&#243;n negativa con la fibrosis intersticial&#46; Al categorizar a los enfermos seg&#250;n la clasificaci&#243;n de Oxford&#44; los enfermos con <span class="elsevierStyleItalic">scores</span> T1 y T2 presentaron niveles significativamente superiores de IL-6&#44; MCP-1 y TGF&#946;1&#44; y niveles de EGF significativamente inferiores que los enfermos con T0&#46; Tanto mediante regresi&#243;n m&#250;ltiple como mediante regresi&#243;n log&#237;stica&#44; los niveles de MCP-1&#44; IL-6 y EGF fueron predictores independientes de la superficie de fibrosis&#44; tras ajustar por edad y FGe&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusi&#243;n</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La determinaci&#243;n de la concentraci&#243;n urinaria de IL-6&#44; EGF y MCP-1 proporciona una informaci&#243;n adicional que mejora de forma significativa la estimaci&#243;n de la superficie de fibrosis intersticial&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objetivo"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Pacientes y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusi&#243;n"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To analyse the associations between urinary levels of IL-6 EGF&#44; MCP-1 and TGF&#946;1 and clinical&#44; biochemical and histopathological characteristics in patients with primary IgA nephropathy and their ability to predict the extent of lesions of glomerular and&#47;or interstitial sclerosis&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A total of 58 patients with IgA nephropathy were studied&#46; We determined the urine levels of IL-6&#44; EGF&#44; MCP-1&#44; and TGF&#946;1 at the time of diagnosis&#46; The extent of glomerular and interstitial fibrosis was analyzed by quantitative morphometry and kidney biopsies were classified according to the Oxford criteria&#46; We analysed the ability of these molecules to predict the extent of glomerular and interstitial fibrosis lesions&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">IL-6&#44; TGF&#946;1 and MCP-1 were associated with focal glomerulosclerosis and interstitial fibrosis extension but not with the presence of mesangial&#44; extracapillary or endocapillary proliferation&#46; EGF showed a negative association with interstitial fibrosis&#46; By categorising patients according to the Oxford classification&#44; patients with T1 and T2 scores had significantly higher levels of IL-6&#44; MCP-1&#44; TGF-&#946;1 and significantly lower levels of EGF than patients with T0 scores&#46; By multiple regression and logistic regression analyses&#44; the levels of MCP-1&#44; IL-6 and EGF were independent predictors of the fibrosis surface&#44; after adjusting for age and eGFR&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusion</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The urinary concentration of IL-6&#44; EGF and MCP-1 provides additional information that significantly improves the estimation of the surface of interstitial fibrosis in patients with IgA nephropathy&#46;</p></span>"
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            "titulo" => "Results"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">EGF&#58; factor de crecimiento epitelial&#59; IL-6&#58; interleucina 6&#59; MCP-1&#58; prote&#237;na quimioatractante de monocitos de tipo 1&#59; PAD&#58; presi&#243;n arterial diast&#243;lica&#59; PAS&#58; presi&#243;n arterial sist&#243;lica&#59; TGF&#946;1&#58; factor de crecimiento transformante &#946;1&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Los datos cualitativos se expresan como frecuencia absoluta &#40;porcentaje&#41;&#46; Los datos cuantitativos representan la media<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DE o la mediana y &#91;P25-P75&#93;&#46;</p>"
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                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Edad a&#241;os</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">48&#44;1 &#40;26&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">85&#44;9 &#40;16&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Proteinuria g&#47;24</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">h</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Hematuria macrosc&#243;pica</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">138 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">76 &#40;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Clasificaci&#243;n de Oxford</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>E1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17 &#40;29&#44;3&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>S1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17 &#40;29&#44;3&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29 &#40;50&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16 &#40;27&#44;5&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13 &#40;22&#44;4&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>IL-6<span class="elsevierStyleHsp" style=""></span>pg&#47;mg o creatinina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#44; 8 &#91;5-131&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>EGF ng&#47;mg o creatinina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&#44;9 &#91;8&#44;1-32&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>MCP-1<span class="elsevierStyleHsp" style=""></span>ng&#47;mg o creatinina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;56 &#91;0&#44;31-0&#44;96&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>TGF&#946;1<span class="elsevierStyleHsp" style=""></span>ng&#47;mg o creatinina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#44;4 &#91;4&#44;1-61&#44;2&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas cl&#237;nicas&#44; bioqu&#237;micas y anatomopatol&#243;gicas de la muestra de enfermos estudiada</p>"
        ]
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        "etiqueta" => "Tabla 2"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">EGF&#58; factor de crecimiento epitelial&#59; ENDO&#58; porcentaje de glom&#233;rulos con proliferaci&#243;n intracapilar&#59; EXTRA&#58; porcentaje de glom&#233;rulos con proliferaci&#243;n extracapilar&#59; FGe&#58; filtrado glomerular estimado por CKD- EPI&#59; FIB&#58; superficie total de fibrosis intersticial&#59; GFS&#58; porcentaje de glom&#233;rulos con esclerosis segmentaria&#59; IL-6&#58; interleucina 6&#59; Int Infilt&#58; superficie total de infiltrado intersticial&#59; MCP-1&#58; prote&#237;na quimioatractante de monocitos de tipo 1&#59; Prot&#58; proteinuria de 24&#160;h&#59; TGF&#946;1&#58; factor de crecimiento transformante &#946;1&#46;</p>"
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                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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FGe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GFS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">ENDO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Infilt int&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IL-6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">EGF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TGF&#946;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MCP-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;46<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GFS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;25<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ENDO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;26<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Infilt int&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;21<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;46<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;28<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IL-6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;39<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;35<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;21<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;25<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EGF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;63<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;63<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;45<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TGF&#946;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;23<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;38<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;20<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;21<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;52<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MCP-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;32<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;40<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;20<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;40<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;38<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;22<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;65<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prot&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;57<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;28<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;26<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;24<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;45<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IL-6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;06-0&#44;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top">R<span class="elsevierStyleSup">2</span>&#58; 0&#44;56 ANOVA p &#60; 0&#44;0001</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1524901.png"
              ]
            ]
            1 => 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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MCP-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Beta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">IC 95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">t&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Sig&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Esclerosis glomerular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;22-0&#44;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">8&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrosis intersticial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;10-0&#44;75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">3&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Infiltrado intersticial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;13-0&#44;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">2&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proteinuria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;81-0&#44;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">3&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;035&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top">R<span class="elsevierStyleSup">2</span>&#58; 0&#44;49 ANOVA p&#58; 0&#44;026</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1524902.png"
              ]
            ]
            2 => 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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">fTGF&#946;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Beta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IC 95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">t&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sig&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Esclerosis glomerular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;13-0&#44;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrosis intersticial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;05-0&#44;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;041&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top">R<span class="elsevierStyleSup">2</span>&#58; 0&#44;47 ANOVA p&#58; 0&#44;035</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1524903.png"
              ]
            ]
            3 => 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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">EGF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Beta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IC 95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">t&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sig&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrosis intersticial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;16-0&#44;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top">R<span class="elsevierStyleSup">2</span>&#58; 0&#44;39 ANOVA p&#58; 0&#44;008</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1524908.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Predictores independientes de los concentraciones de IL-6&#44; MCP-1&#44; TGF&#946;1 y EGF en orina en los modelos de regresi&#243;n m&#250;ltiple</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Tabla 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at5"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tablaImagen" => array:1 [
                0 => array:4 [
                  "imagenFichero" => "fx1.jpeg"
                  "imagenAlto" => 1146
                  "imagenAncho" => 3093
                  "imagenTamanyo" => 180177
                ]
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Modelos predictivos de la extensi&#243;n de la lesiones de fibrosis intersticial mediante an&#225;lisis de regresi&#243;n m&#250;ltiple</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0030"
        "etiqueta" => "Tabla 6"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at6"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Edad &#40;por a&#241;o&#41;&#46; ABC&#58; 0&#44;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;07&#46;</p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">P</span>&#58; 0&#44;0001&#46;</p><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">EGF&#58; <span class="elsevierStyleItalic">epidermal growth factor</span> &#40;por cada aumento en 1<span class="elsevierStyleHsp" style=""></span>ng&#47;mg de creatinina&#41;&#59; FGe&#58; filtrado glomerular estimado mediante la ecuaci&#243;n CKD-EPI &#40;por cada aumento de 1<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#44;73&#160;m<span class="elsevierStyleSup">2</span>&#41;&#59; MCP-1&#58; prote&#237;na quimiotractante de monocitos de tipo 1 &#40;por cada aumento en 1<span class="elsevierStyleHsp" style=""></span>ng&#47;mg de creatinina&#41;&#46;</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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IC&#160;95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sig&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FGe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;68&#8211;0&#44;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Edad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;02&#8211;1&#44;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EGF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;36&#8211;0&#44;96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;034&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MCP-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;07&#8211;1&#44;68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1524904.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Modelo de regresi&#243;n log&#237;stica para estimar la probabilidad de presentar fibrosis grado T1-T2 de Oxford en la biopsia renal</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0035"
        "etiqueta" => "Tabla 7"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at7"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">No se apreciaron diferencias significativas entre el n&#250;mero de enfermos con lesiones de fibrosis intersticial observados y esperados por el modelo en ninguna de las categor&#237;as de riesgo&#46;</p><p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Fibrosis<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#58; presencia de fibrosis de grado T1 o T2&#46;</p><p id="spar0125" class="elsevierStyleSimplePara elsevierViewall">Chi<span class="elsevierStyleSup">2</span>&#58; 6&#44;98&#59; p&#58; 0&#44;90&#46;</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="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">&#42;</span></a>Categor&#237;as de riesgo</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Fibrosis &#61; 1</th><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total</th></tr><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Observados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Esperados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#60;0&#44;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">0&#44;112-0&#44;185&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">0&#44;186-0&#44;244&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">0&#44;245-0&#44;381&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
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Valor de los niveles urinarios de interleucina 6, factor de crecimiento epidérmico, proteína quimioatractante de monocitos de tipo 1 y factor de crecimiento transformante β1 para la predicción de la extensión de las lesiones de fibrosis en biopsias de enfermos con nefropatía IgA
Value of urinary levels of interleukin-6, epidermal growth factor, monocyte chemoattractant protein type1 and transforming growth factor β1 in predicting the extent of fibrosis lesions in kidney biopsies of patients with IgA nephropathy
Alfons Segarra-Medranoa,
Autor para correspondencia
alsegarr@gmail.com

Autor para correspondencia.
, Clara Carnicer-Caceresb, Naiara Valtierra-Carmenoa, Irene Agraz-Pamplonaa, Natalia Ramos-Terradesa, Elías Jatem Escalantea, Elena Ostos-Roldana
a Servicio de Nefrología, Hospital Vall d’Hebron, Universidad Autónoma de Barcelona, Barcelona, España
b Servicio de Bioquímica, Hospital Vall d’Hebron, Universidad Autónoma de Barcelona, Barcelona, España
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">La nefropat&#237;a mesangial IgA es una de las nefropat&#237;as primarias m&#225;s frecuentes y tiene un curso cl&#237;nico muy variable que incluye desde formas indolentes hasta formas con insuficiencia renal r&#225;pidamente progresiva<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#8211;4</span></a>&#46; Aproximadamente un 20-25&#37; de los enfermos presenta evoluci&#243;n a insuficiencia renal cr&#243;nica a largo plazo&#46; Los factores de mal pron&#243;stico identificados hasta la fecha son la presencia de insuficiencia renal&#44; proteinuria persistentemente superior a 1&#160;g&#47;d&#237;a&#44; la hipertensi&#243;n arterial y los dep&#243;sitos mesangiales de C4d<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a>&#46; La extensi&#243;n de las lesiones glomerulares e intersticiales tiene valor pron&#243;stico en enfermos no tratados&#44; pero no en enfermos que han recibido tratamiento con glucocorticoides u otros inmunomoduladores<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">6</span></a>&#46; En la actualidad&#44; se acepta que&#44; tras el dep&#243;sito mesangial de IgA&#44; la lesi&#243;n renal se inicia a trav&#233;s de la activaci&#243;n del complemento por la v&#237;a alternativa&#44; por la v&#237;a de las lectinas o por ambas<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a>&#46; Este proceso resulta en la generaci&#243;n de diversas citocinas y factores de crecimiento que act&#250;an como mediadores del da&#241;o renal&#44; estimulando la proliferaci&#243;n celular y el aumento en la producci&#243;n de la matriz mesangial<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">7&#44;8</span></a>&#46; Hay tambi&#233;n datos que indican que las citocinas producidas por la c&#233;lula mesangial pueden inducir alteraciones en la estructura y funci&#243;n de los podocitos y de las c&#233;lulas del t&#250;bulo proximal&#44; que se relacionan con la aparici&#243;n de lesiones de glomeruloesclerosis y de fibrosis intersticial<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">9&#8211;11</span></a>&#46; De las diferentes mol&#233;culas potencialmente implicadas&#44; la interleucina-6 &#40;IL-6&#41;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">12&#8211;15</span></a>&#44; el factor de crecimiento epid&#233;rmico &#40;EGF&#41;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">16&#8211;18</span></a>&#44; la prote&#237;na quimioatractante de monocitos de tipo 1 &#40;MCP-1&#41;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">19&#8211;23</span></a> y el factor de crecimiento transformante &#946;1 &#40;TGF&#946;1&#41;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a> han sido objeto de estudios detallados&#46; Los datos disponibles demuestran una correlaci&#243;n significativa entre la excreci&#243;n urinaria y la expresi&#243;n renal de IL-6<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">15</span></a> y de EGF<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">15</span></a> y de una correlaci&#243;n significativa entre los niveles urinarios de IL-6<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">15&#44;16</span></a>&#44; EGF<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">15&#44;17&#44;18</span></a>&#44; MCP-1<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">22&#44;23</span></a> y TGF&#946;1<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a> y la extensi&#243;n de las lesiones de fibrosis intersticial y atrofia tubular&#46; Estos datos se&#241;alan que el nivel urinario de estas citocinas y factores de crecimiento podr&#237;a proporcionar informaci&#243;n funcional sobre la patogenia de la lesi&#243;n renal o ser biomarcadores indirectos de la extensi&#243;n de la fibrosis glomerular e intersticial&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Tres estudios independientes han demostrado que la medici&#243;n de la excreci&#243;n urinaria de algunas de estas mol&#233;culas podr&#237;a tener valor pron&#243;stico en la nefropat&#237;a IgA<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">15&#44;17&#44;18</span></a>&#46; En concreto&#44; se ha descrito que el cociente IL-6&#47;EGF<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">15</span></a> podr&#237;a ser un indicador de la progresi&#243;n hacia la fibrosis renal y que la relaci&#243;n MCP-1&#47;EGF identificar&#237;a&#44; en el momento del diagn&#243;stico&#44; a los pacientes con mayor riesgo de progresi&#243;n a la insuficiencia cr&#243;nica renal&#44; con independencia de la funci&#243;n renal y de la proteinuria inicial<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">17&#44;18</span></a>&#46; Por otra parte&#44; el potencial valor pron&#243;stico de la excreci&#243;n urinaria de EGF tambi&#233;n se ha puesto de manifiesto en un reciente estudio que la identific&#243; como predictor de progresi&#243;n independiente en 3<span class="elsevierStyleHsp" style=""></span>cohortes de enfermos con enfermedades glomerulares<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">25</span></a>&#46; Estos datos indican que la medici&#243;n de la excreci&#243;n urinaria de uno o varios de estos biomarcadores podr&#237;a tener utilidad en la pr&#225;ctica cl&#237;nica&#46; Sin embargo&#44; hasta la fecha&#44; no se ha realizado ning&#250;n estudio comparativo para analizar cu&#225;l de ellos es el que se correlaciona mejor con las lesiones de fibrosis renal&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">El objetivo del presente estudio fue analizar las asociaciones entre el nivel urinario de IL-6&#44; EGF&#44; MCP-1 y TGF&#946;1 y las caracter&#237;sticas cl&#237;nicas&#44; bioqu&#237;micas y anatomopatol&#243;gicas en enfermos con nefropat&#237;a IgA primaria&#44; y cu&#225;les de estas mol&#233;culas permiten una estimaci&#243;n m&#225;s precisa de la extensi&#243;n de las lesiones de fibrosis glomerular o intersticial&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes y m&#233;todos</span><p id="par0020" class="elsevierStylePara elsevierViewall">Se estudi&#243; un total de 58 pacientes con nefropat&#237;a IgA idiop&#225;tica diagnosticada por biopsia renal&#46; En el momento de la biopsia renal y antes de iniciar cualquier tratamiento&#44; se registraron las variables demogr&#225;ficas y cl&#237;nicas&#44; se realizaron determinaciones de creatinina s&#233;rica&#44; filtrado glomerular estimado &#40;FGe&#41; mediante la ecuaci&#243;n CKD-EPI<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a>&#44; excreci&#243;n urinaria de sodio y cociente proteinuria&#47;creatinina y se obtuvieron muestras de orina de la segunda micci&#243;n de la ma&#241;ana para medir los niveles de IL-6&#44; EGF&#44; MCP-1 y TGF&#946;1&#46; En las muestras de orina&#44; se descart&#243; la presencia de piuria mediante estudio del sedimento urinario&#46; Las muestras de orina se centrifugaron a 1&#46;500<span class="elsevierStyleHsp" style=""></span>g durante 10&#160;min y se almacenaron a &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C hasta su procesamiento&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">En el momento de obtener las muestras de orina&#44; ning&#250;n paciente recib&#237;a tratamiento con bloqueadores de los receptores de la angiotensina II&#44; inhibidores de la ECA&#44; combinaciones de ambos ni con antagonistas de la aldosterona&#46; Ning&#250;n paciente fue tratado con esteroides ni otros medicamentos inmunosupresores y ning&#250;n paciente recibi&#243; paricalcitol&#46; La adecuaci&#243;n de la colecci&#243;n de 24<span class="elsevierStyleHsp" style=""></span>h se evalu&#243; mediante la comparaci&#243;n de la creatinina total en la muestra con la creatinina predicha&#58; 28<span class="elsevierStyleHsp" style=""></span>-<span class="elsevierStyleHsp" style=""></span> &#40;0&#44;2<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>edad&#41;<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>kg en hombres y 23&#44;8<span class="elsevierStyleHsp" style=""></span>-<span class="elsevierStyleHsp" style=""></span> &#40;0&#44;17<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>edad&#41;<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>kg en mujeres en mg&#47;d&#237;a<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">27</span></a>&#46; Los valores de creatinina se obtuvieron utilizando un compensado IDMS trazable &#40;Hitachi Modular P-800 Roche Diagnostics&#44; Berl&#237;n&#44; Alemania&#41;&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Los niveles de a EGF&#44; IL-6&#44; MCP-1 y TGF&#946;1 en orina se midieron mediante an&#225;lisis ELISA comerciales &#40;Quantikine R &#38; D Systems&#44; Minneapolis&#44; EE&#46;&#160;UU&#46;&#41; siguiendo las instrucciones del fabricante&#46; Para medir el TGF&#946;1 total &#40;latente<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>activo&#41;&#44; las muestras de orina se diluyeron con 4<span class="elsevierStyleHsp" style=""></span>vol&#250;menes de soluci&#243;n salina tamponada con fosfato y se a&#241;adi&#243; HCl hasta obtener un pH de 2&#44;5 a 2&#44;0&#46; Despu&#233;s de 30<span class="elsevierStyleHsp" style=""></span>min a temperatura ambiente&#44; el pH se reajust&#243; a 7&#44;4 con NaOH<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">28</span></a>&#46; Todos los an&#225;lisis se realizaron por duplicado y fueron calibrados con est&#225;ndares purificados y sueros de referencia de los fabricantes&#46; La precisi&#243;n intraan&#225;lisis se calcul&#243; realizando 10 determinaciones en la misma placa de 3 muestras con concentraciones conocidas y fueron &#60;5&#37; para todas las mol&#233;culas&#44; tanto a baja como a alta concentraci&#243;n&#46; La precisi&#243;n interan&#225;lisis se estudi&#243; con 10 determinaciones en distintas placas de 3 muestras con concentraciones conocidas&#44; que fueron &#60;6&#44;8&#37; para todas las mol&#233;culas&#44; tanto a bajas como a altas concentraciones&#46; Las concentraciones urinarias se ajustaron por concentraci&#243;n de creatinina y se expresaron en pg&#47;mg creatinina &#40;IL-6&#41; o ng&#47;mg de creatinina &#40;EGF&#44; MCP-1 y TGF&#223;1&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">El estudio se realiz&#243; siguiendo las normas de Helsinki&#44; fue aprobado por el Comit&#233; de &#201;tica del hospital y todos los pacientes firmaron un consentimiento informado&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Estudio anatomopatol&#243;gico de las biopsias renales</span><p id="par0040" class="elsevierStylePara elsevierViewall">El tejido renal se fij&#243; en parafina&#44; y se realizaron cortes de 4<span class="elsevierStyleHsp" style=""></span>&#956;m&#44; que se ti&#241;eron con hematoxilina-eosina&#44; tricr&#243;mico de Masson&#44; &#225;cido peri&#243;dico de Schiff y metenamina de Jones&#46; Los estudios de inmunofluorescencia se realizaron en muestras de tejido congeladas&#44; utilizando anticuerpos contra las inmunoglobulinas A&#44; G y M&#44; fibrin&#243;geno y C3&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">En las biopsias renales&#44; se contabiliz&#243; la proporci&#243;n de glom&#233;rulos con lesiones de proliferaci&#243;n mesangial y esclerosis segmentaria&#44; la presencia de proliferaci&#243;n intra- y extracapilar y la extensi&#243;n de la fibrosis intersticial mediante morfometr&#237;a cuantitativa&#44; utilizando un autoanalizador Olympus WCE2&#46; Las biopsias renales fueron&#44; adem&#225;s&#44; clasificadas siguiendo el documento de consenso internacional de Oxford 2009<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">29</span></a>&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">An&#225;lisis estad&#237;stico</span><p id="par0050" class="elsevierStylePara elsevierViewall">La comparaci&#243;n de 2<span class="elsevierStyleHsp" style=""></span>medias se realiz&#243; mediante la t de Student para datos independientes&#46; La comparaci&#243;n de proporciones se realiz&#243; mediante la prueba de chi cuadrado o el test exacto de Fischer&#46; Para el an&#225;lisis de correlaciones entre variables cuantitativas se utiliz&#243; el coeficiente de correlaci&#243;n de Pearson&#46; Con objeto de analizar la relaci&#243;n entre cada una de las mol&#233;culas estudiadas y la extensi&#243;n de las lesiones de la fibrosis glomerular e intersticial&#44; se realiz&#243; un an&#225;lisis univariado&#44; seguido de un an&#225;lisis de regresi&#243;n m&#250;ltiple paso a paso&#44; tomando la superficie de fibrosis como variable dependiente tras transformaci&#243;n logar&#237;tmica y tras comprobar de la normalidad de su distribuci&#243;n&#46; Asimismo&#44; se clasific&#243; a los pacientes en 2<span class="elsevierStyleHsp" style=""></span>grupos en funci&#243;n de la presencia &#40;T1<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>T2&#41; o la ausencia &#40;T0&#41; de lesiones de fibrosis intersticial en la clasificaci&#243;n de Oxford y&#44; tras un an&#225;lisis univariado de selecci&#243;n de variables&#44; se realiz&#243; un an&#225;lisis de regresi&#243;n log&#237;stica paso a paso&#44; con un m&#233;todo de introducci&#243;n manual&#44; basado en el cambio de &#8211;LR&#44; para identificar las variables independientemente asociadas a la presencia de fibrosis intersticial&#46; La calibraci&#243;n del modelo por categor&#237;as de riesgo se realiz&#243; mediante la prueba de Hosmer-Lemeshow<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">30</span></a>&#46; En todos los casos se consider&#243; estad&#237;sticamente significativo un valor de p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46; Para el an&#225;lisis estad&#237;stico se utiliz&#243; el programa SPSS versi&#243;n 20&#46;0&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><p id="par0055" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se resumen las caracter&#237;sticas cl&#237;nicas y anatomopatol&#243;gicas de la muestra de enfermos incluida en el estudio&#46; En la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a> se resume la matriz de correlaciones entre las variables analizadas en el estudio&#46; En lo que respecta a la relaci&#243;n con las variables histol&#243;gicas&#44; se apreci&#243; una asociaci&#243;n estad&#237;sticamente significativa entre los niveles de IL-6&#44; MCP-1 y TGF&#946;1 y la extensi&#243;n de la glomeruloesclerosis focal&#44; pero no con la presencia de proliferaci&#243;n intra- o extracapilar&#46; Asimismo&#44; se apreci&#243; una correlaci&#243;n positiva entre la extensi&#243;n de las lesiones de fibrosis intersticial y el nivel urinario de IL-6&#44; MCP-1 y TGF&#946;1 y negativa entre las lesiones de fibrosis intersticial y el nivel urinario de EGF&#46; Al categorizar a los enfermos seg&#250;n la clasificaci&#243;n de Oxford &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#41;&#44; no se apreciaron diferencias significativas en ninguna de las mol&#233;culas estudiadas en funci&#243;n de los criterios M&#44; E o S&#46; Los enfermos con <span class="elsevierStyleItalic">scores</span> de fibrosis intersticial T1 y T2 presentaron niveles significativamente superiores de IL-6&#44; MCP-1 y TGF&#946;1&#44; y niveles de EGF significativamente inferiores que los enfermos T0&#44; pero no se apreciaron diferencias significativas entre T1 y T2&#46; Se apreci&#243; una correlaci&#243;n significativa entre niveles urinarios de IL-6&#44; MCP-1&#44; TGF&#946;1 y proteinuria&#46; Los niveles de EGF solo tuvieron asociaci&#243;n con el grado de esclerosis intersticial y con el filtrado glomerular&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> se resumen los predictores independientes de la excreci&#243;n urinaria de cada una de las mol&#233;culas estudiadas en los an&#225;lisis de regresi&#243;n m&#250;ltiple y el porcentaje de la variabilidad de cada una de ellas explicada por el conjunto de variables independientes&#46; En todos los casos se aprecian asociaciones independientes y significativas con la superficie de fibrosis intersticial&#46; En el caso de la IL-6 y del TGF&#946;1&#44; se aprecian tambi&#233;n asociaciones significativas con la esclerosis glomerular y&#44; en el de la IL-6 y MCP-1&#44; con la proteinuria&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">En los an&#225;lisis de regresi&#243;n m&#250;ltiple para predecir la extensi&#243;n de las lesiones de fibrosis intersticial&#44; la mayor capacidad predictiva se apreci&#243; con los modelos que incluyeron la edad&#44; el FGe&#44; la MCP-1 y&#44; o bien la el EGF o bien la IL-6&#44; pero no ambos a la vez&#44; ya que entre ellos se detect&#243; colinealidad &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Al clasificar a los enfermos en 2<span class="elsevierStyleHsp" style=""></span>categor&#237;as en funci&#243;n de la presencia &#40;T1<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>T2&#41; o ausencia &#40;T0&#41; de fibrosis en las biopsias seg&#250;n la clasificaci&#243;n de Oxford&#44; en el an&#225;lisis de regresi&#243;n log&#237;stica se apreci&#243; que los predictores independientes de fibrosis fueron la edad&#44; el FGe&#44; la MCP-1 y el EGF &#40;<a class="elsevierStyleCrossRef" href="#tbl0030">tabla 6</a>&#41;&#46; El modelo tuvo una buena capacidad predictiva con un &#225;rea bajo la curva de 0&#44;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;07 &#40;p&#58; 0&#44;0001&#41; y una buena calibraci&#243;n para todas las categor&#237;as de riesgo &#40;<a class="elsevierStyleCrossRef" href="#tbl0035">tabla 7</a>&#41;&#46; Los niveles de TGF&#946;1&#44; adem&#225;s de asociarse con la esclerosis glomerular y con la fibrosis intersticial&#44; tuvieron una asociaci&#243;n muy significativa con los de IL-6 y MCP-1&#46; La introducci&#243;n del nivel de TGF&#946;1 en los modelos&#44; manteniendo MCP-1 e IL-6&#44; caus&#243; colinealidad y&#44; al introducir el nivel de TGF&#946;1 en lugar del de MCP-1 o el de IL-6&#44; en los modelos tanto el de regresi&#243;n m&#250;ltiple como el de regresi&#243;n log&#237;stica perdieron capacidad predictiva de forma significativa&#46;</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><elsevierMultimedia ident="tbl0035"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discusi&#243;n</span><p id="par0075" class="elsevierStylePara elsevierViewall">Los resultados de nuestro estudio indican que&#44; en enfermos con nefropat&#237;a IgA&#44; el nivel urinario de IL-6&#44; EGF&#44; MCP-1 y TFG&#946;1 se correlaciona de forma significativa con el grado de esclerosis glomerular e intersticial observado en las biopsias renales&#44; pero no con las lesiones proliferativas intra- o extracapilares ni con el grado de proliferaci&#243;n mesangial&#46; Los niveles de dichas mol&#233;culas no permitieron diferenciar entre subgrupos de la clasificaci&#243;n de Oxford en cuanto al grado de proliferaci&#243;n mesangial&#44; proliferaci&#243;n intracapilar o esclerosis focal&#44; pero fueron significativamente distintos en los enfermos con estadios de fibrosis T1 y T2 con relaci&#243;n a T0&#46; En los modelos multivariados&#44; el mejor predictor de la superficie de fibrosis intersticial fue el filtrado glomerular&#44; pero los modelos que incluyeron FGe&#44; edad&#44; MCP-1 y EGF o IL-6 tuvieron capacidad predictiva significativamente superior&#44; por lo que aportan una informaci&#243;n adicional y m&#225;s precisa sobre la superficie de fibrosis intersticial&#46; Por otra parte&#44; en los modelos de regresi&#243;n log&#237;stica&#44; estas mismas variables tuvieron capacidad para identificar a los enfermos que presentaron niveles de fibrosis T1-T2 en las biopsias&#44; con alto poder predictivo y con buena discriminaci&#243;n para cualquier categor&#237;a de riesgo&#46; En conjunto&#44; estos datos indican que la informaci&#243;n que proporciona la medici&#243;n de la excreci&#243;n del nivel urinario de IL-6&#44; MCP-1 y EGF permite la estimaci&#243;n de la superficie de fibrosis de forma m&#225;s precisa que el filtrado glomerular de forma aislada y&#44; en consecuencia&#44; pueden aportar datos relevantes en la pr&#225;ctica cl&#237;nica&#46; Estudios previos&#44; combinando t&#233;cnicas de hibridaci&#243;n <span class="elsevierStyleItalic">in situ</span> e inmunohistoquimia&#44; han demostrado que&#44; en la nefropat&#237;a IgA&#44; la s&#237;ntesis de IL-6 est&#225; incrementada tanto en las c&#233;lulas mesangiales como en las c&#233;lulas del t&#250;bulo proximal y de las c&#233;lulas del infiltrado intersticial<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">13&#8211;15</span></a>&#46; El aumento en la expresi&#243;n de IL-6 se ha correlacionado con la extensi&#243;n de la fibrosis glomerular y con la de la fibrosis intersticial&#44; con o sin lesi&#243;n proliferativa mesangial<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">13&#8211;15</span></a>&#46; Los niveles de IL-6 urinarios observados en nuestros enfermos y su correlaci&#243;n con las lesiones de fibrosis intersticial concuerdan con los datos previamente publicados<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">12&#8211;15</span></a> y&#44; por tanto&#44; corroboran la idea de que su determinaci&#243;n podr&#237;a ser &#250;til como indicador de la severidad de las lesiones renales&#46; MCP-1<span class="elsevierStyleHsp" style=""></span>ha sido identificada como una de las mol&#233;culas directamente implicadas en el reclutamiento de c&#233;lulas inflamatorias al intersticio renal tanto en modelos experimentales como en diversas enfermedades glomerulares&#44; incluyendo la nefropat&#237;a IgA<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">20&#44;22</span></a>&#46; En nuestros enfermos&#44; MCP-1 se correlaciona con el filtrado glomerular y con la extensi&#243;n de la fibrosis e infiltrado intersticial y&#44; en menor grado&#44; con la proteinuria&#44; lo que coincide con los datos descritos en estudios previos<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">19&#8211;23</span></a>&#46; El TFG&#946;1 es considerado como uno de los moduladores claves en la reparaci&#243;n tras la lesi&#243;n&#46; Sin embargo&#44; un exceso de producci&#243;n se ha asociado a dep&#243;sito de col&#225;geno y cicatrizaci&#243;n<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">31&#44;32</span></a>&#46; En diversas glomerulopat&#237;as cr&#243;nicas&#44; se ha demostrado que la expresi&#243;n renal de TFG&#946;1 se encuentra incrementada y que los niveles urinarios de TFG&#946;1 reflejan su producci&#243;n local a nivel renal<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">24&#44;31</span></a>&#46; Los datos de nuestros enfermos coinciden con los previamente publicados en la nefropat&#237;a IgA&#44; en hallar una correlaci&#243;n entre los niveles urinarios de de TFG&#946;1 y en la severidad de las lesiones de esclerosis glomerular e intersticial&#46; En los enfermos estudiados&#44; los niveles de IL-6&#44; MCP-1 y TFG&#946;1&#44; adem&#225;s de estar correlacionados con la fibrosis glomerular e intersticial&#44; est&#225;n altamente correlacionados entre s&#237;&#44; lo que indica que probablemente reflejan aspectos de un proceso patog&#233;nico com&#250;n&#46; La elevada correlaci&#243;n entre el nivel de TFG&#946;1 y el de MCP-1 motiva que&#44; en los modelos predictivos&#44; la introducci&#243;n de ambas variables resulte en colinealidad y&#44; por ello&#44; no sea posible introducir m&#225;s que una de ellas&#46; Los diferentes modelos analizados tienen mayor poder predictivo y mejor calibraci&#243;n al introducir el nivel de MCP-1 que el de TFG&#946;1&#46; El EGF est&#225; considerado como un factor tr&#243;fico para las c&#233;lulas tubulares renales<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">33&#44;34</span></a>&#46; Diversos estudios indican que su excreci&#243;n urinaria se halla reducida en presencia de lesiones tubulares cr&#243;nicas que implican reducci&#243;n del n&#250;mero de c&#233;lulas tubulares<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">17&#44;18</span></a> y recientemente se ha identificado como un predictor pron&#243;stico independiente en enfermos con diversas glomerulopat&#237;as<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">25</span></a>&#46; En nuestros enfermos&#44; los niveles urinarios de EGF se correlacionaron con el filtrado glomerular y con la extensi&#243;n de las lesiones de fibrosis intersticial y atrofia tubular&#44; lo que concuerda con la evidencia previa e indica que podr&#237;an tambi&#233;n ser un estimador indirecto de la extensi&#243;n de las lesiones de fibrosis intersticial y de atrofia tubular&#46; Nuestros datos&#44; adem&#225;s&#44; indican que la mejora en la predicci&#243;n de la superficie de fibrosis puede tambi&#233;n obtenerse mediante la determinaci&#243;n de la excreci&#243;n de MCP-1 o de IL-6&#46; Los niveles de MCP-1 contribuyen de forma significativa ya que&#44; en los modelos multivariados&#44; tras ajustar por edad y filtrado glomerular&#44; o bien complementan la informaci&#243;n que proporciona el nivel de EGF&#44; o bien aparecen como predictor independiente&#44; en asociaci&#243;n con IL-6&#44; sin tener en cuenta los valores de EGF&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Los datos de nuestro estudio tienen la limitaci&#243;n de carecer de estudios preanal&#237;ticos que permitan definir con exactitud el tipo de muestras y la metodolog&#237;a m&#225;s adecuada para su procesamiento&#44; de haber utilizado una &#250;nica t&#233;cnica de medici&#243;n y de no haber sido validados de forma independiente en otras cohortes de enfermos&#46; Por ello&#44; los modelos predictivos descritos solo pueden considerarse v&#225;lidos para las condiciones en las que se han realizado las mediciones y para el grupo de enfermos estudiado&#46; Hacer extensivos estos resultados a otros grupos de enfermos con nefropat&#237;a IgA requerir&#237;a previamente estandarizar los aspectos t&#233;cnicos relacionados con las mediciones y analizar&#44; de forma independiente&#44; su reproductibilidad&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">En resumen&#44; nuestros datos indican que en la nefropat&#237;a IgA&#44; la concentraci&#243;n urinaria de IL-6&#44; EGF&#44; MCP-1 y TFG&#946;1 no permite estimar adecuadamente la extensi&#243;n de las lesiones de proliferaci&#243;n mesangial&#44; intracapilar o extracapilar ni el grado de esclerosis glomerular&#44; pero proporciona una informaci&#243;n adicional&#44; no invasiva&#44; que complementa la que aporta el filtrado glomerular&#44; tras ajustar por la edad&#44; y mejora de forma significativa la estimaci&#243;n de la superficie de fibrosis intersticial&#46; Entre los biomarcadores estudiados&#44; la combinaci&#243;n de EGF y MCP-1 o de IL-6 y MCP-1 tiene un valor predictivo similar sobre la superficie de fibrosis y parecen las m&#225;s adecuadas para realizar estudios en la pr&#225;ctica cl&#237;nica&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Financiaci&#243;n</span><p id="par0090" class="elsevierStylePara elsevierViewall">El presente estudio ha sido financiado mediante una ayuda del Fondo de Investigaciones Sanitarias FISS n&#46;&#176; de expediente&#58; PI14&#47;01831&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicto de intereses</span><p id="par0095" class="elsevierStylePara elsevierViewall">Ninguno de los autores declara tener conflictos de inter&#233;s&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
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          "identificador" => "xres906678"
          "titulo" => "Resumen"
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            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Objetivo"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Pacientes y m&#233;todos"
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            2 => array:2 [
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              "titulo" => "Resultados"
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            3 => array:2 [
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              "titulo" => "Conclusi&#243;n"
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          "titulo" => "Palabras clave"
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        2 => array:3 [
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          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Objective"
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            1 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Patients and methods"
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            2 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Results"
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            3 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "Conclusion"
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          "titulo" => "Keywords"
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        4 => array:2 [
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          "titulo" => "Introducci&#243;n"
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        5 => array:3 [
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          "titulo" => "Pacientes y m&#233;todos"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Estudio anatomopatol&#243;gico de las biopsias renales"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "An&#225;lisis estad&#237;stico"
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        6 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Resultados"
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        7 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Discusi&#243;n"
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          "titulo" => "Financiaci&#243;n"
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          "identificador" => "sec0040"
          "titulo" => "Conflicto de intereses"
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        10 => array:1 [
          "titulo" => "Bibliograf&#237;a"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2016-03-14"
    "fechaAceptado" => "2016-11-17"
    "PalabrasClave" => array:2 [
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec887011"
          "palabras" => array:7 [
            0 => "Biomarcadores"
            1 => "Interleucina 6"
            2 => "Factor de crecimiento epid&#233;rmico"
            3 => "Prote&#237;na quimioatractante de monocitos de tipo 1"
            4 => "Factor de crecimiento transformante &#946;1"
            5 => "Fibrosis intersticial"
            6 => "Nefropat&#237;a IgA"
          ]
        ]
      ]
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec887010"
          "palabras" => array:7 [
            0 => "Biomarkers"
            1 => "Interleukin-6"
            2 => "Epidermal growth factor"
            3 => "Monocyte chemoattractant protein type1"
            4 => "Transforming growth factor &#946;1"
            5 => "Interstitial fibrosis"
            6 => "IgA nephropathy"
          ]
        ]
      ]
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    "resumen" => array:2 [
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Analizar las asociaciones entre el nivel urinario de IL-6&#44; EGF&#44; MCP-1 y TGF&#946;1 y las caracter&#237;sticas cl&#237;nicas&#44; bioqu&#237;micas y anatomopatol&#243;gicas en enfermos con nefropat&#237;a IgA primaria y determinar su capacidad para realizar una estimaci&#243;n de la extensi&#243;n de las lesiones de esclerosis glomerular e intersticial&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Pacientes y m&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Se estudi&#243; a 58 enfermos con nefropat&#237;a IgA&#46; Se determinaron los niveles urinarios de IL-6&#44; EGF&#44; MCP-1 y TGF&#946;1 en el momento del diagn&#243;stico&#46; Tras realizar un an&#225;lisis de la extensi&#243;n de las lesiones renales mediante morfometr&#237;a cuantitativa y mediante los criterios de Oxford&#44; se analiz&#243; la capacidad de dichas mol&#233;culas para estimar la extensi&#243;n de las lesiones glomerulares e intersticiales de fibrosis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La IL-6&#44; MCP-1 y TGF-&#946;1 se asociaron a glomeruloesclerosis focal y a la extensi&#243;n de la fibrosis intersticial&#44; pero no a la presencia de proliferaci&#243;n mesangial&#44; intracapilar o extracapilar&#46; EGF present&#243; una asociaci&#243;n negativa con la fibrosis intersticial&#46; Al categorizar a los enfermos seg&#250;n la clasificaci&#243;n de Oxford&#44; los enfermos con <span class="elsevierStyleItalic">scores</span> T1 y T2 presentaron niveles significativamente superiores de IL-6&#44; MCP-1 y TGF&#946;1&#44; y niveles de EGF significativamente inferiores que los enfermos con T0&#46; Tanto mediante regresi&#243;n m&#250;ltiple como mediante regresi&#243;n log&#237;stica&#44; los niveles de MCP-1&#44; IL-6 y EGF fueron predictores independientes de la superficie de fibrosis&#44; tras ajustar por edad y FGe&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusi&#243;n</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La determinaci&#243;n de la concentraci&#243;n urinaria de IL-6&#44; EGF y MCP-1 proporciona una informaci&#243;n adicional que mejora de forma significativa la estimaci&#243;n de la superficie de fibrosis intersticial&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Pacientes y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusi&#243;n"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To analyse the associations between urinary levels of IL-6 EGF&#44; MCP-1 and TGF&#946;1 and clinical&#44; biochemical and histopathological characteristics in patients with primary IgA nephropathy and their ability to predict the extent of lesions of glomerular and&#47;or interstitial sclerosis&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Patients and methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A total of 58 patients with IgA nephropathy were studied&#46; We determined the urine levels of IL-6&#44; EGF&#44; MCP-1&#44; and TGF&#946;1 at the time of diagnosis&#46; The extent of glomerular and interstitial fibrosis was analyzed by quantitative morphometry and kidney biopsies were classified according to the Oxford criteria&#46; We analysed the ability of these molecules to predict the extent of glomerular and interstitial fibrosis lesions&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">IL-6&#44; TGF&#946;1 and MCP-1 were associated with focal glomerulosclerosis and interstitial fibrosis extension but not with the presence of mesangial&#44; extracapillary or endocapillary proliferation&#46; EGF showed a negative association with interstitial fibrosis&#46; By categorising patients according to the Oxford classification&#44; patients with T1 and T2 scores had significantly higher levels of IL-6&#44; MCP-1&#44; TGF-&#946;1 and significantly lower levels of EGF than patients with T0 scores&#46; By multiple regression and logistic regression analyses&#44; the levels of MCP-1&#44; IL-6 and EGF were independent predictors of the fibrosis surface&#44; after adjusting for age and eGFR&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusion</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The urinary concentration of IL-6&#44; EGF and MCP-1 provides additional information that significantly improves the estimation of the surface of interstitial fibrosis in patients with IgA nephropathy&#46;</p></span>"
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            "titulo" => "Objective"
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          2 => array:2 [
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            "titulo" => "Results"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">EGF&#58; factor de crecimiento epitelial&#59; IL-6&#58; interleucina 6&#59; MCP-1&#58; prote&#237;na quimioatractante de monocitos de tipo 1&#59; PAD&#58; presi&#243;n arterial diast&#243;lica&#59; PAS&#58; presi&#243;n arterial sist&#243;lica&#59; TGF&#946;1&#58; factor de crecimiento transformante &#946;1&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Los datos cualitativos se expresan como frecuencia absoluta &#40;porcentaje&#41;&#46; Los datos cuantitativos representan la media<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>DE o la mediana y &#91;P25-P75&#93;&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N&#58; 58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Edad a&#241;os</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">48&#44;1 &#40;26&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Sexo H&#47;M</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40 &#40;68&#44;9&#41;&#47;18 &#40;31&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Creatinina mg&#47;dL</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;18 &#40;1&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">FGe ml&#47;min&#47;1&#44;73 m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">85&#44;9 &#40;16&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Proteinuria g&#47;24</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">h</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Hem cel&#47;&#956;l</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">99 &#40;45&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Hematuria macrosc&#243;pica</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">PAS mmHg</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">PAD mmHg</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">76 &#40;19&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Clasificaci&#243;n de Oxford</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>M1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15 &#40;26&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>E1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17 &#40;29&#44;3&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>S1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17 &#40;29&#44;3&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29 &#40;50&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16 &#40;27&#44;5&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>T2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13 &#40;22&#44;4&#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="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>IL-6<span class="elsevierStyleHsp" style=""></span>pg&#47;mg o creatinina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&#44; 8 &#91;5-131&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>EGF ng&#47;mg o creatinina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&#44;9 &#91;8&#44;1-32&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>MCP-1<span class="elsevierStyleHsp" style=""></span>ng&#47;mg o creatinina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;56 &#91;0&#44;31-0&#44;96&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>TGF&#946;1<span class="elsevierStyleHsp" style=""></span>ng&#47;mg o creatinina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#44;4 &#91;4&#44;1-61&#44;2&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Caracter&#237;sticas cl&#237;nicas&#44; bioqu&#237;micas y anatomopatol&#243;gicas de la muestra de enfermos estudiada</p>"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">EGF&#58; factor de crecimiento epitelial&#59; ENDO&#58; porcentaje de glom&#233;rulos con proliferaci&#243;n intracapilar&#59; EXTRA&#58; porcentaje de glom&#233;rulos con proliferaci&#243;n extracapilar&#59; FGe&#58; filtrado glomerular estimado por CKD- EPI&#59; FIB&#58; superficie total de fibrosis intersticial&#59; GFS&#58; porcentaje de glom&#233;rulos con esclerosis segmentaria&#59; IL-6&#58; interleucina 6&#59; Int Infilt&#58; superficie total de infiltrado intersticial&#59; MCP-1&#58; prote&#237;na quimioatractante de monocitos de tipo 1&#59; Prot&#58; proteinuria de 24&#160;h&#59; TGF&#946;1&#58; factor de crecimiento transformante &#946;1&#46;</p>"
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                  <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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FGe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">GFS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">ENDO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Infilt int&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IL-6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">EGF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TGF&#946;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MCP-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;46<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GFS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;25<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ENDO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;26<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Infilt int&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;21<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;46<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;28<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IL-6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;39<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;35<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;21<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;25<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EGF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;63<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;63<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;45<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TGF&#946;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;23<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;38<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;20<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;21<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;52<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MCP-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;32<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;40<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;20<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;40<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;38<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;22<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;65<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prot&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;57<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;28<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;26<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;24<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;29<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#44;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;44<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;45<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
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                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IL-6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">E1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#44;6<br>&#91;4&#44;2&#8211;15&#44;3&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#44;8<br>&#91;4&#44;6&#8211;59&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">E0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#44;9<br>&#91;1&#44;2&#8211;12&#44;4&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">S0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;18-0&#44;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proteinuria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;06-0&#44;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top">R<span class="elsevierStyleSup">2</span>&#58; 0&#44;56 ANOVA p &#60; 0&#44;0001</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1524901.png"
              ]
            ]
            1 => 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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MCP-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Beta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">IC 95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">t&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Sig&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Esclerosis glomerular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;22-0&#44;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">8&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrosis intersticial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;10-0&#44;75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">3&#44;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Infiltrado intersticial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;13-0&#44;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">2&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proteinuria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;81-0&#44;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">3&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="center" valign="top">0&#44;035&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top">R<span class="elsevierStyleSup">2</span>&#58; 0&#44;49 ANOVA p&#58; 0&#44;026</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1524902.png"
              ]
            ]
            2 => 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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">fTGF&#946;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Beta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IC 95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">t&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sig&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Esclerosis glomerular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;13-0&#44;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#44;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrosis intersticial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;05-0&#44;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#44;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;041&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top">R<span class="elsevierStyleSup">2</span>&#58; 0&#44;47 ANOVA p&#58; 0&#44;035</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1524903.png"
              ]
            ]
            3 => 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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">EGF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Beta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IC 95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">t&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sig&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fibrosis intersticial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;16-0&#44;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&#44;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top">R<span class="elsevierStyleSup">2</span>&#58; 0&#44;39 ANOVA p&#58; 0&#44;008</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1524908.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Predictores independientes de los concentraciones de IL-6&#44; MCP-1&#44; TGF&#946;1 y EGF en orina en los modelos de regresi&#243;n m&#250;ltiple</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0025"
        "etiqueta" => "Tabla 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at5"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tablaImagen" => array:1 [
                0 => array:4 [
                  "imagenFichero" => "fx1.jpeg"
                  "imagenAlto" => 1146
                  "imagenAncho" => 3093
                  "imagenTamanyo" => 180177
                ]
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Modelos predictivos de la extensi&#243;n de la lesiones de fibrosis intersticial mediante an&#225;lisis de regresi&#243;n m&#250;ltiple</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0030"
        "etiqueta" => "Tabla 6"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at6"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Edad &#40;por a&#241;o&#41;&#46; ABC&#58; 0&#44;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;07&#46;</p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">P</span>&#58; 0&#44;0001&#46;</p><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">EGF&#58; <span class="elsevierStyleItalic">epidermal growth factor</span> &#40;por cada aumento en 1<span class="elsevierStyleHsp" style=""></span>ng&#47;mg de creatinina&#41;&#59; FGe&#58; filtrado glomerular estimado mediante la ecuaci&#243;n CKD-EPI &#40;por cada aumento de 1<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#44;73&#160;m<span class="elsevierStyleSup">2</span>&#41;&#59; MCP-1&#58; prote&#237;na quimiotractante de monocitos de tipo 1 &#40;por cada aumento en 1<span class="elsevierStyleHsp" style=""></span>ng&#47;mg de creatinina&#41;&#46;</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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IC&#160;95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sig&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FGe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;68&#8211;0&#44;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Edad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;02&#8211;1&#44;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EGF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;36&#8211;0&#44;96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;034&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MCP-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#44;07&#8211;1&#44;68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1524904.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Modelo de regresi&#243;n log&#237;stica para estimar la probabilidad de presentar fibrosis grado T1-T2 de Oxford en la biopsia renal</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "tbl0035"
        "etiqueta" => "Tabla 7"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at7"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">No se apreciaron diferencias significativas entre el n&#250;mero de enfermos con lesiones de fibrosis intersticial observados y esperados por el modelo en ninguna de las categor&#237;as de riesgo&#46;</p><p id="spar0120" class="elsevierStyleSimplePara elsevierViewall">Fibrosis<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#58; presencia de fibrosis de grado T1 o T2&#46;</p><p id="spar0125" class="elsevierStyleSimplePara elsevierViewall">Chi<span class="elsevierStyleSup">2</span>&#58; 6&#44;98&#59; p&#58; 0&#44;90&#46;</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="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">&#42;</span></a>Categor&#237;as de riesgo</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Fibrosis &#61; 1</th><th class="td" title="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total</th></tr><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Observados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Esperados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#60;0&#44;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#44;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">0&#44;112-0&#44;185&nbsp;\t\t\t\t\t\t\n
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