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uno de ellos es la protecci&#243;n endotelial<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">9&#44;10</span></a>&#46; Distintos estudios han demostrado que calcitriol y AVDR protegen al endotelio de la calcificaci&#243;n al inhibir prote&#237;nas calcificantes como <span class="elsevierStyleItalic">matrix</span> gla prote&#237;na y reduciendo citoquinas proinflamatorias<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">11&#44;12</span></a>&#46; No obstante el efecto de calcitriol podr&#237;a diferir al de PRCT<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">13&#44;14</span></a>&#59; calcitriol&#44; a nivel vascular&#44; podr&#237;a tener dos consecuencias antag&#243;nicas</p><p id="par0015" class="elsevierStylePara elsevierViewall">dosis-dependiente&#58; a dosis hipercalcemiantes calcitriol presenta un efecto procalcificante sobre la CMLV mediado en parte por las acciones del P y mol&#233;culas procalcificantes a nivel celular&#59; PRCT no parece presentar esa dualidad</p><p id="par0020" class="elsevierStylePara elsevierViewall">dosis-dependiente<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">13&#44;14</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Por esta raz&#243;n estudiamos el efecto de PRCT sobre la EOM-ERC y mol&#233;culas asociadas a calcificaci&#243;n vascular&#44; inflamaci&#243;n y fibrosis en pacientes con ERC &#40;estadios III-V sin di&#225;lisis&#41; en b&#250;squeda de un efecto modulador sobre los mismos&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Material y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Pacientes</span><p id="par0030" class="elsevierStylePara elsevierViewall">Se trata de un estudio prospectivo no controlado realizado en el Hospital Universitario de La Princesa &#40;Madrid&#41;&#46; Preseleccionamos a 59 pacientes estadio III-V sin di&#225;lisis&#44; mayores de edad susceptibles de utilizar PRCT por aumento de PTH seg&#250;n estadificaci&#243;n de su ERC<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">1</span></a>&#58; estadio III<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>70 pg&#47;mL&#44; IV<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>110 pg&#47;mL&#44; estadio V<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>150 pg&#47;mL &#40;Gu&#237;as SEN&#41;&#46; Los criterios de exclusi&#243;n fueron&#58; inclusi&#243;n en terapia sustitutiva renal&#44; fallo card&#237;aco y&#47;o hep&#225;tico agudo&#44; enfermedad infecciosa o inmunol&#243;gica activa y alergia a PRCT &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Finalmente seleccionamos a 46 pacientes con un seguimiento de cuatro meses en tratamiento con PRCT&#58; 1mcg diario si PTH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>500 pg&#47;mL y 2 mcg diario si PTH<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>500 pg&#47;mL&#46; Ning&#250;n paciente super&#243; los 500 pg&#47;mL de PTH&#46; Las dosis de PRCT se suspender&#237;an si PTH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>70 pg&#47;mL&#46; Siete pacientes ten&#237;an prescrito calcidiol&#59; no hubo otros tratamientos relacionados con vitamina D o an&#225;logos&#44; por lo que se realiz&#243; periodo de lavado de un mes previo al inicio del estudio&#46; No hubo p&#233;rdidas de pacientes en el seguimiento durante estos cuatro meses&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Determinaciones</span><p id="par0035" class="elsevierStylePara elsevierViewall">Se realizaron determinaciones anal&#237;ticas sangu&#237;neas y urinarias en el momento basal&#44; al mes y a los cuatro meses de iniciado PRCT&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Las muestras sangu&#237;neas de los test espec&#237;ficos se centrifugaron a 1200 revoluciones por minuto durante 10 minutos&#44; se extrajo el suero&#44; se alicuot&#243; y almacen&#243; a -80<span class="elsevierStyleHsp" style=""></span>&#176;C para su posterior an&#225;lisis&#46; Las determinaciones de ELISA fueron efectuadas de acuerdo al protocolo descrito por el fabricante&#46; Las concentraciones de los par&#225;metros se determinaron por la curva est&#225;ndar y respectivas diluciones&#46; Los par&#225;metros bioqu&#237;micos valorados en cada una de las visitas fueron&#58; creatinina &#40;Cr&#41;&#44; MDRD 4 tasa de filtrado glomerular &#40;TFG&#41;&#44; proteinuria mg&#47;24<span class="elsevierStyleHsp" style=""></span>h&#44; Ca&#44; Pi&#44; calcidiol &#40;Roche&#47;Hitachi Cobas&#41;&#44; PTHi &#40;Roche&#47;Hitachi Cobas&#174;&#58; fragmentos 1-84&#41;&#44; fracci&#243;n soluble Klotho &#40;ELISA Cusabio&#174;&#44; 7&#44;8-500 pg&#47;mL&#41;&#44; iFGF-23 &#40;Millipore&#174;&#59; 9&#44;9-2400 pg&#47;mL&#41;&#46; Par&#225;metros relacionados con la inflamaci&#243;n&#58; interleucina &#40;IL&#41; 6 &#40;R &#38; D&#174;&#44; HS600B&#59; 0&#44;156-10 pg&#47;mL&#41;&#44; TNF<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>&#945; &#40;ELISA R &#38; D&#44; HSTA00D&#59; 0&#44;52-32 pg&#47;mL&#41;&#44; IL10 &#40;R &#38; D&#44; 0&#44;78-50 pg&#47;mL&#41;&#44; prote&#237;na C reactiva &#40;PCR&#41; &#40;Roche&#47;Hitachi Cobas&#41; &#174;&#46; Par&#225;metros relacionados con calcificaci&#243;n y fibrosis&#58; Ft-A &#40;Bio Vendor&#59; 0&#44;698-2&#46;330<span class="elsevierStyleHsp" style=""></span>g&#47;L&#41;&#44; BMP-7 &#40;R &#38; D&#59; 31&#46;20-2000 pg&#47;mL&#41; &#174;&#44; TGF-&#946;1 &#40;R &#38; D systems Quantikine ELISA&#174;&#59; 31&#46;20-2000 pg&#47;mL&#41;&#8901;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">An&#225;lisis estad&#237;stico</span><p id="par0045" class="elsevierStylePara elsevierViewall">Realizamos un estudio anal&#237;tico prospectivo no controlado antes-despu&#233;s&#46; Las variables recogidas fueron analizadas por el programa estad&#237;stico SPSS-21&#46; El an&#225;lisis se hizo considerando las tres evaluaciones bioqu&#237;micas de los pacientes &#40;basal&#44; uno y cuatro meses&#41;&#46; Las variables dimensionales se muestran como promedio<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>desviaci&#243;n est&#225;ndar &#40;DE&#41;&#46; Las variables nominales se muestran como n&#250;meros o porcentajes&#46; Las diferencias intragrupo fueron analizadas mediante <span class="elsevierStyleItalic">ANOVA</span> one way para muestras repetidas<span class="elsevierStyleItalic">&#46;</span> Se consider&#243; como resultado significativo un valor p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Medidas de seguridad y consideraciones &#233;ticas</span><p id="par0050" class="elsevierStylePara elsevierViewall">El presente estudio es considerado categor&#237;a II&#44; con riesgo m&#237;nimo&#46; En cada visita se indag&#243; sobre la presencia de eventos adversos tomando las medidas oportunas&#46; Se obtuvo consentimiento informado por parte de los pacientes<span class="elsevierStyleItalic">&#46;</span> La recogida de datos se realiz&#243; respetando la confidencialidad del paciente seg&#250;n la Ley de Protecci&#243;n de Datos de Car&#225;cter Personal y se respetaron los aspectos &#233;ticos de la investigaci&#243;n en seres humanos en Espa&#241;a&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Resultados</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Descripci&#243;n de la cohorte</span><p id="par0055" class="elsevierStylePara elsevierViewall">Seleccionamos 46 pacientes&#58; 38 hombres &#40;82&#37;&#41; y 8 &#40;18&#37;&#41; mujeres&#44; con una edad media de 73 a&#241;os&#46; Los porcentajes seg&#250;n estadificaci&#243;n de ERC y etiolog&#237;a se muestran en la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#46; En cuanto a los tratamientos farmacol&#243;gicos 7 pacientes &#40;15&#37;&#41; tomaban previamente calcidiol &#40;periodo de lavado durante un mes previo al inicio del estudio&#41;&#44; 6 pacientes &#40;13&#37;&#41; estaban en tratamiento con captores del f&#243;sforo y 33 pacientes &#40;71&#44;8&#37;&#41; ten&#237;an prescrito inhibidores del sistema renina angiotensina aldosterona &#40;SRAA&#41;&#46; Ninguno de ellos presentaba tratamiento concomitante con cinacalcet&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Efecto de paricalcitol sobre las variables bioqu&#237;micas generales&#44; tasa de filtrado glomerular y proteinuria</span><p id="par0060" class="elsevierStylePara elsevierViewall">Los cambios experimentados&#44; tras la administraci&#243;n de PRCT&#44; sobre las variables hemoglobina&#44; hierro&#44; saturaci&#243;n de trasferrina&#44; CO2 total&#44; alb&#250;mina&#44; prealb&#250;mina&#44; perfil hep&#225;tico y lip&#237;dico no mostraron cambios significativos&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">La proteinuria no vari&#243; significativamente &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;299&#41;&#59; tampoco se produjo descenso significativo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;766&#41; entre los pacientes que no presentaban tratamiento con inhibidores del SRAA &#40;28&#44;2&#37;&#41;&#46; S&#237; se produjo un aumento de creatinina significativo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#41; y cercano a la significaci&#243;n estad&#237;stica en la TFG &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;053&#41;&#59; ante estos datos subdividimos a los pacientes seg&#250;n grado de ERC catalog&#225;ndola como grave si TFG<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#44;73m<span class="elsevierStyleSup">2</span> &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41; o moderada si TFG<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#44;73m<span class="elsevierStyleSup">2</span> &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#41;&#46; En los pacientes con ERC grave se produjo un descenso significativo de la TFG &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;&#59; sin embargo&#44; entre los pacientes con ERC moderada&#44; no hubo significaci&#243;n estad&#237;stica &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;652&#41;&#46; Estos datos los mostramos en la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Efecto de PRCT sobre la EOM-ERC</span><p id="par0070" class="elsevierStylePara elsevierViewall">Los marcadores cl&#225;sicos de la EOM-ERC como Ca y P no se vieron modificados &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;112&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;066 respectivamente&#41;&#46; No hubo aumentos de Ca por encima<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL ni de P<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>5&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; por lo que no hubo que modificar la pauta de captores del P ni dosis de PRCT&#46; S&#237; se observ&#243; un descenso significativo de PTHi &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41;&#59; no obstante&#44; los valores de PTHi se mantuvieron en rango seg&#250;n estadificaci&#243;n en todos los pacientes &#40;Gu&#237;as SEN&#41; por lo que no hubo que suspender PRCT en ning&#250;n paciente&#46; Tambi&#233;n observamos un aumento de calcidiol significativo &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;010&#41;&#46; Datos desglosados en la <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">En cuanto a los par&#225;metros m&#225;s novedosos de la EOM-ERC &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#44; iFGF-23 no se modific&#243; significativamente a lo largo del estudio &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;577&#41;&#59; tampoco entre los pacientes en tratamiento con captores del P &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;125&#41;&#46; Calculamos la diferencia de medias al finalizar el estudio &#40;t de Student para muestras independientes&#41; entre pacientes con o sin captores del P&#44; el resultado no alcanz&#243; la significaci&#243;n estad&#237;stica &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;953&#44; con una diferencia de medias de 2&#44;48&#41;&#46; Se produjo un aumento significativo de los niveles de Klotho &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Efectos de PRCT sobre par&#225;metros relacionados con inflamaci&#243;n&#44; fibrosis y calcificaci&#243;n vascular</span><p id="par0080" class="elsevierStylePara elsevierViewall">No apreciamos cambios estad&#237;sticamente significativos en los niveles de PCR&#44; aunque la tendencia fue descendente&#46; IL6 y TNF-&#945; descendieron de forma significativa tras el uso de PRCT&#58; IL6 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y TNF-&#945; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;005&#41;&#46; IL10&#44; par&#225;metro antiinflamatorio&#44; aument&#243; significativamente &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; En cuanto a par&#225;metros relacionados con la fibrosis y calcificaci&#243;n vascular&#44; observamos aumento significativo de Ft-A &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y BMP-7 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y descenso de TGF-&#946;1 &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Datos mostrados en la <a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a> y <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a>&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Efectos adversos</span><p id="par0085" class="elsevierStylePara elsevierViewall">Durante el estudio no se produjeron reacciones adversas al medicamento&#44; ni cambios en el tratamiento&#46; No se produjeron ingresos ni eventos cardiovasculares&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discusi&#243;n</span><p id="par0090" class="elsevierStylePara elsevierViewall">En nuestro estudio los pacientes presentaban una mejor&#237;a de par&#225;metros relacionados con los procesos inflamatorio&#44; fibr&#243;tico y de calcificaci&#243;n vascular&#46; El impacto sobre marcadores de EOM-ERC muestran estabilidad en variables como Ca&#44; P&#44; FGF-23 y mejor&#237;a en otros como Klotho o PTH&#46; La EOM-ERC y la inflamaci&#243;n son determinantes en el inicio y la progresi&#243;n de la ERC y del RCV en estos enfermos<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">15&#44;16</span></a>&#46; PRCT ha demostrado&#44; en m&#250;ltiples estudios experimentales&#44; su perfil seguro y beneficioso para regular la EOM-ERC y marcadores inflamatorios en la ERC sin agravar el proceso renal<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">17&#44;18</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">En diferentes estudios se ha evaluado el efecto sobre la funci&#243;n renal y proteinuria de PRCT&#46; El estudio VITAL<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">19</span></a> demostr&#243;&#44; en pacientes diab&#233;ticos tipo 2&#44; una reducci&#243;n de proteinuria significativa a dosis de 2 ug&#47;d&#237;a de PRCT&#46; Similares resultados mostr&#243; el estudio de Agarwal et al&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">20</span></a> en pacientes con ERC EIII-IV&#46; El efecto antiprotein&#250;rico de PRCT&#44; y vitamina D activa&#44; tiene relaci&#243;n con la regulaci&#243;n del proceso proliferativo y fibr&#243;tico<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">21&#44;22</span></a> y bloqueo del SRAA<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">19&#44;23</span></a>&#59; la inhibici&#243;n farmacol&#243;gica de este eje puede condicionar que haya que aumentar la dosis de PRCT para conseguir el descenso de proteinuria&#46; En nuestro estudio no obtuvimos diferencias significativas en la evoluci&#243;n de la proteinuria&#44; tal vez debido al amplio uso de los inhibidores del SRAA &#40;71&#44;8&#37;&#41;&#46; En cuanto a la TFG&#44; no obtuvimos datos estad&#237;sticos significativos aunque s&#237; una tendencia al descenso tal vez debido al deterioro significativo que mostraban los enfermos con TFG<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#44;73m<span class="elsevierStyleSup">2</span>&#46; En cuanto al aumento significativo de Cr podr&#237;a estar en relaci&#243;n a la influencia de variables externas como sexo&#44; edad&#44; masa muscular y estado nutricional sobre esta variable&#46; Podr&#237;amos concluir que la activaci&#243;n del receptor de vitamina D con PRCT mantiene la TFG estable&#44; coincidiendo con otros estudios<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">24&#44;25</span></a>&#46; Este efecto de PRCT podr&#237;a conllevar la atenuaci&#243;n sobre el da&#241;o glomerular&#44; tubulointersticial y endotelial que ha demostrado en ensayos experimentales mediante efectos antiinflamatorios<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">26&#44;27</span></a>&#44; antifibr&#243;ticos<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">28</span></a> y antiprotein&#250;ricos<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">19&#44;20</span></a> como comentaremos a posteriori&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Como era de esperar&#44; PRCT redujo PTHi de manera significativa coincidiendo con diversos estudios<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">29&#44;30</span></a>&#46; Evidenciamos estabilidad en los niveles de Ca y P&#44; aunque en el caso del P la tendencia era al alza&#46; Este efecto menos hipercalcemiante e hiperfosfatemiante de PRCT viene determinado al producirse menos calbindina intestinal y a su menor afinidad por los receptores intestinales de vitamina D<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">31</span></a>&#44; lo cual podr&#237;a influir en la g&#233;nesis de la calcificaci&#243;n vascular&#46; No hay un claro mecanismo del aumento de calcidiol en nuestro estudio&#59; tal vez sea debido a la estabilidad de FGF-23 &#40;estimulante de la 24-hidroxilasa que inactiva calcidiol&#41; que obtuvimos&#46; En este sentido&#44; y siguiendo en el marco de la EOM&#44; el efecto de PRCT sobre marcadores como FGF-23 y Klotho ser&#237;a relevante dado que ambos par&#225;metros podr&#237;an modular la calcificaci&#243;n vascular&#44; el estado inflamatorio y la funci&#243;n renal&#46; En el caso de Klotho obtuvimos un aumento significativo de sus niveles s&#233;ricos&#59; Klotho posee efectos beneficiosos a nivel mioc&#225;rdico y la hipertrofia ventricular izquierda<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">33&#44;34</span></a>&#44; antiinflamatorios<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">32&#44;36</span></a> &#40;descenso de los niveles de IL6 y 18&#41;&#44; antifibr&#243;ticos<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">35</span></a> &#40;descenso de TGF-&#946;&#41; y efectos antiapoptoicos<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">37</span></a> que podr&#237;an influir en la g&#233;nesis de la calcificaci&#243;n vascular<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">32&#44;36</span></a>&#46; PRCT ha demostrado regular al alza los niveles de Klotho en diversos estudios como el de Lau et al&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">11</span></a> donde el tratamiento de PRCT y calcitriol&#44; en ratones ur&#233;micos con calcificaci&#243;n vascular&#44; aument&#243; de forma significativa los niveles de Klotho urinarios y s&#233;ricos&#46; En lo referente a los niveles FGF-23 nuestro estudio mostr&#243; resultados dispares frente a otros como el IMPACT<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">38</span></a> o PARADIGM<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">39</span></a> donde el uso de PRCT o calcitriol&#44; en pacientes en hemodi&#225;lisis&#44; aumentaba FGF-23&#46; Esta discordancia podr&#237;a ser debida a que nuestros pacientes no estaban incluidos en di&#225;lisis y se les presupone mayor funci&#243;n renal residual&#46; No hay duda de que el aumento de FGF-23 en la ERC se relaciona con la calcificaci&#243;n vascular&#44; aunque no como inductor<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">40</span></a>&#44; y con un aumento en la morbimortalidad vascular<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">41&#8211;43</span></a>&#46; FGF-23 suprime los niveles de calcitriol<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">3&#44;6</span></a> y de Ft-A<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">41</span></a> &#40;potente anticalcificante&#41;&#44; provoca disfunci&#243;n endotelial&#44; desarrollo de hipertrofia ventricular izquierda y proteinuria<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">41&#44;42</span></a>&#46; Muchos de estos mecanismos procalcificantes de FGF-23 tienen como agravante el ambiente inflamatorio de la ERC<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">3&#44;44</span></a> que es estimulado por FGF-23 induciendo el aumento de IL6 y TNF-&#945; <a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">45</span></a>&#46; A su vez&#44; el propio estado inflamatorio regula al alza los niveles de FGF-23&#58; TNF-&#945; y NF-&#954;B pueden inhibir la matriz &#243;sea y aumentar la producci&#243;n de FGF-23 en el osteocito<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">45</span></a>&#46; Adem&#225;s el estado proinflamatorio y fibr&#243;tico de la ERC modula los niveles de Klotho a la baja<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">36</span></a>&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">La propia inflamaci&#243;n es un target terap&#233;utico en la ERC donde PRCT ha demostrado sus efectos beneficiosos<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">13&#44;14</span></a>&#46; Tras el uso de PRCT nuestros pacientes presentaban un efecto bioqu&#237;mico antiinflamatorio favorable al descender de manera significativamente los niveles de IL6 y TNF-&#945; y aumentar IL10&#44; mediado tal vez por el aumento de Klotho y estabilidad de FGF-23 o por un efecto directo del f&#225;rmaco&#46; Donate et al&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">22</span></a> coinciden con nuestros resultados&#59; estos autores demostraron en pacientes con ERC y elevaci&#243;n de PTH &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#59; estadiajes IIIB-IV&#41; que el tratamiento con PRCT provoc&#243; un descenso significativo de IL6 y TNF-&#945;&#46; El efecto antiinflamatorio de PRCT podr&#237;a estar condicionado por la disminuci&#243;n de la producci&#243;n de citoquinas por las c&#233;lulas T<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">26&#44;27</span></a>&#46; Estos efectos antiinflamatorios de PRCT podr&#237;an influir sobre par&#225;metros anticalcificantes como Ft-A o BMP-7 &#40;descendidos en pacientes con ERC<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">8&#44;46</span></a>&#41;&#44; y fibr&#243;ticos como TGF-&#946; &#40;aumentado en ERC&#41;&#46; El aumento de Ft-A tras el uso de PRCT que obtuvimos podr&#237;a mejorar el perfil procalcificante&#44; al igual que los resultados que obtuvimos sobre BMP-7 que&#44; adem&#225;s de sus efectos anticalcificantes<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">47&#44;48</span></a> &#40;inhibe el cotransportador Na&#47;Pi de las CMLV&#41;&#44; promueve la formaci&#243;n &#243;sea y presenta efectos antiinflamatorios<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">47&#44;49</span></a>&#46; El caso de TGF-&#946; es el contrario a BMP-7&#59; su descenso&#44; significativo en nuestro estudio&#44; podr&#237;a implicar nefroprotecci&#243;n y una atenuaci&#243;n del da&#241;o vascular<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">50</span></a> al disminuir la migraci&#243;n de stem cells mesenquimales osteoprogenitoras a las zonas da&#241;adas<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">51</span></a> promovida por TGF-&#946; y disminuyendo la apoptosis&#44; proliferaci&#243;n y diferenciaci&#243;n celular<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">52</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Nuestro estudio tiene limitaciones&#59; los pacientes son controles de s&#237; mismos&#44; no poseemos grupo placebo&#44; el tiempo de observaci&#243;n es corto y nuestra cohorte peque&#241;a lo cual puede conllevar alteraciones en la interpretaci&#243;n de resultados&#46; Adem&#225;s&#44; no diferenciamos los meses de inclusi&#243;n de los pacientes que podr&#237;a influir en los niveles de calcidiol al variar estacionalmente&#46; Basamos nuestros resultados en marcadores sangu&#237;neos y no en modelos experimentales de lesi&#243;n vascular&#59; as&#237; mismo no hemos aportado datos sobre otras mol&#233;culas como RANK-L &#40;ligando de r<span class="elsevierStyleItalic">eceptor</span>&#160;activador del factor nuclear &#954; beta&#41;&#44; osteopontina u osteoprotegerina&#46; Como contrapunto los par&#225;metros analizados abarcan una importante influencia en la calcificaci&#243;n vascular&#44; la inflamaci&#243;n y la fibrosis con una posible regulaci&#243;n favorable tras el tratamiento con PRCT&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusiones</span><p id="par0115" class="elsevierStylePara elsevierViewall">El tratamiento con PRCT&#44; en el paciente renal sin di&#225;lisis&#44; parece ser beneficioso en la regulaci&#243;n de par&#225;metros inflamatorios&#44; fibr&#243;ticos y anticalcificantes&#59; as&#237; como sobre marcadores cl&#225;sicos y no cl&#225;sicos de la EOM-ERC preservando la funci&#243;n renal&#46; No existe un marcador que valore los efectos pleiotr&#243;picos de PRCT en la enfermedad renal&#46; Los marcadores elegidos en nuestro estudio podr&#237;an indicarnos su efecto en la enfermedad &#243;seo-mineral renal y&#44; en concreto&#44; en el proceso de calcificaci&#243;n vascular&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Los datos obtenidos podr&#237;an indicar un efecto modulador de PRCT positivos sobre marcadores relacionados con la calcificaci&#243;n vascular&#44; el estado inflamatorio y fibr&#243;tico de la ERC&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">El abordaje terap&#233;utico de los AVDR sigue sin ser explorado en la cl&#237;nica de los pacientes con ERC&#44; quedando relegado como uso exclusivo en el hiperparatiroidismo secundario y sin la realizaci&#243;n de ensayos cl&#237;nicos con expectativas m&#225;s amplias en los &#250;ltimos a&#241;os en la pr&#225;ctica cl&#237;nica&#46; Esto deja un campo a&#250;n por explorar especialmente en lo que ata&#241;e a la calcificaci&#243;n vascular en pacientes con enfermedad renal cr&#243;nica&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicto de intereses</span><p id="par0130" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
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              "titulo" => "Pacientes"
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            1 => array:2 [
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              "titulo" => "Determinaciones"
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            2 => array:2 [
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              "titulo" => "An&#225;lisis estad&#237;stico"
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              "titulo" => "Descripci&#243;n de la cohorte"
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              "titulo" => "Efecto de paricalcitol sobre las variables bioqu&#237;micas generales&#44; tasa de filtrado glomerular y proteinuria"
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              "titulo" => "Efecto de PRCT sobre la EOM-ERC"
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              "titulo" => "Efectos de PRCT sobre par&#225;metros relacionados con inflamaci&#243;n&#44; fibrosis y calcificaci&#243;n vascular"
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    "fechaRecibido" => "2019-02-16"
    "fechaAceptado" => "2019-08-23"
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            1 => "FGF-23"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Antecedentes</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">La principal causa de morbimortalidad en el paciente con enfermedad renal cr&#243;nica &#40;ERC&#41; es la cardiovascular&#46; La inflamaci&#243;n y las alteraciones en el metabolismo &#243;seo-mineral en estos pacientes conllevan aumento del riesgo cardiovascular&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Valorar el papel de paricalcitol sobre distintos par&#225;metros s&#233;ricos relacionados con inflamaci&#243;n&#44; fibrosis y enfermedad &#243;seo-mineral en la ERC&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Material y m&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo&#44; no controlado en 46 pacientes con ERC estadios III-V sin di&#225;lisis&#44; con niveles elevados de paratohormona&#44; seg&#250;n su estadio de ERC&#44; por lo que se introdujo tratamiento con el an&#225;logo de vitamina D paricalcitol&#46; Durante 4 meses de tratamiento valoramos los par&#225;metros cl&#225;sicos y novedosos del metabolismo &#243;seo-mineral en suero &#40;calcio&#44; f&#243;sforo&#44; paratohormona&#44; factor de crecimiento fibrobl&#225;stico-23 &#91;FGF-23&#93;&#44; Klotho y calcidiol&#41; y par&#225;metros relacionados con el proceso de inflamaci&#243;n-fibrosis y anticalcificantes &#40;interleucina-6 y 10&#44; factor de necrosis tumoral alfa &#91;TNF-a&#93;&#44; factor de crecimiento transformante beta &#91;TGF-b&#93;&#44; prote&#237;na &#243;sea morfog&#233;nica-7 &#91;BMP-7&#93;&#44; y fetu&#237;na-A&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Tras el uso de paricalcitol los niveles de Klotho aumentaron &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y los de FGF-23 se mantuvieron estables al igual que los de calcio y f&#243;sforo&#59; calcidiol aument&#243; de forma significativa &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;010&#41; y paratohormona descendi&#243; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;&#46; Los par&#225;metros de inflamaci&#243;n&#44; fibrosis y calcificaci&#243;n mostraron una regulaci&#243;n benigna con descenso significativo de interleucina-6 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; TNF-&#945; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;005&#41; y TGF-&#946; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y aumento de BMP-7 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; fetu&#237;na-A &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; e interleucina-10 &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; El filtrado glomerular y la proteinuria se mantuvieron estables&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusiones</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El tratamiento con paricalcitol en el paciente renal sin di&#225;lisis parece ser beneficioso en la regulaci&#243;n de los par&#225;metros inflamatorios y anticalcificantes&#44; preservando la funci&#243;n renal y el eje &#243;seo-mineral&#46; Los marcadores elegidos en nuestro estudio podr&#237;an indicarnos un efecto positivo de paricalcitol a nivel vascular&#46;</p></span>"
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      "en" => array:3 [
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Backward</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular events are the major cause of morbidity and mortality in patients with chronic kidney disease &#40;CKD&#41;&#46; Inflammation and mineral-bone disorder are pathological conditions that have been associated with an increased cardiovascular risk&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objective</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Show paricalcitol regulation overinflammatory&#44; fibrotic and mineral disorder parameters in CKD&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material and methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Prospective Study in 46 CKD stages III-V patients without dialysis patients whith elevated parathormone in which we introduced paricalcitol&#46; We evaluated classic and newest mineral and bone metabolism serum parameters &#40;calcium&#44; phosphorus&#44; parathormone&#44; fibroblast growth factor-23 &#91;FGF-23&#93;&#44; Klotho&#44; calcidiol&#41;&#44; inflammatory-fibrosis and anticalcifying parameters &#40;interleukin-6 and 10&#44; tumor necrosis factor-a &#91;TNF- &#945;&#93;&#44; transforming growth factor-b &#91;TGF-&#946;&#93;&#44;bone morphogenic protein-7 &#91;BMP-7&#93; and fetuin-A&#41; for four months&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">At the end of study soluble Klotho increased &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; FGF-23 remained stable&#44; calcium and phosphorus levels were not increased&#44; calcidiol increased &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;010&#41; and PTH decreased &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleMonospace">&#46;</span>002&#41;&#46; Inflammation-fibrosis and calcification parameters showed positive regulation after paricalcitol treatment&#58; interleukin-6 decreased significantly &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; and also TNF-&#945; did &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;005&#41;&#44; on the contrary&#44; interleukin-10 and fetuin-A increased &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001 for both&#41;&#46; Anti-fibrosis marker BMP-7 increased &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; and TGF-b decreased &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; We did not find significant changes in renal function&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusions</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Paricalcitol treatment might be profitable in regulating inflammatory and anticalcificant parameters&#44; unmodified calcium or phosphorus seric levels and preserving kidney function in renal patients with no dialysis&#46; Our selected parameters could indicate paricalcitol effects in mineral and endothelial disorder related to renal disease&#46;</p></span>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p valor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Creatinina &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&#44;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;05&#40;1&#44;3-6&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;08&#40;1&#44;2-6&#44;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;69<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;18&#40;1&#44;1-7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">0&#44;007</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TFG MDRD 4 &#40;mL&#47;min&#47;1&#44;73m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Positivo&#60;<span class="elsevierStyleHsp" style=""></span>60&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#44;8&#40;8&#44;2-59&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;52<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#44;70&#40;7&#44;4-59&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">27&#44;81<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44;31&#40;6&#44;3-63&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;053&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>30 mL&#47;min&#47;1&#44;73m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">36&#44;11<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;17&#40;24&#44;2-59&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44;77&#40;30&#44;2-59&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&#44;69<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#44;62&#40;30&#44;3-63&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;652&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;<span class="elsevierStyleHsp" style=""></span>30 mL&#47;min&#47;1&#44;73m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">22&#44;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#44;57&#40;8&#44;2-29&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">28&#44;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#44;98&#40;7&#44;4-29&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#44;55<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;98&#40;6&#44;3-28&#44;6&#44;2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Proteinuria &#40;mg&#47;24h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">9&#44;39<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;52&#40;8&#44;5-10&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">P &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#44;57<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;80&#40;2&#44;2-5&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">119<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>87&#44;79&#40;40-368&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Fetu&#237;na A g&#47;L&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">0&#44;0001</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">TGF-&#946;1 pg&#47;mL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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