Estadísticas

 array:25 [
  "pii" => "S0211699516300078"
  "issn" => "02116995"
  "doi" => "10.1016/j.nefro.2016.01.011"
  "estado" => "S300"
  "fechaPublicacion" => "2016-07-01"
  "aid" => "175"
  "copyright" => "Sociedad Española de Nefrología"
  "copyrightAnyo" => "2016"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "ssu"
  "cita" => "Nefrologia. 2016;36:368-75"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 21168
    "formatos" => array:3 [
      "EPUB" => 357
      "HTML" => 18584
      "PDF" => 2227
    ]
  ]
  "Traduccion" => array:1 [
    "en" => array:20 [
      "pii" => "S2013251416300700"
      "issn" => "20132514"
      "doi" => "10.1016/j.nefroe.2016.08.001"
      "estado" => "S300"
      "fechaPublicacion" => "2016-07-01"
      "aid" => "175"
      "copyright" => "Sociedad Española de Nefrología"
      "documento" => "article"
      "crossmark" => 0
      "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
      "subdocumento" => "ssu"
      "cita" => "Nefrologia (English Version). 2016;36:368-75"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:2 [
        "total" => 7564
        "formatos" => array:3 [
          "EPUB" => 371
          "HTML" => 6254
          "PDF" => 939
        ]
      ]
      "en" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
        "titulo" => "Bone mineral disorder in chronic kidney disease&#58; Klotho and FGF23&#59; cardiovascular implications"
        "tienePdf" => "en"
        "tieneTextoCompleto" => "en"
        "tieneResumen" => array:2 [
          0 => "en"
          1 => "es"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "368"
            "paginaFinal" => "375"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "es" => array:1 [
            "titulo" => "Enfermedad &#243;seo mineral relacionada con la enfermedad renal cr&#243;nica&#58; Klotho y FGF23&#59; implicaciones cardiovasculares"
          ]
        ]
        "contieneResumen" => array:2 [
          "en" => true
          "es" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "en" => true
        ]
        "contienePdf" => array:1 [
          "en" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0010"
            "etiqueta" => "Fig&#46; 2"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr2.jpeg"
                "Alto" => 1764
                "Ancho" => 2332
                "Tamanyo" => 295812
              ]
            ]
            "descripcion" => array:1 [
              "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Diagram of BMD-CKD abnormalities and involvement in vascular calcification&#46; CVD&#58; cardiovascular disease&#59; uP&#58; urine phosphorus&#59; pP&#58; plasma phosphorus&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Laura Salanova Villanueva, Carmen S&#225;nchez Gonz&#225;lez, Jos&#233; Antonio S&#225;nchez Tomero, Abelardo Aguilera, Esther Ortega Junco"
            "autores" => array:5 [
              0 => array:2 [
                "nombre" => "Laura"
                "apellidos" => "Salanova Villanueva"
              ]
              1 => array:2 [
                "nombre" => "Carmen"
                "apellidos" => "S&#225;nchez Gonz&#225;lez"
              ]
              2 => array:2 [
                "nombre" => "Jos&#233; Antonio"
                "apellidos" => "S&#225;nchez Tomero"
              ]
              3 => array:2 [
                "nombre" => "Abelardo"
                "apellidos" => "Aguilera"
              ]
              4 => array:2 [
                "nombre" => "Esther"
                "apellidos" => "Ortega Junco"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "en"
      "Traduccion" => array:1 [
        "es" => array:9 [
          "pii" => "S0211699516300078"
          "doi" => "10.1016/j.nefro.2016.01.011"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => true
            "ES2" => true
            "LATM" => true
          ]
          "gratuito" => true
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "es"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699516300078?idApp=UINPBA000064"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251416300700?idApp=UINPBA000064"
      "url" => "/20132514/0000003600000004/v1_201612030031/S2013251416300700/v1_201612030031/en/main.assets"
    ]
  ]
  "itemSiguiente" => array:20 [
    "pii" => "S0211699516300121"
    "issn" => "02116995"
    "doi" => "10.1016/j.nefro.2016.03.009"
    "estado" => "S300"
    "fechaPublicacion" => "2016-07-01"
    "aid" => "180"
    "copyright" => "Sociedad Espa&#241;ola de Nefrolog&#237;a"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Nefrologia. 2016;36:376-80"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 7656
      "formatos" => array:3 [
        "EPUB" => 363
        "HTML" => 6131
        "PDF" => 1162
      ]
    ]
    "es" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Art&#237;culo especial</span>"
      "titulo" => "Plan PrEFiNE&#58; Plan estrat&#233;gico para la enfermedad de Fabry en Nefrolog&#237;a"
      "tienePdf" => "es"
      "tieneTextoCompleto" => "es"
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "376"
          "paginaFinal" => "380"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "PrEFiNe Plan&#58; Strategic plan for Fabry diseases in Nephrology"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "es" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figura 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 2638
              "Ancho" => 3167
              "Tamanyo" => 411469
            ]
          ]
          "descripcion" => array:1 [
            "es" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Acciones&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "M&#46;D&#46; del Pino, A&#46; Ortiz, R&#46; Torra, D&#46; Hernandez"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "M&#46;D&#46;"
              "apellidos" => "del Pino"
            ]
            1 => array:2 [
              "nombre" => "A&#46;"
              "apellidos" => "Ortiz"
            ]
            2 => array:2 [
              "nombre" => "R&#46;"
              "apellidos" => "Torra"
            ]
            3 => array:2 [
              "nombre" => "D&#46;"
              "apellidos" => "Hernandez"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S201325141630089X"
        "doi" => "10.1016/j.nefroe.2016.10.002"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S201325141630089X?idApp=UINPBA000064"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699516300121?idApp=UINPBA000064"
    "url" => "/02116995/0000003600000004/v2_201611160150/S0211699516300121/v2_201611160150/es/main.assets"
  ]
  "itemAnterior" => array:20 [
    "pii" => "S0211699516300303"
    "issn" => "02116995"
    "doi" => "10.1016/j.nefro.2016.03.023"
    "estado" => "S300"
    "fechaPublicacion" => "2016-07-01"
    "aid" => "198"
    "copyright" => "Sociedad Espa&#241;ola de Nefrolog&#237;a"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "ssu"
    "cita" => "Nefrologia. 2016;36:354-67"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 11316
      "formatos" => array:3 [
        "EPUB" => 335
        "HTML" => 9518
        "PDF" => 1463
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
      "titulo" => "Immune response and histology of humoral rejection in kidney transplantation"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "354"
          "paginaFinal" => "367"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Respuesta inmune e histolog&#237;a de rechazo humoral en el trasplante renal"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Fig&#46; 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1897
              "Ancho" => 3327
              "Tamanyo" => 310171
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Non-covalent antigen&#8211;antibody binding regulated by hydrogen bonds and electrostatic&#44; van der Waals and hydrophobic forces&#46; Structure of an IgG antibody&#46; The antigen binding sites are formed by the juxtaposition of variable light chain &#40;VL&#41; and heavy chain &#40;VH&#41; domains&#46; The CH2 domain of the Fc region is the binding site for C1q or Fc&#947;R of inflammatory cells&#46; CDRs&#58; complementarity domain regions&#46; HC&#58; heavy chain&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Miguel Gonz&#225;lez-Molina, Pedro Ruiz-Esteban, Abelardo Caballero, Dolores Burgos, Mercedes Cabello, Miriam Leon, Laura Fuentes, Domingo Hernandez"
          "autores" => array:8 [
            0 => array:2 [
              "nombre" => "Miguel"
              "apellidos" => "Gonz&#225;lez-Molina"
            ]
            1 => array:2 [
              "nombre" => "Pedro"
              "apellidos" => "Ruiz-Esteban"
            ]
            2 => array:2 [
              "nombre" => "Abelardo"
              "apellidos" => "Caballero"
            ]
            3 => array:2 [
              "nombre" => "Dolores"
              "apellidos" => "Burgos"
            ]
            4 => array:2 [
              "nombre" => "Mercedes"
              "apellidos" => "Cabello"
            ]
            5 => array:2 [
              "nombre" => "Miriam"
              "apellidos" => "Leon"
            ]
            6 => array:2 [
              "nombre" => "Laura"
              "apellidos" => "Fuentes"
            ]
            7 => array:2 [
              "nombre" => "Domingo"
              "apellidos" => "Hernandez"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S2013251416300712"
        "doi" => "10.1016/j.nefroe.2016.08.002"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251416300712?idApp=UINPBA000064"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699516300303?idApp=UINPBA000064"
    "url" => "/02116995/0000003600000004/v2_201611160150/S0211699516300303/v2_201611160150/en/main.assets"
  ]
  "es" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Revisi&#243;n</span>"
    "titulo" => "Enfermedad &#243;seo mineral relacionada con la enfermedad renal cr&#243;nica&#58; Klotho y FGF23&#59; implicaciones cardiovasculares"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "368"
        "paginaFinal" => "375"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Laura Salanova Villanueva, Carmen S&#225;nchez Gonz&#225;lez, Jos&#233; Antonio S&#225;nchez Tomero, Abelardo Aguilera, Esther Ortega Junco"
        "autores" => array:5 [
          0 => array:4 [
            "nombre" => "Laura"
            "apellidos" => "Salanova Villanueva"
            "email" => array:1 [
              0 => "aelita&#46;sv&#64;gmail&#46;com"
            ]
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:2 [
            "nombre" => "Carmen"
            "apellidos" => "S&#225;nchez Gonz&#225;lez"
          ]
          2 => array:2 [
            "nombre" => "Jos&#233; Antonio"
            "apellidos" => "S&#225;nchez Tomero"
          ]
          3 => array:2 [
            "nombre" => "Abelardo"
            "apellidos" => "Aguilera"
          ]
          4 => array:2 [
            "nombre" => "Esther"
            "apellidos" => "Ortega Junco"
          ]
        ]
        "afiliaciones" => array:1 [
          0 => array:2 [
            "entidad" => "Servicio de Nefrolog&#237;a&#44; Hospital de La Princesa&#44; Madrid&#44; Espa&#241;a"
            "identificador" => "aff0005"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "<span class="elsevierStyleItalic">Autor para correspondencia</span>&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "en" => array:1 [
        "titulo" => "Bone mineral disorder in chronic kidney disease&#58; Klotho and FGF23&#59; cardiovascular implications"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figura 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1764
            "Ancho" => 2333
            "Tamanyo" => 284372
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Escenario de las alteraciones de la EOM-ERC e implicaci&#243;n en la calcificaci&#243;n vascular&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">ECV&#58; enfermedad cardiovascular&#59; Po&#58; f&#243;sforo urinario&#59; Pp&#58; f&#243;sforo plasm&#225;tico&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introducci&#243;n</span><p id="par0005" class="elsevierStylePara elsevierViewall">La <span class="elsevierStyleItalic">enfermedad renal cr&#243;nica</span> &#40;ERC&#41; es un problema de salud p&#250;blica que va en aumento&#44; con una incidencia y una prevalencia cada vez mayores &#40;10&#37; de la poblaci&#243;n general&#41;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">1&#44;2</span></a>&#46; La principal causa de mortalidad en el paciente con ERC es la cardiovascular &#40;CV&#41;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">3</span></a>&#44; con un incremento del riesgo de hasta 20 veces el de la poblaci&#243;n general incluso en estadios iniciales<a class="elsevierStyleCrossRefs" href="#bib0490"><span class="elsevierStyleSup">4&#8211;6</span></a>&#46; Hasta un 80&#37; de los pacientes con ERC presentan enfermedad CV asociada&#58; hipertensi&#243;n arterial &#40;36&#37;&#41;&#44; cardiopat&#237;a isqu&#233;mica &#40;22-39&#37;&#41;&#44; fibrilaci&#243;n auricular &#40;30&#37;&#41;&#44; valvulopat&#237;a &#40;24&#37;&#41; e hipertrofia ventricular izquierda &#40;HVI&#41; &#40;50-75&#37; en estadios 3-4 de ERC&#41;<a class="elsevierStyleCrossRefs" href="#bib0505"><span class="elsevierStyleSup">7&#44;8</span></a>&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Factores de riesgo cardiovascular en el paciente con enfermedad renal cr&#243;nica</span><p id="par0010" class="elsevierStylePara elsevierViewall">El mayor RCV de los pacientes con ERC se explica por la elevada presencia de factores de riesgo cl&#225;sicos y la superposici&#243;n de factores espec&#237;ficos del estado ur&#233;mico as&#237; como por el estado inflamatorio de la ERC&#59; en el estadio 5 se a&#241;aden otros factores relacionados con la di&#225;lisis o el trasplante que provocan un exceso de calcificaci&#243;n vascular<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">9&#44;10</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; La enfermedad &#243;seo mineral relacionada con la ERC &#40;EOM-ERC&#41; tiene un papel crucial en la ERC&#46; La EOM-ERC integra anomal&#237;as bioqu&#237;micas&#44; esquel&#233;ticas y calcificaciones extraesquel&#233;ticas que se producen por las alteraciones del metabolismo mineral en la ERC secundarias a la p&#233;rdida progresiva de masa y funci&#243;n renal&#46; Se manifiesta por una o por la combinaci&#243;n de las siguientes manifestaciones<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">11</span></a>&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0015" class="elsevierStylePara elsevierViewall">Anormalidades del calcio &#40;Ca&#41;&#44; f&#243;sforo &#40;P&#41;&#44; hormona paratiroidea &#40;PTH&#41; y vitamina D&#44; klotho y factor de crecimiento fibrobl&#225;stico 23 &#40;FGF23&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Alteraciones del remodelado&#44; mineralizaci&#243;n&#44; volumen&#44; crecimiento o fragilidad del esqueleto&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0025" class="elsevierStylePara elsevierViewall">Calcificaciones cardiovasculares o de otros tejidos blandos&#46;</p></li></ul></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">El estudio de los marcadores de EOM-ERC&#44; en algunas ocasiones&#44; nos permite predecir el RCV&#46; En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> resumimos el papel de los factores implicados en la EOM-ERC y a continuaci&#243;n revisaremos el papel de klotho y del FGF23 en la ECV&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">FGF23</span><p id="par0035" class="elsevierStylePara elsevierViewall">Es una prote&#237;na de 251 amino&#225;cidos de 32&#160;kDa&#44; sintetizada y secretada por las c&#233;lulas &#243;seas&#44; principalmente el osteoblasto&#46; Se incluye en el grupo de las hormonas &#171;fosfatoninas&#187;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">12</span></a> por su implicaci&#243;n en la eliminaci&#243;n renal de P&#46; Ha sido relacionada fisiopatol&#243;gicamente en los llamados &#171;s&#237;ndromes hipofosfat&#233;micos raros&#187;<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">13</span></a>&#44; caracterizados por defecto en la mineralizaci&#243;n y deformidades &#243;seas&#44; hipofosfatemia&#44; p&#233;rdida renal de P y niveles inapropiadamente bajos de calcitriol&#46; Es considerado uno de los principales factores en la regulaci&#243;n del metabolismo del P<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">14&#8211;16</span></a>&#46; La acci&#243;n biol&#243;gica del FGF23 depende del gen klotho<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">14&#44;17&#8211;19</span></a> que act&#250;a como su correceptor&#46; El FGF23 tambi&#233;n se expresa en el coraz&#243;n&#44; h&#237;gado&#44; gl&#225;ndula tiroides y paratiroides&#44; intestino y m&#250;sculo esquel&#233;tico<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">19</span></a>&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Regulaci&#243;n de FGF23</span><p id="par0040" class="elsevierStylePara elsevierViewall">La regulaci&#243;n del FGF23 viene determinada por&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">1&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Vitamina D activa&#58; el calcitriol aumenta la transcripci&#243;n de FGF23 de manera directa y de manera indirecta mediante v&#237;as de se&#241;alizaci&#243;n extracelulares mediadas por leptina e interleucina 6<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">20</span></a>&#46; El calcitriol tambi&#233;n aumenta la expresi&#243;n del receptor nuclear asociado a la prote&#237;na 1 &#40;Nurr1&#41; en c&#233;lulas &#243;seas y de PTH&#44; lo que conlleva el aumento de FGF23<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">21</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">2&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Niveles de Ca&#58; efecto estimulante de la secreci&#243;n de FGF23<a class="elsevierStyleCrossRefs" href="#bib0580"><span class="elsevierStyleSup">22&#44;23</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">3&#46;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Hiperparatiroidismo&#58; el aumento de PTH relacionado con la ERC puede estimular la secreci&#243;n de FGF23 a trav&#233;s de Nurr1<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">19&#44;21</span></a>&#46; En el hiperparatiroidismo primario &#40;HPTHP&#41;&#44; hipot&#233;ticamente&#44; FGF23 quedar&#237;a suprimido ya que la hipersecreci&#243;n de PTH causar&#237;a hipofosfatemia y se suprimir&#237;a uno de los est&#237;mulos de secreci&#243;n de FGF23<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">24</span></a>&#46; Sin embargo&#44; en estudios experimentales&#44; se ha demostrado que ratones con HPTHP presentan niveles de FGF23 m&#225;s elevados que los controles y que PTH es el factor estimulador<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">25</span></a>&#44; ya que el FGF23 disminuye tras la paratiroidectom&#237;a<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">25</span></a>&#46; Yamashita et al&#46;<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">24</span></a> demostraron en pacientes con HPTHP que los niveles de FGF23 estaban elevados frente a los controles sanos&#46; No obstante&#44; en este mismo estudio&#44; los pacientes sin ERC ni HPTHP no presentaron diferencias en los niveles de FGF23 frente a los controles<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">24</span></a>&#44; y concluyeron que en el HPTHP la funci&#243;n renal es determinante en los niveles de FGF23<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">24</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">4&#46;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Niveles de P&#58; los niveles s&#233;ricos de P se correlacionan positivamente con las elevaciones de FGF23 en los pacientes con ERC<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">26</span></a>&#46; Sin embargo&#44; la restricci&#243;n de P en la dieta de los pacientes con ERC muestra resultados contradictorios en el control de FGF23&#46; Algunos estudios demuestran que la restricci&#243;n de P en la dieta fracasa en descender los niveles de FGF23 en los pacientes con ERC estadio 3-4<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">27</span></a> y no los modifica en voluntarios sanos<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">28</span></a>&#46; A pesar de ello&#44; el descenso de la absorci&#243;n de P con captores de f&#243;sforo&#44; como sevelamero&#44; disminuyen los niveles de FGF23<a class="elsevierStyleCrossRefs" href="#bib0615"><span class="elsevierStyleSup">29&#44;30</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">5&#46;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Descenso de la s&#237;ntesis renal de klotho&#58; la afinidad de FGF23 por su receptor &#40;especialmente FGFR1 a nivel renal&#41; es muy baja<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">31</span></a>&#46; En condiciones fisiol&#243;gicas&#44; el FGF23&#44; al unirse al FGFR1&#44; no ser&#237;a capaz de generar transducci&#243;n de se&#241;al<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">31</span></a>&#46; Al agregar klotho&#44; la afinidad del receptor aumenta significativamente y permite la activaci&#243;n de FGFR1 con concentraciones fisiol&#243;gicas de FGF23<a class="elsevierStyleCrossRef" href="#bib0625"><span class="elsevierStyleSup">31</span></a>&#46; El descenso de klotho podr&#237;a causar una resistencia a la acci&#243;n de FGF23&#59; en la ERC esta resistencia conllevar&#237;a una reducci&#243;n de la fracci&#243;n de excreci&#243;n de fosfato&#44; y un aumento del P plasm&#225;tico y&#44; por tanto&#44; secreci&#243;n de FGF23<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">32</span></a>&#46;</p></li></ul></p><p id="par0070" class="elsevierStylePara elsevierViewall">Como curiosidad&#44; la infusi&#243;n de hierro y los niveles bajos de hierro pueden inducir s&#237;ntesis de FGF23&#44; aunque no en su forma activa<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">22</span></a>&#46; La acidosis metab&#243;lica&#44; los estr&#243;genos y la leptina tambi&#233;n provocan aumentos de FGF23<a class="elsevierStyleCrossRefs" href="#bib0635"><span class="elsevierStyleSup">33&#44;34</span></a>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Acciones biol&#243;gicas de FGF23</span><p id="par0075" class="elsevierStylePara elsevierViewall">El FGF23 presenta receptores diana denominados FGFR 1&#44; 3 y 4 y el receptor transmembrana &#946; glucuronidasa&#46; Para ejercer su acci&#243;n sobre FGFR1 a nivel renal necesita de su correceptor klotho<a class="elsevierStyleCrossRefs" href="#bib0625"><span class="elsevierStyleSup">31&#44;35</span></a>&#46;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0080" class="elsevierStylePara elsevierViewall">Hueso&#58; en aquellos procesos caracterizados por defecto en la mineralizaci&#243;n &#40;raquitismo y osteomalacia&#41; existe un exceso de producci&#243;n o actividad biol&#243;gica de FGF23<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">36</span></a>&#46; Diversos grupos est&#225;n investigando el efecto directo del FGF23 sobre el hueso&#44; sin embargo&#44; todav&#237;a no se ha demostrado evidencia de un efecto directo de FGF23 sobre el hueso<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">37</span></a>&#46; En la regulaci&#243;n de la s&#237;ntesis y la secreci&#243;n del FGF23 han sido implicadas diversas prote&#237;nas expresadas predominantemente en el hueso como Phex &#40;endopeptidasa reguladora del P ligada al cromosoma X&#41; y glucoprote&#237;nas como la derivada de la matriz proteica de la dentina &#40;DMP1&#41; y de la matriz extracelular<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">36&#44;37</span></a>&#46; Determinadas alteraciones de estas prote&#237;nas producen un incremento de la actividad biol&#243;gica por aumento de la expresi&#243;n de FGF23&#44; potenciando la fosfaturia y la hipofosfatemia&#44; e inhibiendo la formaci&#243;n &#243;sea<a class="elsevierStyleCrossRefs" href="#bib0650"><span class="elsevierStyleSup">36&#44;37</span></a>&#46; Otras veces se puede producir el efecto contrario&#58; un descenso de la actividad de FGF23 con incremento de los niveles de P s&#233;rico y calcificaci&#243;n an&#243;mala &#40;calcicosis tumoral&#41;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">38</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0085" class="elsevierStylePara elsevierViewall">Ri&#241;&#243;n&#58; act&#250;a sobre la homeostasis del P inhibiendo la expresi&#243;n de los cotransportadores sodio-fosfato tipo <span class="elsevierStyleSmallCaps">ii</span> &#40;Na&#47;P IIa y Na&#47;P IIc&#41;&#44; disminuyendo la reabsorci&#243;n tubular de P a nivel de t&#250;bulo proximal e incrementando la excreci&#243;n renal de P<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">17&#44;19&#44;39</span></a>&#46; Tambi&#233;n disminuye los niveles de calcitriol&#44; suprimiendo la actividad de la enzima 1&#945; hidroxilasa &#40;v&#237;a CYP27B1&#41; y estimulando la enzima 24 hidroxilasa &#40;v&#237;a CYP24A1&#41;<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">19&#44;39&#44;40</span></a>&#46; Por &#250;ltimo&#44; a nivel renal&#44; inhibe la transcripci&#243;n del gen klotho<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">41</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Paratiroides&#58; el FGF23 disminuye la producci&#243;n y secreci&#243;n de PTH&#44; esto ha sido demostrado por varios grupos de investigaci&#243;n&#58; trabajos como el de Ben-Dov et al&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">42</span></a> y Krajisnk et al&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">43</span></a> indican que FGF23 produce una supresi&#243;n de PTH <span class="elsevierStyleItalic">in vivo</span> e <span class="elsevierStyleItalic">in vitro</span> y disminuye la expresi&#243;n-trascripci&#243;n del ARNm y la secreci&#243;n proteica de PTH<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">43</span></a>&#46; No obstante&#44; en gl&#225;ndulas paratiroideas ur&#233;micas hiperpl&#225;sicas de rata&#44; el FGF23 falla en la inhibici&#243;n de la PTH frente a gl&#225;ndulas paratiroideas sanas&#59; tal vez&#44; debido a un descenso en la expresi&#243;n de FGFR1 y klotho en las gl&#225;ndulas hiperpl&#225;sicas ur&#233;micas<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">44</span></a>&#46; El impacto de la paratiroidectom&#237;a&#44; en pacientes con ERC&#44; sobre los niveles de FGF23 fue estudiado por Takahashi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">45</span></a>&#44; que dise&#241;aron un estudio en 30 pacientes en hemodi&#225;lisis tratados mediante paratiroidectom&#237;a&#44; con implante en antebrazo&#44; y determinaron niveles de FGF23 y klotho&#44; y concluyeron que FGF23 descend&#237;a y que klotho presentaba un descenso inicial con posterior elevaci&#243;n con respecto a los valores posparatiroidectom&#237;a&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0095" class="elsevierStylePara elsevierViewall">Coraz&#243;n&#58; en los miocardiocitos de ratones se ha demostrado que&#44; a trav&#233;s de su receptor &#40;FGFR-4&#41;&#44; el FGF23 activa la v&#237;a de la calcineurina <span class="elsevierStyleItalic">nuclear factor of activated T cells</span> &#40;NFAT&#41; y provoca HVI de forma independiente de klotho<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">46</span></a>&#46;</p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Implicaciones de FGF23 en la ERC y el RCV</span><p id="par0100" class="elsevierStylePara elsevierViewall">El paciente con ERC en estadios finales puede llegar a presentar valores de FGF23 de hasta 100 veces su valor normal<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">28</span></a>&#59; adem&#225;s&#44; los altos niveles de FGF23 predicen la progresi&#243;n de ERC&#44; como se ha ratificado en numerosos estudios<a class="elsevierStyleCrossRefs" href="#bib0705"><span class="elsevierStyleSup">47&#8211;49</span></a>&#46; Los niveles elevados de FGF23 se asocian a un aumento de la mortalidad ajustado para factores de riesgo cl&#225;sico cardiovasculares y otros marcadores tradicionales de ERC<a class="elsevierStyleCrossRefs" href="#bib0705"><span class="elsevierStyleSup">47&#44;50</span></a>&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Se ha demostrado una asociaci&#243;n de FGF23 con la calcificaci&#243;n vascular&#44; aunque no parece que FGF23 sea el inductor<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">51</span></a>&#46; Scialla et al&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">51</span></a> estudiaron la asociaci&#243;n entre FGF23&#44; P&#44; calcificaci&#243;n coronaria y de la aorta tor&#225;cica medida por TAC en 1&#46;501 participantes con ERC &#40;filtrado glomerular &#91;FG&#93; medio de 47<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;1&#44;73&#160;m<span class="elsevierStyleSup">2</span>&#59; estadios 2-4&#41;&#46; Estos autores demostraron que FGF23 no se asociaba con la calcificaci&#243;n vascular medida por TAC y que&#44; en estudios <span class="elsevierStyleItalic">in vitro</span>&#44; el FGF23 no produce calcificaci&#243;n ni induc&#237;a calcificaci&#243;n en medios de cultivo con c&#233;lulas del m&#250;sculo liso &#40;CMLV&#41;&#44; ni presentaba expresi&#243;n en la aorta de ratones y humanos<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">51</span></a>&#46; El papel del FGF23 en la calcificaci&#243;n vascular vendr&#237;a marcado por la hiperfosfatemia que s&#237; induce calcificaci&#243;n vascular&#58; las CMLV presentan una diferenciaci&#243;n osteobl&#225;stica en medios ricos en P<a class="elsevierStyleCrossRefs" href="#bib0730"><span class="elsevierStyleSup">52&#44;53</span></a>&#46; S&#237; parece que hay asociaci&#243;n entre la gravedad de la calcificaci&#243;n y el FGF23 en la ERC&#44; por lo que FGF23 podr&#237;a ser un marcador de seguimiento y no de g&#233;nesis de la calcificaci&#243;n vascular<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">51</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">El exceso de FGF23 conlleva un aumento de la morbimortalidad CV en la ERC<a class="elsevierStyleCrossRefs" href="#bib0740"><span class="elsevierStyleSup">54&#44;55</span></a> de forma independiente del FG<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">56</span></a>&#44; esto puede ser debido&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">1&#46;</span><p id="par0115" class="elsevierStylePara elsevierViewall">A que el FGF23 reduce los niveles de vitamina D activa &#40;calcitriol&#41; al inhibir la 1&#945; hidroxilasa y estimular la 24 hidroxilasa<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">19&#44;39</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">2&#46;</span><p id="par0120" class="elsevierStylePara elsevierViewall">A que el FGF23 se relaciona con la presencia de marcadores inflamatorios<a class="elsevierStyleCrossRefs" href="#bib0755"><span class="elsevierStyleSup">57&#44;58</span></a> y de estr&#233;s oxidativo como los productos de glucosilaci&#243;n avanzada que se asocian a calcificaci&#243;n vascular<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">57</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">3&#46;</span><p id="par0125" class="elsevierStylePara elsevierViewall">A que&#44; en algunos estudios&#44; el FGF23 se asocia con la proteinuria<a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">59</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">4&#46;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Al papel del FGF23 en la g&#233;nesis de la HVI &#40;importante generador de arritmias y de fallo card&#237;aco&#41;&#58; el elegante estudio de Faul et al&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">46</span></a> evidenci&#243;&#44; en una cohorte de m&#225;s de 3&#46;000 pacientes con ERC con FG entre 20-70<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#44; que hab&#237;a una correlaci&#243;n entre los niveles de FGF23 y la HVI&#46; En este mismo estudio se detall&#243; como FGF23 provocaba un aumento de &#945;&#8211;actina en miocardiocitos de rata con un aumento de la expresi&#243;n de marcadores de HVI&#44; como &#946;-miosina de cadena pesada fetal&#44; y un descenso de la &#945;-miosina de cadena pesada adulta&#46; Este mecanismo es independiente de klotho y es mediado por la activaci&#243;n de la v&#237;a de la calcineurina NFAT<span class="elsevierStyleItalic">&#46;</span></p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Klotho</span><p id="par0135" class="elsevierStylePara elsevierViewall">Es una prote&#237;na transmembrana de 130&#160;kDa que se expresa predominantemente en el ri&#241;&#243;n &#40;t&#250;bulo distal&#44; proximal y colector&#41;&#44; en la gl&#225;ndula paratiroidea&#44; plexo coroideo y tambi&#233;n a nivel endotelial<a class="elsevierStyleCrossRefs" href="#bib0770"><span class="elsevierStyleSup">60&#44;61</span></a>&#46; Presenta 3 formas diferentes<a class="elsevierStyleCrossRefs" href="#bib0780"><span class="elsevierStyleSup">62&#44;63</span></a>&#58; <span class="elsevierStyleItalic">klotho-cut</span> de poca repercusi&#243;n biol&#243;gica&#44; la forma completa&#44; unida a la membrana &#40;act&#250;a como correceptor de FGF23&#41;&#44; y la forma secretada&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Regulaci&#243;n de klotho</span><p id="par0140" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">1&#46;</span><p id="par0145" class="elsevierStylePara elsevierViewall">En modelos experimentales <span class="elsevierStyleItalic">in vitro</span> se ha demostrado que la se&#241;al <span class="elsevierStyleItalic">peroxisome proliferator activated receptor</span> &#947; &#40;PPAR &#947;&#41;<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">64</span></a> aumenta la s&#237;ntesis de klotho&#46; El calcitriol tambi&#233;n aumenta la expresi&#243;n de klotho en modelos animales con ERC e ingesta elevada de P<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">65</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">2&#46;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Los factores que disminuyen la s&#237;ntesis de klotho son&#58; el FGF23<a class="elsevierStyleCrossRefs" href="#bib0800"><span class="elsevierStyleSup">66&#8211;68</span></a> el estr&#233;s oxidativo<a class="elsevierStyleCrossRef" href="#bib0815"><span class="elsevierStyleSup">69</span></a> y la angiotensina <span class="elsevierStyleSmallCaps">II</span> &#40;a trav&#233;s de sus receptores tipo I y del aumento de la enzima conversora del factor de necrosis tumoral &#945; TACE&#41;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">17&#44;70&#44;71</span></a>&#46; El gen klotho&#44; al ser de s&#237;ntesis predominantemente renal&#44; est&#225; disminuido en los pacientes con ERC<a class="elsevierStyleCrossRefs" href="#bib0780"><span class="elsevierStyleSup">62&#44;72</span></a>&#46;</p></li></ul></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Acciones biol&#243;gicas de klotho</span><p id="par0155" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">&#8226;</span><p id="par0160" class="elsevierStylePara elsevierViewall">Ri&#241;&#243;n&#58; el klotho induce fosfaturia directamente&#44; actuando a nivel de t&#250;bulo proximal al inhibir el cotransportador Na&#47;P IIa y Na&#47;P IIc<a class="elsevierStyleCrossRefs" href="#bib0830"><span class="elsevierStyleSup">72&#8211;74</span></a>&#46; Adem&#225;s&#44; klotho es correceptor de FGFR-1 y&#44; por lo tanto&#44; facilita la acci&#243;n fosfat&#250;rica de FGF23<a class="elsevierStyleCrossRefs" href="#bib0780"><span class="elsevierStyleSup">62&#44;63</span></a>&#46; A su vez&#44; tambi&#233;n regula la homeostasis del Ca al modular los canales renales <span class="elsevierStyleItalic">transient receptor potential ion channel</span> &#40;TRPV5&#41;<a class="elsevierStyleCrossRef" href="#bib0845"><span class="elsevierStyleSup">75</span></a> y de potasio &#40;K&#41; al regular el canal medular <span class="elsevierStyleItalic">renal outer medullary K</span> &#40;ROMK 1<a class="elsevierStyleCrossRef" href="#bib0850"><span class="elsevierStyleSup">76</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">&#8226;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Endotelio&#58; el klotho puede inhibir la calcificaci&#243;n vascular&#44; una disminuci&#243;n de klotho se asocia a un aumento en la expresi&#243;n de los trasportadores de P Pit1&#47;2 y del factor osteog&#233;nico Runx2&#44; lo que conllevar&#237;a un aumento del trasporte de P en las CMLV y su transformaci&#243;n osteog&#233;nica<a class="elsevierStyleCrossRefs" href="#bib0855"><span class="elsevierStyleSup">77&#44;78</span></a>&#46; No obstante&#44; los estudios sobre la expresi&#243;n de klotho a nivel vascular son contradictorios&#46; Lim et al&#46;<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">79</span></a> evidenciaron su expresi&#243;n en las arterias de individuos sanos&#59; esta expresi&#243;n se ve descendida en los pacientes con ERC<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">79</span></a>&#46; Contrariamente&#44; Scialla et al&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">51</span></a> no detectaron expresi&#243;n de klotho en las CMLV en controles sanos ni en ratones con ERC&#44; tampoco Lindberg et al&#46;<a class="elsevierStyleCrossRef" href="#bib0870"><span class="elsevierStyleSup">80</span></a> detectaron niveles de prote&#237;na klotho en arterias de ratones <span class="elsevierStyleItalic">wild type</span>&#46; En ratas ur&#233;micas&#44; Ritter et al&#46;<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">81</span></a> hallaron que la expresi&#243;n de klotho estaba elevada en la adventicia a&#243;rtica y disminuida en la zona &#237;ntima media<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">81</span></a>&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">&#8226;</span><p id="par0170" class="elsevierStylePara elsevierViewall">Inhibici&#243;n de la 1&#945; hidroxilasa que se encarga de la hidroxilaci&#243;n de la 25OH a 1&#44;25&#40;OH&#41;<span class="elsevierStyleInf">2</span>D3<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">17&#44;82</span></a>&#58; Yoshida et al&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">82</span></a> demostraron en ratones homocigotos para el gen klotho Kl&#40;-&#47;-&#41;&#44; que los niveles de 1&#44;25-dihidroxivitamina D estaban aumentados frente a los ratones <span class="elsevierStyleItalic">wild type</span>&#59; a su vez&#44; comprobaron que la expresi&#243;n del gen 1&#945; hidroxilasa se encontraba aumentado en los ratones Kl &#40;-&#47;-&#41; y que la administraci&#243;n de calcitriol fallaba en inhibir 1&#945; hidroxilasa&#46;</p></li></ul></p><p id="par0175" class="elsevierStylePara elsevierViewall">Klotho presenta efectos pleiotr&#243;picos a nivel sist&#233;mico&#58; aumenta la transcripci&#243;n de receptores de eritropoyetina<a class="elsevierStyleCrossRef" href="#bib0885"><span class="elsevierStyleSup">83</span></a>&#44; aminora el da&#241;o provocado por angiotensina <span class="elsevierStyleSmallCaps">II</span><a class="elsevierStyleCrossRefs" href="#bib0820"><span class="elsevierStyleSup">70&#44;84</span></a>&#44; inhibe la se&#241;al insulina&#47;IGF-1&#44; pudiendo provocar resistencia al estr&#233;s oxidativo<a class="elsevierStyleCrossRef" href="#bib0895"><span class="elsevierStyleSup">85</span></a>&#44; posee efectos antifibr&#243;ticos ya que puede inhibir la se&#241;al TGF &#946;<a class="elsevierStyleCrossRef" href="#bib0900"><span class="elsevierStyleSup">86</span></a> &#40;factor de crecimiento fibrobl&#225;stico&#41;&#44; y posee efectos antisenescentes y antiapopt&#243;ticos<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">87</span></a>&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Implicaciones de klotho en la ERC y el RCV</span><p id="par0180" class="elsevierStylePara elsevierViewall">Como ya se ha mencionado&#44; klotho disminuye precozmente en la ERC<a class="elsevierStyleCrossRefs" href="#bib0565"><span class="elsevierStyleSup">19&#44;72</span></a>&#46; Su d&#233;ficit podr&#237;a provocar&#58; calcificaci&#243;n vascular al fomentarse la entrada de P a las CMLV&#44; arterioesclerosis&#44; osteoporosis&#44; calcificaci&#243;n ect&#243;pica&#44; envejecimiento prematuro&#44; apoptosis y progresi&#243;n de la ERC<a class="elsevierStyleCrossRefs" href="#bib0830"><span class="elsevierStyleSup">72&#44;78&#44;79&#44;87</span></a>&#46; Su supresi&#243;n tambi&#233;n implica descenso de la fosfaturia con aumento de P y de los niveles s&#233;ricos de calcitriol&#46; En el fracaso renal agudo&#44; en modelos experimentales&#44; se ha demostrado el descenso de klotho y&#44; por tanto&#44; su papel como posible biomarcador de fallo renal agudo<a class="elsevierStyleCrossRefs" href="#bib0910"><span class="elsevierStyleSup">88&#44;89</span></a>&#46; As&#237; mismo&#44; su reposici&#243;n podr&#237;a conllevar la recuperaci&#243;n del da&#241;o renal<a class="elsevierStyleCrossRefs" href="#bib0910"><span class="elsevierStyleSup">88&#44;89</span></a>&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">A nivel card&#237;aco&#44; klotho puede influir directamente sobre la funci&#243;n y el remodelado card&#237;aco protegi&#233;ndolo frente a la HVI&#46; Xie et al&#46;<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">90</span></a> valoraron la funci&#243;n card&#237;aca y la HVI en ratones heterocigotos hipom&#243;rficos para el alelo de klotho &#40;Kl&#47;&#43;&#41; con o sin ERC y ratones <span class="elsevierStyleItalic">wild type</span> con o sin ERC&#46; En los ratones con ERC se objetiv&#243; un descenso de klotho&#44; HVI y fibrosis mioc&#225;rdica&#59; todo ello m&#225;s pronunciado en los Het-klotho&#46; Los ratones sin ERC<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Het-klotho tambi&#233;n presentaron niveles de klotho menores&#44; pero no datos de HVI&#46; La fracci&#243;n de eyecci&#243;n estaba reducida significativamente en los ratones ERC<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>Het-klotho&#46; Al inyectar soluciones de klotho soluble a estos ratones&#44; mejoraban los datos de disfunci&#243;n mioc&#225;rdica con independencia de P&#44; FGF23&#44; tensi&#243;n arterial y FG<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">90</span></a>&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">El mecanismo cardioprotector de klotho se debe a la inhibici&#243;n del canal TRPC6 &#40;familia de canales de cationes potencial transitoria a subfamilia can&#243;nica&#41; que est&#225; aumentado en el estado ur&#233;mico<a class="elsevierStyleCrossRefs" href="#bib0920"><span class="elsevierStyleSup">90&#8211;92</span></a>&#46; Ante una agresi&#243;n cardiol&#243;gica&#44; TRPC6 permite mayor entrada de Ca al interior celular&#44; se activa la fosfatasa calcineurina&#44; lo que provoca la desfosforilaci&#243;n de NFAT que se transloca al n&#250;cleo para inducir la expresi&#243;n de genes fetales &#40;por ejemplo&#58; &#946;-miosina de cadena pesada&#41;&#44; lo cual conlleva la alteraci&#243;n en el remodelamiento card&#237;aco y la HVI&#46; El gen TRPC6 posee elementos de respuesta frente a NFAT y aumenta su expresi&#243;n al aumentar el influjo de Ca&#44; causando una activaci&#243;n directa de todo el proceso<a class="elsevierStyleCrossRefs" href="#bib0935"><span class="elsevierStyleSup">93&#44;94</span></a>&#46; Al inhibir el canal TRPC6&#44; klotho podr&#237;a ser&#44; en un futuro&#44; una medida terap&#233;utica en la HVI&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#fig0010">figura 2</a> esquematizamos la implicaci&#243;n de FGF23&#44; klotho y RCV&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conclusiones</span><p id="par0200" class="elsevierStylePara elsevierViewall">La b&#250;squeda de marcadores precoces de RCV&#44; inflamaci&#243;n y fibrosis que puedan afectar a la econom&#237;a corporal y a la funci&#243;n renal es extensa&#46; La EOM-ERC tiene un papel crucial en la salud endotelial y renal&#59; por ello&#44; es prioritario su control y su conocimiento&#46; La investigaci&#243;n en FGF23 y klotho y su relaci&#243;n en ECV abre nuevas expectativas tanto en la prevenci&#243;n como en el tratamiento&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicto de intereses</span><p id="par0205" class="elsevierStylePara elsevierViewall">Los autores declaran no tener ning&#250;n conflicto de intereses&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:17 [
        0 => array:3 [
          "identificador" => "xres757386"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec759472"
          "titulo" => "Palabras clave"
        ]
        2 => array:3 [
          "identificador" => "xres757385"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec759471"
          "titulo" => "Keywords"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introducci&#243;n"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Factores de riesgo cardiovascular en el paciente con enfermedad renal cr&#243;nica"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "FGF23"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Regulaci&#243;n de FGF23"
        ]
        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Acciones biol&#243;gicas de FGF23"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Implicaciones de FGF23 en la ERC y el RCV"
        ]
        10 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Klotho"
        ]
        11 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Regulaci&#243;n de klotho"
        ]
        12 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Acciones biol&#243;gicas de klotho"
        ]
        13 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Implicaciones de klotho en la ERC y el RCV"
        ]
        14 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Conclusiones"
        ]
        15 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Conflicto de intereses"
        ]
        16 => array:1 [
          "titulo" => "Bibliograf&#237;a"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2015-06-22"
    "fechaAceptado" => "2016-01-02"
    "PalabrasClave" => array:2 [
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec759472"
          "palabras" => array:4 [
            0 => "Riesgo cardiovascular"
            1 => "Enfermedad renal cr&#243;nica"
            2 => "Klotho"
            3 => "FGF23"
          ]
        ]
      ]
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec759471"
          "palabras" => array:4 [
            0 => "Cardiovascular risk"
            1 => "Chronic kidney disease"
            2 => "Klotho"
            3 => "FGF23"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Una de las principales causas de morbimortalidad en el paciente con enfermedad renal cr&#243;nica es la cardiovascular&#46; La inflamaci&#243;n y las alteraciones en el metabolismo &#243;seo mineral son una condici&#243;n patol&#243;gica que conlleva aumento del riesgo cardiovascular en la enfermedad renal cr&#243;nica&#46; Los par&#225;metros bioqu&#237;micos cl&#225;sicos del metabolismo &#243;seo mineral como f&#243;sforo&#44; calcio&#44; vitamina D y PTH tienen una implicaci&#243;n muy conocida en el riesgo cardiovascular&#46; Los nuevos marcadores&#44; FGF23 y klotho&#44; tambi&#233;n podr&#237;an estar implicados en la enfermedad cardiovascular&#46;</p></span>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Cardiovascular factors are one of the main causes of morbidity and mortality in patients with chronic kidney disease&#46; Bone mineral metabolism disorders and inflammation are pathological conditions that involve increased cardiovascular risk in chronic kidney disease&#46; The cardiovascular risk involvement of bone mineral metabolism classical biochemical parameters such as phosphorus&#44; calcium&#44; vitamin D and PTH is well known&#46; The newest markers&#44; FGF23 and klotho&#44; could also be implicated in cardiovascular disease&#46;</p></span>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 874
            "Ancho" => 2150
            "Tamanyo" => 267375
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Factores de RCV implicados en la afecci&#243;n renal y card&#237;aca&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figura 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1764
            "Ancho" => 2333
            "Tamanyo" => 284372
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Escenario de las alteraciones de la EOM-ERC e implicaci&#243;n en la calcificaci&#243;n vascular&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">ECV&#58; enfermedad cardiovascular&#59; Po&#58; f&#243;sforo urinario&#59; Pp&#58; f&#243;sforo plasm&#225;tico&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabla 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="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="center" valign="top" scope="col" style="border-bottom: 2px solid black">PTH&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">Vit D activa&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">FGF 23&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">Klotho&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">S&#237;ntesis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Gl&#225;ndula paratiroidea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25OHD3&#58; hep&#225;tica<br>1&#44;25&#40;OH&#41;<span class="elsevierStyleInf">2</span>D3&#58; ri&#241;&#243;n&#44; monocitos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hueso &#40;osteoblasto&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ri&#241;&#243;n<br>Plexos coroideos&#44; gl&#225;ndula paratiroidea&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">Regulaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleUnderline">Estimulantes&#58;</span>Ca&#44; P<br><span class="elsevierStyleUnderline">Inhibidores&#58;</span>Vitamina D&#44; FGF 23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleUnderline">Est&#237;mulo 1&#945; hidroxilasa&#58;</span> PTH&#44; hormona de crecimiento&#44; prolactina<br><span class="elsevierStyleUnderline">Inhibici&#243;n 1&#945; hidroxilasa</span>&#58; FGF 23&#44; Klotho<br><span class="elsevierStyleUnderline">Est&#237;mulo 24 hidroxilasa&#58;</span> an&#225;logos de vitamina D&#44; FGF 23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleUnderline">Est&#237;mulo&#58;</span>FGF 23&#44; PTH&#44; Nurr1&#44; sobrecarga de P&#44; Ca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleUnderline">Est&#237;mulo&#58;</span> PPA&#947;&#44; vitamina D<br><span class="elsevierStyleUnderline">Inhibe&#58;</span> angiotensina II&#44; FGF 23&#44; inflamaci&#243;n&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">Acciones &#243;seas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Aumento de la reabsorci&#243;n &#243;sea&#58; liberaci&#243;n de Ca y P en sangre<br>Est&#237;mulo secreci&#243;n FGF 23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Aumento de la resorci&#243;n &#243;sea<br>Estimula s&#237;ntesis FGF 23&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">Acci&#243;n renal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Aumenta reabsorci&#243;n de Ca e inhibe la de P<br>Estimula 1&#945; hidroxilasa&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="left" valign="top">Acci&#243;n fosfat&#250;rica<br>Inhibe 1&#945; y activa 24 hidroxilasa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Aumenta fosfaturia &#40;FGF 23&#41;<br>Inhibe 1&#945; hidroxilasa<br>Reabsorci&#243;n de Ca&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">Acci&#243;n intestinal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">De forma indirecta al estimular calcitriol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Absorci&#243;n de Ca y P&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">Otras acciones&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Toxina ur&#233;mica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Inhibici&#243;n de PTH<br>Pleiotropismo<br>Inhibici&#243;n de RAAS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Inhibe PTH&#44; HVI&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Antioxidante<br>Antiapoptoico<br>Protecci&#243;n endotelial<br>Protecci&#243;n del fallo renal<br>Protecci&#243;n frente a HVI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1252232.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Regulaci&#243;n de la enfermedad &#243;seo mineral relacionada con la enfermedad renal cr&#243;nica</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Bibliograf&#237;a"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:94 [
            0 => array:3 [
              "identificador" => "bib0475"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Hernando Avenda&#241;o P&#44; Arias M&#44; Caramelo C&#44; Egido J&#44; Lamas S&#46; Nefrolog&#237;a Cl&#237;nica&#46; 3&#46;&#170;edici&#243;n&#46; Panamericana&#46; p&#46; 801&#46;"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0480"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of chronic kidney disease in the United States"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.298.17.2038"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2007"
                        "volumen" => "298"
                        "paginaInicial" => "2038"
                        "paginaFinal" => "2047"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0485"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic kidney disease and the risks of death&#44; cardiovascular events&#44; and hospitalization"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa041031"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2004"
                        "volumen" => "351"
                        "paginaInicial" => "1296"
                        "paginaFinal" => "1305"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0490"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfh217"
                      "Revista" => array:7 [
                        "tituloSerie" => "Nephrol Dial Transplant&#46;"
                        "fecha" => "2004"
                        "volumen" => "19"
                        "numero" => "6"
                        "paginaInicial" => "1480"
                        "paginaFinal" => "1488"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0495"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality&#58; A pooled analysis of community-based studies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol&#46;"
                        "fecha" => "2004"
                        "volumen" => "15"
                        "paginaInicial" => "1307"
                        "paginaFinal" => "1315"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0500"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Albuminuria and risk of cardiovascular events&#44; death&#44; and heart failure in diabetic and nondiabetic individuals"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2001"
                        "volumen" => "286"
                        "paginaInicial" => "421"
                        "paginaFinal" => "426"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0505"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evidence-based cardiology in hemodialysis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2013060632"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2013"
                        "volumen" => "24"
                        "paginaInicial" => "1934"
                        "paginaFinal" => "1943"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0510"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Riesgo cardiovascular en pacientes con enfermedad renal cr&#243;nica"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Urug Cardiol"
                        "fecha" => "2006"
                        "volumen" => "21"
                        "numero" => "2"
                        "paginaInicial" => "143"
                        "paginaFinal" => "157"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0515"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Traditional and emerging cardiovascular risk factors in end-stage renal disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int Suppl"
                        "fecha" => "2003"
                        "volumen" => "63"
                        "numero" => "85"
                        "paginaInicial" => "S105"
                        "paginaFinal" => "S110"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0520"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ri&#241;&#243;n y enfermedad cardiovascular"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Nefrolog&#237;a"
                        "fecha" => "2004"
                        "volumen" => "24"
                        "numero" => "6&#46;"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0525"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recomendaciones de la Sociedad Espa&#241;ola de Nefrolog&#237;a para el manejo de las alteraciones del metabolismo &#243;seo-mineral en los pacientes con enfermedad renal cr&#243;nica"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Nefrolog&#237;a"
                        "fecha" => "2011"
                        "volumen" => "31"
                        "numero" => "1&#46;"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0530"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The phosphatonin pathway&#58; New insights in phosphatehomeostasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1523-1755.2004.00355.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int&#46;"
                        "fecha" => "2004"
                        "volumen" => "65"
                        "paginaInicial" => "1"
                        "paginaFinal" => "14"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0535"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fibroblast growth factor 23&#58; Roles in health and disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2005050573"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol&#46;"
                        "fecha" => "2005"
                        "volumen" => "16"
                        "paginaInicial" => "2565"
                        "paginaFinal" => "2575"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0540"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2005111185"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol&#46;"
                        "fecha" => "2006"
                        "volumen" => "17"
                        "paginaInicial" => "1305"
                        "paginaFinal" => "1315"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0545"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "FGF23-mediated regulation of systemic phosphate homeostasis&#58; Is Klotho an essential player&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajprenal.90538.2008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Renal Physiol"
                        "fecha" => "2009"
                        "volumen" => "296"
                        "paginaInicial" => "F470"
                        "paginaFinal" => "F476"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0550"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanistic insights into vascular calcification in CKD"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am Soc Nephrol&#46;"
                        "fecha" => "2013"
                        "volumen" => "24"
                        "paginaInicial" => "179"
                        "paginaFinal" => "189"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0555"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cross talk between the renin- angiotensin aldosterone system and vitamin D-FGF-23-klotho in chronic kidney disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2010121251"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2011"
                        "volumen" => "22"
                        "paginaInicial" => "1603"
                        "paginaFinal" => "1609"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0560"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regulation of fibroblast growth factor-23 signaling by klotho"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.C500457200"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2006"
                        "volumen" => "281"
                        "paginaInicial" => "6120"
                        "paginaFinal" => "6123"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0565"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CKD&#8211;mineral and bone disorder&#58; Core curriculum 2011"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.ajkd.2011.08.009"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Kidney Dis"
                        "fecha" => "2011"
                        "volumen" => "58"
                        "numero" => "6"
                        "paginaInicial" => "1022"
                        "paginaFinal" => "1036"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0570"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "1&#44;25-dihydroxyvitamin D-3 regulation of fibroblast growth factor-23 expression in bone cells&#58; Evidence for primary and secondary mechanisms modulated by leptin and interleukin- 6"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00223-012-9683-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Calcif Tissue Int"
                        "fecha" => "2013"
                        "volumen" => "92"
                        "paginaInicial" => "339"
                        "paginaFinal" => "353"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0575"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Parathyroid hormone activates the orphan nuclear receptor Nurr1 to induce FGF23 transcription"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.2014.215"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int&#46;"
                        "fecha" => "2014"
                        "volumen" => "86"
                        "paginaInicial" => "1106"
                        "paginaFinal" => "1115"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0580"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Update on fibroblast growth factor 23 in chronic kidney disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.2012.176"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int&#46;"
                        "fecha" => "2012"
                        "volumen" => "82"
                        "paginaInicial" => "737"
                        "paginaFinal" => "747"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0585"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PTH&#44; FGF23&#44; and calcium&#58; It takes 3 to tango&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [ …3]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.2011.350"
                      "Revista" => array:5 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2011"
                        "volumen" => "80"
                        "paginaInicial" => "1377"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0590"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fibroblast growth factor &#40;FGF&#41;-23 in patients with primary hyperparathyroidism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Endocrinol"
                        "fecha" => "2004"
                        "volumen" => "151"
                        "paginaInicial" => "55"
                        "paginaFinal" => "60"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0595"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2006070783"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol&#46;"
                        "fecha" => "2007"
                        "volumen" => "18"
                        "paginaInicial" => "2683"
                        "paginaFinal" => "2688"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0600"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serum FGF23 levels in normal and disordered phosphorus homeostasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1359/jbmr.2003.18.7.1227"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Bone Miner Res&#46;"
                        "fecha" => "2003"
                        "volumen" => "18"
                        "paginaInicial" => "1227"
                        "paginaFinal" => "1234"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0605"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfq419"
                      "Revista" => array:7 [
                        "tituloSerie" => "Nephrol Dial Transplant&#46;"
                        "fecha" => "2011"
                        "volumen" => "26"
                        "numero" => "2"
                        "paginaInicial" => "584"
                        "paginaFinal" => "591"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0610"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease&#44; but does not change in response to variation in phosphate intake in healthy volunteers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1046/j.1523-1755.2003.00328.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int&#46;"
                        "fecha" => "2003"
                        "volumen" => "64"
                        "paginaInicial" => "2272"
                        "paginaFinal" => "2279"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0615"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sevelamer hydrochloride and calcium bicarbonate reduce serum fibroblast growth factor 23 levels in dialysis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1744-9987.2005.00293.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ther Apher Dial"
                        "fecha" => "2005"
                        "volumen" => "9"
                        "paginaInicial" => "336"
                        "paginaFinal" => "339"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0620"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early control of PTH and FGF23 in normophosphatemic CKD patients&#58; A new target in CKD&#8211;MBD therapy&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2215/CJN.05420709"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin J Am Soc Nephrol"
                        "fecha" => "2010"
                        "volumen" => "5"
                        "paginaInicial" => "286"
                        "paginaFinal" => "291"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0625"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Klotho converts canonical FGF receptor into a specific receptor for FGF23"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nature05315"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "2006"
                        "volumen" => "444"
                        "paginaInicial" => "770"
                        "paginaFinal" => "774"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0630"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of dietary phosphate and calcium intake on fibroblast growth factor-23"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2215/CJN.04730510"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin J Am Soc Nephrol"
                        "fecha" => "2010"
                        "volumen" => "6"
                        "paginaInicial" => "383"
                        "paginaFinal" => "389"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0635"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metabolic acidosis increases fibroblast growth factor 23 in neonatal mouse bone"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajprenal.00199.2012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Renal Physiol"
                        "fecha" => "2012"
                        "volumen" => "303"
                        "paginaInicial" => "F431"
                        "paginaFinal" => "F436"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0640"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Leptin stimulates fibroblast growth factor 23 expression in bone and suppresses renal 1alpha&#44; 25-dihydroxyvitamin D&#40;3&#41; synthesis in leptin-deficient ob&#47;ob mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [ …5]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jbmr.65"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Bone Miner Res&#46;"
                        "fecha" => "2010"
                        "volumen" => "25"
                        "numero" => "8"
                        "paginaInicial" => "1711"
                        "paginaFinal" => "1723"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0645"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regulation of fibroblast growth factor-23 signaling by klotho"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.C500457200"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem&#46;"
                        "fecha" => "2006"
                        "volumen" => "281"
                        "paginaInicial" => "6120"
                        "paginaFinal" => "6123"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0650"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "FGF23 PHEX&#44; and MEPE regulation of phosphate homeostasis and skeletal mineralization"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajpendo.00016.2003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Endocrinol Metab&#46;"
                        "fecha" => "2003"
                        "volumen" => "285"
                        "paginaInicial" => "E1"
                        "paginaFinal" => "E9"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0655"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets&#47;osteomalacia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2002-021105"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab&#46;"
                        "fecha" => "2002"
                        "volumen" => "87"
                        "paginaInicial" => "4957"
                        "paginaFinal" => "4960"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0660"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An FGF23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [ …4]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/hmg/ddi034"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hum Mol Genet&#46;"
                        "fecha" => "2005"
                        "volumen" => "14"
                        "paginaInicial" => "385"
                        "paginaFinal" => "390"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0665"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1359/JBMR.0301264"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Bone Miner Res&#46;"
                        "fecha" => "2004"
                        "volumen" => "19"
                        "paginaInicial" => "429"
                        "paginaFinal" => "435"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0670"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI19081"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest&#46;"
                        "fecha" => "2004"
                        "volumen" => "113"
                        "paginaInicial" => "561"
                        "paginaFinal" => "568"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0675"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of FGF23 in vitamin D and phosphate metabolism&#58; Implications in chronic kidney disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [ …1]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.yexcr.2012.02.027"
                      "Revista" => array:7 [
                        "tituloSerie" => "Exp Cell Res&#46;"
                        "fecha" => "2012"
                        "volumen" => "318"
                        "numero" => "9"
                        "paginaInicial" => "1040"
                        "paginaFinal" => "1048"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0680"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The parathyroid is a target organ for FGF23 in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [ …6]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI32409"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest&#46;"
                        "fecha" => "2007"
                        "volumen" => "117"
                        "paginaInicial" => "4003"
                        "paginaFinal" => "4008"
                        "link" => array:1 [
                          0 => array:2 [ …2]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0685"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fibroblast growth factor-23 regulates parathyroid hormone and 1- hydroxylase expression in cultured bovine parathyroid cells"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1677/JOE-07-0267"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Endocrinol&#46;"
                        "fecha" => "2007"
                        "volumen" => "195"
                        "paginaInicial" => "125"
                        "paginaFinal" => "131"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0690"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "FGF23 fails to inhibit uremic parathyroid glands"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2009040427"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2010"
                        "volumen" => "21"
                        "paginaInicial" => "1125"
                        "paginaFinal" => "1135"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0695"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of parathyroidectomy on serum FGF23 and soluble Klotho in hemodialysis patients with severe secondary hyperparathyroidism"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2013-4050"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Endocrinol Metab&#46;"
                        "fecha" => "2014"
                        "volumen" => "99"
                        "numero" => "4"
                        "paginaInicial" => "E652"
                        "paginaFinal" => "E658"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0700"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "FGF 23 induces left ventricular hipertrophy"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2011"
                        "volumen" => "121"
                        "numero" => "11"
                        "paginaInicial" => "2393"
                        "paginaFinal" => "4408"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0705"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.2011.826"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2011"
                        "volumen" => "305"
                        "paginaInicial" => "2432"
                        "paginaFinal" => "2439"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0710"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "FGF-23 as a predictor of renal outcome in diabetic nephropathy"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2215/CJN.04250510"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin J Am Soc Nephrol"
                        "fecha" => "2011"
                        "volumen" => "6"
                        "paginaInicial" => "241"
                        "paginaFinal" => "247"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0715"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fibroblast growth factor 23 &#40;FGF23&#41; predicts progression of chronic kidney disease&#58; The Mild to Moderate Kidney Disease &#40;MMKD&#41; Study"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2006080936"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2007"
                        "volumen" => "18"
                        "paginaInicial" => "2600"
                        "paginaFinal" => "2608"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0720"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High levels of serum fibroblast growth factor &#40;FGF&#41;-23 are associated with increased mortality in long haemodialysis patients"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfp191"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2009"
                        "volumen" => "24"
                        "paginaInicial" => "2792"
                        "paginaFinal" => "2796"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0725"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fibroblast growth factor 23 is not associated with and does not induce arterial calcification"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.2013.3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2013"
                        "volumen" => "83"
                        "paginaInicial" => "1159"
                        "paginaFinal" => "1168"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0730"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Phosphate regulation of vascular smooth muscle cell calcification"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Circ Res"
                        "fecha" => "2000"
                        "volumen" => "87"
                        "paginaInicial" => "e10"
                        "paginaFinal" => "e17"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0735"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Phosphorus and uremic serum up-regulate osteopontin expression in vascular smooth muscle cells"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1046/j.1523-1755.2002.00625.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2002"
                        "volumen" => "62"
                        "paginaInicial" => "1724"
                        "paginaFinal" => "1731"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0740"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfq309"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant&#46;"
                        "fecha" => "2010"
                        "volumen" => "25"
                        "paginaInicial" => "3983"
                        "paginaFinal" => "3989"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0745"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fibroblast growth factor-23 and cardiovascular events in CKD"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2013050465"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2014"
                        "volumen" => "25"
                        "paginaInicial" => "349"
                        "paginaFinal" => "360"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0750"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serum FGF23 and risk of cardiovascular events in relation to mineral metabolism and cardiovascular pathology"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2215/CJN.09570912"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin J Am Soc Nephrol"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "paginaInicial" => "781"
                        "paginaFinal" => "786"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0755"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The association between fibroblast growth factor-23 and vascular calcification is mitigated by inflammation markers"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000356118"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephron Extra"
                        "fecha" => "2013"
                        "volumen" => "3"
                        "paginaInicial" => "106"
                        "paginaFinal" => "112"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0760"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "e44161"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A comparative transcriptome analysis identifying FGF23 regulated genes in the kidney of a mouse CKD model"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "PLoS One"
                        "fecha" => "2012"
                        "volumen" => "7"
                        "numero" => "9"
                        "paginaInicial" => "1"
                        "paginaFinal" => "15"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0765"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Fibroblast growth factor 23 is associated with proteinuria and smoking in chronic kidney disease&#58; An analysis of the MASTERPLAN cohort"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Bio Med Central Nephrology"
                        "fecha" => "2012"
                        "volumen" => "24"
                        "paginaInicial" => "13"
                        "paginaFinal" => "20"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0770"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mutation of the mouse klotho gene leads to a syndrome resembling ageing"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/36285"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nature"
                        "fecha" => "1997"
                        "volumen" => "390"
                        "paginaInicial" => "45"
                        "paginaFinal" => "51"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0775"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunohistochemical localization of Klotho protein in brain&#44; kidney&#44; and reproductive organs of mice"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Struct Funct"
                        "fecha" => "2004"
                        "volumen" => "29"
                        "paginaInicial" => "91"
                        "paginaFinal" => "99"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0780"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The emerging role of Klotho in clinical nephrology"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfs160"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2012"
                        "volumen" => "27"
                        "paginaInicial" => "2650"
                        "paginaFinal" => "2657"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0785"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Identification of the human klotho gene and its 2 transcripts encoding membrane and secreted klotho protein"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Biochem Biophys Res Commun"
                        "fecha" => "1998"
                        "volumen" => "242"
                        "paginaInicial" => "626"
                        "paginaFinal" => "630"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0790"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PPAR-g and aging&#58; One link through klotho&#63;"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidnet Int&#46;"
                        "fecha" => "2008"
                        "volumen" => "64"
                        "numero" => "6"
                        "paginaInicial" => "732"
                        "paginaFinal" => "739"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0795"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D receptor agonist increase Klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.2012.322"
                      "Revista" => array:7 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2012"
                        "volumen" => "82"
                        "numero" => "12"
                        "paginaInicial" => "1261"
                        "paginaFinal" => "1270"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0800"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gene expression analysis of kidneys from transgenic mice expressing fibroblast growth factor-23"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfm672"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant&#46;"
                        "fecha" => "2008"
                        "volumen" => "23"
                        "paginaInicial" => "827"
                        "paginaFinal" => "833"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0805"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alpha-Klotho as a regulator of calcium homeostasis"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.1135901"
                      "Revista" => array:6 [
                        "tituloSerie" => "Science&#46;"
                        "fecha" => "2007"
                        "volumen" => "316"
                        "paginaInicial" => "1615"
                        "paginaFinal" => "1618"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0810"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regulation and function of the FGF23&#47;klotho endocrine pathways"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/physrev.00002.2011"
                      "Revista" => array:7 [
                        "tituloSerie" => "Physiol Rev&#46;"
                        "fecha" => "2012"
                        "volumen" => "92"
                        "numero" => "1"
                        "paginaInicial" => "131"
                        "paginaFinal" => "155"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0815"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative stress decreases klotho expression in a mouse kidney cell line"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000086500"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephron Exp Nephrol"
                        "fecha" => "2005"
                        "volumen" => "101"
                        "paginaInicial" => "e67"
                        "paginaFinal" => "e74"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0820"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Hypertension"
                        "fecha" => "2002"
                        "volumen" => "39"
                        "paginaInicial" => "838"
                        "paginaFinal" => "843"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0825"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Angiotensin II and EGF receptor cross-talk in chronic kidney diseases&#58; A new therapeutic approach"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nm1275"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Med"
                        "fecha" => "2005"
                        "volumen" => "11"
                        "paginaInicial" => "867"
                        "paginaFinal" => "874"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0830"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal and extra-renal actions of Klotho"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.semnephrol.2012.12.013"
                      "Revista" => array:7 [
                        "tituloSerie" => "Semin Nephrol"
                        "fecha" => "2013"
                        "volumen" => "33"
                        "numero" => "2"
                        "paginaInicial" => "118"
                        "paginaFinal" => "129"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0835"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in klotho mice"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajprenal.00248.2006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Renal Physiol&#46;"
                        "fecha" => "2007"
                        "volumen" => "292"
                        "paginaInicial" => "F769"
                        "paginaFinal" => "F779"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0840"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Downregulation of NaPi-IIa and NaPi-IIb Na-coupled phosphate transporters by coexpression of Klotho"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000331737"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Physiol Biochem&#46;"
                        "fecha" => "2011"
                        "volumen" => "28"
                        "paginaInicial" => "251"
                        "paginaFinal" => "258"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            74 => array:3 [
              "identificador" => "bib0845"
              "etiqueta" => "75"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The betaglucuronidase klotho hydrolyzes and activates the TRPV5 channel"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.1114245"
                      "Revista" => array:6 [
                        "tituloSerie" => "Science&#46;"
                        "fecha" => "2005"
                        "volumen" => "310"
                        "paginaInicial" => "490"
                        "paginaFinal" => "493"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            75 => array:3 [
              "identificador" => "bib0850"
              "etiqueta" => "76"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Regulation of renal outer medullary potassium channel and renal K&#40;&#43;&#41; excretion by Klotho"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1124/mol.109.055780"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Pharmacol&#46;"
                        "fecha" => "2009"
                        "volumen" => "76"
                        "paginaInicial" => "38"
                        "paginaFinal" => "46"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            76 => array:3 [
              "identificador" => "bib0855"
              "etiqueta" => "77"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An elixir of youth for the vasculature&#63;"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2010111190"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2011"
                        "volumen" => "22"
                        "paginaInicial" => "5"
                        "paginaFinal" => "7"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            77 => array:3 [
              "identificador" => "bib0860"
              "etiqueta" => "78"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Klotho deficiency causes vascular calcification in chronic kidney disease"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2009121311"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2011"
                        "volumen" => "22"
                        "paginaInicial" => "124"
                        "paginaFinal" => "136"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            78 => array:3 [
              "identificador" => "bib0865"
              "etiqueta" => "79"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vascular klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/CIRCULATIONAHA.111.053405"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2012"
                        "volumen" => "125"
                        "paginaInicial" => "2243"
                        "paginaFinal" => "2255"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            79 => array:3 [
              "identificador" => "bib0870"
              "etiqueta" => "80"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Arterial Klotho expression and FGF23 effects on vascular calcification and function"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0060658"
                      "Revista" => array:6 [
                        "tituloSerie" => "Plos One"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "numero" => "4"
                        "paginaInicial" => "e60658"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            80 => array:3 [
              "identificador" => "bib0875"
              "etiqueta" => "81"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Differential expression and regulation of Klotho by paricalcitol in the kidney&#44; parathyroid&#44; and aorta of uremic rats"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.2015.22"
                      "Revista" => array:7 [
                        "tituloSerie" => "Kidney Int&#46;"
                        "fecha" => "2015"
                        "volumen" => "87"
                        "numero" => "6"
                        "paginaInicial" => "1141"
                        "paginaFinal" => "1152"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            81 => array:3 [
              "identificador" => "bib0880"
              "etiqueta" => "82"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mediation of unusually high concentrations of 1&#44;25-dihydroxyvitamin D in homozygous klotho mutant mice by increased expression of renal 1alpha-hydroxylase gene"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/endo.143.2.8657"
                      "Revista" => array:7 [
                        "tituloSerie" => "Endocrinology&#46;"
                        "fecha" => "2002"
                        "volumen" => "143"
                        "numero" => "2"
                        "paginaInicial" => "683"
                        "paginaFinal" => "689"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            82 => array:3 [
              "identificador" => "bib0885"
              "etiqueta" => "83"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The erythropoietin receptor is a downstream effector of Klotho-induced cytoprotection"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.2013.149"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "2013"
                        "volumen" => "84"
                        "paginaInicial" => "468"
                        "paginaFinal" => "481"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            83 => array:3 [
              "identificador" => "bib0890"
              "etiqueta" => "84"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "In vivo klotho gene transfer ameliorates angiotensin II-induced renal damage"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Hypertension&#46;"
                        "fecha" => "2002"
                        "volumen" => "39"
                        "paginaInicial" => "838"
                        "paginaFinal" => "843"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            84 => array:3 [
              "identificador" => "bib0895"
              "etiqueta" => "85"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Suppression of aging in mice by the hormone Klotho"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.1112766"
                      "Revista" => array:6 [
                        "tituloSerie" => "Science&#46;"
                        "fecha" => "2005"
                        "volumen" => "309"
                        "paginaInicial" => "1829"
                        "paginaFinal" => "1833"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            85 => array:3 [
              "identificador" => "bib0900"
              "etiqueta" => "86"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Klotho inhibits transforming growth factor-beta1 &#40;TGF-beta1&#41; signaling and suppresses renal fibrosis and cancer metastasis in mice"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.M110.174037"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem&#46;"
                        "fecha" => "2011"
                        "volumen" => "286"
                        "paginaInicial" => "8655"
                        "paginaFinal" => "8665"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            86 => array:3 [
              "identificador" => "bib0905"
              "etiqueta" => "87"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "20"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti-apoptotic and antisenescence effects of Kloto on vascular endotelial cells"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Biochem Biophys Res Com&#250;n"
                        "fecha" => "2006"
                        "volumen" => "339"
                        "numero" => "3"
                        "paginaInicial" => "827"
                        "paginaFinal" => "832"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            87 => array:3 [
              "identificador" => "bib0910"
              "etiqueta" => "88"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Klotho deficiency is an early biomarker of renal ischemia&#8211;reperfusion injury and its replacement is protective"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.2010.328"
                      "Revista" => array:7 [
                        "tituloSerie" => "Kidney Int&#46;"
                        "fecha" => "2010"
                        "volumen" => "78"
                        "numero" => "12"
                        "paginaInicial" => "1240"
                        "paginaFinal" => "1251"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            88 => array:3 [
              "identificador" => "bib0915"
              "etiqueta" => "89"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Klotho as a potential biomarker and therapy for acute kidney injury"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrneph.2012.92"
                      "Revista" => array:7 [
                        "tituloSerie" => "Nat Rev Nephrol&#46;"
                        "fecha" => "2012"
                        "volumen" => "8"
                        "numero" => "7"
                        "paginaInicial" => "423"
                        "paginaFinal" => "429"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            89 => array:3 [
              "identificador" => "bib0920"
              "etiqueta" => "90"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Soluble Klotho protects against uremic cardiomyopathy independently of fibroblast growth factor 23 and phosphate"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2014040325"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2015"
                        "volumen" => "26"
                        "paginaInicial" => "1150"
                        "paginaFinal" => "1160"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            90 => array:3 [
              "identificador" => "bib0925"
              "etiqueta" => "91"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ncomms2240"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Commun"
                        "fecha" => "2012"
                        "volumen" => "3"
                        "paginaInicial" => "1238"
                        "paginaFinal" => "1259"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            91 => array:3 [
              "identificador" => "bib0930"
              "etiqueta" => "92"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Control of cardiac growth and function by calcineurin signaling"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.R300023200"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2003"
                        "volumen" => "278"
                        "paginaInicial" => "36981"
                        "paginaFinal" => "36984"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            92 => array:3 [
              "identificador" => "bib0935"
              "etiqueta" => "93"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI27702"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2006"
                        "volumen" => "116"
                        "paginaInicial" => "3114"
                        "paginaFinal" => "3126"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            93 => array:3 [
              "identificador" => "bib0940"
              "etiqueta" => "94"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "TRP-ing up heart and vessels&#58; Canonical transient receptor potential channels and cardiovascular disease"
                      "autores" => array:1 [
                        0 => array:2 [ …2]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12265-010-9208-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cardiovasc Transl Res"
                        "fecha" => "2010"
                        "volumen" => "3"
                        "paginaInicial" => "516"
                        "paginaFinal" => "524"
                        "link" => array:1 [ …1]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "es"
  "url" => "/02116995/0000003600000004/v2_201611160150/S0211699516300078/v2_201611160150/es/main.assets"
  "Apartado" => array:4 [
    "identificador" => "53477"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Revisiones"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/02116995/0000003600000004/v2_201611160150/S0211699516300078/v2_201611160150/es/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699516300078?idApp=UINPBA000064"
]