array:24 [
  "pii" => "S021169951730098X"
  "issn" => "02116995"
  "doi" => "10.1016/j.nefro.2017.03.025"
  "estado" => "S300"
  "fechaPublicacion" => "2017-11-01"
  "aid" => "378"
  "copyright" => "Sociedad Española de Nefrología"
  "copyrightAnyo" => "2017"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "fla"
  "cita" => "Nefrologia. 2017;37:592-7"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 4747
    "formatos" => array:3 [
      "EPUB" => 467
      "HTML" => 3441
      "PDF" => 839
    ]
  ]
  "itemSiguiente" => array:20 [
    "pii" => "S0211699517301431"
    "issn" => "02116995"
    "doi" => "10.1016/j.nefro.2017.05.015"
    "estado" => "S300"
    "fechaPublicacion" => "2017-11-01"
    "aid" => "408"
    "copyright" => "Sociedad Española de Nefrología"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Nefrologia. 2017;37:598-607"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 24617
      "formatos" => array:3 [
        "EPUB" => 378
        "HTML" => 23431
        "PDF" => 808
      ]
    ]
    "es" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original</span>"
      "titulo" => "La disminuci&#243;n de triyodotironina se asocia con la elevaci&#243;n del p&#233;ptido natriur&#233;tico cerebral N-terminal y con la mortalidad en pacientes en di&#225;lisis"
      "tienePdf" => "es"
      "tieneTextoCompleto" => "es"
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "598"
          "paginaFinal" => "607"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Low triiodothyronine is associated with elevation of N-terminal pro-brain natriuretic peptide &#40;NT-proBNP&#41; and mortality in dialysis patients"
        ]
      ]
      "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" => "fig0010"
          "etiqueta" => "Figura 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 1585
              "Ancho" => 1547
              "Tamanyo" => 99185
            ]
          ]
          "descripcion" => array:1 [
            "es" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La relaci&#243;n entre el n&#250;mero de hormonas tiroideas en rangos bajos y la TSH elevada se asocia con la supervivencia&#46; Un mayor n&#250;mero de hormonas anormales se asocia con menor supervivencia&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Mar&#237;a del Carmen Prado-Uribe, Mar&#237;a-de-Jes&#250;s Ventura, Marcela &#193;vila-D&#237;az, Carmen J&#46; Mora, Antonio M&#233;ndez-Dur&#225;n, Diana Villanueva-Noches, Alejandra Cisneros, Bego&#241;a Ilabaca, Alfonso Cueto-Manzano, Fernando Garc&#237;a-Contreras, Bengt Lindholm, Elvia Garc&#237;a-L&#243;pez, Ram&#243;n Paniagua"
          "autores" => array:13 [
            0 => array:2 [
              "nombre" => "Mar&#237;a del Carmen"
              "apellidos" => "Prado-Uribe"
            ]
            1 => array:2 [
              "nombre" => "Mar&#237;a-de-Jes&#250;s"
              "apellidos" => "Ventura"
            ]
            2 => array:2 [
              "nombre" => "Marcela"
              "apellidos" => "&#193;vila-D&#237;az"
            ]
            3 => array:2 [
              "nombre" => "Carmen J&#46;"
              "apellidos" => "Mora"
            ]
            4 => array:2 [
              "nombre" => "Antonio"
              "apellidos" => "M&#233;ndez-Dur&#225;n"
            ]
            5 => array:2 [
              "nombre" => "Diana"
              "apellidos" => "Villanueva-Noches"
            ]
            6 => array:2 [
              "nombre" => "Alejandra"
              "apellidos" => "Cisneros"
            ]
            7 => array:2 [
              "nombre" => "Bego&#241;a"
              "apellidos" => "Ilabaca"
            ]
            8 => array:2 [
              "nombre" => "Alfonso"
              "apellidos" => "Cueto-Manzano"
            ]
            9 => array:2 [
              "nombre" => "Fernando"
              "apellidos" => "Garc&#237;a-Contreras"
            ]
            10 => array:2 [
              "nombre" => "Bengt"
              "apellidos" => "Lindholm"
            ]
            11 => array:2 [
              "nombre" => "Elvia"
              "apellidos" => "Garc&#237;a-L&#243;pez"
            ]
            12 => array:2 [
              "nombre" => "Ram&#243;n"
              "apellidos" => "Paniagua"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S2013251417301979"
        "doi" => "10.1016/j.nefroe.2017.11.013"
        "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/S2013251417301979?idApp=UINPBA000064"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699517301431?idApp=UINPBA000064"
    "url" => "/02116995/0000003700000006/v2_201712010640/S0211699517301431/v2_201712010640/es/main.assets"
  ]
  "itemAnterior" => array:20 [
    "pii" => "S0211699517301017"
    "issn" => "02116995"
    "doi" => "10.1016/j.nefro.2017.03.027"
    "estado" => "S300"
    "fechaPublicacion" => "2017-11-01"
    "aid" => "381"
    "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. 2017;37:587-91"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 6822
      "formatos" => array:3 [
        "EPUB" => 352
        "HTML" => 5415
        "PDF" => 1055
      ]
    ]
    "es" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Revisi&#243;n breve</span>"
      "titulo" => "Insuficiencia card&#237;aca en la enfermedad renal y d&#233;ficit de hierro&#58; importancia de la ferroterapia"
      "tienePdf" => "es"
      "tieneTextoCompleto" => "es"
      "tieneResumen" => array:2 [
        0 => "es"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "587"
          "paginaFinal" => "591"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Heart failure in patients with kidney disease and iron deficiency&#59; the role of iron therapy"
        ]
      ]
      "contieneResumen" => array:2 [
        "es" => true
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "es" => true
      ]
      "contienePdf" => array:1 [
        "es" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Aleix Cases Amen&#243;s, Raquel Ojeda L&#243;pez, Jos&#233; Mar&#237;a Portol&#233;s P&#233;rez"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Aleix"
              "apellidos" => "Cases Amen&#243;s"
            ]
            1 => array:2 [
              "nombre" => "Raquel"
              "apellidos" => "Ojeda L&#243;pez"
            ]
            2 => array:2 [
              "nombre" => "Jos&#233; Mar&#237;a"
              "apellidos" => "Portol&#233;s P&#233;rez"
            ]
            3 => array:1 [
              "colaborador" => "en representaci&#243;n del Grupo de Anemia de la S&#46;E&#46;N&#46;"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "es"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S2013251417301931"
        "doi" => "10.1016/j.nefroe.2017.11.009"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251417301931?idApp=UINPBA000064"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699517301017?idApp=UINPBA000064"
    "url" => "/02116995/0000003700000006/v2_201712010640/S0211699517301017/v2_201712010640/es/main.assets"
  ]
  "en" => array:20 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "Telomerase activity in patients with stage 2&#8211;5D chronic kidney disease"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "592"
        "paginaFinal" => "597"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Veysel Kidir, Ayse Aynali, Atila Altuntas, Salih Inal, Buket Aridogan, Mehmet Tugrul Sezer"
        "autores" => array:6 [
          0 => array:4 [
            "nombre" => "Veysel"
            "apellidos" => "Kidir"
            "email" => array:1 [
              0 => "veyselkdr&#64;gmail&#46;com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Ayse"
            "apellidos" => "Aynali"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Atila"
            "apellidos" => "Altuntas"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Salih"
            "apellidos" => "Inal"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Buket"
            "apellidos" => "Aridogan"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Mehmet Tugrul"
            "apellidos" => "Sezer"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:2 [
          0 => array:3 [
            "entidad" => "Division of Nephrology&#44; Department of Internal Medicine&#44; Suleyman Demirel University Medical Faculty&#44; Isparta&#44; Turkey"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Department of Medical Microbiology&#44; Suleyman Demirel University Medical Faculty&#44; Isparta&#44; Turkey"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Actividad de la telomerasa en pacientes en etapas de 2-5D con enfermedad renal cr&#243;nica"
      ]
    ]
    "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" => 941
            "Ancho" => 1585
            "Tamanyo" => 64601
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Telomerase activity in relation to CKD stage&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Epidemiological studies have shown that biological age is older than chronologic age in chronic kidney disease &#40;CKD&#41; patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">1&#8211;3</span></a> Molecular mechanisms of increased cardiovascular mortality in CKD associated with biological age are not well understood&#46; Recent studies suggest that factors such as cellular aging and telomere dysfunction may be the responsible factors&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">4&#8211;6</span></a> Studies conducted in hemodialysis patients have shown that telomere length in peripheral blood mononuclear cells &#40;PBMC&#41; was reduced compared to healthy individuals&#44; irrespective of age and gender&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">7&#44;8</span></a> Telomerase enzyme maintains the length and structure of telomeres&#44; thus provides longer cell survival&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">9&#44;10</span></a> Telomerase activity in PBMC was found significantly lower in hemodialysis patients compared to the healthy control group&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">11</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Telomerase activity levels in various CKD stages and its relation to CKD progression are not well understood&#46; This study was aimed to determine the relation between telomerase activity and CKD stages&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Materials and method</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study design and patient assignment</span><p id="par0015" class="elsevierStylePara elsevierViewall">This study was approved by the University Clinical Research Ethics Committee with approval number 2014&#47;35 and was conducted with the support of Scientific Research Projects Coordination Unit&#46; Written consent was obtained from all participants&#46; This cross-sectional study was conducted at the S&#252;leyman Demirel University Medical School Nephrology Department between May 2014 and November 2014&#46; The study included 120 patients who were followed-up for CKD stage 2&#8211;5D&#44; composed of 30 patients of each stage&#44; and 30 healthy volunteers&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Inclusion criteria were age over 18 years and having CKD stage 2&#8211;5D diagnosis&#46; Exclusion criteria included presence of an acute infection and a malignancy and using immunosuppressive therapy&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Blood sampling</span><p id="par0025" class="elsevierStylePara elsevierViewall">Complete blood count&#44; blood levels of fasting blood glucose&#44; serum creatinine &#40;Cr&#41;&#44; sodium &#40;Na&#41;&#44; potassium &#40;K&#41;&#44; calcium &#40;Ca&#41;&#44; phosphorus &#40;P&#41;&#44; albumin&#44; alanine aminotransferase &#40;ALT&#41;&#44; aspartat aminotransferase &#40;AST&#41;&#44; uric acid&#44; triglyceride&#44; total cholesterol&#44; LDL-cholesterol &#40;LDL-C&#41;&#44; HDL-cholesterol &#40;HDL-C&#41;&#44; 25-hydroxy-vitamin D &#40;25&#40;OH&#41;D&#41;&#44; parathormone &#40;iPTH&#41;&#44; C-reactive protein &#40;CRP&#41; and spot urine protein&#47;creatinine &#40;Upr&#47;Ucr&#41; values were measured in each patient&#46; Blood samples of hemodialysis patients were collected just before mid-week dialysis session&#46; Body mass index &#40;BMI&#41; was calculated&#46; Estimated GFR &#40;eGFR&#41; levels were calculated using Chronic Kidney Disease Epidemiology Collaboration &#40;CKD-EPI&#41; formula&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Measurement of telomerase activity in PBMC</span><p id="par0030" class="elsevierStylePara elsevierViewall">Telomerase activity in PBMC was measured using TeloTAGGG Telomerase PCR ELISA kit &#40;Roche Applied Science&#44; Indianapolis&#44; IN&#44; USA&#41; with telomeric repeat amplification protocol &#40;TRAP&#41; method&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">13</span></a> All samples with an optical density 450<span class="elsevierStyleHsp" style=""></span>nm<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>0&#46;2 were considered telomerase positive&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0035" class="elsevierStylePara elsevierViewall">Data analysis was performed using SPSS for Windows 15&#46;0 software&#46; Results were expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation or percent values&#46; Chi-square test&#44; variance analysis &#40;ANOVA&#41; and Kruskal&#8211;Wallis variance analysis tests were used for group comparisons&#46; Tukey&#39;s HSD test was used for post hoc analysis&#46; Associations between qualitative variables were assessed by Spearman&#39;s or Pearson&#39;s correlation analysis&#46; A multivariate linear regression model was used to estimate the independent effects of various predictors &#40;analyzed variables were age&#44; BMI&#44; eGFR&#44; platelet count&#44; serum Ca&#44; K&#44; LDL-C&#44; iPTH&#41; on telomerase activity&#46; The level of statistical significance was <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><p id="par0040" class="elsevierStylePara elsevierViewall">Mean age was 58&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;4 years in the control group and 59&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;4 years in the patient group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; Baseline characteristics of the patient groups are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Patient groups were similar regarding BMI and smoking &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; Among the CKD stage 5D patients&#44; 20 were on hemodialysis while 10 were on peritoneal dialysis&#46; Mean dialysis duration for dialysis patients was 31&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>29&#46;7 &#40;range&#44; 4&#8211;120&#41; months&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">In CKD stage 5D patients&#44; serum Ca &#40;8&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#44; serum albumin &#40;3&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41; and hemoglobin levels &#40;11&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41; and eGFR &#40;7&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;2<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#46;&#41; were significantly lower &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; while serum Cr &#40;7&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;1<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#44; serum P &#40;4&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;1<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41;&#44; iPTH &#40;323<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>216<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; levels and Upr&#47;Ucr ratio &#40;3&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;4&#41; were significantly higher &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Serum LDL-C levels were found highest in CKD stage 2 patients &#40;124<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>45<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;026&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Comorbidity rates for CKD patients were&#44; hypertension 64&#46;2&#37;&#44; diabetes mellitus 29&#46;2&#37;&#44; coronary artery disease 11&#46;7&#37; and heart failure 5&#46;8&#37;&#46; Hypertension was most prevalent in CKD stage 4 patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Telomerase activity in PBMC</span><p id="par0055" class="elsevierStylePara elsevierViewall">Telomerase activity in PBMC was positive in 86&#37; &#40;26&#47;30&#41; of CKD stage 5D patients while healthy control group was only 3&#37; positive &#40;1&#47;30&#41;&#46; Telomerase activity was increased with CKD stage &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; A significant difference was found for telomerase activity between patient and control groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The levels were lowest in the healthy control group &#40;0&#46;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; and highest in CKD stage 5 group &#40;0&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#46; Telomerase activities in PBMC were similar in CKD stages 2&#44; 3 and 4 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; while in stage 5 CKD it was significantly higher compared to the other stages &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; It was significantly lower in the healthy control group compared to all other groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Dialysis patients were grouped according to dialysis duration &#40;median duration 20 months&#41;&#59; among the 30 patients dialysis duration was long &#40;range 39&#8211;120 months&#41; in 6 of the patients and short &#40;range 4&#8211;38 months&#41; in 24 of the patients&#46; Telomerase activity in PBMC was similar in both subgroups &#40;0&#46;24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#44; 0&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In CKD patients&#44; telomerase activity in PBMC was positively correlated with CKD stage &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;412&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; serum Cr &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;404&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; serum K &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;189&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;038&#41; and iPTH levels &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;245&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#41; and&#59; negatively correlated with BMI &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;248&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41;&#44; eGFR &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;407&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; platelet count &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;252&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;006&#41;&#44; LDL-C &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;243&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#41; and serum Ca levels &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;357&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; A positive correlation was found between telomerase activity and age in healthy controls &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;623&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Telomerase activity in CKD patients and dependent variables age&#44; BMI&#44; eGFR&#44; platelet count&#44; serum Ca&#44; LDL-C&#44; iPTH and K levels were evaluated by linear regression analysis&#46; Only eGFR and BMI were found to be independent predictors for high telomerase activity &#40;<span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;257&#44; <span class="elsevierStyleItalic">&#946;</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001 for eGFR&#44; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;001 to 0&#46;000&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;020&#59; <span class="elsevierStyleItalic">&#946;</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;001 for BMI&#44; CI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#8722;0&#46;003 to 0&#46;000&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;020&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">To our knowledge&#44; unlike the previous studies&#44; the current study is the first to report increased telomerase activity in PBMC in CKD patients&#46; In this study&#44; telomerase activity in PBMC was found significantly increased in CKD patients compared to healthy controls&#46; This increase was found independent of age&#44; gender&#44; inflammation&#44; hyperlipidemia and hyperparathyroidism but it was correlated with eGFR and BMI&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Telomere length was reported to decrease independent of age and gender in hemodialysis patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">7&#44;8</span></a> In renal cells of cats with CKD&#44; increased cellular aging and short telomeres were detected accompanied by normal telomerase activity&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">15</span></a> Tsirpanlis et al&#46; reported that telomerase activity in PBMC was lower in hemodialysis patients compared to the healthy control group&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">11</span></a> In contrast with this study&#44; telomerase activity in PBMC was found increased in our study&#46; Despite being an unexpected result&#44; higher prevalence of diabetes in CKD stage 5D patients in our study might be the reason for high detected telomerase activity considering high telomerase activity reported in patients with metabolic syndrome in previous studies&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a> Additionally&#44; insignificantly lower BMI in CKD stage 5D patients might have contributed to the detected high telomerase activity in this subgroup&#46; Thus&#44; previous studies have reported that obesity associated with telomere shortening&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">17&#8211;19</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Telomerase activity was reported to decrease with age&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">20</span></a> Although no correlation was found between age and telomerase activity in CKD patients&#44; a positive correlation was detected between age and telomerase activity in the healthy controls in our study&#46; This may be associated with other factors other than age that influence telomerase activity&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The combination of high telomerase activity and short telomere was suggested to be a sign of activated cell stress&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">21</span></a> Epel et al&#46; in their study on caregivers of dementia patients found increased telomerase activity in PBMC accompanied by increased serum cortisol levels related to acute psychological stress&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">22</span></a> Lack of acute stress and serum cortisol levels assessments is a limitation of this study&#46; Further studies may clarify this issue&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Telomerase activity in PBMC was reported to be potentially associated with inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">23</span></a> In cell cultures&#44; increased telomerase activity in macrophages was shown in response to inflammatory stimulants&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">24</span></a> In the study by Rentoukas et al&#46; telomerase activity in PBMC&#44; IL6&#44; TNF&#945; and asymmetric dimethylarginine &#40;ADMA&#41; levels were found significantly higher in metabolic syndrome patients compared to healthy controls&#46; Additionally&#44; a positive correlation was observed between telomerase activity and ADMA levels while no correlation was found between telomerase activity and IL6 or TNF&#945;&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a> In this study&#44; CRP was the only evaluated inflammatory marker&#46; A significant relation was not found between telomerase activity in PBMC and CRP&#46; However&#44; this result may be due to the fact that this study excluded patients with acute infection&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Lin et al&#46; measured telomerase activity and telomere length in various subtypes of T and B cells &#40;CD4&#43;&#44; CD8<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CD28&#43; and CD8<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CD28&#8722; T and B cells&#41;&#46; They found the longest telomere and highest telomerase activity was in B cells&#44; while shortest telomere and lowest telomerase activity was in CD8<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CD28&#8722; cells&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">25</span></a> In patients with unstable angina&#44; telomerase activity in polymorphonuclear neutrophils in aterosclerotic plaques was found significantly higher compared to circulating neutrophils and this was suggested to be related to activation of inflammatory cells in early stage of instability and their locally prolonged survival&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">26</span></a> In our study&#44; telomerase activity assessment in T and B subtypes was lacking since subtype analysis for PBMC was not performed&#46; However&#44; accelerated atherosclerosis and chronic micro-inflammation can be speculated as contributing factors to the findings in this study&#46; Further studies will set light to this issue&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Obesity was reported to accelerate cellular aging and was found associated with telomere shortening&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">17&#8211;19</span></a> In our study&#44; high BMI was associated with low telomerase activity in CKD patients&#46; Telomerase activity levels were lower in obese patients&#46; This result supports the previous observations suggesting obesity is related with telomere shortening in CKD patients&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Telomerase activity in PBMC was found negatively correlated with oxidized LDL-C&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">27</span></a> Statin treatment was associated with high telomerase activity and long telomeres&#44; independent from age&#44; lipid levels and inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">28</span></a> In our study&#44; unlike previous studies&#44; telomerase activity in PBMC was not associated with LDL-C&#46; This result may be due to the fact that 1&#47;5 of our patients were on statins&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Cross-sectional design and relatively small number of patients and controls are the other limitations of our study&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In conclusion&#59; to our knowledge&#44; this study is important for being the first to evaluate the relation between CKD stages and telomerase activity in PBMC&#46; Based on the results of our study&#44; it can be concluded that telomerase activity in PBMC is increased in CKD patients compared to healthy individuals&#46; Telomerase activity in PBMC is increased with advancing stage in CKD patients and particularly in end-stage renal failure&#46; Confirmation of this result in further studies may open new horizons in prevention of biological aging&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Author contributions</span><p id="par0125" class="elsevierStylePara elsevierViewall">Concept &#8211; V&#46;K&#46;&#59; design &#8211; V&#46;K&#46;&#44; AY&#46;A&#46;&#59; supervision &#8211; M&#46;T&#46;S&#46;&#44; B&#46;A&#46;&#59; resource &#8211; V&#46;K&#46;&#44; AY&#46;A&#46;&#59; materials &#8211; V&#46;K&#46;&#44; AY&#46;A&#46;&#59; data collection and&#47;or processing &#8211; V&#46;K&#46;&#44; AY&#46;A&#46;&#44; AT&#46;A&#46;&#44; S&#46;I&#46;&#59; analysis and&#47;or interpretation &#8211; V&#46;K&#46;&#44; S&#46;I&#46;&#59; literature search &#8211; V&#46;K&#46;&#59; writing &#8211; V&#46;K&#46;&#59; critical reviews &#8211; M&#46;T&#46;S&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflict of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:11 [
        0 => array:3 [
          "identificador" => "xres949495"
          "titulo" => "Abstract"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Background"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Objectives"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Methods"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Results"
            ]
            4 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Conclusion"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec921471"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres949494"
          "titulo" => "Resumen"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Antecedentes"
            ]
            1 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Objetivos"
            ]
            2 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "M&#233;todos"
            ]
            3 => array:2 [
              "identificador" => "abst0045"
              "titulo" => "Resultados"
            ]
            4 => array:2 [
              "identificador" => "abst0050"
              "titulo" => "Conclusi&#243;n"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec921472"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Materials and method"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Study design and patient assignment"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Blood sampling"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Measurement of telomerase activity in PBMC"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0035"
          "titulo" => "Results"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Telomerase activity in PBMC"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Author contributions"
        ]
        9 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Conflict of interest"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-12-14"
    "fechaAceptado" => "2017-03-18"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec921471"
          "palabras" => array:3 [
            0 => "Chronic kidney disease"
            1 => "Stage"
            2 => "Telomerase"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec921472"
          "palabras" => array:3 [
            0 => "Enfermedad renal cr&#243;nica"
            1 => "Etapa"
            2 => "Telomerasa"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Molecular mechanisms of increased cardiovascular mortality in chronic kidney disease &#40;CKD&#41; associated with biological age are not well understood&#46; Recent studies support the hypothesis that common factors responsible for this phenomenon are cellular aging and telomere dysfunction&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The purpose of this study was to investigate the relation between telomerase activity and CKD stages&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The study included 120 patients who were followed-up for CKD stage 2&#8211;5D&#44; composed of 30 patients of each stage and 30 healthy volunteers without any known disease who were admitted to our hospital for routine check-ups&#46; Telomerase activity in peripheral blood mononuclear cells &#40;PBMC&#41; was measured using the TRAP assay&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A significant difference was observed for telomerase activity in PBMC between groups&#46; The detected levels were lowest in the healthy control group &#40;0&#46;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#44; and highest in CKD stage 5D patients &#40;0&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#46; In CKD patients&#44; telomerase activity in PBMC was positively correlated with the CKD stage&#44; serum creatinine&#44; potassium and parathormone levels&#44; and negatively correlated with estimated glomerular filtration rate &#40;eGFR&#41;&#44; body mass index &#40;BMI&#41;&#44; platelet count and serum calcium levels&#46; According to the linear regression analysis&#44; independent predictors for high telomerase activity in CKD patients were eGFR and BMI&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Telomerase activity in PBMC increases with advancing CKD stage in CKD patients&#46; Increased telomerase activity in PBMC is associated with eGFR and BMI&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objectives"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Conclusion"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Los mecanismos moleculares responsables del aumento de la mortalidad cardiovascular en la enfermedad renal cr&#243;nica &#40;ERC&#41; asociada a la edad biol&#243;gica no se conocen bien&#46; Los estudios recientes apoyan la hip&#243;tesis de que los factores comunes responsables de este fen&#243;meno son el envejecimiento celular y la disfunci&#243;n telom&#233;rica&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El objetivo de este estudio fue investigar la relaci&#243;n entre la actividad de la enzima telomerasa y los estadios de ERC&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El estudio incluy&#243; a 120 pacientes que fueron seguidos para la ERC en los estadios 2-5D&#59; cada estadio incluy&#243; a 30 pacientes y a 30 voluntarios sanos sin ninguna enfermedad conocida que fueron admitidos en nuestro hospital para los controles peri&#243;dicos&#46; La actividad de la telomerasa en c&#233;lulas mononucleares de sangre perif&#233;rica &#40;CMSP&#41; se midi&#243; usando el m&#233;todo de TRAP&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se observ&#243; una diferencia significativa en la actividad telomerasa en las CMSP entre los diferentes grupos&#46; Los niveles m&#225;s bajos fueron los del grupo de controles sanos &#40;0&#44;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;02&#41; y los m&#225;s altos los del grupo de pacientes con ERC en el estadio 5D &#40;0&#44;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41;&#46; En los pacientes con ERC&#44; la actividad telomerasa en las CMSP se correlacion&#243; positivamente con el estadio de ERC y los niveles plasm&#225;ticos de potasio&#44; hormona paratiroidea y creatinina&#44; y se correlacion&#243; negativamente con la tasa de filtraci&#243;n glomerular estimada &#40;eTFG&#41;&#44; el &#237;ndice de masa corporal &#40;IMC&#41;&#44; el recuento de plaquetas y el calcio en suero&#46; Los predictores independientes para la actividad telomerasa alta en pacientes con ERC fueron la eTFG y el IMC&#44; de acuerdo con el an&#225;lisis de regresi&#243;n lineal&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusi&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La actividad telomerasa en CMSP aumenta con el avance en el estadio de ERC&#46; El aumento de la actividad telomerasa en CMSP se asocia con la eTFG y el IMC&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Antecedentes"
          ]
          1 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Objetivos"
          ]
          2 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "M&#233;todos"
          ]
          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0050"
            "titulo" => "Conclusi&#243;n"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">This study was presented at the ASN Kidney Week 2015&#44; 3&#8211;8 November 2015&#44; San Diego&#44; USA&#46;</p>"
      ]
    ]
    "multimedia" => array:5 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 941
            "Ancho" => 1585
            "Tamanyo" => 64601
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Telomerase activity in relation to CKD stage&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">CKD&#58; chronic kidney disease&#59; BMI&#58; body mass index&#59; eGFR&#58; estimated glomerular filtration rate&#59; ALT&#58; alanine aminotransferase&#59; AST&#58; aspartate aminotransferase&#59; LDL-C&#58; low density lipoprotein cholesterol&#59; HDL-C&#58; high density lipoprotein cholesterol&#59; WBC&#58; white blood cell&#59; PLT&#58; platelet&#59; CRP&#58; C-reactive protein&#59; iPTH&#58; intact parathyroid hormone&#59; 25&#40;OH&#41;D&#58; 25-hydroxy vitamin D&#59; Upr&#47;Ucr&#58; protein&#47;creatinine ratio in spot urine&#59; DM&#58; diabetes mellitus&#59; CAD&#58; coronary artery disease&#46; Data are indicated as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation or percent&#46; <span class="elsevierStyleSup">a&#44;b&#44;c&#44;d&#44;e</span>There is a significant difference between the parameters marked with the same letter &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; For the comparison between groups&#44; analysis of variance &#40;ANOVA&#41; or Kruskal&#8211;Wallis test was applied&#44; and for the post hoc study Tukey HSD test was used&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Stage 2<br>CKD<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&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">Stage 3<br>CKD<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&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">Stage 4<br>CKD<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&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">Stage 5D<br>CKD<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&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"><span class="elsevierStyleItalic">p</span>&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">Age&#44; years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;997&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">Male&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;268&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">Smoking&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;093&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">eGFR &#40;ml&#47;dk&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;4<span class="elsevierStyleSup">a&#44;b&#44;c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">37&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;2<span class="elsevierStyleSup">a&#44;d&#44;e</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;5<span class="elsevierStyleSup">b&#44;d&#44;f</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;2<span class="elsevierStyleSup">c&#44;e&#44;f</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glucose &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">113<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">118<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">115<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">142<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;068&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">Creatinine &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;1<span class="elsevierStyleSup">a&#44;b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;2<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7<span class="elsevierStyleSup">a&#44;d</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;1<span class="elsevierStyleSup">b&#44;c&#44;d</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sodium &#40;mEq&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">139<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">138<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">133<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">136<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;164&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">Potassium &#40;mEq&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleSup">a&#44;b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;4<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;005&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">Calcium &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleSup">a&#44;b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6<span class="elsevierStyleSup">c&#44;d</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleSup">a&#44;c&#44;e</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8<span class="elsevierStyleSup">b&#44;d&#44;e</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Phosphorus &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;1<span class="elsevierStyleSup">a&#44;b&#44;c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Uric acid &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;197&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">Albumin &#40;g&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;3<span class="elsevierStyleSup">a&#44;b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8<span class="elsevierStyleSup">c&#44;d</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;4<span class="elsevierStyleSup">a&#44;c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleSup">b&#44;d</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ALT &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;940&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">AST &#40;U&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;748&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">Triglyceride &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">166<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">177<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">144<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">171<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;436&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">LDL-C &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">124<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>45<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">103<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">98<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;026&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">HDL-C &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;104&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">Hemoglobin &#40;g&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8<span class="elsevierStyleSup">a&#44;b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4<span class="elsevierStyleSup">c&#44;d</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6<span class="elsevierStyleSup">a&#44;c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7<span class="elsevierStyleSup">b&#44;d</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">WBC &#40;&#215;10<span class="elsevierStyleSup">3</span>&#47;&#956;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;877&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">PLT &#40;&#215;10<span class="elsevierStyleSup">3</span>&#47;&#956;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">245<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>51<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">216<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">232<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">204<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>56<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;040&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">CRP &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;1<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;7<span class="elsevierStyleSup">a&#44;b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">iPTH &#40;pg&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>46<span class="elsevierStyleSup">a&#44;b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">153<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>102<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">323<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>216<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">25&#40;OH&#41;D &#40;ng&#47;ml&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;084&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">Upr&#47;Ucr&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;2<span class="elsevierStyleSup">a&#44;b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9<span class="elsevierStyleSup">c</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2<span class="elsevierStyleSup">a&#44;d</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;4<span class="elsevierStyleSup">b&#44;c&#44;d</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypertension&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12 &#40;40&#41;<span class="elsevierStyleSup">a&#44;b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19 &#40;63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24 &#40;80&#41;<span class="elsevierStyleSup">a</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23 &#40;77&#41;<span class="elsevierStyleSup">b</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;005&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">DM&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9 &#40;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12 &#40;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;444&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">CAD&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;081&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">Heart failure&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0 &#40;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 &#40;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;255&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1607904.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Baseline clinical and laboratory data of CKD patients&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">CKD&#58; chronic kidney disease&#46; Chi-square test was applied for the comparison between groups&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&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">Telomerase positive cases &#37;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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"><span class="elsevierStyleItalic">p</span>&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">Control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;3 &#40;1&#47;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="5" align="left" valign="top">&#60;0&#46;001</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage 2 CKD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20 &#40;6&#47;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage 3 CKD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&#46;3 &#40;13&#47;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage 4 CKD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30 &#40;9&#47;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Stage 5D CKD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">86&#46;6 &#40;26&#47;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1607901.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Values in parentheses correspond to&#58; no&#46; of telomerase positive cases&#47;total no&#46; of cases&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Group comparisons for telomerase activity positivity&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">CKD&#58; chronic kidney disease&#46; <span class="elsevierStyleSup">a&#44;b&#44;c&#44;d&#44;e&#44;f&#44;g</span>Data are indicated as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#46; There is a significant difference between the parameters marked with the same letter &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46; For the comparison between groups&#44; analysis of variance &#40;ANOVA&#41; was applied&#44; and for the post hoc study Tukey HSD test was used&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&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">Control<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&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">Stage 2<br>CKD<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&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">Stage 3<br>CKD<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&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">Stage 4<br>CKD<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&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">Stage 5D<br>CKD<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&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"><span class="elsevierStyleItalic">p</span>&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">Telomerase activity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;02<span class="elsevierStyleSup">a&#44;b&#44;c&#44;d</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;17<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;03<span class="elsevierStyleSup">a&#44;e</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;03<span class="elsevierStyleSup">b&#44;f</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;04<span class="elsevierStyleSup">c&#44;g</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;04<span class="elsevierStyleSup">d&#44;e&#44;f&#44;g</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1607902.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Group comparisons for telomerase activity&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">eGFR&#58; estimated glomerular filtration rate&#59; BMI&#58; body mass index&#46; Dependent variables included in the analysis were age&#44; BMI&#44; eGFR&#44; platelet count&#44; Ca&#44; LDL-C&#44; iPTH and K levels&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameter&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"><span class="elsevierStyleItalic">B</span>&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">95&#37; Confidence Interval&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"><span class="elsevierStyleItalic">p</span>&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"><span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span>&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">eGFR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;001 to 0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;257&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">BMI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;003 to 0&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;020&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></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1607903.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Linear regression analysis of factors associated with telomerase activity in CKD patients&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:28 [
            0 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Controlling the epidemic of cardiovascular disease in chronic renal disease&#58; What do we know&#63;&#44; What do we need to learn&#63;&#46; Where do we go from here&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;S&#46; Levey"
                            1 => "J&#46;A&#46; Beto"
                            2 => "B&#46;E&#46; Coronado"
                            3 => "G&#46; Eknoyan"
                            4 => "R&#46;N&#46; Foley"
                            5 => "B&#46;L&#46; Kasiske"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Kidney Dis"
                        "fecha" => "1998"
                        "volumen" => "32"
                        "paginaInicial" => "853"
                        "paginaFinal" => "906"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9820460"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiovascular disease determinants in chronic renal failure&#58; clinical approach and treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Locatelli"
                            1 => "J&#46; Bommer"
                            2 => "G&#46;M&#46; London"
                            3 => "A&#46; Mart&#237;n-Malo"
                            4 => "C&#46; Wanner"
                            5 => "M&#46; Yaqoob"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2001"
                        "volumen" => "16"
                        "paginaInicial" => "459"
                        "paginaFinal" => "468"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11239016"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The pattern of inflammation and a potential new clinical meaning and usefulness of C-reactive protein in endstage renal failure patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "G&#46; Tsirpanlis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000082165"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Blood Press Res"
                        "fecha" => "2005"
                        "volumen" => "28"
                        "paginaInicial" => "55"
                        "paginaFinal" => "61"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15550763"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vascular cell senescence&#58; contribution to atherosclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "T&#46; Minamino"
                            1 => "I&#46; Komuro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/01.RES.0000256837.40544.4a"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circ Res"
                        "fecha" => "2007"
                        "volumen" => "100"
                        "paginaInicial" => "15"
                        "paginaFinal" => "26"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17204661"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Telomere biology and cardiovascular disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;J&#46; Fuster"
                            1 => "V&#46; Andres"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/01.RES.0000251281.00845.18"
                      "Revista" => array:6 [
                        "tituloSerie" => "Circ Res"
                        "fecha" => "2006"
                        "volumen" => "99"
                        "paginaInicial" => "1167"
                        "paginaFinal" => "1180"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17122447"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Premature senescence of endothelial cells&#58; Methusaleh&#39;s dilemma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46; Chen"
                            1 => "M&#46;S&#46; Goligorsky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Physiol Heart Circ Physiol"
                        "fecha" => "2006"
                        "volumen" => "290"
                        "paginaInicial" => "1729"
                        "paginaFinal" => "1739"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Stressinduced premature senescence in mononuclear cells from patients on longterm hemodialysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Ram&#237;rez"
                            1 => "J&#46; Carracedo"
                            2 => "S&#46; Soriano"
                            3 => "R&#46; Jim&#233;nez"
                            4 => "A&#46; Mart&#237;n-Malo"
                            5 => "M&#46; Rodr&#237;guez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Kidney Dis"
                        "fecha" => "2005"
                        "volumen" => "45"
                        "paginaInicial" => "353"
                        "paginaFinal" => "359"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15685514"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Assessment of the potential role of active vitamin D treatment in telomere length&#58; a casecontrol study in hemodialysis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Borras"
                            1 => "S&#46; Panizo"
                            2 => "F&#46; Sarr&#243;"
                            3 => "J&#46;M&#46; Valdivielso"
                            4 => "E&#46; Fernandez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.clinthera.2012.02.016"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Ther"
                        "fecha" => "2012"
                        "volumen" => "34"
                        "paginaInicial" => "849"
                        "paginaFinal" => "856"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22417715"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "When cells get stressed&#58; an integrative view of cellular senescence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "I&#46; BenPorath"
                            1 => "R&#46;A&#46; Weinberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI20663"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2004"
                        "volumen" => "113"
                        "paginaInicial" => "8"
                        "paginaFinal" => "13"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14702100"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Telomeres and telomerase&#58; their mechanisms of action and the effects of altering their functions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "E&#46;H&#46; Blackburn"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.febslet.2004.11.036"
                      "Revista" => array:6 [
                        "tituloSerie" => "FEBS Lett"
                        "fecha" => "2005"
                        "volumen" => "579"
                        "paginaInicial" => "859"
                        "paginaFinal" => "862"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15680963"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Telomerase activity is decreased in peripheral blood mononuclear cells of hemodialysis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Tsirpanlis"
                            1 => "S&#46; Chatzipanagiotou"
                            2 => "F&#46; Boufidou"
                            3 => "V&#46; Kordinas"
                            4 => "F&#46; Alevyzaki"
                            5 => "M&#46; Zoga"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000092031"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Nephrol"
                        "fecha" => "2006"
                        "volumen" => "26"
                        "paginaInicial" => "91"
                        "paginaFinal" => "96"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16543712"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A new equation to estimate glomerular filtration rate"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "CKDEPI &#40;Chronic Kidney Disease Epidemiology Collaboration"
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;S&#46; Levey"
                            1 => "L&#46;A&#46; Stevens"
                            2 => "C&#46;H&#46; Schmid"
                            3 => "Y&#46;L&#46; Zhang"
                            4 => "A&#46;F&#46; Castro 3rd"
                            5 => "H&#46;I&#46; Feldman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2009"
                        "volumen" => "150"
                        "paginaInicial" => "604"
                        "paginaFinal" => "612"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19414839"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Advances in quantification and characterization of telomerase activity by the telomeric repeat amplification protocol &#40;TRAP&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "N&#46;W&#46; Kim"
                            1 => "F&#46; Wu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Nucleic Acids Res"
                        "fecha" => "1997"
                        "volumen" => "25"
                        "paginaInicial" => "2595"
                        "paginaFinal" => "2597"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9185569"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Telomere shortening is associated with poor prognosis and telomerase activity correlates with DNA repair impairment in non-small cell lung cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Fr&#237;as"
                            1 => "C&#46; Garc&#237;a-Aranda"
                            2 => "C&#46; de Juan"
                            3 => "A&#46; Mor&#225;n"
                            4 => "P&#46; Ortega"
                            5 => "A&#46; G&#243;mez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.lungcan.2007.11.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lung Cancer"
                        "fecha" => "2008"
                        "volumen" => "60"
                        "paginaInicial" => "416"
                        "paginaFinal" => "425"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18077053"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Feline chronic kidney disease is associated with shortened telomeres and increased cellular senescence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46;M&#46; Quimby"
                            1 => "D&#46;G&#46; Maranon"
                            2 => "C&#46;L&#46; Battaglia"
                            3 => "S&#46;M&#46; McLeland"
                            4 => "W&#46;T&#46; Brock"
                            5 => "S&#46;M&#46; Bailey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajprenal.00527.2012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Renal Physiol"
                        "fecha" => "2013"
                        "volumen" => "305"
                        "paginaInicial" => "F295"
                        "paginaFinal" => "F303"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23720342"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Connection between telomerase activity in PBMC and markers of inflammation and endothelial dysfunction in patients with metabolic syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Rentoukas"
                            1 => "K&#46; Tsarouhas"
                            2 => "I&#46; Kaplanis"
                            3 => "E&#46; Korou"
                            4 => "M&#46; Nikolaou"
                            5 => "G&#46; Marathonitis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0035739"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS One"
                        "fecha" => "2012"
                        "volumen" => "7"
                        "paginaInicial" => "e35739"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22558213"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Obesity&#44; cigarette smoking&#44; and telomere length in women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;M&#46; Valdes"
                            1 => "T&#46; Andrew"
                            2 => "J&#46;P&#46; Gardner"
                            3 => "M&#46; Kimura"
                            4 => "E&#46; Oelsner"
                            5 => "L&#46;F&#46; Cherkas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(05)66630-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2005"
                        "volumen" => "366"
                        "paginaInicial" => "662"
                        "paginaFinal" => "664"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16112303"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Obesity and weight gain in adulthood and telomere length"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Kim"
                            1 => "C&#46;G&#46; Parks"
                            2 => "L&#46;A&#46; DeRoo"
                            3 => "H&#46; Chen"
                            4 => "J&#46;A&#46; Taylor"
                            5 => "R&#46;M&#46; Cawthon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Cancer Epidemiol Biomark Prev"
                        "fecha" => "2009"
                        "volumen" => "18"
                        "paginaInicial" => "816"
                        "paginaFinal" => "820"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inverse association between adiposity and telomere length&#58; the Fels Longitudinal Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Lee"
                            1 => "H&#46; Martin"
                            2 => "M&#46;A&#46; Firpo"
                            3 => "E&#46;W&#46; Demerath"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ajhb.21109"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hum Biol"
                        "fecha" => "2011"
                        "volumen" => "23"
                        "paginaInicial" => "100"
                        "paginaFinal" => "106"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21080476"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Age-associated telomere attrition of lymphocytes in vivo is coordinated with changes in telomerase activity&#44; composition of lymphocyte subsets and health conditions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Lin"
                            1 => "A&#46; Damjanovic"
                            2 => "E&#46;J&#46; Metter"
                            3 => "H&#46; Nguyen"
                            4 => "T&#46; Truong"
                            5 => "K&#46; Najarro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Clin Sci &#40;Lond&#41;"
                        "fecha" => "2015"
                        "volumen" => "128"
                        "paginaInicial" => "367"
                        "paginaFinal" => "377"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Shorter telomeres with high telomerase activity are associated with raised allostatic load and impoverished psychosocial resources"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Zalli"
                            1 => "L&#46;A&#46; Carvalho"
                            2 => "J&#46; Lin"
                            3 => "M&#46; Hamer"
                            4 => "J&#46;D&#46; Erusalimsky"
                            5 => "E&#46;H&#46; Blackburn"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.1322145111"
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci U S A"
                        "fecha" => "2014"
                        "volumen" => "111"
                        "paginaInicial" => "4519"
                        "paginaFinal" => "4524"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24616496"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dynamics of telomerase activity in response to acute psychological stress"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;S&#46; Epel"
                            1 => "J&#46; Lin"
                            2 => "F&#46;S&#46; Dhabhar"
                            3 => "O&#46;M&#46; Wolkowitz"
                            4 => "E&#46; Puterman"
                            5 => "L&#46; Karan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbi.2009.11.018"
                      "Revista" => array:6 [
                        "tituloSerie" => "Brain Behav Immun"
                        "fecha" => "2010"
                        "volumen" => "24"
                        "paginaInicial" => "531"
                        "paginaFinal" => "539"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20018236"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Telomerase levels control the lifespan of human T lymphocytes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Roth"
                            1 => "H&#46; Yssel"
                            2 => "J&#46; Pene"
                            3 => "E&#46;A&#46; Chavez"
                            4 => "M&#46; Schertzer"
                            5 => "P&#46;M&#46; Lansdorp"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2002-07-2015"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2003"
                        "volumen" => "102"
                        "paginaInicial" => "849"
                        "paginaFinal" => "857"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12689947"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Telomerase activation in atherosclerosis and induction of telomerase reverse transcriptase expression by inflammatory stimuli in macrophages"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Gizard"
                            1 => "E&#46;B&#46; Heywood"
                            2 => "H&#46;M&#46; Findeisen"
                            3 => "Y&#46; Zhao"
                            4 => "K&#46;L&#46; Jones"
                            5 => "C&#46; Cudejko"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1161/ATVBAHA.110.219808"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arterioscler Thromb Vasc Biol"
                        "fecha" => "2011 Feb"
                        "volumen" => "31"
                        "paginaInicial" => "245"
                        "paginaFinal" => "252"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21106948"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Analyses and comparisons of telomerase activity and telomere length in human T and B cells&#58; insights for epidemiology of telomere maintenance"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Lin"
                            1 => "E&#46; Epel"
                            2 => "J&#46; Cheon"
                            3 => "C&#46; Kroenke"
                            4 => "E&#46; Sinclair"
                            5 => "M&#46; Bigos"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jim.2009.09.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol Methods"
                        "fecha" => "2010"
                        "volumen" => "352"
                        "paginaInicial" => "71"
                        "paginaFinal" => "80"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19837074"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High telomerase activity in neutrophils from unstable coronary plaques"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;L&#46; Narducci"
                            1 => "A&#46; Grasselli"
                            2 => "L&#46;M&#46; Biasucci"
                            3 => "A&#46; Farsetti"
                            4 => "A&#46; Mul&#232;"
                            5 => "G&#46; Liuzzo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2007.08.048"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2007 Dec 18"
                        "volumen" => "50"
                        "paginaInicial" => "2369"
                        "paginaFinal" => "2374"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18154960"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serum oxidized lowdensity lipoprotein is inversely correlated to telomerase activity in peripheral blood mononuclear cells of haemodialysis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Tsirpanlis"
                            1 => "S&#46; Chatzipanagiotou"
                            2 => "F&#46; Boufidou"
                            3 => "V&#46; Kordinas"
                            4 => "M&#46; Zoga"
                            5 => "F&#46; Alevyzaki"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Nephrology &#40;Carlton&#41;"
                        "fecha" => "2006"
                        "volumen" => "11"
                        "paginaInicial" => "506"
                        "paginaFinal" => "509"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A new pleiotropic effect of statins in elderly&#58; modulation of telomerase activity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46; Boccardi"
                            1 => "M&#46; Barbieri"
                            2 => "M&#46;R&#46; Rizzo"
                            3 => "R&#46; Marfella"
                            4 => "A&#46; Esposito"
                            5 => "L&#46; Marano"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1096/fj.13-232066"
                      "Revista" => array:6 [
                        "tituloSerie" => "FASEB J"
                        "fecha" => "2013"
                        "volumen" => "27"
                        "paginaInicial" => "3879"
                        "paginaFinal" => "3885"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23748973"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/02116995/0000003700000006/v2_201712010640/S021169951730098X/v2_201712010640/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "42448"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Originales"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/02116995/0000003700000006/v2_201712010640/S021169951730098X/v2_201712010640/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S021169951730098X?idApp=UINPBA000064"
]
Compartir
Información de la revista
Vol. 37. Núm. 6.noviembre - diciembre 2017
Páginas 563-670
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Visitas
11280
Vol. 37. Núm. 6.noviembre - diciembre 2017
Páginas 563-670
Original article
Open Access
Telomerase activity in patients with stage 2–5D chronic kidney disease
Actividad de la telomerasa en pacientes en etapas de 2-5D con enfermedad renal crónica
Visitas
11280
Veysel Kidira,
Autor para correspondencia
veyselkdr@gmail.com

Corresponding author.
, Ayse Aynalib, Atila Altuntasa, Salih Inala, Buket Aridoganb, Mehmet Tugrul Sezera
a Division of Nephrology, Department of Internal Medicine, Suleyman Demirel University Medical Faculty, Isparta, Turkey
b Department of Medical Microbiology, Suleyman Demirel University Medical Faculty, Isparta, Turkey
Este artículo ha recibido

Under a Creative Commons license
Información del artículo
Resumen
Texto completo
Bibliografía
Descargar PDF
Estadísticas
Figuras (1)
Tablas (4)
Table 1. Baseline clinical and laboratory data of CKD patients.
Table 2. Group comparisons for telomerase activity positivity.
Table 3. Group comparisons for telomerase activity.
Table 4. Linear regression analysis of factors associated with telomerase activity in CKD patients.
Mostrar másMostrar menos
Abstract
Background

Molecular mechanisms of increased cardiovascular mortality in chronic kidney disease (CKD) associated with biological age are not well understood. Recent studies support the hypothesis that common factors responsible for this phenomenon are cellular aging and telomere dysfunction.

Objectives

The purpose of this study was to investigate the relation between telomerase activity and CKD stages.

Methods

The study included 120 patients who were followed-up for CKD stage 2–5D, composed of 30 patients of each stage and 30 healthy volunteers without any known disease who were admitted to our hospital for routine check-ups. Telomerase activity in peripheral blood mononuclear cells (PBMC) was measured using the TRAP assay.

Results

A significant difference was observed for telomerase activity in PBMC between groups. The detected levels were lowest in the healthy control group (0.15±0.02), and highest in CKD stage 5D patients (0.23±0.04). In CKD patients, telomerase activity in PBMC was positively correlated with the CKD stage, serum creatinine, potassium and parathormone levels, and negatively correlated with estimated glomerular filtration rate (eGFR), body mass index (BMI), platelet count and serum calcium levels. According to the linear regression analysis, independent predictors for high telomerase activity in CKD patients were eGFR and BMI.

Conclusion

Telomerase activity in PBMC increases with advancing CKD stage in CKD patients. Increased telomerase activity in PBMC is associated with eGFR and BMI.

Keywords:
Chronic kidney disease
Stage
Telomerase
Resumen
Antecedentes

Los mecanismos moleculares responsables del aumento de la mortalidad cardiovascular en la enfermedad renal crónica (ERC) asociada a la edad biológica no se conocen bien. Los estudios recientes apoyan la hipótesis de que los factores comunes responsables de este fenómeno son el envejecimiento celular y la disfunción telomérica.

Objetivos

El objetivo de este estudio fue investigar la relación entre la actividad de la enzima telomerasa y los estadios de ERC.

Métodos

El estudio incluyó a 120 pacientes que fueron seguidos para la ERC en los estadios 2-5D; cada estadio incluyó a 30 pacientes y a 30 voluntarios sanos sin ninguna enfermedad conocida que fueron admitidos en nuestro hospital para los controles periódicos. La actividad de la telomerasa en células mononucleares de sangre periférica (CMSP) se midió usando el método de TRAP.

Resultados

Se observó una diferencia significativa en la actividad telomerasa en las CMSP entre los diferentes grupos. Los niveles más bajos fueron los del grupo de controles sanos (0,15±0,02) y los más altos los del grupo de pacientes con ERC en el estadio 5D (0,23±0,04). En los pacientes con ERC, la actividad telomerasa en las CMSP se correlacionó positivamente con el estadio de ERC y los niveles plasmáticos de potasio, hormona paratiroidea y creatinina, y se correlacionó negativamente con la tasa de filtración glomerular estimada (eTFG), el índice de masa corporal (IMC), el recuento de plaquetas y el calcio en suero. Los predictores independientes para la actividad telomerasa alta en pacientes con ERC fueron la eTFG y el IMC, de acuerdo con el análisis de regresión lineal.

Conclusión

La actividad telomerasa en CMSP aumenta con el avance en el estadio de ERC. El aumento de la actividad telomerasa en CMSP se asocia con la eTFG y el IMC.

Palabras clave:
Enfermedad renal crónica
Etapa
Telomerasa
Texto completo
Introduction

Epidemiological studies have shown that biological age is older than chronologic age in chronic kidney disease (CKD) patients.1–3 Molecular mechanisms of increased cardiovascular mortality in CKD associated with biological age are not well understood. Recent studies suggest that factors such as cellular aging and telomere dysfunction may be the responsible factors.4–6 Studies conducted in hemodialysis patients have shown that telomere length in peripheral blood mononuclear cells (PBMC) was reduced compared to healthy individuals, irrespective of age and gender.7,8 Telomerase enzyme maintains the length and structure of telomeres, thus provides longer cell survival.9,10 Telomerase activity in PBMC was found significantly lower in hemodialysis patients compared to the healthy control group.11

Telomerase activity levels in various CKD stages and its relation to CKD progression are not well understood. This study was aimed to determine the relation between telomerase activity and CKD stages.

Materials and methodStudy design and patient assignment

This study was approved by the University Clinical Research Ethics Committee with approval number 2014/35 and was conducted with the support of Scientific Research Projects Coordination Unit. Written consent was obtained from all participants. This cross-sectional study was conducted at the Süleyman Demirel University Medical School Nephrology Department between May 2014 and November 2014. The study included 120 patients who were followed-up for CKD stage 2–5D, composed of 30 patients of each stage, and 30 healthy volunteers.

Inclusion criteria were age over 18 years and having CKD stage 2–5D diagnosis. Exclusion criteria included presence of an acute infection and a malignancy and using immunosuppressive therapy.

Blood sampling

Complete blood count, blood levels of fasting blood glucose, serum creatinine (Cr), sodium (Na), potassium (K), calcium (Ca), phosphorus (P), albumin, alanine aminotransferase (ALT), aspartat aminotransferase (AST), uric acid, triglyceride, total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), 25-hydroxy-vitamin D (25(OH)D), parathormone (iPTH), C-reactive protein (CRP) and spot urine protein/creatinine (Upr/Ucr) values were measured in each patient. Blood samples of hemodialysis patients were collected just before mid-week dialysis session. Body mass index (BMI) was calculated. Estimated GFR (eGFR) levels were calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.12

Measurement of telomerase activity in PBMC

Telomerase activity in PBMC was measured using TeloTAGGG Telomerase PCR ELISA kit (Roche Applied Science, Indianapolis, IN, USA) with telomeric repeat amplification protocol (TRAP) method.13 All samples with an optical density 450nm0.2 were considered telomerase positive.14

Statistical analysis

Data analysis was performed using SPSS for Windows 15.0 software. Results were expressed as mean±standard deviation or percent values. Chi-square test, variance analysis (ANOVA) and Kruskal–Wallis variance analysis tests were used for group comparisons. Tukey's HSD test was used for post hoc analysis. Associations between qualitative variables were assessed by Spearman's or Pearson's correlation analysis. A multivariate linear regression model was used to estimate the independent effects of various predictors (analyzed variables were age, BMI, eGFR, platelet count, serum Ca, K, LDL-C, iPTH) on telomerase activity. The level of statistical significance was p<0.05.

Results

Mean age was 58.6±10.4 years in the control group and 59.4±9.4 years in the patient group (p>0.05). Baseline characteristics of the patient groups are shown in Table 1. Patient groups were similar regarding BMI and smoking (p>0.05). Among the CKD stage 5D patients, 20 were on hemodialysis while 10 were on peritoneal dialysis. Mean dialysis duration for dialysis patients was 31.1±29.7 (range, 4–120) months.

Table 1.

Baseline clinical and laboratory data of CKD patients.

  Stage 2
CKD
(n=30) 
Stage 3
CKD
(n=30) 
Stage 4
CKD
(n=30) 
Stage 5D
CKD
(n=30) 
p 
Age, years  59.6±9.7  59.3±8.7  59.2±9.6  59.6±10.1  0.997 
Male, n (%)  14 (47)  14 (47)  14 (47)  14 (47) 
BMI (kg/m227.8±5.2  28.8±5.4  28.2±4.6  26.2±5.6  0.268 
Smoking, n (%)  3 (10)  8 (27)  2 (7)  3 (10)  0.093 
eGFR (ml/dk)  65.9±8.4a,b,c  37.1±6.2a,d,e  23.1±5.5b,d,f  7.6±3.2c,e,f  <0.001 
Glucose (mg/dl)  113±33  118±41  115±39  142±68  0.068 
Creatinine (mg/dl)  1.03±0.1a,b  1.7±0.2c  2.6±0.7a,d  7.5±3.1b,c,d  <0.001 
Sodium (mEq/l)  139±138±133±22  136±0.164 
Potassium (mEq/l)  4.5±0.5a,b  4.8±0.5  4.8±0.4a  4.9±0.7b  0.005 
Calcium (mg/dl)  9.7±0.5a,b  9.6±0.6c,d  9.2±0.5a,c,e  8.5±0.8b,d,e  <0.001 
Phosphorus (mg/dl)  3.7±0.7a  3.6±0.7b  4.1±0.7c  4.8±1.1a,b,c  <0.001 
Uric acid (mg/dl)  6.0±1.9  6.8±1.6  6.4±1.4  5.9±1.6  0.197 
Albumin (g/dl)  4.3±0.3a,b  4.3±0.8c,d  3.8±0.4a,c  3.7±0.5b,d  <0.001 
ALT (U/l)  19±11  19±18  17±10  19±15  0.940 
AST (U/l)  21±22±10  20±10  19±13  0.748 
Triglyceride (mg/dl)  166±68  177±95  144±71  171±89  0.436 
LDL-C (mg/dl)  124±45a  103±37  96±30a  98±42  0.026 
HDL-C (mg/dl)  48±10  44±13  43±12  41±11  0.104 
Hemoglobin (g/dl)  13.6±1.8a,b  13.5±1.4c,d  11.5±1.6a,c  11.1±1.7b,d  <0.001 
WBC (×103/μl)  8.1±3.4  7.8±1.6  7.8±2.2  8.2±2.2  0.877 
PLT (×103/μl)  245±51a  216±65  232±61  204±56a  0.040 
CRP (mg/dl)  4.7±1.7a  4.7±2.1b  8.9±7.7a,b  6.8±4.3  0.001 
iPTH (pg/ml)  65±46a,b  97±51  153±102a  323±216b  <0.001 
25(OH)D (ng/ml)  13.5±8.4  15.3±9.5  9.1±5.7  11.8±13.4  0.084 
Upr/Ucr  0.2±0.2a,b  0.8±0.9c  1.4±1.2a,d  3.4±2.4b,c,d  <0.001 
Hypertension, n (%)  12 (40)a,b  19 (63)  24 (80)a  23 (77)b  0.005 
DM, n (%)  7 (23)  9 (30)  7 (23)  12 (40)  0.444 
CAD, n (%)  0 (0)  6 (20)  5 (17)  3 (10)  0.081 
Heart failure, n (%)  0 (0)  1 (3)  3 (10)  3 (10)  0.255 

CKD: chronic kidney disease; BMI: body mass index; eGFR: estimated glomerular filtration rate; ALT: alanine aminotransferase; AST: aspartate aminotransferase; LDL-C: low density lipoprotein cholesterol; HDL-C: high density lipoprotein cholesterol; WBC: white blood cell; PLT: platelet; CRP: C-reactive protein; iPTH: intact parathyroid hormone; 25(OH)D: 25-hydroxy vitamin D; Upr/Ucr: protein/creatinine ratio in spot urine; DM: diabetes mellitus; CAD: coronary artery disease. Data are indicated as mean±standard deviation or percent. a,b,c,d,eThere is a significant difference between the parameters marked with the same letter (p<0.05). For the comparison between groups, analysis of variance (ANOVA) or Kruskal–Wallis test was applied, and for the post hoc study Tukey HSD test was used.

In CKD stage 5D patients, serum Ca (8.5±0.8mg/dl), serum albumin (3.7±0.5g/dl) and hemoglobin levels (11.1±1.7g/dl) and eGFR (7.6±3.2ml/min.) were significantly lower (p<0.001) while serum Cr (7.5±3.1mg/dl), serum P (4.8±1.1mg/dl), iPTH (323±216pg/ml) levels and Upr/Ucr ratio (3.4±2.4) were significantly higher (p<0.001). Serum LDL-C levels were found highest in CKD stage 2 patients (124±45mg/dl) (p=0.026) (Table 1).

Comorbidity rates for CKD patients were, hypertension 64.2%, diabetes mellitus 29.2%, coronary artery disease 11.7% and heart failure 5.8%. Hypertension was most prevalent in CKD stage 4 patients (Table 1).

Telomerase activity in PBMC

Telomerase activity in PBMC was positive in 86% (26/30) of CKD stage 5D patients while healthy control group was only 3% positive (1/30). Telomerase activity was increased with CKD stage (Table 2) (p<0.001). A significant difference was found for telomerase activity between patient and control groups (p<0.001) (Fig. 1). The levels were lowest in the healthy control group (0.15±0.02) and highest in CKD stage 5 group (0.23±0.04). Telomerase activities in PBMC were similar in CKD stages 2, 3 and 4 (p>0.05) while in stage 5 CKD it was significantly higher compared to the other stages (p<0.05). It was significantly lower in the healthy control group compared to all other groups (p<0.05) (Table 3).

Table 2.

Group comparisons for telomerase activity positivity.

  N  Telomerase positive cases %a  p 
Control  30  3.3 (1/30)  <0.001
Stage 2 CKD  30  20 (6/30) 
Stage 3 CKD  30  43.3 (13/30) 
Stage 4 CKD  30  30 (9/30) 
Stage 5D CKD  30  86.6 (26/30) 

CKD: chronic kidney disease. Chi-square test was applied for the comparison between groups.

a

Values in parentheses correspond to: no. of telomerase positive cases/total no. of cases.

Fig. 1.

Telomerase activity in relation to CKD stage.

(0.06MB).
Table 3.

Group comparisons for telomerase activity.

  Control
(n=30) 
Stage 2
CKD
(n=30) 
Stage 3
CKD
(n=30) 
Stage 4
CKD
(n=30) 
Stage 5D
CKD
(n=30) 
p 
Telomerase activity  0.15±0.02a,b,c,d  0.17±0.03a,e  0.18±0.03b,f  0.18±0.04c,g  0.23±0.04d,e,f,g  <0.001 

CKD: chronic kidney disease. a,b,c,d,e,f,gData are indicated as mean±standard deviation. There is a significant difference between the parameters marked with the same letter (p<0.05). For the comparison between groups, analysis of variance (ANOVA) was applied, and for the post hoc study Tukey HSD test was used.

Dialysis patients were grouped according to dialysis duration (median duration 20 months); among the 30 patients dialysis duration was long (range 39–120 months) in 6 of the patients and short (range 4–38 months) in 24 of the patients. Telomerase activity in PBMC was similar in both subgroups (0.24±0.03, 0.23±0.03; p>0.05).

In CKD patients, telomerase activity in PBMC was positively correlated with CKD stage (r=0.412, p<0.001) serum Cr (r=0.404, p<0.001), serum K (r=0.189, p=0.038) and iPTH levels (r=0.245, p=0.007) and; negatively correlated with BMI (r=−0.248, p=0.006), eGFR (r=−0.407, p<0.001), platelet count (r=−0.252, p=0.006), LDL-C (r=−0.243, p<0.007) and serum Ca levels (r=−0.357, p<0.001). A positive correlation was found between telomerase activity and age in healthy controls (r=0.623, p<0.001).

Telomerase activity in CKD patients and dependent variables age, BMI, eGFR, platelet count, serum Ca, LDL-C, iPTH and K levels were evaluated by linear regression analysis. Only eGFR and BMI were found to be independent predictors for high telomerase activity (R2=0.257, β=0.001 for eGFR, CI=−0.001 to 0.000, p=0.020; β=−0.001 for BMI, CI=−0.003 to 0.000, p=0.020) (Table 4).

Table 4.

Linear regression analysis of factors associated with telomerase activity in CKD patients.

Parameter  B  95% Confidence Interval  p  R2 
eGFR  0.000  −0.001 to 0.000  0.020  0.257 
BMI  −0.001  −0.003 to 0.000  0.020   

eGFR: estimated glomerular filtration rate; BMI: body mass index. Dependent variables included in the analysis were age, BMI, eGFR, platelet count, Ca, LDL-C, iPTH and K levels.

Discussion

To our knowledge, unlike the previous studies, the current study is the first to report increased telomerase activity in PBMC in CKD patients. In this study, telomerase activity in PBMC was found significantly increased in CKD patients compared to healthy controls. This increase was found independent of age, gender, inflammation, hyperlipidemia and hyperparathyroidism but it was correlated with eGFR and BMI.

Telomere length was reported to decrease independent of age and gender in hemodialysis patients.7,8 In renal cells of cats with CKD, increased cellular aging and short telomeres were detected accompanied by normal telomerase activity.15 Tsirpanlis et al. reported that telomerase activity in PBMC was lower in hemodialysis patients compared to the healthy control group.11 In contrast with this study, telomerase activity in PBMC was found increased in our study. Despite being an unexpected result, higher prevalence of diabetes in CKD stage 5D patients in our study might be the reason for high detected telomerase activity considering high telomerase activity reported in patients with metabolic syndrome in previous studies.16 Additionally, insignificantly lower BMI in CKD stage 5D patients might have contributed to the detected high telomerase activity in this subgroup. Thus, previous studies have reported that obesity associated with telomere shortening.17–19

Telomerase activity was reported to decrease with age.20 Although no correlation was found between age and telomerase activity in CKD patients, a positive correlation was detected between age and telomerase activity in the healthy controls in our study. This may be associated with other factors other than age that influence telomerase activity.

The combination of high telomerase activity and short telomere was suggested to be a sign of activated cell stress.21 Epel et al. in their study on caregivers of dementia patients found increased telomerase activity in PBMC accompanied by increased serum cortisol levels related to acute psychological stress.22 Lack of acute stress and serum cortisol levels assessments is a limitation of this study. Further studies may clarify this issue.

Telomerase activity in PBMC was reported to be potentially associated with inflammation.23 In cell cultures, increased telomerase activity in macrophages was shown in response to inflammatory stimulants.24 In the study by Rentoukas et al. telomerase activity in PBMC, IL6, TNFα and asymmetric dimethylarginine (ADMA) levels were found significantly higher in metabolic syndrome patients compared to healthy controls. Additionally, a positive correlation was observed between telomerase activity and ADMA levels while no correlation was found between telomerase activity and IL6 or TNFα.16 In this study, CRP was the only evaluated inflammatory marker. A significant relation was not found between telomerase activity in PBMC and CRP. However, this result may be due to the fact that this study excluded patients with acute infection.

Lin et al. measured telomerase activity and telomere length in various subtypes of T and B cells (CD4+, CD8+CD28+ and CD8+CD28− T and B cells). They found the longest telomere and highest telomerase activity was in B cells, while shortest telomere and lowest telomerase activity was in CD8+CD28− cells.25 In patients with unstable angina, telomerase activity in polymorphonuclear neutrophils in aterosclerotic plaques was found significantly higher compared to circulating neutrophils and this was suggested to be related to activation of inflammatory cells in early stage of instability and their locally prolonged survival.26 In our study, telomerase activity assessment in T and B subtypes was lacking since subtype analysis for PBMC was not performed. However, accelerated atherosclerosis and chronic micro-inflammation can be speculated as contributing factors to the findings in this study. Further studies will set light to this issue.

Obesity was reported to accelerate cellular aging and was found associated with telomere shortening.17–19 In our study, high BMI was associated with low telomerase activity in CKD patients. Telomerase activity levels were lower in obese patients. This result supports the previous observations suggesting obesity is related with telomere shortening in CKD patients.

Telomerase activity in PBMC was found negatively correlated with oxidized LDL-C.27 Statin treatment was associated with high telomerase activity and long telomeres, independent from age, lipid levels and inflammation.28 In our study, unlike previous studies, telomerase activity in PBMC was not associated with LDL-C. This result may be due to the fact that 1/5 of our patients were on statins.

Cross-sectional design and relatively small number of patients and controls are the other limitations of our study.

In conclusion; to our knowledge, this study is important for being the first to evaluate the relation between CKD stages and telomerase activity in PBMC. Based on the results of our study, it can be concluded that telomerase activity in PBMC is increased in CKD patients compared to healthy individuals. Telomerase activity in PBMC is increased with advancing stage in CKD patients and particularly in end-stage renal failure. Confirmation of this result in further studies may open new horizons in prevention of biological aging.

Author contributions

Concept – V.K.; design – V.K., AY.A.; supervision – M.T.S., B.A.; resource – V.K., AY.A.; materials – V.K., AY.A.; data collection and/or processing – V.K., AY.A., AT.A., S.I.; analysis and/or interpretation – V.K., S.I.; literature search – V.K.; writing – V.K.; critical reviews – M.T.S.

Conflict of interest

The authors declare that they have no conflict of interest.

References
[1]
A.S. Levey, J.A. Beto, B.E. Coronado, G. Eknoyan, R.N. Foley, B.L. Kasiske, et al.
Controlling the epidemic of cardiovascular disease in chronic renal disease: What do we know?, What do we need to learn?. Where do we go from here?.
Am J Kidney Dis, 32 (1998), pp. 853-906
[2]
F. Locatelli, J. Bommer, G.M. London, A. Martín-Malo, C. Wanner, M. Yaqoob, et al.
Cardiovascular disease determinants in chronic renal failure: clinical approach and treatment.
Nephrol Dial Transplant, 16 (2001), pp. 459-468
[3]
G. Tsirpanlis.
The pattern of inflammation and a potential new clinical meaning and usefulness of C-reactive protein in endstage renal failure patients.
Kidney Blood Press Res, 28 (2005), pp. 55-61
[4]
T. Minamino, I. Komuro.
Vascular cell senescence: contribution to atherosclerosis.
[5]
J.J. Fuster, V. Andres.
Telomere biology and cardiovascular disease.
[6]
J. Chen, M.S. Goligorsky.
Premature senescence of endothelial cells: Methusaleh's dilemma.
Am J Physiol Heart Circ Physiol, 290 (2006), pp. 1729-1739
[7]
R. Ramírez, J. Carracedo, S. Soriano, R. Jiménez, A. Martín-Malo, M. Rodríguez, et al.
Stressinduced premature senescence in mononuclear cells from patients on longterm hemodialysis.
Am J Kidney Dis, 45 (2005), pp. 353-359
[8]
M. Borras, S. Panizo, F. Sarró, J.M. Valdivielso, E. Fernandez.
Assessment of the potential role of active vitamin D treatment in telomere length: a casecontrol study in hemodialysis patients.
[9]
I. BenPorath, R.A. Weinberg.
When cells get stressed: an integrative view of cellular senescence.
J Clin Invest, 113 (2004), pp. 8-13
[10]
E.H. Blackburn.
Telomeres and telomerase: their mechanisms of action and the effects of altering their functions.
FEBS Lett, 579 (2005), pp. 859-862
[11]
G. Tsirpanlis, S. Chatzipanagiotou, F. Boufidou, V. Kordinas, F. Alevyzaki, M. Zoga, et al.
Telomerase activity is decreased in peripheral blood mononuclear cells of hemodialysis patients.
Am J Nephrol, 26 (2006), pp. 91-96
[12]
A.S. Levey, L.A. Stevens, C.H. Schmid, Y.L. Zhang, A.F. Castro 3rd, H.I. Feldman, CKDEPI (Chronic Kidney Disease Epidemiology Collaboration, et al.
A new equation to estimate glomerular filtration rate.
Ann Intern Med, 150 (2009), pp. 604-612
[13]
N.W. Kim, F. Wu.
Advances in quantification and characterization of telomerase activity by the telomeric repeat amplification protocol (TRAP).
Nucleic Acids Res, 25 (1997), pp. 2595-2597
[14]
C. Frías, C. García-Aranda, C. de Juan, A. Morán, P. Ortega, A. Gómez, et al.
Telomere shortening is associated with poor prognosis and telomerase activity correlates with DNA repair impairment in non-small cell lung cancer.
Lung Cancer, 60 (2008), pp. 416-425
[15]
J.M. Quimby, D.G. Maranon, C.L. Battaglia, S.M. McLeland, W.T. Brock, S.M. Bailey.
Feline chronic kidney disease is associated with shortened telomeres and increased cellular senescence.
Am J Physiol Renal Physiol, 305 (2013), pp. F295-F303
[16]
E. Rentoukas, K. Tsarouhas, I. Kaplanis, E. Korou, M. Nikolaou, G. Marathonitis, et al.
Connection between telomerase activity in PBMC and markers of inflammation and endothelial dysfunction in patients with metabolic syndrome.
[17]
A.M. Valdes, T. Andrew, J.P. Gardner, M. Kimura, E. Oelsner, L.F. Cherkas, et al.
Obesity, cigarette smoking, and telomere length in women.
[18]
S. Kim, C.G. Parks, L.A. DeRoo, H. Chen, J.A. Taylor, R.M. Cawthon, et al.
Obesity and weight gain in adulthood and telomere length.
Cancer Epidemiol Biomark Prev, 18 (2009), pp. 816-820
[19]
M. Lee, H. Martin, M.A. Firpo, E.W. Demerath.
Inverse association between adiposity and telomere length: the Fels Longitudinal Study.
Am J Hum Biol, 23 (2011), pp. 100-106
[20]
Y. Lin, A. Damjanovic, E.J. Metter, H. Nguyen, T. Truong, K. Najarro, et al.
Age-associated telomere attrition of lymphocytes in vivo is coordinated with changes in telomerase activity, composition of lymphocyte subsets and health conditions.
Clin Sci (Lond), 128 (2015), pp. 367-377
[21]
A. Zalli, L.A. Carvalho, J. Lin, M. Hamer, J.D. Erusalimsky, E.H. Blackburn, et al.
Shorter telomeres with high telomerase activity are associated with raised allostatic load and impoverished psychosocial resources.
Proc Natl Acad Sci U S A, 111 (2014), pp. 4519-4524
[22]
E.S. Epel, J. Lin, F.S. Dhabhar, O.M. Wolkowitz, E. Puterman, L. Karan, et al.
Dynamics of telomerase activity in response to acute psychological stress.
Brain Behav Immun, 24 (2010), pp. 531-539
[23]
A. Roth, H. Yssel, J. Pene, E.A. Chavez, M. Schertzer, P.M. Lansdorp, et al.
Telomerase levels control the lifespan of human T lymphocytes.
Blood, 102 (2003), pp. 849-857
[24]
F. Gizard, E.B. Heywood, H.M. Findeisen, Y. Zhao, K.L. Jones, C. Cudejko, et al.
Telomerase activation in atherosclerosis and induction of telomerase reverse transcriptase expression by inflammatory stimuli in macrophages.
Arterioscler Thromb Vasc Biol, 31 (2011 Feb), pp. 245-252
[25]
J. Lin, E. Epel, J. Cheon, C. Kroenke, E. Sinclair, M. Bigos, et al.
Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance.
J Immunol Methods, 352 (2010), pp. 71-80
[26]
M.L. Narducci, A. Grasselli, L.M. Biasucci, A. Farsetti, A. Mulè, G. Liuzzo, et al.
High telomerase activity in neutrophils from unstable coronary plaques.
J Am Coll Cardiol, 50 (2007 Dec 18), pp. 2369-2374
[27]
G. Tsirpanlis, S. Chatzipanagiotou, F. Boufidou, V. Kordinas, M. Zoga, F. Alevyzaki, et al.
Serum oxidized lowdensity lipoprotein is inversely correlated to telomerase activity in peripheral blood mononuclear cells of haemodialysis patients.
Nephrology (Carlton), 11 (2006), pp. 506-509
[28]
V. Boccardi, M. Barbieri, M.R. Rizzo, R. Marfella, A. Esposito, L. Marano, et al.
A new pleiotropic effect of statins in elderly: modulation of telomerase activity.
FASEB J, 27 (2013), pp. 3879-3885

This study was presented at the ASN Kidney Week 2015, 3–8 November 2015, San Diego, USA.

Copyright © 2017. Sociedad Española de Nefrología
Descargar PDF
Idiomas
Nefrología
Opciones de artículo
Herramientas
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?