Brief review
Hyperaldosteronism and hyperparathyroidism. A disturbing friendship
Hiperaldosteronismo e hiperparatiroidismo. Una amistad inquietante
Juan A. Martín Navarro
, Laura Medina Zahonero, Fabio L. Procaccini, Raquel Barba Teba, Veronica Rubio Menendez, Esther Valle Alvarez, Miryam Elena PoloCánovas, Mayra Ortega-Díaz, Marta Puerta Carretero, Rafael Lucena Valverde, Patricia Muñoz Ramos, Roberto Alcázar Arroyo, Patricia de Sequera Ortiz
Autor para correspondencia
Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid, Spain
Leído
799
Vecesse ha leído el artículo
220
Total PDF
579
Total HTML
Compartir estadísticas
array:24 [ "pii" => "S2013251424001597" "issn" => "20132514" "doi" => "10.1016/j.nefroe.2024.07.007" "estado" => "S300" "fechaPublicacion" => "2024-07-01" "aid" => "1231" "copyright" => "Sociedad Española de Nefrología" "copyrightAnyo" => "2024" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Nefrologia (English Version). 2024;44:496-502" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0211699523001935" "issn" => "02116995" "doi" => "10.1016/j.nefro.2023.12.005" "estado" => "S300" "fechaPublicacion" => "2024-07-01" "aid" => "1231" "copyright" => "Sociedad Española de Nefrología" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Nefrologia. 2024;44:496-502" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Revisión breve</span>" "titulo" => "Hiperaldosteronismo e hiperparatiroidismo. Una amistad inquietante" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "496" "paginaFinal" => "502" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Hyperaldosteronism and hyperparathyroidism: A disturbing friendship" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2010 "Ancho" => 2923 "Tamanyo" => 373869 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Relación clásica entre el transporte de calcio y sodio.</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleUnderline">1)</span><span class="elsevierStyleHsp" style=""></span>El calcio se transporta por vía paracelular en el asa de Henle gruesa ascendente, y de esta forma aumenta su concentración en el intersticio. 2<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>Cuando su concentración se eleva, estimula al receptor sensible de calcio, que inhibe al receptor ROMK. 3<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>La menor excreción de potasio establece una menor electropositividad del líquido tubular. 4<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>La menor electropositividad inhibe el transporte paracelular de calcio. 5<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>Paralelamente la alta concentración de calcio inhibe al transportador NKCC2. 6<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>Esta acción disminuye la reabsorción de sodio. El efecto global es un aumento de sodio y calcio a nivel tubular que llega a segmentos distales. 7<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>El calcio estimula al rSCa en las células intercaladas del TCC. 8<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>La bomba H<span class="elsevierStyleSup">+</span>-ATP<span class="elsevierStyleInf">asa</span> aumenta la excreción de protones a la luz tubular y 9<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>hace la orina más ácida, lo que dificulta la precipitación del calcio. 10<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>Así mismo estimula el rSCa en las células principales del TCC, 11<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>lo que provoca la inhibición de las aquaporinas (AQP) y de la arginina vasopresina (AVP). 12<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>El efecto global es la consecución de una orina más diluida. 13<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>La menor reabsorción de sodio induce el estímulo de la aldosterona por mecanismos dependientes de la hipovolemia, lo que pone en marcha su acción clásica sobre los receptores ENAC y ROMK. 14<span class="elsevierStyleUnderline">)</span><span class="elsevierStyleHsp" style=""></span>La aldosterona interactúa en el estímulo de la AVP.</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">AQP: aquaporinas; Ca<span class="elsevierStyleSup">+2</span>: calcio; H<span class="elsevierStyleSup">+</span>: protones; K<span class="elsevierStyleSup">+</span>: potasio; Na<span class="elsevierStyleSup">+</span>: sodio; rMC: receptor mineralocorticoide; rSCa: receptor sensible de calcio.</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Fuente: modificado de Ranieri<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">1</span></a>.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Juan A. Martín Navarro, Laura Medina Zahonero, Fabio L. Procaccini, Raquel Barba Teba, Verónica Rubio Menéndez, Esther Valle Álvarez, Miryam Elena Polo Cánovas, Mayra Ortega-Díaz, Marta Puerta Carretero, Rafael Lucena Valverde, Patricia Muñoz Ramos, Roberto Alcázar Arroyo, Patricia de Sequera Ortiz" "autores" => array:13 [ 0 => array:2 [ "nombre" => "Juan A." "apellidos" => "Martín Navarro" ] 1 => array:2 [ "nombre" => "Laura" "apellidos" => "Medina Zahonero" ] 2 => array:2 [ "nombre" => "Fabio L." "apellidos" => "Procaccini" ] 3 => array:2 [ "nombre" => "Raquel" "apellidos" => "Barba Teba" ] 4 => array:2 [ "nombre" => "Verónica" "apellidos" => "Rubio Menéndez" ] 5 => array:2 [ "nombre" => "Esther" "apellidos" => "Valle Álvarez" ] 6 => array:2 [ "nombre" => "Miryam Elena" "apellidos" => "Polo Cánovas" ] 7 => array:2 [ "nombre" => "Mayra" "apellidos" => "Ortega-Díaz" ] 8 => array:2 [ "nombre" => "Marta" "apellidos" => "Puerta Carretero" ] 9 => array:2 [ "nombre" => "Rafael" "apellidos" => "Lucena Valverde" ] 10 => array:2 [ "nombre" => "Patricia" "apellidos" => "Muñoz Ramos" ] 11 => array:2 [ "nombre" => "Roberto" "apellidos" => "Alcázar Arroyo" ] 12 => array:2 [ "nombre" => "Patricia" "apellidos" => "de Sequera Ortiz" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2013251424001597" "doi" => "10.1016/j.nefroe.2024.07.007" "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/S2013251424001597?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699523001935?idApp=UINPBA000064" "url" => "/02116995/0000004400000004/v1_202407151348/S0211699523001935/v1_202407151348/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2013251424001470" "issn" => "20132514" "doi" => "10.1016/j.nefroe.2023.05.020" "estado" => "S300" "fechaPublicacion" => "2024-07-01" "aid" => "1177" "copyright" => "Sociedad Española de Nefrología" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Nefrologia (English Version). 2024;44:503-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Notes on techniques</span>" "titulo" => "Urine beyond electrolytes: diagnosis through extracellular vesicles" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "503" "paginaFinal" => "508" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La orina más allá de los electrolitos: diagnóstico a través de las vesículas extracelulares" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2175 "Ancho" => 3258 "Tamanyo" => 806322 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0080" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) ExoView® workflow. Urine, without previous isolation of EVs, is added on the central part of the chip, which contains the wells where the EVs are captured by the different tetraspanins (CD63, CD81 and CD9). These EVs are fluorescently labeled in green if they express AMN or in red if they express SFRP1. The chips are read and analysed in the ExoView® R200. (B) Analysis of AMN and SFRP1 in human renal tissue by immunohistochemistry. Both glomeruli and tubules are visible (×10 magnification), with only the latter being stained, as they are the functional structures related to our proteins of interest. (C) Visualization of the capture of the proteins of interest (AMN, SFRP1). An image of one of the wells of the CD63 capture tetraspanin is shown, in which the specific and delimited binding of EVs can be appreciated. On the right, a magnification of a well for each capture tetraspanin (CD63, CD81 and CD9, respectively) is included, with each coloured dot being a vesicle expressing AMN (membrane protein, in green) or SFRP1 (intracellular protein, in red). In addition, the co-localization of both proteins (yellow) in the same EV is indicated by arrows. (D) Distribution (%) of AMN and SFRP1 proteins by capture tetraspanin (CD63 in red, CD81 in green and CD9 in blue). (E) Quantification of captured EVs containing either of the two studied proteins (AMN in green and SFRP1 in red), for each of the tetraspanins (CD63, CD81 and CD9). Average values are shown for the 3 wells for each capture tetraspanin.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Miriam Anfaiha-Sanchez, Nerea Lago-Baameiro, Aranzazu Santiago-Hernandez, Ariadna Martin-Blazquez, María Pardo, Martin-Lorenzo Marta, Gloria Alvarez-Llamas" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Miriam" "apellidos" => "Anfaiha-Sanchez" ] 1 => array:2 [ "nombre" => "Nerea" "apellidos" => "Lago-Baameiro" ] 2 => array:2 [ "nombre" => "Aranzazu" "apellidos" => "Santiago-Hernandez" ] 3 => array:2 [ "nombre" => "Ariadna" "apellidos" => "Martin-Blazquez" ] 4 => array:2 [ "nombre" => "María" "apellidos" => "Pardo" ] 5 => array:2 [ "nombre" => "Martin-Lorenzo" "apellidos" => "Marta" ] 6 => array:2 [ "nombre" => "Gloria" "apellidos" => "Alvarez-Llamas" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0211699523000796" "doi" => "10.1016/j.nefro.2023.05.010" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699523000796?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251424001470?idApp=UINPBA000064" "url" => "/20132514/0000004400000004/v1_202408300447/S2013251424001470/v1_202408300447/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2013251424001433" "issn" => "20132514" "doi" => "10.1016/j.nefroe.2024.01.021" "estado" => "S300" "fechaPublicacion" => "2024-07-01" "aid" => "1233" "copyright" => "Sociedad Española de Nefrología" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Nefrologia (English Version). 2024;44:486-95" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Hepatitis C virus infection is associated with proteinuria according to a systematic review with meta-analysis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "486" "paginaFinal" => "495" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La infección por el virus de la hepatitis C se asocia con proteinuria según una revisión sistemática de la literatura con metaanálisis" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1211 "Ancho" => 2508 "Tamanyo" => 125030 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Funnel plot of precision by log odds ratio (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>16 cross-sectional studies; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>163,979 unique patients) (outcome: prevalence of proteinuria).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Fabrizio Fabrizi, Maria F. Donato, Luca Nardelli, Federica Tripodi, Francesca Zanoni, Giuseppe Castellano" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Fabrizio" "apellidos" => "Fabrizi" ] 1 => array:2 [ "nombre" => "Maria F." "apellidos" => "Donato" ] 2 => array:2 [ "nombre" => "Luca" "apellidos" => "Nardelli" ] 3 => array:2 [ "nombre" => "Federica" "apellidos" => "Tripodi" ] 4 => array:2 [ "nombre" => "Francesca" "apellidos" => "Zanoni" ] 5 => array:2 [ "nombre" => "Giuseppe" "apellidos" => "Castellano" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S021169952400002X" "doi" => "10.1016/j.nefro.2024.01.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S021169952400002X?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251424001433?idApp=UINPBA000064" "url" => "/20132514/0000004400000004/v1_202408300447/S2013251424001433/v1_202408300447/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Brief review</span>" "titulo" => "Hyperaldosteronism and hyperparathyroidism. A disturbing friendship" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "496" "paginaFinal" => "502" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Juan A. Martín Navarro, Laura Medina Zahonero, Fabio L. Procaccini, Raquel Barba Teba, Veronica Rubio Menendez, Esther Valle Alvarez, Miryam Elena PoloCánovas, Mayra Ortega-Díaz, Marta Puerta Carretero, Rafael Lucena Valverde, Patricia Muñoz Ramos, Roberto Alcázar Arroyo, Patricia de Sequera Ortiz" "autores" => array:13 [ 0 => array:4 [ "nombre" => "Juan A." "apellidos" => "Martín Navarro" "email" => array:1 [ 0 => "juanmartinnav@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Laura" "apellidos" => "Medina Zahonero" "email" => array:1 [ 0 => "laura.medina.zahonero@gmail.com" ] ] 2 => array:3 [ "nombre" => "Fabio L." "apellidos" => "Procaccini" "email" => array:1 [ 0 => "fabioprc11@gmail.com" ] ] 3 => array:3 [ "nombre" => "Raquel" "apellidos" => "Barba Teba" "email" => array:1 [ 0 => "rbarteb@gmail.com" ] ] 4 => array:3 [ "nombre" => "Veronica" "apellidos" => "Rubio Menendez" "email" => array:1 [ 0 => "vrmenendez@salud.madrid.org" ] ] 5 => array:3 [ "nombre" => "Esther" "apellidos" => "Valle Alvarez" "email" => array:1 [ 0 => "esther.valle@salud.madrid.org" ] ] 6 => array:3 [ "nombre" => "Miryam Elena" "apellidos" => "PoloCánovas" "email" => array:1 [ 0 => "miryamelena.polo@senefro.org" ] ] 7 => array:3 [ "nombre" => "Mayra" "apellidos" => "Ortega-Díaz" "email" => array:1 [ 0 => "mayraortegadiaz@hotmail.com" ] ] 8 => array:3 [ "nombre" => "Marta" "apellidos" => "Puerta Carretero" "email" => array:1 [ 0 => "marta.puerta@salud.madrid.org" ] ] 9 => array:3 [ "nombre" => "Rafael" "apellidos" => "Lucena Valverde" "email" => array:1 [ 0 => "rafael.lucena@salud.madrid.org" ] ] 10 => array:3 [ "nombre" => "Patricia" "apellidos" => "Muñoz Ramos" "email" => array:1 [ 0 => "pmramos@salud.madrid.org" ] ] 11 => array:3 [ "nombre" => "Roberto" "apellidos" => "Alcázar Arroyo" "email" => array:1 [ 0 => "ralcazar@senefro.org" ] ] 12 => array:3 [ "nombre" => "Patricia" "apellidos" => "de Sequera Ortiz" "email" => array:1 [ 0 => "patricia.desequera@salud.madrid.org" ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Nefrología, Hospital Universitario Infanta Leonor, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hiperaldosteronismo e hiperparatiroidismo. Una amistad inquietante" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1378 "Ancho" => 2923 "Tamanyo" => 274730 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">PTH/HA relationship.</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">ANG II: angiotensin II; PL: phospholipase C; PQ: protein kinase C; PTH: parathyroid hormone; R/ANG/ALD: renin/angiotensin II/aldosterone system.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Case 1</span><p id="par0005" class="elsevierStylePara elsevierViewall">A 44-year-old man with Whiteveen-Kolk syndrome (15q24 microdeletion) visits the clinical center due to obesity and unstudied arterial hypertension (HTN) that had not been evaluated. Laboratory tests showed preserved renal function, hypernatremia, hypokalemia with inadequate urinary potassium excretion, normocalcemia with hypercalciuria, hypophosphatemia with hyperphosphaturia, elevated parathormone (PTH), decreased renin (R) levels with elevated aldosterone (ALD) and ALD/R ratio. Thyroid ultrasound and parathyroid (PT) and PT scan were normal. Abdominal CT scan showed bilateral adrenal hyperplasia (ARH). The patient was treated with spironolactone and potassium supplementation. The serum potassium levels became normal and the hypercalciuria subsides (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case 2</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 72-year-old male who has been evaluated in outpatient clinic for suspected primary hyperparathyroidism (PTH). He suffered from HTN, overweight and analytically hypercalcemia with hypercalciuria, hypophosphatemia with hyperphosphaturia and occasional elevation of PTH. Neither neck ultrasound nor sestaMIBI parathyroid scintigraphy with Tc 99<span class="elsevierStyleSup">m</span> clearly identified PT adenoma. No nephrolithiasis, densitometry with femoral and lumbar osteopenia. Given the persistence of hypercalcemia and hypophosphatemia compatible with hyperparathyroidism, the ultrasound was repeated, which identified an intrathyroidal nodule, so elective nodulectomy was performed to diagnose PT adenoma. After surgery, calcemia and PTH levels were immediately normalized, but hypophosphatemia with hyperphosphaturia persisted for several months despite adequate vitamin D levels. After 6 months calcium/phosphorus metabolism normalizes, but he develops de novo hypokalemia, hyperkaliuria with metabolic alkalosis, R in normal range and ALD at high limit of normality. An abdominal CT scan identifies images of bilateral adrenal gland hyperplasia. Blood pressure (BP) normalizes and the analytical alterations disappear after initiating treatment with spironolactone (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">What we know about aldosterone and PTH</span><p id="par0015" class="elsevierStylePara elsevierViewall">It should not be difficult to understand that the mechanisms of calcium regulation are interconnected to the mechanisms responsible for maintaining an adequate extracellular volume. The most efficient way to decrease the excess of extracellular calcium is to increase calciuria. An increase in calciuria occurs when hypercalcemia is detected by calcium sensing receptor (CaSR), which in addition to parathyroids it is also contained in the basolateral side of the thick ascending loop of Henle cells. The hypercalcemia activate the CaSR of these cells which in turn inhibit the renal outer medullary potassium channel (ROMK) resulting in a decreases in the content of potassium to the tubular lumen and becomes less positively charged, thus calcium (positively charged) remains in the tubular lumen, it is not reabsorbed and circulates to the distal and collecting tubules to be excreted in urine.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In addition, to prevent precipitation of this excess calcium in the tubule, the Na+/K+/2Cl- transporter (NKCC2) is also inhibited, which leads to an increase in sodium content in the tubular lumen, its increased excretion and arrival at the distal level, both to the intercalated cells and to the main cells of the cortical collecting tubule (CCT), which also have CaSR. At this level the activation of the CaSR stimulates proton transport in the intercalated cells, which acidifies the urine and also decreases aquaporins in the principal cells, resulting in more diluted urine. Furthermore, the non-reabsorption of sodium triggers, by hypovolemia-dependent mechanisms, the synthesis of aldosterone, which, through the mineralocorticoid receptor (MCR) in the principal and intercalated cells of the CT, stimulates, through phosphorylation of the Na+/K + ATPase pump, the apical sodium channels (ENAC), ROMK, H+-ATPase and H+/K+-ATPase. These changes lead to an increase in the excretion of protons into the lumen<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In short, in order to excrete excess calcium without crystal precipitation, a greater amount of urine is required, more diluted and more acidic, to which the calcium and sodium balance contributes and in which aldosterone, as the ultimate effector of the hormonal axis that includes renin and angiotensin II (ANG II), plays a major role in the balance of the effective circulating volume. Hence, in situations of hyperaldosteronism we will find volume-dependent hypertension, hypokalemia and metabolic alkalosis.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">PTH secretion is stimulated by hyperphosphatemia, hypocalcemia, the decrease in calcitriol and the increase in FGF23. HPT can cause a decrease in vitamin D receptors (VDR), resulting in a lower response to calcitriol and, secondarily, a greater secretion of PTH. PTH, through stimulation of the CyP27b1 gene, increases the synthesis of calcitriol and, therefore, the intestinal absorption of calcium, and at the bone, osteoclastogenesis, which causes the bone release of calcium and phosphorus. In the initial stages of chronic renal disease its overall effect is to increase phosphatemia, calcemia and phosphaturia and decrease calciuria, but as renal disease progresses and renal elimination of P decreases, phosphatemia will progressively increase, directly stimulating PTH secretion by post-transcriptional stimulation of the PTH gene, PT cell proliferation by activation of epidermal growth factor (EGFR) which causes TGF- αupregulation, inhibits CaSR expression and increases VDR expression in the intestine and decreases in the kidney.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Despite an extensive literature on the subject, the relationship between hyperaldosteronism (HA) and HPT is not completely clarified. Wermer<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and Sizemore et al.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>, in 1963 and 1980, when defining MEN type 1 and 2 syndromes, already spoke of the relationship between the PT/adrenal axis. In the 1980s, the first cases of HA/HPT association were described,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–6</span></a> and since then the number of published cases has multiplied.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7–11</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">What we should know about the close relationship between aldosterone and PTH</span><p id="par0035" class="elsevierStylePara elsevierViewall">ALD and PTH levels are directly and bidirectionally related through mechanisms involving the ionic and acid/base balance of the internal environment.</p><p id="par0040" class="elsevierStylePara elsevierViewall">ALD, through its actions on different tubular receptors, can induce hypercalciuria and chronically a negative calcium balance at a systemic level and hypocitraturia.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The first mechanism by which HA causes hypercalciuria depends on the expansion of circulating volume, which induces, through stimulation of tubulo-glomerular retrofiltration, a reduced reabsorption of sodium and calcium in the proximal tubule (PT), since both transports are coupled.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">However, in addition to chronic negative calcium balance, the mechanism by which HA can induce HPT appears to be mediated by other metabolic factors.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The expansion of circulating volume causes suppression of ANG II and increased expression of the ROMK channel, which determines hypokalemia due to increased renal excretion of potassium.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Hypokalemia favors intracellular acidosis, which, when becomes chronic, determines increased bicarbonate absorption at the proximal level and its reduced arrival at the distal level.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Therefore, in the HA there is a greater calcium supply and a lower bicarbonate supply at the distal level. Calcium should be reabsorbed through the apical calcium channel, but for it to function properly it needs to be stimulated by bicarbonate, and its lower arrival inactivates it, thus increasing hypercalciuria.</p><p id="par0070" class="elsevierStylePara elsevierViewall">At the same time, acidosis in PT increases metabolism and citrate consumption, which will lead to hypocitraturia.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Complementarily, hypokalemia induces phosphate depletion in PT, with compensatory increase of calcitriol, which causes increased intestinal calcium absorption and decreased expression of aquaporins stimulating ammoniagenesis, which could result in chronic interstitial damage.</p><p id="par0080" class="elsevierStylePara elsevierViewall">In addition, ALD stimulates the Na+/Cl- cotransporter in the distal tubule, which decreases calcium reabsorption in that segment and accentuates hypercalciuria and inhibition of the Na+/H + transporter, inducing incomplete distal renal tubular acidosis that boosts hypocitraturia.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Hypocitraturia, hypercalciuria and the negative calcium balance that would stimulate PTH secretion would increase the possibility of nephrolithiasis and medullary nephrocalcinosis<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,15</span></a> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">It is hypothesized that an alteration of the calcium sensitive receptor (CaSR) would cause the calcium threshold for PTH synthesis by parathyroid cells to be higher than under normal conditions.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">A high percentage of studies show that calciuria decreases after treating HA, as we have seen in our case 1. The lack of unanimity is explained by the different stages of evolution of the disease in the reported cases.</p><p id="par0100" class="elsevierStylePara elsevierViewall">It has been found that after treatment with R/ANG/ALD axis inhibitors in HA, PTH values decrease only when ALD levels are not elevated, which seems to demonstrate an effector mechanism of ALD in the control of PTH synthesis independent of renin and ANG II stimulation. ANG II increases PTH levels acutely through its direct action on the PT gland and chronically through the mineralocorticoid receptor (MCr) genomic pathway. With the chronic stimulus, secondary HPT becomes independent and can become tertiary, and latent HA can coexist with a clinically more evident hypercalcemia.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Additionally, genes that reflect ALD synthesis are present in the metabolic pathways of bone metabolism and hypercalcemia activates CaSr.</p><p id="par0110" class="elsevierStylePara elsevierViewall">PTH acts on ACTH receptors, on the R/ANG/ALD system and on calcium. The passage of calcium into the intracellular space exerts an initiating effect on the phosphorylation cascade that concludes in the activation of transcription factors (NURR1, NGF1B, CREB). These bind to the promoter region and positively regulate aldosterone secretion by stimulating the phospholipase C, protein kinase C and CYP11B2 transcription pathways (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">The action of PTH on the adrenal glands, calcium and R/ANG/ALD allows it to control ALD secretion at the adrenal glands. Both PTH and PTHr have secretagogue capacity in the adrenal gland.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,19</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">The fact that PTs possess adrenal metabolism receptors (MCr and ANGIIr) and adrenal PT receptors (PTH1 r, VDR and SCar), especially in cells of the zona glomerulosa,<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20,21</span></a> would speak in favor of a bidirectional regulatory pathway between bone metabolism and ALD (cytochrome p450 21 hydroxylase) adrenal steroidogenesis.</p><p id="par0125" class="elsevierStylePara elsevierViewall">There are adjuvant factors that can influence in the behavior of the renal tubule in bone metabolism that are independent of this pathway, such as the salt-rich diet, which favors hypercalciuria by direct exchange and secondarily induces a stimulus for PTH secretion, independent of vitamin D levels; and vitamin D itself, which induces inhibition of ANG II and, by improving calcemia, has an inhibitory action on aldosterone through its effects on the vascular endothelium, but it has been shown in numerous studies that the HA/HPT ratio is independent of these factors.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">What we would like to know</span><p id="par0130" class="elsevierStylePara elsevierViewall">An interesting unanswered question is why calcium and sodium metabolism, carried out in the anatomically close Na+/Ca+2 and Na+/Cl- receptors in the distal tubule, and the synthesis of the hormones ALD and PTH are so intrinsically and undeniably linked. One possible explanation is circumstantial. Just as endocrine pathologies affecting different glands (PT, pituitary, pancreas, and adrenal) are found in MEN 1 and MEN 2 syndrome, there may be another undescribed multiple endocrine disorder that brings together PT and adrenal pathology in the clinical form described in these cases.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Another possible explanation would be related to an integrative conception of the balance of the internal environment, partially explained in the first section of this review. In the same way that it is essential to maintain stability between effective circulating volume and water balance, and this is achieved by means of a coordinated response of antidiuretic hormone and aldosterone,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> it is stimulating to think about the importance of extra- and intracellular calcium levels in the function regulation of the of blood vessels, and about the second messenger mechanisms that the ionic influx of calcium exerts directly in cells that may justify a common interrelation pathway between both systems, with which there would be inter-regulatory pathways between aldosterone and ADH balance and between aldosterone and PTH balance.</p><p id="par0140" class="elsevierStylePara elsevierViewall">These two cases are illustrations of a specular reality, represent a primary HA due to bilateral adrenal hyperplasia that clinically presents with primary HPT that resolves when the HA is treated, and a primary HPT that, when treated, unmasks a subclinical HA that was not evident until that moment. The reality that this fact represents may have importance in the clinical practice of patients affected with both entities and should be taken into account when approaching the treatment of these patients.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Key concepts</span><p id="par0145" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0150" class="elsevierStylePara elsevierViewall">ALD controls effective circulating volume and blood pressure. PTH controls bone mineral metabolism. Both hormones have common pathways of interrelation.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0155" class="elsevierStylePara elsevierViewall">HA induces hypercalciuria and hypocitraturia, which justifies a greater tendency to nephrolithiasis and medullary nephrocalcinosis by 5 interrelated mechanisms:</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">1</span><p id="par0160" class="elsevierStylePara elsevierViewall">Lower distal tubular calcium absorption.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">2</span><p id="par0165" class="elsevierStylePara elsevierViewall">Hypokalemia, hypophosphatemia and increased synthesis of calcitriol.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">3</span><p id="par0170" class="elsevierStylePara elsevierViewall">Intracelular acidosis and hypocitraturia.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">4</span><p id="par0175" class="elsevierStylePara elsevierViewall">Incomplete distal tubulorenal acidosis.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">5</span><p id="par0180" class="elsevierStylePara elsevierViewall">ENaC receptor stimulation with volume expansion and angiotensin II suppression.</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0185" class="elsevierStylePara elsevierViewall">HA causes chronic interstitial damage through ammoniogenesis-dependent mechanisms which involve the function of aquaporins.</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0190" class="elsevierStylePara elsevierViewall">Hypercalciuria and chronic negative calcium balance in HA are direct stimuli for PTH secretion.</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0195" class="elsevierStylePara elsevierViewall">PTH induces adrenal steroidogenesis by mechanisms dependent on calcium second messenger pathways, direct renin and ACTH stimulation.</p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Funding</span><p id="par0200" class="elsevierStylePara elsevierViewall">This article has no sources of funding.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of interest</span><p id="par0205" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres2230893" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1868120" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2230892" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1868119" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Case 1" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case 2" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "What we know about aldosterone and PTH" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "What we should know about the close relationship between aldosterone and PTH" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "What we would like to know" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Key concepts" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-10-17" "fechaAceptado" => "2023-12-26" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1868120" "palabras" => array:4 [ 0 => "Hyperaldosteronism" 1 => "Hyperparathyroidism" 2 => "Calcium-sensing receptor" 3 => "Blood pressure" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1868119" "palabras" => array:4 [ 0 => "Hiperaldosteronismo" 1 => "Hiperparatiroidismo" 2 => "Receptor sensible de calcio" 3 => "Tensión arterial" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Classically, aldosterone actions are associated with the stability of the effective circulating volume and with blood pressure control, while parathormone actions are linked to bone mineral metabolism, calcium, and phosphate homeostasis. Nevertheless, the relationship between these two hormonal axes surpasses these areas. A bidirectional interrelation between calcium-phosphorus metabolism and blood pressure control can lead to alterations in both. This can have significant implications for the evolution and treatment of patients. To illustrate this relationship, we present two clinical cases that demonstrate the pathophysiology involved.)</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Clásicamente, asociamos la acción de la aldosterona (ALD) con la estabilidad del volumen circulante eficaz y el control de la tensión arterial (TA) y la acción de la parathormona (PTH) con el control del metabolismo óseo mineral y la normalidad de calcemia y fosforemia, sin embargo, la relación entre estos dos ejes hormonales trasciende estos ámbitos y podemos definir una interrelación bidireccional entre ambos, que determina la patogenia de las alteraciones en el metabolismo calcio- fósforo y el control de la TA, lo que implica consecuencias en la evolución y tratamiento de los pacientes. La exposición de dos casos clínicos nos permite exponer la fisiopatología de esta relación.</p></span>" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2014 "Ancho" => 2923 "Tamanyo" => 463936 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Classic relationship between calcium and sodium transport.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(1) Calcium is transported by the paracellular pathway in the thick ascending loop of Henle, and thus increases its concentration in the interstitium. (2) When its concentration rises, the calcium-sensitive receptor is stimulated, which inhibits the ROMK activity. (3) The lower potassium excretion establishes a lower electropositivity of the tubular fluid. (4) Lower electropositivity inhibits paracellular calcium transport. (5) Parallel to this, the high calcium concentration inhibits the NKCC2 transporter. (6) This action decreases sodium reabsorption. The overall effect is an increase in sodium and calcium at the tubular level reaching distal segments. (7) Calcium stimulates CaSr in the intercalated cells of the CCT. (8) The H+-ATPase pump increases proton excretion into the tubular lumen and (9) makes the urine more acidic, which hinders calcium precipitation. (10) It also stimulates CaSr in CCT principal cells, (11) which causes inhibition of aquaporins (AQP) and arginine vasopressin (AVP). (12) The overall effect is the achievement of more dilute urine. (13) The lower sodium reabsorption induces aldosterone stimulation by hypovolemia-dependent mechanisms, which sets in motion its classic action on ENaC and ROMK receptors. (14) Aldosterone is involved in stimulating AVP.</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">AQP: aquaporins; Ca+2: calcium; H+: protons; K+: potassium; Na+: sodium; MCr: mineralocorticoid receptor; CaSr: calcium-sensitive receptor.</p> <p id="spar9015" class="elsevierStyleSimplePara elsevierViewall">Source: modified from Ranieri.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1621 "Ancho" => 2922 "Tamanyo" => 391666 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Generation of chronic renal damage.</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Abs: absorption; ANG II: angiotensin II; AQP: aquaporins; TRA: tubulorenal acidosis; BIC: bicarbonate; Ca+2: calcium; H+: protons; Na+: sodium; P: phosphorus; MCr: mineralocorticoid receptor; DT: distal tubule; PT: proximal tubule; AT-1r: angiotensin I receptor; +: stimulus; >: major; <: minor.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1378 "Ancho" => 2923 "Tamanyo" => 274730 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">PTH/HA relationship.</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">ANG II: angiotensin II; PL: phospholipase C; PQ: protein kinase C; PTH: parathyroid hormone; R/ANG/ALD: renin/angiotensin II/aldosterone system.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><elsevierMultimedia ident="202408300448114891"></elsevierMultimedia> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3637207.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Laboratory values in the two cases.</p>" ] ] 4 => array:5 [ "identificador" => "202408300448114891" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 2534 "Ancho" => 2508 "Tamanyo" => 474187 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:22 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal Ca<span class="elsevierStyleSup">2+</span> and water handling in response to calcium sensing receptor signaling: physiopathological aspects and role of CaSR-regulated microRNAs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M. Ranieri" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Int J Mol Sci." "fecha" => "2019" "volumen" => "20" "numero" => "21" "paginaInicial" => "5341" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Endocrine adenomatosis and peptic ulcer in a arge kindred. Inherited multiple tumrs and Mosaic pleiotropism in man" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P. Wermer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Med" "fecha" => "1963" "volumen" => "35" "paginaInicial" => "205" "paginaFinal" => "212" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multiple endocrine neoplasia type 2" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G.W. Sizemore" 1 => "H. Health 3rd" 2 => "J.A. Carney" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0300-595x(80)80035-1" "Revista" => array:7 [ "tituloSerie" => "Clin Endocrinol Metab." "fecha" => "1980" "volumen" => "9" "numero" => "2" "paginaInicial" => "299" "paginaFinal" => "315" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6994943" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary hyperparathyroidism in a patient with Conn’s syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Fertig" 1 => "M. Webley" 2 => "J.A. Lynn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/pgmj.56.651.45" "Revista" => array:7 [ "tituloSerie" => "Postgrad Med J" "fecha" => "1980" "volumen" => "56" "paginaInicial" => "45" "paginaFinal" => "47" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7383950" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022347618318237" "estado" => "S300" "issn" => "00223476" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary hyperparathyroidism: possible cause of primary hyperaldosteronism in a 60-year-old woman" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Barkan" 1 => "R. Marilus" 2 => "G. Winkelsberg" 3 => "D. Yeshurun" 4 => "I. Blum" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jcem-51-1-144" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "1980" "volumen" => "51" "paginaInicial" => "144" "paginaFinal" => "147" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6991517" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A case of primary hyperparathyroidism, primary hyperaldosteronism and Cushing’s disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.W. Herd" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1530/acta.0.1070371" "Revista" => array:7 [ "tituloSerie" => "Acta Endocrinol (Copenh)" "fecha" => "1984" "volumen" => "107" "numero" => "3" "paginaInicial" => "371" "paginaFinal" => "374" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6150593" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Severe hypercalcemic hyperparathyroidism developing in a patient with hyperaldosteronism and renal resistance to parathyroid hormone" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Park-Sigal" 1 => "B.R. Don" 2 => "A. Porzig" 3 => "R. Recker" 4 => "V. Griswold" 5 => "A. Sebastian" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jbmr.1791" "Revista" => array:7 [ "tituloSerie" => "J Bone Miner Res" "fecha" => "2013" "volumen" => "28" "numero" => "3" "paginaInicial" => "700" "paginaFinal" => "708" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23074096" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Calcium metabolism and parathyroid function in primary aldosteronism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L. Resnick" 1 => "J.H. Laragh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/0002-9343(85)90328-6" "Revista" => array:6 [ "tituloSerie" => "Am J Med." "fecha" => "1985" "volumen" => "78" "paginaInicial" => "385" "paginaFinal" => "390" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3883768" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alterations of calcium metabolism and of parathyroid function in primary aldosteronism, and their reversal by spironolactone or by surgical removal of aldosterone-producing adenomas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "E. Rossi" 1 => "C. Sani" 2 => "F. Perazzoli" 3 => "M.C. Casoli" 4 => "A. Negro" 5 => "C. Dotti" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Hypertens." "fecha" => "1995" "volumen" => "8" "paginaInicial" => "884" "paginaFinal" => "893" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serum aldosterone is correlated positively to parathyroid hormone (PTH) levels in patients with primary hyperparathyroidism" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Brunaud" 1 => "A. Germain" 2 => "R. Zarnegar" 3 => "M. Rancier" 4 => "S. Alrasheedi" 5 => "C. Caillard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.surg.2009.09.041" "Revista" => array:6 [ "tituloSerie" => "Surgery." "fecha" => "2009" "volumen" => "146" "paginaInicial" => "1035" "paginaFinal" => "1041" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19958930" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary hyperparathyroidism associated with primary hyperaldosteronism" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Ferriss" 1 => "J.J. Brown" 2 => "A.M. Cumming" 3 => "R. Fraser" 4 => "A.F. Lever" 5 => "M. Peacock" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1530/acta.0.1030365" "Revista" => array:6 [ "tituloSerie" => "Acta Endocrinol (Copenh)." "fecha" => "1983" "volumen" => "103" "paginaInicial" => "365" "paginaFinal" => "370" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6349207" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Codependence of renal calcium and sodium transport" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.A. Friedman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1146/annurev.physiol.60.1.179" "Revista" => array:6 [ "tituloSerie" => "Annu Rev Physiol." "fecha" => "1998" "volumen" => "60" "paginaInicial" => "179" "paginaFinal" => "197" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9558460" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal sodium handling in normal humans subjected to low, normal, and extremely high sodium supplies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.C. Roos" 1 => "H.A. Koomans" 2 => "E.J. Dorhout Mees" 3 => "I.M. Delawi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajprenal.1985.249.6.F941" "Revista" => array:7 [ "tituloSerie" => "Am J Physiol." "fecha" => "1985" "volumen" => "249" "numero" => "6 Pt 2" "paginaInicial" => "F941" "paginaFinal" => "7" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3907374" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recurrent calcium nephrolithiasis associated with primary aldosteronism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Shey" 1 => "M.A. Cameron" 2 => "K. Sakhaee" 3 => "O.W. Moe" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.ajkd.2004.03.037" "Revista" => array:8 [ "tituloSerie" => "Am J Kidney Dis." "fecha" => "2004" "volumen" => "44" "numero" => "1" "paginaInicial" => "e7" "paginaFinal" => "12" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15211456" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022347618317402" "estado" => "S300" "issn" => "00223476" ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An association of chronic hyperaldosteronism with medullary nephrocalcinosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Mittal" 1 => "K. Anandpara" 2 => "A.K. Dey" 3 => "R. Sharma" 4 => "H. Thakkar" 5 => "P. Hira" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.12659/PJR.894674" "Revista" => array:6 [ "tituloSerie" => "Pol J Radiol." "fecha" => "2015" "volumen" => "80" "paginaInicial" => "417" "paginaFinal" => "424" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26413177" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mild hyperparathyroidism: a novel surgically correctable feature of primary aldosteronism" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Maniero" 1 => "A. Fassina" 2 => "T.M. Seccia" 3 => "A. Toniato" 4 => "M. Iacobone" 5 => "M. Plebani" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Hypertens" "fecha" => "2012" "volumen" => "30" "paginaInicial" => "390" "paginaFinal" => "395" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association between aldosterone and parathyroid hormone levels in patients with adrenocortical tumors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Zavatta" 1 => "G. Di Dalmazi" 2 => "P. Altieri" 3 => "C. Pelusi" 4 => "R. Golfieri" 5 => "C. Mosconi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.eprac.2021.09.002" "Revista" => array:7 [ "tituloSerie" => "Endocr Pract." "fecha" => "2022" "volumen" => "28" "numero" => "1" "paginaInicial" => "90" "paginaFinal" => "95" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34508903" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Parathyroid gland function in primary aldosteronism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E. Asbach" 1 => "M. Bekeran" 2 => "M. Reincke" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Horm Metab Res." "fecha" => "2015" "volumen" => "47" "numero" => "13" "paginaInicial" => "994" "paginaFinal" => "999" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Aldosterone and parathyroid hormone: a precarious couple for cardiovascular disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Tomaschitz" 1 => "E. Ritz" 2 => "B. Pieske" 3 => "A. Fahrleitner-Pammer" 4 => "K. Kienreich" 5 => "J.H. Horina" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/cvr/cvs092" "Revista" => array:6 [ "tituloSerie" => "Cardiovasc Res" "fecha" => "2012" "volumen" => "94" "paginaInicial" => "10" "paginaFinal" => "19" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22334595" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary hyperparathyroidism with concurrent primary aldosteronism" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Maniero" 1 => "A. Fassina" 2 => "V. Guzzardo" 3 => "L. Lenzini" 4 => "G. Amadori" 5 => "M.R. Pelizzo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Hypertension" "fecha" => "2011" "volumen" => "58" "paginaInicial" => "341" "paginaFinal" => "346" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Brown" 1 => "J.S. Williams" 2 => "J.M. Luther" 3 => "R. Garg" 4 => "A.E. Garza" 5 => "L.H. Pojoga" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1161/HYPERTENSIONAHA.113.01910" "Revista" => array:6 [ "tituloSerie" => "Hypertension" "fecha" => "2014" "volumen" => "63" "paginaInicial" => "273" "paginaFinal" => "280" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24191286" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vasopressin V1a and V1b receptors: from molecules to physiological systems" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "T.A. Koshimizu" 1 => "K. Nakamura" 2 => "N. Egashira" 3 => "M. Hiroyama" 4 => "H. Nonoguchi" 5 => "A. Tanoue" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/physrev.00035.2011" "Revista" => array:7 [ "tituloSerie" => "Physiol Rev." "fecha" => "2012" "volumen" => "92" "numero" => "4" "paginaInicial" => "1813" "paginaFinal" => "1864" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23073632" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000004400000004/v1_202408300447/S2013251424001597/v1_202408300447/en/main.assets" "Apartado" => array:4 [ "identificador" => "97793" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000004400000004/v1_202408300447/S2013251424001597/v1_202408300447/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251424001597?idApp=UINPBA000064" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Octubre | 318 | 50 | 368 |
| 2024 Septiembre | 122 | 72 | 194 |
| 2024 Agosto | 139 | 98 | 237 |
