Renal diseases that course with hypomagnesemia. Comments on a new hereditary hypomagnesemic tubulopathy

array:23 ["pii" => "S2013251424000452" "issn" => "20132514" "doi" => "10.1016/j.nefroe.2024.02.003" "estado" => "S300" "fechaPublicacion" => "2024-01-01" "aid" => "1148" "copyrightAnyo" => "2024" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Nefrologia (English Version). 2024;44:23-31" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0211699523000310" "issn" => "02116995" "doi" => "10.1016/j.nefro.2023.02.008" "estado" => "S300" "fechaPublicacion" => "2024-01-01" "aid" => "1148" "copyright" => "Sociedad Española de Nefrología" "documento" => "article" "crossmark" => 0 "subdocumento" => "rev" "cita" => "Nefrologia. 2024;44:23-31" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "Revisión" "titulo" => "Enfermedades renales que cursan con hipomagnesemia. Comentarios acerca de una nueva tubulopatía hipomagnesémica de origen genético" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "23" "paginaFinal" => "31" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Renal diseases that course with hypomagnesemia. Comments on a new hereditary hypomagnesemic tubulopathy" ] ] "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" => 1791 "Ancho" => 3175 "Tamanyo" => 448649 ] ] "descripcion" => array:1 [ "es" => "Algoritmo diagnóstico de las hipomagnesemias a partir de los niveles de calcemia y de calciuria. Entre paréntesis figuran, en la mayoría de los casos, los transportadores anómalos (AD: autosómico dominante; EAB: equilibrio ácido-base)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Víctor M. Garcia-Nieto, Félix Claverie-Martin, Teresa Moraleda-Mesa, Ana Perdomo-Ramírez, Gloria Ma Fraga-Rodríguez, María Isabel Luis-Yanes, Elena Ramos-Trujillo" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Víctor M." "apellidos" => "Garcia-Nieto" ] 1 => array:2 [ "nombre" => "Félix" "apellidos" => "Claverie-Martin" ] 2 => array:2 [ "nombre" => "Teresa" "apellidos" => "Moraleda-Mesa" ] 3 => array:2 [ "nombre" => "Ana" "apellidos" => "Perdomo-Ramírez" ] 4 => array:2 [ "nombre" => "Gloria Ma" "apellidos" => "Fraga-Rodríguez" ] 5 => array:2 [ "nombre" => "María Isabel" "apellidos" => "Luis-Yanes" ] 6 => array:2 [ "nombre" => "Elena" "apellidos" => "Ramos-Trujillo" ] 7 => array:1 [ "colaborador" => "Grupo RenalTube" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2013251424000452" "doi" => "10.1016/j.nefroe.2024.02.003" "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/S2013251424000452?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699523000310?idApp=UINPBA000064" "url" => "/02116995/0000004400000001/v1_202401141155/S0211699523000310/v1_202401141155/es/main.assets" ] ] "itemSiguiente" => array:17 [ "pii" => "S2013251422001481" "issn" => "20132514" "doi" => "10.1016/j.nefroe.2022.11.022" "estado" => "S300" "fechaPublicacion" => "2024-01-01" "aid" => "1002" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Nefrologia (English Version). 2024;44:32-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "No difference in follow-up estimated glomerular filtration rate between hypertensive and matched nonhypertensive kidney donors" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "32" "paginaFinal" => "39" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "No hay diferencia en la tasa de filtración glomerular estimada de seguimiento entre donantes de riñón hipertensos y no hipertensos compatibles" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1642 "Ancho" => 2925 "Tamanyo" => 292571 ] ] "descripcion" => array:1 [ "en" => "Patient selection algorithm." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Eun Hye Yang, Sung Shin, Young Hoon Kim, In Gab Jeong, Bumsik Hong, Chung Hee Baek, Hyosang Kim, Soon Bae Kim" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Eun Hye" "apellidos" => "Yang" ] 1 => array:2 [ "nombre" => "Sung" "apellidos" => "Shin" ] 2 => array:2 [ "nombre" => "Young Hoon" "apellidos" => "Kim" ] 3 => array:2 [ "nombre" => "In Gab" "apellidos" => "Jeong" ] 4 => array:2 [ "nombre" => "Bumsik" "apellidos" => "Hong" ] 5 => array:2 [ "nombre" => "Chung Hee" "apellidos" => "Baek" ] 6 => array:2 [ "nombre" => "Hyosang" "apellidos" => "Kim" ] 7 => array:2 [ "nombre" => "Soon Bae" "apellidos" => "Kim" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251422001481?idApp=UINPBA000064" "url" => "/20132514/0000004400000001/v1_202403090635/S2013251422001481/v1_202403090635/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S2013251423000755" "issn" => "20132514" "doi" => "10.1016/j.nefroe.2023.04.006" "estado" => "S300" "fechaPublicacion" => "2024-01-01" "aid" => "1126" "copyright" => "Sociedad Española de Nefrología" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Nefrologia (English Version). 2024;44:10-22" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "RIPK3 and kidney disease" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "10" "paginaFinal" => "22" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "RIPK3 y nefropatía" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3008 "Ancho" => 3510 "Tamanyo" => 665340 ] ] "descripcion" => array:1 [ "en" => "Different pathways of RIPK3 activation. Canonical activation of RIPK3 is dependent on its RHIM domain that binds to other RHIM-containing proteins: RIPK1 following activation by TNF receptor superfamily proteins, TRIF in response to Toll like receptor (TLR) activation, and DAI/ZBP1 activated by z-RNA from viral infection. The interaction of the RHIM domain of RIPK3 with RHIM-containing proteins allows autophosphorylation and activation of RIPK3. Non-canonical RIPK3 activation is independent of the RHIM domain, and it is mediated by osmotic stress-induced intracellular acidification through NHE1." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Juan Guerrero-Mauvecin, Miguel Fontecha-Barriuso, Ana M. López-Diaz, Alberto Ortiz, Ana B. Sanz" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Juan" "apellidos" => "Guerrero-Mauvecin" ] 1 => array:2 [ "nombre" => "Miguel" "apellidos" => "Fontecha-Barriuso" ] 2 => array:2 [ "nombre" => "Ana M." "apellidos" => "López-Diaz" ] 3 => array:2 [ "nombre" => "Alberto" "apellidos" => "Ortiz" ] 4 => array:2 [ "nombre" => "Ana B." "apellidos" => "Sanz" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251423000755?idApp=UINPBA000064" "url" => "/20132514/0000004400000001/v1_202403090635/S2013251423000755/v1_202403090635/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Renal diseases that course with hypomagnesemia. Comments on a new hereditary hypomagnesemic tubulopathy" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "23" "paginaFinal" => "31" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Víctor M. Garcia-Nieto, Félix Claverie-Martin, Teresa Moraleda-Mesa, Ana Perdomo-Ramírez, Gloria Mª Fraga-Rodríguez, María Isabel Luis-Yanes, Elena Ramos-Trujillo" "autores" => array:8 [ 0 => array:4 [ "nombre" => "Víctor M." "apellidos" => "Garcia-Nieto" "email" => array:1 [ 0 => "vgarcianieto@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Félix" "apellidos" => "Claverie-Martin" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Teresa" "apellidos" => "Moraleda-Mesa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Ana" "apellidos" => "Perdomo-Ramírez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Gloria Mª" "apellidos" => "Fraga-Rodríguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "María Isabel" "apellidos" => "Luis-Yanes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Elena" "apellidos" => "Ramos-Trujillo" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 7 => array:1 [ "colaborador" => "Grupo RenalTube" ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Unidad de Nefrología Pediátrica, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Nefrologia Pediàtrica, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Departamento de Medicina Física y Farmacología, Facultad de Medicina, Universidad de la Laguna, Santa Cruz de Tenerife, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedades renales que cursan con hipomagnesemia. Comentarios acerca de una nueva tubulopatía hipomagnesémica de origen genético" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1791 "Ancho" => 3175 "Tamanyo" => 511606 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Diagnostic algorithm for hypomagnesemias based on calcium and calciuria levels. Abnormal transporters (AD: autosomal dominant; ABB: acid–base balance) are shown in parentheses in most cases." ] ] ] "textoCompleto" => "IntroductionRenal tubules select the filtered solutes necessary to maintain body homeostasis. Most solutes are reabsorbed and returned to the blood; those that are not needed will be eliminated in the urine.In the first tubular regions the process of reabsorption is very intense (for example, 65% of the sodium filtered is reabsorbed in the proximal tubule and 25% in the ascending branch of the loop of Henle). For this reason, tubulopathies with intense damage in these segments (Toni-Debré-Fanconi syndrome and Bartter syndrome, for example) can be very serious and difficult to treat due to the difficulty of compensating for the loss of solutes.It is therefore up to the distal tubule and collecting duct to fine-tune, to put the finishing touches on recovering the solutes necessary for the body and therefore must not be lost in the urine. This task is very complex and requires appropriate specialization.Distal convoluted tubuleTo highlight its importance, it is enough to recall the functional interest of the macula densa as a sensor of intratubular sodium concentration within the structure of the juxtaglomerular apparatus. Suffice to emphasize that the distal tubule contains the only renal specific channel for calcium reabsorption (ECaC) whose function is modulated by various hormones and that the regulation of the thiazide-sensitive sodium chloride (NaCl) transporter is very complex, as can be seen when studying the pathophysiology of Gordon’s syndrome. In addition, the distal tubule has an important functional involvement in calcium and magnesium reabsorption (Mg2+) and has the highest Na+, K+-ATPase activity of the nephron in the basolateral membrane and supplies the energy necessary for ionic transport in this segment. The complexity of the regulation of tubular Mg reabsorption2+ is manifested in the large number and diversity of hypomagnesemic tubulopathies.Physiology of renal tubular handling of Mg2+The ion Mg2+ is filtered by the glomerulus. In the proximal tubule, 10%–25% of the initially filtered load is reabsorbed via a passive paracellular pathway that is poorly understood. The ascending thick branch of the loop of Henle reabsorbs approximately 50%–70% of the filtered Mg load2+ via passive paracellular transport. The remaining 5%–10% of the filtered Mg2+ is reabsorbed in the distal convoluted tubule via an active transcellular route. Thus, the causes of renal hypomagnesemia are in the loop of Henle and distal tubule. In the end, more than 96% of the filtered Mg2+ is reabsorbed along the nephron.Historical description of the main causes of hypomagnesemia<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">a)In 1962, Bartter et al. reported clinical and biochemical data observed in two male patients aged 5 and 25 years respectively, with a new disease characterized by growth retardation, hyperplasia of the juxtaglomerular apparatus, hyperaldosteronism, normal blood pressure, hypokalemic and hypochloremic metabolic alkalosis, and defect in renal concentrating ability resistant to the action of pitresin.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> It eventually became clear that the term Bartter syndrome refers to up to five diseases that share a defective reabsorption of salt, potassium, calcium and water in the ascending limb of the loop of Henle. Two clinical patterns were established that allow distinguishing between a severe form of antenatal presentation (neonatal Bartter corresponding to types 1 and 2) and a form of later onset during the first years of life (classic Bartter or type 3).</li><li class="elsevierStyleListItem" id="lsti0010">b)In 1966, Gitelman et al. published clinical data on three adult patients, two of them brothers, with hypokalemia, hypomagnesemia and metabolic alkalosis.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> For many years, patients with these features were misdiagnosed as a variant of Bartter syndrome. The presence of hyperreninemia and hyperaldosteronism contributed to this confusion. Clinical onset usually appears in adolescence, generally with mild neuromuscular symptoms. The spectrum of manifestations, however, is broad. Thus, the disease may be asymptomatic or manifest itself as mild and sometimes intermittent symptoms (muscle weakness, cramps, fatigue, polyuria, nocturia or joint pain) or more severe symptoms (tetany, convulsions). Paresthesias occur frequently, especially in the face. Salt craving is common and blood pressure values are lower than in the general population. Growth is usually unaffected, although failure to thrive and short stature have been reported in a minority of cases. Hypomagnesemia and hypokalemia prolong ventricular repolarization which predisposes to severe arrhythmias.</li><li class="elsevierStyleListItem" id="lsti0015">c)In 1968, Paunier et al. reported the case of a male infant who at six weeks of age presented with generalized seizures and tetany associated with hypomagnesemia and hypocalcemia.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> The hypomagnesemia was associated with elevated fractional excretion of Mg2+. Treatment with Mg2+ corrected tetany and normalized calcium levels. Renal biopsy showed hyalinization of some glomeruli, interstitial fibrosis and calcium salt deposition. This was the first case of what later became known as hypomagnesemia with secondary hypocalcemia. Shortly thereafter, another case was published in a five-month-old infant with tetany due to secondary hypomagnesemia and hypocalcemia.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Treatment with vitamin D corrected the hypocalcemia without changing the clinical situation. The child died shortly thereafter; biopsy showed calcinosis of the myocardium, kidneys and in one of the cerebral arteries.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Later, in another family, the association with incomplete distal renal tubular acidosis was described.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> In the cases described later, muscle cramps and convulsions coincided.</li><li class="elsevierStyleListItem" id="lsti0020">d)Although some cases combining hypomagnesemia and nephrocalcinosis had been reported<a class="elsevierStyleCrossRefs" href="#bib0030">6–8</a> previously, the first article reporting the presence of hypomagnesemia and nephrocalcinosis was related to hypercalciuria and bilateral macular coloboma appeared in 1979.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> The authors reported that the condition suffered by the two affected siblings could be included in a new variant of the oculorenal syndrome because it had some similarities with Lowe syndrome.<a class="elsevierStyleCrossRef" href="#bib0045">9</a></li></ul>Subsequently, some cases of isolated tubular hypomagnesemia of unknown origin were published. Thus, hypomagnesemias of renal tubular origin were not systematized well into the 1980s. The Spanish pediatric nephrologist Juan Rodríguez Soriano and his collaborators described in 1987 in an anthological article that at least three hereditary diseases with hypomagnesemia should be considered, caused by defects in renal tubular reabsorption of Mg2+, namely, familial isolated hypomagnesemia, familial hypomagnesemia–hypokalemia or Gitelman syndrome and familial hypomagnesemia–hypercalciuria.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> Of the latter, at least 15 patients had been described, to which the authors added three new cases. The authors wrote that “Hypomagnesaemia is always accompanied by hypercalciuria and nephrocalcinosis. Ocular abnormalities such as myopia and horizontal nystagmus are often present. Hypermagnesiuria is of a greater degree than that observed in the previous entity and reflects a low [maximal transport] of Mg reabsorption.” They further emphasized that, “The defect must be situated at the level of the ascending limb of the loop of Henle and affects the transport of both calcium and Mg2+”.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>In 1995, Praga et al., members of the Hospital 12 de Octubre in Madrid, published clinical and biochemical data corresponding to eight patients belonging to five families with familial hypomagnesemia–hypercalciuria. The authors found that, in this autosomal recessive tubulopathy, there is a progressive deterioration of renal glomerular function and that the tubular damage did not recur after transplantation. The title of their article is the one that has passed to posterity and given the disease its name: familial hypomagnesemia with hypercalciuria and nephrocalcinosis.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>Molecular genetics describes the etiology of the four tubulopathies mentioned aboveSince the mid-1990s and within seven years, the etiology of the four causes of hypomagnesemia mentioned above was described. Later, other variants were discovered and have recently been reviewed by our group.<a class="elsevierStyleCrossRef" href="#bib0060">12</a><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025">a)Bartter’s syndrome type 3 is caused by recessive mutations that result in a loss of function of the CLCNKB gene encoding a Cl channel− (ClC-Kb) that is expressed in the basolateral membrane of the ascending thick branch cells of the loop of Henle and in the distal convoluted tubule<a class="elsevierStyleCrossRef" href="#bib0065">13</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Loss of ClC-Kb function alters the intracellular regulation of Cl- concentration which subsequently interferes with the generation of the lumen-positive potential resulting in salt loss and possibly hypomagnesemia. Patients with this subtype develop reduced Mg levels2+ during infancy or thereafter.<a class="elsevierStyleCrossRef" href="#bib0070">14</a><elsevierMultimedia ident="fig0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0030">b)In patients with Gitelman syndrome, the observation that the electrolyte abnormalities resembled the effects produced by chronic administration of thiazides,<a class="elsevierStyleCrossRef" href="#bib0075">15</a> as well as the results obtained in clearance studies,<a class="elsevierStyleCrossRef" href="#bib0080">16</a> suggested that the defect must lie in the distal tubular transport of sodium and chloride sensitive to thiazides. Indeed, in 1996, it was established that Gitelman syndrome is caused by a reduction in NaCl transport in the distal convoluted tubule due to mutations in the SLC12A3 gene encoding the thiazide-sensitive NaCl cotransporter (NCC) located in the luminal membrane of the distal convoluted tubule cells<a class="elsevierStyleCrossRef" href="#bib0085">17</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). It has been suggested that hypomagnesemia in this disease is secondary to a reduction in the activity of the epithelial Mg channel2+ TRPM6 also located in the apical membrane of the distal convoluted tubule<a class="elsevierStyleCrossRef" href="#bib0090">18</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</li><li class="elsevierStyleListItem" id="lsti0035">c)In 2002, two independent groups demonstrated that hypomagnesemia with secondary hypocalcemia is an autosomal recessive inherited entity caused by mutations in the Transient receptor potential melastatin type 6 (TRPM6) gene.<a class="elsevierStyleCrossRefs" href="#bib0095">19,20</a> Soon after, new mutations in this gene were described.<a class="elsevierStyleCrossRefs" href="#bib0105">21,22</a> The TRPM6 protein is a Ca2+ and Mg2+ permeable channel expressed in the luminal membranes of the intestinal epithelium and the cells of the distal convoluted tubule and the collecting duct (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Inactivating mutations of TRPM6 combine an impaired intestinal absorption of Mg2+ and excessive renal loss of Mg.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>The hypocalcemia that is associated with hypomagnesemia is primarily due to a decrease in parathormone synthesis and release because of decreased calcium-sensitive receptor (CaSR) activity, as well as increased parathormone receptor resistance in bone tissue. Thus, parathormone levels are inappropriately low for the concentration of serum calcium. Treatment requires high doses of oral Mg2+ if tolerated, as passive, unsaturable paracellular transport of Mg2+ at the level of the intestine is normal.</li><li class="elsevierStyleListItem" id="lsti0040">d)In 1999, Simon et al. described the existence of a protein, paracellin-1, which is necessary for paracellular tubular reabsorption of Mg2+.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> This protein exists in the tight junction zones of the ascending thick branch cells of the loop of Henle. This work established that mutations in the PCLN-1 gene encoding paracellin-1 were the cause of familial hypomagnesemia with hypercalciuria and nephrocalcinosis.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> When it was found that paracellin-1 is a member of the claudin family, it was renamed claudin-16 (CLDN16 gene). Shortly after, it was observed that there were subjects with the disease who did not carry mutations in the CLDN16 gene. In this regard, it was striking that Spanish patients, except for a very few,<a class="elsevierStyleCrossRef" href="#bib0125">25</a> did not have mutations in the gene.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> In 2006, Konrad et al. resolved the issue by identifying subjects carrying mutations in a new gene, CLDN19, another member of the multigene family of claudins, who had hypomagnesemia, chronic kidney disease and severe ocular abnormalities.<a class="elsevierStyleCrossRef" href="#bib0135">27</a> The gene product, claudin-19, performs its function, like claudin-16, at the tight junctions of the renal tubule and retina. Under physiological conditions, claudin-19 acts as a selective barrier to cations at tight junctions and regulates permeability to monovalent and divalent cations.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> In 2008, Hou et al. demonstrated that claudin-16 interacts with claudin-19,<a class="elsevierStyleCrossRef" href="#bib0145">29</a> such that this association confers tight junctions the ability to contain a selective mechanism in cation reabsorption.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> Our group demonstrated that most Spanish patients carry the same mutation (p.G20D) located in the CLDN19 gene, which facilitates the molecular diagnosis of the disease in our country.<a class="elsevierStyleCrossRefs" href="#bib0155">31–33</a></li></ul>Basic biochemical patterns in renal tubular hypomagnesemias (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>)At present, clinicians know of more than 15 genetic causes of renal tubular hypomagnesemia. According to biochemical criteria they can be classified into three subtypes<a class="elsevierStyleCrossRef" href="#bib0060">12</a>:Tubulopathies with hypokalemia and metabolic alkalosis. The anomalous protein can be in the thick ascending branch of the loop of Henle and/or the distal convoluted tubule. This subgroup includes, among others, Bartter syndrome type 3,<a class="elsevierStyleCrossRefs" href="#bib0005">1,13,14</a> Gitelman syndrome,<a class="elsevierStyleCrossRefs" href="#bib0010">2,15–18</a> seizure syndrome, sensorineural deafness, ataxia, intellectual disability, tubulopathy (EAST/SeSAME)<a class="elsevierStyleCrossRefs" href="#bib0170">34–36</a> and HFN1β nephropathy (malformations of the urinary and genital tracts, renal cysts, gout, urinary Mg2+ loss, elevated liver enzymes and juvenile diabetes type MODY).<a class="elsevierStyleCrossRefs" href="#bib0185">37–39</a> Renal biochemical data of EAST/SeSAME syndrome and HFN1β nephropathy are similar to those of Gitelman syndrome, including hypocalciuria.Tubulopathies with hypercalciuria. This subgroup includes entities in which the abnormal proteins are expressed in the thick ascending branch of the loop of Henle. We refer to the two variants of familial hypomagnesemia with hypercalciuria and nephrocalcinosis<a class="elsevierStyleCrossRefs" href="#bib0030">6–11,24–33</a> and the heterozygous “gain-of-function” mutations in the CASR gene encoding the calcium-sensitive receptor CaSR that produce autosomal dominant hypocalcemia with hypercalciuria.<a class="elsevierStyleCrossRefs" href="#bib0200">40,41</a> In this case, the parathyroid CaSR becomes more sensitive and will detect hypocalcemia as normal calcium and will not stimulate parathyroid hormone secretion. Hypocalcemia is mild to moderate and may be symptomatic in about half of cases (paresthesias, carpopedal spasm and seizures). Activation of CaSR present in the basolateral membrane of the ascending limb of Henle’s loop inhibits the activity of the luminal ROMK channel (Kir 1.1) and produces a pseudo-Bartter’s syndrome. Secondarily, NaCl reabsorption and cation permeability of the claudin-16/claudin-19 channel are reduced with the consequence of salt loss, hypercalciuria, hypermagnesuria and activation of the renin-angiotensin-aldosterone system. Hypokalemic alkalosis may be present.Tubulopathies without hypercalciuria or hypokalemic metabolic alkalosis. In this subgroup, the abnormal proteins are expressed in the distal convoluted tubule. They are rare isolated hypomagnesemias that, in some cases, present with neurological symptoms.<a class="elsevierStyleCrossRefs" href="#bib0210">42–46</a> In addition to hypomagnesemia with secondary hypocalcemia<a class="elsevierStyleCrossRefs" href="#bib0015">3–5,19–23</a> this subgroup includes, among others, autosomal dominant hypomagnesemia with hypocalciuria characterized by dysfunction of the ɣ-subunit of the Na+, K+-ATPase caused by mutations in the FXYD2 gene,<a class="elsevierStyleCrossRefs" href="#bib0210">42,43</a>autosomal recessive hypomagnesemia caused by mutations in the epidermal growth factor (EGF) gene<a class="elsevierStyleCrossRefs" href="#bib0220">44,45</a> and hypomagnesemia with seizures and intellectual disability type 1 caused by mutations in the CNNM2 gene encoding cyclin M2.<a class="elsevierStyleCrossRef" href="#bib0230">46</a>Multisystemic tubulopathies. This subgroup includes some diseases caused by mutations in mitochondrial genes in which there may also be urinary loss of Mg2+. This is the case for Kearns-Sayre syndrome (progressive external ophthalmoplegia, retinitis pigmentosa, hearing loss, cerebellar ataxia and heart block with clinical debut before the age of 20 years) and for HUPRA syndrome: hyperuricemia (HU), pulmonary hypertension (P), renal failure (R) and metabolic alkalosis (A) (SARS2 gene).<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows a diagnostic algorithm for hypomagnesemias constructed based on calcium and calciuria levels.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Transport modalities and interaction between transporters involved in Mg2+ reabsorption in the distal convoluted tubule (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).Mg2+transporters. The main one is the epithelial Mg2+ channel TRPM6 which, as indicated, is located in the apical membrane of the distal convoluted tubule and brings Mg2+ from the tubular lumen into the cytosol.<a class="elsevierStyleCrossRefs" href="#bib0095">19–23</a> Mg2+ is thought to exit the cell through the action of the Mg2+ exchanger/sodium solute carrier family 41, member 1 (SLC41A1) in the basolateral membrane. Mutations in the SLC41A1 gene result in a nephronophthisis-like.<a class="elsevierStyleCrossRefs" href="#bib0235">47–49</a> Loss of Na+, K+-ATPase activity hinders the activity of the Mg2+ exchanger -Na+ as Mg2+ extrusion on the basolateral side is dependent on the Na gradient+. Cyclin M2 (CNNM2) is a candidate for basolateral Mg2+ outflow or a regulator of Mg2+ transport but has not yet been confirmed experimentally.<a class="elsevierStyleCrossRef" href="#bib0230">46</a>A regulator of Mg2+channel activity TRPM6. EGF encoded by the EGF gene<a class="elsevierStyleCrossRefs" href="#bib0220">44,45</a> binds with high affinity to its receptor EGFR (encoded by the EGFR gene) located on the basolateral membrane of the distal convoluted tubule thereby initiating a signaling cascade for Akt-mediated activation of Rac1, resulting in an increase in TRPM6 channels.Channels and proteins involved in Mg2+transport by favoring NaCl reabsorption. Mg2+ reabsorption benefits from the generation of a gradient in the apical membrane that enables the NCC cotransporter to transport sodium to the cytosol. Conversely, under pathological conditions, if sodium outflow at the basolateral membrane is reduced, the intracellular Na+ concentration rises and the activity of the NCC transporter is inhibited and, secondarily, that of the Mg2+ channel TRPM6 is reduced. The Na+ pump, K+-ATPase, the Cl channel– ClC-Kb and the heteromeric channel Kir4.1/Kir5.1 (Kir: inwardly rectifying potassium) are all involved in the basolateral membrane. The proper function of the α<a class="elsevierStyleCrossRef" href="#bib0250">50</a> and ɣ<a class="elsevierStyleCrossRefs" href="#bib0210">42,43</a> subunits of the Na+, K+-ATPase pump is necessary for Mg2+ reabsorption. Kir4.1/Kir5.1 is a rectifying channel of the intracellular potassium concentration that participates in a K+ recycling mechanism together with the Na+–K+–ATPase (“pump-leak coupling”). An alteration in the function of Kir4.1 favors the uncoupling of the K+ recycling mechanism and reduces the activity of Na+, K+-ATPase, with the consequent inhibition of the activity of the NCC cotransporter.<a class="elsevierStyleCrossRefs" href="#bib0170">34–36</a> This is what occurs in EAST/SeSAME syndrome. Mutations have been described in the gene encoding Kir 5.1 that cause the association of distal (hypokalemia, salt loss) and proximal (proximal renal tubular acidosis) tubulopathy with sensorineural deafness; only one of the patients studied had hypomagnesemia.<a class="elsevierStyleCrossRefs" href="#bib0255">51,52</a>K+ secretory channels directed toward the tubular lumen are in the apical membrane. Under physiological conditions, potassium that enters the cell via the basolateral Na+, K+-ATPase and escapes the K+ recycling mechanism mentioned above, exits into the tubular lumina through the action of Kv1.1 and ROMK channels (Kir 1.1). The voltage-gated K+ channel Kv1.1 encoded by the KCNA1 gene directly regulates the activity of the Mg2+ channel TRPM6. Thus, when Kv1.1 is non-functional the luminal membrane potential is lost and TRPM6<a class="elsevierStyleCrossRefs" href="#bib0265">53,54</a> activity is reduced.A transcription factor, a dimerization cofactor and a transcriptional regulator. Hepatocyte nuclear transcription factor 1 (HNF1β) encoded by the hepatocyte nuclear factor-1β gene (TCF2)<a class="elsevierStyleCrossRefs" href="#bib0185">37,38</a> regulates the transcription of the FXYD2 gene encoding the ɣ subunit of the Na+, K+-ATPase which, on the basolateral side, extracts Na+ from the cell in exchange by K+. It is a subunit that adapts the functional properties of this pump to the cellular requirements.<a class="elsevierStyleCrossRefs" href="#bib0210">42,43</a>The coactivator pterin-4-alpha-carbinolamine dehydratase 1 (PCBD1) is an HNF1β dimerization cofactor that increases the transcriptional activity of the Na+, K+-ATPase subunitγ. Several mutations in the PCBD1 gene cause reduced activity of the promoter of the FXYD2 gene and lead to renal Mg2+ loss and hypomagnesemia.<a class="elsevierStyleCrossRef" href="#bib0275">55</a> Its association with transient neonatal hyperphenylalaninemia and primapterinuria has been described in a benign neonatal case without long-term sequelae.FAM111A, a nuclear trypsin-like serine protease, is involved in the regulation of PTH production, calcium homeostasis and bone development and growth. Its nuclear localization suggests that it may be involved in transcriptional regulation. Heterozygous missense mutations in the FAM111A gene that cause Kenny-Caffey syndrome type 2 result in hyperactivation of its intrinsic protein activity that may cause abnormal degradation of DNA-binding proteins.<a class="elsevierStyleCrossRefs" href="#bib0280">56,57</a> Kenny-Caffey syndrome is a rare dysmorphological picture characterized by short proportionate stature with heights below 150 cm at adulthood, cortical thickening and medullary stenosis of tubular bones, delayed closure of the anterior fontanel, ocular abnormalities, hypomagnesemia, hypoparathyroidism and hypocalcemia.<a class="elsevierStyleCrossRef" href="#bib0290">58</a> Hypomagnesemia in patients with Kenny-Caffey syndrome type 2 could be attributed to degradation of transcription factors involved in Mg2+ homeostasis.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>Description of a new hypomagnesemic tubulopathyTRPM6 interacts specifically with its closest homologue, the Mg2+-permeable cation channel Transient receptor potential melastatin 7 (TRPM7), resulting in the assembly of functional TRPM6/TRPM7 complexes forming heterotetramers at the luminal cell membrane.<a class="elsevierStyleCrossRef" href="#bib0295">59</a> So far, it had been reported that the TRPM7 channel promotes neuronal death by non-glutamate-dependent calcium overload during ischemic hypoxia injury. Furthermore, a model of cerebral ischemia in experimental animals<a class="elsevierStyleCrossRef" href="#bib0300">60</a> established the relationship between the TRPM7 channel and tissue injury.As indicated, hypomagnesemia with secondary hypocalcemia of autosomal recessive inheritance is related to mutations in the TRPM6 gene, but, until now, no variants in the TRPM7 gene had been described in patients with hypomagnesemia.In an international collaborative work, our group has participated in the study of two families affected by hypomagnesemia and hypocalcemia that were not carriers of mutations in TRPM6 in which it was demonstrated for the first time that they had mutations in the TRPM7 gene. The patients suffered seizures and muscle cramps associated with hypomagnesemia (0.25–0.51 mmol/L; normal: 0.70–1 mmol/L) and hypocalcemia (0.94–1.1 mmol/L; normal: 2.13–2.55 mmol/L). In the first family, a splice site variant induced the incorporation of intron 1 sequences into the TRPM7 messenger RNA (mRNA) and generated a premature stop codon. Fibroblasts from one of the patients showed reduced cell growth. In the second family, a heterozygous missense variant in the pore domain led to decreased TRPM7 channel activity.<a class="elsevierStyleCrossRef" href="#bib0305">61</a>A few weeks later, Lei et al. confirmed our findings. These authors studied a patient with recurrent hemiplegic migraine attacks accompanied by “intractable hypomagnesemia” (0.41−0.54 mmol/L). The fractional urinary excretion of Mg2+ was 9.7 % (normal: <4%) and calcium levels were 1.1 mmol/L. The authors located a heterozygous mutation in the TRPM7 gene that produces a variant in the transmembrane region of the TRPM7 protein that is possibly crucial for the normal function of the ion channel.<a class="elsevierStyleCrossRef" href="#bib0310">62</a> Both in this case and in the second family included in our publication these were de novo mutations. Since both cases are heterozygous variants, we believe that this is a new tubulopathy, namely hypomagnesemia with secondary hypocalcemia type 2, possibly of autosomal dominant inheritance.FinancingThis work was funded by project PI20/00652, integrated in the National R&D&I Plan 2013–2016 and co-funded by the ISCIII-Subdirectorate General for Evaluation and Promotion of Research and the European Regional Development Fund “A way to make Europe”.Conflict of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres2103452" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1792422" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2103453" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1792423" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Distal convoluted tubule" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Physiology of renal tubular handling of Mg" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Historical description of the main causes of hypomagnesemia" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Molecular genetics describes the etiology of the four tubulopathies mentioned above" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Basic biochemical patterns in renal tubular hypomagnesemias (Fig. 1)" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Description of a new hypomagnesemic tubulopathy" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Financing" ] 12 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interest" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-01-26" "fechaAceptado" => "2023-02-15" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1792422" "palabras" => array:5 [ 0 => "Hypomagnesemia" 1 => "Loop of Henle" 2 => "Distal convoluted tubule" 3 => "TRPM7 channel" 4 => "Tubulopathies" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1792423" "palabras" => array:5 [ 0 => "Hipomagnesemia" 1 => "Asa de Henle" 2 => "Tubulo contorneado distal" 3 => "Canal TRPM7" 4 => "Tubulopathies" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Renal diseases associated with hypomagnesemia are a complex and diverse group of tubulopathies caused by mutations in genes encoding proteins that are expressed in the thick ascending limb of the loop of Henle and in the distal convoluted tubule. In this paper, we review the initial description, the clinical expressiveness and etiology of four of the first hypomagnesemic tubulopathies described: type 3 Bartter and Gitelman diseases, Autosomal recessive hypomagnesemia with secondary hypocalcemia and Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. The basic biochemical patterns observed in renal tubular hypomagnesemias and the modalities of transport and interaction that occur between the transporters involved in the reabsorption of magnesium in the distal convoluted tubule are described below. Finally, the recent report of a new renal disease with hypomagnesemia, type 2 hypomagnesemia with secondary hypocalcemia caused by reduced TRPM7 channel activity is described." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Las enfermedades renales que cursan con hipomagnesemia son un grupo complejo y variopinto de tubulopatías producidas por mutaciones en genes que codifican proteínas que se expresan en la rama gruesa ascendente del asa de Henle y en el túbulo contorneado distal. En el presente artículo revisamos la descripción inicial, la expresividad clínica y la etiología de cuatro de las primeras causas de tubulopatías hipomagnesémicas que se describieron: las enfermedades de Bartter tipo 3 y Gitelman, la hipomagnesemia con hipocalcemia secundaria autosómica recesiva y la hipomagnesemia familiar con hipercalciuria y nefrocalcinosis. A continuación, se describen los patrones bioquímicos básicos que se observan en las hipomagnesemias tubulares renales y las modalidades de transporte e interacción que concurren entre los transportadores implicados en la reabsorción de magnesio en el túbulo contorneado distal. Finalmente, se comunica la reciente descripción de una nueva tubulopatía hipomagnesémica, la hipomagnesemia con hipocalcemia secundaria tipo 2 causada por una reducción de la actividad del canal TRPM7." ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2185 "Ancho" => 2508 "Tamanyo" => 277362 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Physiological mechanisms of transport in the distal convoluted tubule. Na+ and Cl− pass from the tubular lumen into the cell via the thiazide-sensitive NaCl cotransporter (NCC) (mutations in the coding gene cause Gitelman syndrome). Cl− leaves the cell via the chloride channel ClC-Kb (mutations in the gene lead to Bartter syndrome type 3). Na+ leaves the cell via Na+, K+-ATPase (mutations in the gene encoding the ɣ subunit of Na+, K+-ATPase cause autosomal dominant hypomagnesemia with hypocalciuria and those encoding the α subunit cause hypomagnesemia with seizures and type 2 intellectual disability). Hepatocyte nuclear transcription factor 1 (HNF1β) regulates transcription of the gene encoding the ɣ-subunit of the Na+, K+-ATPase (mutations in the coding gene produce HNF1β nephropathy). The coactivator pterin-4-alpha-carbinolamine dehydratase 1 (PCBD1) is a cofactor of HNF1β and increases the transcriptional activity of theγ subunit of Na+, K+-ATPase (mutations in the coding gene produce transient neonatal hyperphenylalaninemia with primapterinuria). FAM111A is a regulator of certain nuclear transcription factors (heterozygous missense mutations in the coding gene cause Kenny-Caffey syndrome type 2 which can present with hypomagnesemia). In the distal tubule, the reabsorption of Mg2+ is an active transport process by transcellular routes, driven by the potential difference between the tubular lumen and the interior of the cell. Mg2+ ions pass from the tubular lumen to the cytosol via the apical TRPM6/TRPM7 channel (mutations in the TRPM6 and TRPM7 coding genes produce hypomagnesemia with autosomal recessive secondary hypocalcemia type 1 and type 2, respectively). Mg2+ ions may exit the cell via CNNM2 (mutations in the coding gene produce hypomagnesemia with seizures and intellectual disability type 1) and the Mg2+ exchanger/Na+ SLC41A1 (mutations in the coding gene produce a nephronophthisis-like phenotype). Epidermal growth factor (EGF) is an activator of the TRPM6 channel (mutations in the coding gene produce autosomal recessive hypomagnesemia; mutations in the EGF receptor [EGFR] produce neonatal inflammatory skin and bowel disease type 2). The apical force required for Mg2+ transport is created by the cooperative action of the basolateral Na+, K+-ATPase, the chloride channel ClC-Kb, the heteromeric channel Kir4.1/Kir5.1 that recycles K+ (mutations in the gene encoding Kir 4.1 produce EAST/SeSAME syndrome), the NCC and K+ extruding channels, ROMK (Kir1.1) (mutations in the coding gene produce Bartter syndrome type II) and Kv1.1 (mutations in the coding gene produce autosomal dominant hypomagnesemia or episodic ataxia type 1). Note: the names of the coding genes are not included here as they are given in the text." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1791 "Ancho" => 3175 "Tamanyo" => 511606 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Diagnostic algorithm for hypomagnesemias based on calcium and calciuria levels. Abnormal transporters (AD: autosomal dominant; ABB: acid–base balance) are shown in parentheses in most cases." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:62 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperplasia of the yuxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F.C. Bartter" 1 => "P. Pronove" 2 => "J.R. Gill Jr" 3 => "R.C. MacCardle" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/0002-9343(62)90214-0" "Revista" => array:6 [ "tituloSerie" => "Am J Med" "fecha" => "1962" "volumen" => "33" "paginaInicial" => "811" "paginaFinal" => "828" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13969763" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A new familial disorder characterized by hypokalemia and hypomagnesemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H.J. Gitelman" 1 => "J.B. Graham" 2 => "L.G. Welt" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Trans Assoc Am Physicians" "fecha" => "1966" "volumen" => "79" "paginaInicial" => "221" "paginaFinal" => "235" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5929460" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary hypomagnesemia with secondary hypocalcemia in an infant" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "L. Paunier" 1 => "I.C. Radde" 2 => "S.W. Kooh" 3 => "P.E. Conen" 4 => "D. Fraser" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pediatrics" "fecha" => "1968" "volumen" => "41" "paginaInicial" => "385" "paginaFinal" => "402" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5637791" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tetany due to hypomagnesaemia with secondary hypocalcaemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Vainsel" 1 => "G. Vandevelde" 2 => "J. Smulders" 3 => "M. Vosters" 4 => "P. Hubain" 5 => "H. Loeb" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/adc.45.240.254" "Revista" => array:6 [ "tituloSerie" => "Arch Dis Child" "fecha" => "1970" "volumen" => "45" "paginaInicial" => "254" "paginaFinal" => "258" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5419995" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incomplete distal renal tubular acidosis in hypomagnesemia-dependent hypocalcemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Passer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med" "fecha" => "1976" "volumen" => "136" "paginaInicial" => "462" "paginaFinal" => "466" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1267554" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Magnesium losing nephropathy associated with hypomagnesemic tetany and nephrocalcinosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Alfrey" 1 => "D. Jenkins" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Clin Res" "fecha" => "1969" "volumen" => "17" "paginaInicial" => "128" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Decreased bicarbonate threshold and renal magnesium wasting in a sibship with distal renal tubular acidosis. (Evaluation of the pathophysiologic role of parathyroid hormone)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.F. Michelis" 1 => "A.L. Drash" 2 => "L.G. Linarelli" 3 => "F.R. De Rubertis" 4 => "B.B. Davis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/0026-0495(72)90025-x" "Revista" => array:6 [ "tituloSerie" => "Metabolism" "fecha" => "1972" "volumen" => "21" "paginaInicial" => "905" "paginaFinal" => "920" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5071957" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal magnesium wasting, incomplete tubular acidosis, hypercalciuria and nephrocalcinosis in siblings" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F. Manz" 1 => "K. Schärer" 2 => "P. Janka" 3 => "J. Lombeck" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/BF00496992" "Revista" => array:6 [ "tituloSerie" => "Eur J Pediatr" "fecha" => "1978" "volumen" => "128" "paginaInicial" => "67" "paginaFinal" => "79" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/668721" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Idiopathic hypercalciuria with bilateral macular colobomata: a new variant of oculo-renal syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "W. Meier" 1 => "A. Blumberg" 2 => "W. Imahorn" 3 => "F. De Luca" 4 => "H. Wildberger" 5 => "O. Oetliker" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Helv Paediatr Acta" "fecha" => "1979" "volumen" => "34" "paginaInicial" => "257" "paginaFinal" => "269" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/500385" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypomagnesaemia of hereditary renal origin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Rodríguez-Soriano" 1 => "A. Vallo" 2 => "M. García-Fuentes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/BF00849255" "Revista" => array:6 [ "tituloSerie" => "Pediatr Nephrol" "fecha" => "1987" "volumen" => "1" "paginaInicial" => "465" "paginaFinal" => "472" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3153319" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Familial hypomagnesemia with hypercalciuria and nephrocalcinosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Praga" 1 => "J. Vara" 2 => "E. González-Parra" 3 => "A. Andrés" 4 => "C. Álamo" 5 => "A. Araque" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ki.1995.199" "Revista" => array:5 [ "tituloSerie" => "Kidney Int" "fecha" => "1995" "volumen" => "47" "paginaInicial" => "1419" "paginaFinal" => "1425" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hereditary kidney diseases associated with hypomagnesemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F. Claverie-Martin" 1 => "A. Perdomo-Ramirez" 2 => "V. Garcia-Nieto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.23876/j.krcp.21.112" "Revista" => array:6 [ "tituloSerie" => "Kidney Res Clin Pract" "fecha" => "2021" "volumen" => "40" "paginaInicial" => "512" "paginaFinal" => "526" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34784661" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in the chloride channel gene, CLCNKB, cause Bartter’s syndrome type III" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.B. Simon" 1 => "R.S. Bindra" 2 => "T.A. Mansfield" 3 => "C. Nelson-Williams" 4 => "E. Mendonca" 5 => "R. Stone" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng1097-171" "Revista" => array:5 [ "tituloSerie" => "Nat Genet" "fecha" => "1997" "volumen" => "17" "paginaInicial" => "171" "paginaFinal" => "178" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and genetic spectrum of Bartter syndrome type 3" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Seys" 1 => "O. Andrini" 2 => "M. Keck" 3 => "L. Mansour-Hendili" 4 => "P.Y. Courand" 5 => "C. Simian" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2016101057" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2017" "volumen" => "28" "paginaInicial" => "2540" "paginaFinal" => "2552" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28381550" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanism of calcium transport stimulated by chlorothiazide in mouse distal convoluted tubule cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F.A. Gesek" 1 => "P.A. Friedman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI115878" "Revista" => array:5 [ "tituloSerie" => "J Clin Invest" "fecha" => "1992" "volumen" => "90" "paginaInicial" => "429" "paginaFinal" => "438" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bartter’s syndrome: evidence suggesting a distal tubular defect in a hypocalciuric variant of the syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.A.L. Sutton" 1 => "V. Marichak" 2 => "A. Halebe" 3 => "G.E. Wilkins" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Miner Electrolyte Metab" "fecha" => "1992" "volumen" => "18" "paginaInicial" => "43" "paginaFinal" => "51" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1406504" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gitelman’s variant of Bartter’s syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.B. Simon" 1 => "C. Nelson-Williams" 2 => "M.J. Bia" 3 => "D. Ellison" 4 => "F.E. Karet" 5 => "A.M. Molina" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng0196-24" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "1996" "volumen" => "12" "paginaInicial" => "24" "paginaFinal" => "30" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8528245" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "T. Nijenhuis" 1 => "V. Vallon" 2 => "A.W. van der Kemp" 3 => "J. Loffing" 4 => "J.G. Hoenderop" 5 => "R.J. Bindels" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI24134" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "2005" "volumen" => "115" "paginaInicial" => "1651" "paginaFinal" => "1658" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15902302" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.P. Schlingmann" 1 => "S. Weber" 2 => "M. Peters" 3 => "L. Niemann Nejsum" 4 => "H. Vitzthum" 5 => "K. Klingel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng889" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2002" "volumen" => "31" "paginaInicial" => "166" "paginaFinal" => "170" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12032568" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.Y. Walder" 1 => "D. Landau" 2 => "P. Meyer" 3 => "H. Shalev" 4 => "M. Tsolia" 5 => "Z. Borochowitz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng901" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2002" "volumen" => "31" "paginaInicial" => "171" "paginaFinal" => "174" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12032570" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Novel TRPM6 mutations in 21 families with primary hypomagnesemia and secondary hypocalcemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.P. Schlingmann" 1 => "M.C. Sassen" 2 => "S. Weber" 3 => "U. Pechmann" 4 => "K. Kusch" 5 => "L. Pelken" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2004110989" "Revista" => array:5 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2005" "volumen" => "16" "paginaInicial" => "3061" "paginaFinal" => "3069" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hypomagnesemia with secondary hypocalcemia due to a missense mutation in the putative pore-forming region of TRPM6" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Chubanov" 1 => "K.P. Schlingmann" 2 => "J. Wäring" 3 => "J. Heinzinger" 4 => "S. Kaske" 5 => "S. Waldegger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1074/jbc.M611117200" "Revista" => array:6 [ "tituloSerie" => "J Biol Chem" "fecha" => "2007" "volumen" => "282" "paginaInicial" => "7656" "paginaFinal" => "7667" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17197439" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A critical role of TRPM channel-kinase for human magnesium transport" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.P. Schlingmann" 1 => "T. Gudermann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1113/jphysiol.2004.080200" "Revista" => array:6 [ "tituloSerie" => "J Physiol" "fecha" => "2005" "volumen" => "566" "paginaInicial" => "301" "paginaFinal" => "308" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15845589" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.B. Simon" 1 => "Y. Lu" 2 => "K.A. Choate" 3 => "H. Velázquez" 4 => "E. Al-Sabban" 5 => "M. Praga" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1126/science.285.5424.103" "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "1999" "volumen" => "285" "paginaInicial" => "103" "paginaFinal" => "106" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10390358" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A novel claudin 16 mutation associated with childhood hypercalciuria abolished binding to ZO-1 and results in lysosomal mistargeting" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Müller" 1 => "J. Kausalya" 2 => "F. Claverie-Martin" 3 => "I.C. Meij" 4 => "P. Eggert" 5 => "V. García-Nieto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/380418" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2003" "volumen" => "73" "paginaInicial" => "1293" "paginaFinal" => "1301" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14628289" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Familial hypomagnesemia with hypercalciuria and nephrocalcinosis non associated to mutations in gene CLDN16" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "V. García Nieto" 1 => "H. González Acosta" 2 => "M.C. Vega Hernández" 3 => "M.I. Luis Yanes" 4 => "L. Espinosa" 5 => "F. Claverie Martín" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Pediatr Nephrol" "fecha" => "2007" "volumen" => "22" "paginaInicial" => "1069" ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in the tight-junction gene claudin 19 (CLDN 19) are associated with renal magnesium wasting, renal failure and severe ocular involvement" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Konrad" 1 => "A. Schaller" 2 => "D. Seelow" 3 => "A.V. Pandey" 4 => "S. Waldegger" 5 => "A. Lesslauer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/508617" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2006" "volumen" => "79" "paginaInicial" => "949" "paginaFinal" => "957" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17033971" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Renal localization and function of the tight junction protein, claudin-19" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Angelow" 1 => "R. El-Husseini" 2 => "S.A. Kanzawa" 3 => "A.S. Yu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajprenal.00087.2007" "Revista" => array:6 [ "tituloSerie" => "Am J Physiol Renal Physiol" "fecha" => "2007" "volumen" => "293" "paginaInicial" => "F166" "paginaFinal" => "F177" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17389678" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Hou" 1 => "A. Renigunta" 2 => "M. Konrad" 3 => "A.S. Gomes" 4 => "E.E. Schneeberger" 5 => "D.L. Paul" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI33970" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "2008" "volumen" => "118" "paginaInicial" => "619" "paginaFinal" => "628" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18188451" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The biology of epithelial cell tight junctions in the kidney" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B.M. Denker" 1 => "E. Sabath" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2010090922" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2011" "volumen" => "22" "paginaInicial" => "622" "paginaFinal" => "625" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21415157" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Claudin-19 mutations and clinical phenotype in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Claverie-Martín" 1 => "V. García-Nieto" 2 => "C. Loris" 3 => "G. Ariceta" 4 => "I. Nadal" 5 => "L. Espinosa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0053151" "Revista" => array:4 [ "tituloSerie" => "PLoS One" "fecha" => "2013" "volumen" => "8" "paginaInicial" => "e53151" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Haplotype analysis of CLDN19 single nucleotide polymorphisms in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "E. Martin-Nuñez" 1 => "E. Cordoba-Lanus" 2 => "H. Gonzalez-Acosta" 3 => "A. Oliet" 4 => "E. Izquierdo" 5 => "F. Claverie-Martin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s12519-014-0528-3" "Revista" => array:6 [ "tituloSerie" => "World J Pediatr" "fecha" => "2015" "volumen" => "11" "paginaInicial" => "272" "paginaFinal" => "275" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25410674" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hipomagnesemia familiar con hipercalciuria y nefrocalcinosis. Su historia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "V.M. García Nieto" 1 => "F. Claverie-Martín" 2 => "C. Loris Pablo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3265/Nefrologia.pre2013.Nov.12230" "Revista" => array:6 [ "tituloSerie" => "Nefrología" "fecha" => "2014" "volumen" => "34" "paginaInicial" => "5" "paginaFinal" => "10" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24463860" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "In vivo formation of a proton-sensitive K+ channel by heteromeric subunit assembly of Kir5.1 with Kir4.1" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Tanemoto" 1 => "N. Kittaka" 2 => "A. Inanobe" 3 => "Y. Kurachi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1469-7793.2000.00587.x" "Revista" => array:6 [ "tituloSerie" => "J Physiol" "fecha" => "2000" "volumen" => "525" "paginaInicial" => "587" "paginaFinal" => "592" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10856114" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epilepsy, ataxia, sensorineural deafness, tubulopathy, and KCNJ10 mutations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Bockenhauer" 1 => "S. Feather" 2 => "H.C. Stanescu" 3 => "S. Bandulik" 4 => "A.A. Zdebik" 5 => "M. Reichold" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0810276" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2009" "volumen" => "360" "paginaInicial" => "1960" "paginaFinal" => "1970" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19420365" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "U.I. Scholl" 1 => "M. Choi" 2 => "T. Liu" 3 => "V.T. Ramaekers" 4 => "M.G. Häusler" 5 => "J. Grimmer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.0901749106" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci USA" "fecha" => "2009" "volumen" => "106" "paginaInicial" => "5842" "paginaFinal" => "5847" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19289823" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutation in hepatocyte nuclear factor-1β gene (TCF2) associated with MODY" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Horikawa" 1 => "N. Iwasaki" 2 => "M. Hara" 3 => "H. Furuta" 4 => "Y. Hinokio" 5 => "B.N. Cockburn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng1297-384" "Revista" => array:5 [ "tituloSerie" => "Nat Genet" "fecha" => "1997" "volumen" => "17" "paginaInicial" => "384" "paginaFinal" => "385" ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in the hepatocyte nuclear factor-1β gene are associated with familial hypoplastic glomerulocystic kidney disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Bingham" 1 => "M.P. Bulman" 2 => "S. Ellard" 3 => "L.I. Allen" 4 => "G.W. Lipkin" 5 => "W.G. Hoff" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/316945" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2001" "volumen" => "68" "paginaInicial" => "219" "paginaFinal" => "224" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11085914" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nefropatía HNF1β. Otra causa de pérdida renal distal de cloro y potasio (CC17)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.L. Luis Yanes" 1 => "P. Tejera Carreño" 2 => "T. Moraleda Mesa" 3 => "L. Madariaga" 4 => "A. García Castaño" 5 => "V.M. Garcia Nieto" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Vox Paediatrica" "fecha" => "2019" "volumen" => "26" "numero" => "Supl 1" "paginaInicial" => "165" ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association between activating mutations of calcium-sensing receptor and Bartter’s syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Watanabe" 1 => "S. Fukumoto" 2 => "H. Chang" 3 => "Y. Takeuchi" 4 => "Y. Hasegawa" 5 => "R. Okazaki" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(02)09842-2" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2002" "volumen" => "360" "paginaInicial" => "692" "paginaFinal" => "694" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12241879" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Vargas-Poussou" 1 => "C. Huang" 2 => "P. Hulin" 3 => "P. Houillier" 4 => "X. Jeunemaitre" 5 => "M. Paillard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.asn.0000025781.16723.68" "Revista" => array:5 [ "tituloSerie" => "Am Soc Nephrol" "fecha" => "2002" "volumen" => "13" "paginaInicial" => "2259" "paginaFinal" => "2266" ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dominant isolated renal magnesium loss is caused by misrouting of the Na(+)K(+)-ATPase gamma-subunit" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I.C. Meij" 1 => "J.B. Koenderink" 2 => "H. van Bokhoven" 3 => "K.F. Assink" 4 => "W.T. Groenestege" 5 => "J.J. de Pont" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/81543" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2000" "volumen" => "26" "paginaInicial" => "265" "paginaFinal" => "266" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11062458" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recurrent FXYD2 p.Gly41Arg mutation in patients with isolated dominant hypomagnesaemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.H. de Baaij" 1 => "E.M. Dorresteijn" 2 => "E.A. Hennekam" 3 => "E.J. Kamsteeg" 4 => "R. Meijer" 5 => "K. Dahan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ndt/gfv014" "Revista" => array:6 [ "tituloSerie" => "Nephrol Dial Transplant" "fecha" => "2015" "volumen" => "30" "paginaInicial" => "952" "paginaFinal" => "957" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25765846" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W.M. Groenestege" 1 => "S. Thebault" 2 => "J. van der Wijst" 3 => "D. van den Berg" 4 => "R. Janssen" 5 => "S. Tejpar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI31680" "Revista" => array:5 [ "tituloSerie" => "J Clin Invest" "fecha" => "2007" "volumen" => "117" "paginaInicial" => "2260" "paginaFinal" => "2267" ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EGF increases TRPM6 activity and surface expression" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Thebault" 1 => "R.T. Alexander" 2 => "W.M. Tiel Groenestege" 3 => "J.G. Hoenderop" 4 => "R.J. Bindels" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2008030327" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2009" "volumen" => "20" "paginaInicial" => "78" "paginaFinal" => "85" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19073827" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CNNM2, encoding a basolateral protein required for renal Mg2+ handling, is mutated in dominant hypomagnesemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Stuiver" 1 => "S. Lainez" 2 => "C. Will" 3 => "S. Terryn" 4 => "D. Gunzel" 5 => "H. Debaix" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajhg.2011.02.005" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2011" "volumen" => "88" "paginaInicial" => "333" "paginaFinal" => "343" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21397062" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human gene SLC41A1 encodes for the Na+/Mg²+ exchanger" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Kolisek" 1 => "A. Nestler" 2 => "J. Vormann" 3 => "M. Schweigel-Röntgen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajpcell.00289.2011" "Revista" => array:5 [ "tituloSerie" => "Am J Physiol Cell Physiol" "fecha" => "2012" "volumen" => "302" "paginaInicial" => "C318" "paginaFinal" => "C326" ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutation of the Mg2+ transporter SLC41A1 results in a nephronophthisis-like phenotype" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.W. Hurd" 1 => "E.A. Otto" 2 => "E. Mishima" 3 => "H.Y. Gee" 4 => "H. Inoue" 5 => "M. Inazu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2012101034" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2013" "volumen" => "24" "paginaInicial" => "967" "paginaFinal" => "977" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23661805" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0245" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "SLC41A1 is essential for magnesium homeostasis in vivo" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.J. Arjona" 1 => "F. Latta" 2 => "S.G. Mohammed" 3 => "M. Thomassen" 4 => "E. van Wijk" 5 => "R.J.M. Bindels" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00424-018-2234-9" "Revista" => array:6 [ "tituloSerie" => "Pflugers Arch" "fecha" => "2019" "volumen" => "471" "paginaInicial" => "845" "paginaFinal" => "860" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30417250" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0250" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Germline de novo mutations in ATP1A1 cause renal hypomagnesemia, refractory seizures, and intellectual disability" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.P. Schlingmann" 1 => "S. Bandulik" 2 => "C. Mammen" 3 => "M. Tarailo-Graovac" 4 => "R. Holm" 5 => "M. Baumann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajhg.2018.10.004" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2018" "volumen" => "103" "paginaInicial" => "808" "paginaFinal" => "816" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30388404" "web" => "Medline" ] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0255" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The human inward rectifier K(+) channel subunit kir5.1 (KCNJ16) maps to chromosome 17q25 and is expressed in kidney and pancreas" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Liu" 1 => "E. McKenna" 2 => "D.J. Figueroa" 3 => "R. Blevins" 4 => "C.P. Austin" 5 => "P.B. Bennett" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000015662" "Revista" => array:6 [ "tituloSerie" => "Cytogenet Cell Genet" "fecha" => "2000" "volumen" => "90" "paginaInicial" => "60" "paginaFinal" => "63" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11060447" "web" => "Medline" ] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0260" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Defects in KCNJ16 cause a novel tubulopathy with hypokalemia. Salt wasting, disturbed acid-base homeostasis, and sensorineural deafness" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.P. Schlingmann" 1 => "A. Renigunta" 2 => "E.J. Hoorn" 3 => "A.L. Forst" 4 => "V. Renigunta" 5 => "V. Atanasov" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2020111587" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2021" "volumen" => "32" "paginaInicial" => "1498" "paginaFinal" => "1512" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33811157" "web" => "Medline" ] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0265" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.L. Browne" 1 => "S.T. Gancher" 2 => "J.G. Nutt" 3 => "E.R. Brunt" 4 => "E.A. Smith" 5 => "P. Kramer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng1094-136" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "1994" "volumen" => "8" "paginaInicial" => "136" "paginaFinal" => "140" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7842011" "web" => "Medline" ] ] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0270" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A missense mutation in the Kv1.1 voltage-gated potassium channel-encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Glaudemans" 1 => "J. van der Wijst" 2 => "R.H. Scola" 3 => "P.J. Lorenzoni" 4 => "A. Heister" 5 => "A.W. van der Kemp" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI36948" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "2009" "volumen" => "119" "paginaInicial" => "936" "paginaFinal" => "942" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19307729" "web" => "Medline" ] ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0275" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Ferrè" 1 => "J.H. de Baaij" 2 => "P. Ferreira" 3 => "R. Germann" 4 => "J.B. de Klerk" 5 => "M. Lavrijsen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1681/ASN.2013040337" "Revista" => array:6 [ "tituloSerie" => "J Am Soc Nephrol" "fecha" => "2014" "volumen" => "25" "paginaInicial" => "574" "paginaFinal" => "586" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24204001" "web" => "Medline" ] ] ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0280" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "FAM111A mutations result in hypoparathyroidism and impaired skeletal development" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Unger" 1 => "M.W. Górna" 2 => "A. Le Béchec" 3 => "S. Do Vale-Pereira" 4 => "M.F. Bedeschi" 5 => "S. Geiberger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajhg.2013.04.020" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2013" "volumen" => "92" "paginaInicial" => "990" "paginaFinal" => "995" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23684011" "web" => "Medline" ] ] ] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0285" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A recurrent de novo FAM111A mutation causes Kenny-Caffey syndrome type 2" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Isojima" 1 => "K. Doi" 2 => "J. Mitsui" 3 => "Y. Oda" 4 => "E. Tokuhiro" 5 => "A. Yasoda" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jbmr.2091" "Revista" => array:6 [ "tituloSerie" => "J Bone Miner Res" "fecha" => "2014" "volumen" => "29" "paginaInicial" => "992" "paginaFinal" => "998" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23996431" "web" => "Medline" ] ] ] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0290" "etiqueta" => "58" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estenosis tubular diafisaria (síndrome de Kenny-Caffey)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Sarría" 1 => "F. Toledo" 2 => "J. Toledo" 3 => "M.L. Vega" 4 => "S. López" 5 => "M. Bueno" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "An Esp Pediatr" "fecha" => "1980" "volumen" => "13" "paginaInicial" => "373" "paginaFinal" => "380" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7406361" "web" => "Medline" ] ] ] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0295" "etiqueta" => "59" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Chubanov" 1 => "S. Waldegger" 2 => "Mederos" 3 => "M. Schnitzler" 4 => "H. Vitzthum" 5 => "M.C. Sassen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.0305252101" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci USA" "fecha" => "2004" "volumen" => "101" "paginaInicial" => "2894" "paginaFinal" => "2899" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14976260" "web" => "Medline" ] ] ] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0300" "etiqueta" => "60" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Electroacupuncture regulates TRPM7 expression through the trkA/PI3K pathway after cerebral ischemia reperfusion in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "L. Zhao" 1 => "Y. Wang" 2 => "N. Sun" 3 => "X. Liu" 4 => "L. Li" 5 => "J. Shi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.lfs.2007.08.034" "Revista" => array:6 [ "tituloSerie" => "Life Sci" "fecha" => "2007" "volumen" => "81" "paginaInicial" => "1211" "paginaFinal" => "1222" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17904584" "web" => "Medline" ] ] ] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0305" "etiqueta" => "61" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Possible role for rare TRPM7 variants in patients with hypomagnesemia with secondary hypocalcemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Vargas-Poussou" 1 => "F. Claverie-Martin" 2 => "C. Prot-Bertoye" 3 => "V. Carotti" 4 => "J. van der Wijst" 5 => "A. Perdomo-Ramirez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/ndt/gfac182" "Revista" => array:3 [ "tituloSerie" => "Nephrol Dial Transplant" "fecha" => "2022" "paginaInicial" => "gfac182" ] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0310" "etiqueta" => "62" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Case report: recurrent hemiplegic migraine attacks accompanied by intractable hypomagnesemia due to a de novo TRPM7 gene variant" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Lei" 1 => "P. Wang" 2 => "H. Li" 3 => "X. Liu" 4 => "J. Shu" 5 => "Q. Zhang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fped.2022.880242" "Revista" => array:5 [ "tituloSerie" => "Front Pediatr" "fecha" => "2022" "volumen" => "10" "paginaInicial" => "880242" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35712613" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000004400000001/v1_202403090635/S2013251424000452/v1_202403090635/en/main.assets" "Apartado" => array:4 [ "identificador" => "35443" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Reviews" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000004400000001/v1_202403090635/S2013251424000452/v1_202403090635/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251424000452?idApp=UINPBA000064"]

Estadísticas

Review

Enfermedades renales que cursan con hipomagnesemia. Comentarios acerca de una nueva tubulopatía hipomagnesémica de origen genético

Víctor M. Garcia-Nietoa,

Autor para correspondencia

vgarcianieto@gmail.com

Corresponding author.

, Félix Claverie-Martinb, Teresa Moraleda-Mesaa, Ana Perdomo-Ramírezb, Gloria Mª Fraga-Rodríguezc, María Isabel Luis-Yanesa, Elena Ramos-Trujillob,d, Grupo RenalTube

a Unidad de Nefrología Pediátrica, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain

b Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain

c Nefrologia Pediàtrica, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain

d Departamento de Medicina Física y Farmacología, Facultad de Medicina, Universidad de la Laguna, Santa Cruz de Tenerife, Spain

Leído

2218

Veces
se ha leído el artículo

645

Total PDF

1573

Total HTML

Compartir estadísticas

 array:23 [
  "pii" => "S2013251424000452"
  "issn" => "20132514"
  "doi" => "10.1016/j.nefroe.2024.02.003"
  "estado" => "S300"
  "fechaPublicacion" => "2024-01-01"
  "aid" => "1148"
  "copyrightAnyo" => "2024"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "rev"
  "cita" => "Nefrologia &#40;English Version&#41;. 2024;44:23-31"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0211699523000310"
      "issn" => "02116995"
      "doi" => "10.1016/j.nefro.2023.02.008"
      "estado" => "S300"
      "fechaPublicacion" => "2024-01-01"
      "aid" => "1148"
      "copyright" => "Sociedad Espa&#241;ola de Nefrolog&#237;a"
      "documento" => "article"
      "crossmark" => 0
      "subdocumento" => "rev"
      "cita" => "Nefrologia. 2024;44:23-31"
      "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">Revisi&#243;n</span>"
        "titulo" => "Enfermedades renales que cursan con hipomagnesemia&#46; Comentarios acerca de una nueva tubulopat&#237;a hipomagnes&#233;mica de origen gen&#233;tico"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "23"
            "paginaFinal" => "31"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Renal diseases that course with hypomagnesemia&#46; Comments on a new hereditary hypomagnesemic tubulopathy"
          ]
        ]
        "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" => 1791
                "Ancho" => 3175
                "Tamanyo" => 448649
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Algoritmo diagn&#243;stico de las hipomagnesemias a partir de los niveles de calcemia y de calciuria&#46; Entre par&#233;ntesis figuran&#44; en la mayor&#237;a de los casos&#44; los transportadores an&#243;malos &#40;AD&#58; autos&#243;mico dominante&#59; EAB&#58; equilibrio &#225;cido-base&#41;&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "V&#237;ctor M&#46; Garcia-Nieto, F&#233;lix Claverie-Martin, Teresa Moraleda-Mesa, Ana Perdomo-Ram&#237;rez, Gloria Ma Fraga-Rodr&#237;guez, Mar&#237;a Isabel Luis-Yanes, Elena Ramos-Trujillo"
            "autores" => array:8 [
              0 => array:2 [
                "nombre" => "V&#237;ctor M&#46;"
                "apellidos" => "Garcia-Nieto"
              ]
              1 => array:2 [
                "nombre" => "F&#233;lix"
                "apellidos" => "Claverie-Martin"
              ]
              2 => array:2 [
                "nombre" => "Teresa"
                "apellidos" => "Moraleda-Mesa"
              ]
              3 => array:2 [
                "nombre" => "Ana"
                "apellidos" => "Perdomo-Ram&#237;rez"
              ]
              4 => array:2 [
                "nombre" => "Gloria Ma"
                "apellidos" => "Fraga-Rodr&#237;guez"
              ]
              5 => array:2 [
                "nombre" => "Mar&#237;a Isabel"
                "apellidos" => "Luis-Yanes"
              ]
              6 => array:2 [
                "nombre" => "Elena"
                "apellidos" => "Ramos-Trujillo"
              ]
              7 => array:1 [
                "colaborador" => "Grupo RenalTube"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2013251424000452"
          "doi" => "10.1016/j.nefroe.2024.02.003"
          "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/S2013251424000452?idApp=UINPBA000064"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699523000310?idApp=UINPBA000064"
      "url" => "/02116995/0000004400000001/v1_202401141155/S0211699523000310/v1_202401141155/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:17 [
    "pii" => "S2013251422001481"
    "issn" => "20132514"
    "doi" => "10.1016/j.nefroe.2022.11.022"
    "estado" => "S300"
    "fechaPublicacion" => "2024-01-01"
    "aid" => "1002"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "cita" => "Nefrologia &#40;English Version&#41;. 2024;44:32-9"
    "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">Original article</span>"
      "titulo" => "No difference in follow-up estimated glomerular filtration rate between hypertensive and matched nonhypertensive kidney donors"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "32"
          "paginaFinal" => "39"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "No hay diferencia en la tasa de filtraci&#243;n glomerular estimada de seguimiento entre donantes de ri&#241;&#243;n hipertensos y no hipertensos compatibles"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Fig&#46; 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1642
              "Ancho" => 2925
              "Tamanyo" => 292571
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Patient selection algorithm&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Eun Hye Yang, Sung Shin, Young Hoon Kim, In Gab Jeong, Bumsik Hong, Chung Hee Baek, Hyosang Kim, Soon Bae Kim"
          "autores" => array:8 [
            0 => array:2 [
              "nombre" => "Eun Hye"
              "apellidos" => "Yang"
            ]
            1 => array:2 [
              "nombre" => "Sung"
              "apellidos" => "Shin"
            ]
            2 => array:2 [
              "nombre" => "Young Hoon"
              "apellidos" => "Kim"
            ]
            3 => array:2 [
              "nombre" => "In Gab"
              "apellidos" => "Jeong"
            ]
            4 => array:2 [
              "nombre" => "Bumsik"
              "apellidos" => "Hong"
            ]
            5 => array:2 [
              "nombre" => "Chung Hee"
              "apellidos" => "Baek"
            ]
            6 => array:2 [
              "nombre" => "Hyosang"
              "apellidos" => "Kim"
            ]
            7 => array:2 [
              "nombre" => "Soon Bae"
              "apellidos" => "Kim"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251422001481?idApp=UINPBA000064"
    "url" => "/20132514/0000004400000001/v1_202403090635/S2013251422001481/v1_202403090635/en/main.assets"
  ]
  "itemAnterior" => array:18 [
    "pii" => "S2013251423000755"
    "issn" => "20132514"
    "doi" => "10.1016/j.nefroe.2023.04.006"
    "estado" => "S300"
    "fechaPublicacion" => "2024-01-01"
    "aid" => "1126"
    "copyright" => "Sociedad Espa&#241;ola de Nefrolog&#237;a"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "rev"
    "cita" => "Nefrologia &#40;English Version&#41;. 2024;44:10-22"
    "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" => "RIPK3 and kidney disease"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "10"
          "paginaFinal" => "22"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "RIPK3 y nefropat&#237;a"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Fig&#46; 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 3008
              "Ancho" => 3510
              "Tamanyo" => 665340
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Different pathways of RIPK3 activation&#46; Canonical activation of RIPK3 is dependent on its RHIM domain that binds to other RHIM-containing proteins&#58; RIPK1 following activation by TNF receptor superfamily proteins&#44; TRIF in response to Toll like receptor &#40;TLR&#41; activation&#44; and DAI&#47;ZBP1 activated by z-RNA from viral infection&#46; The interaction of the RHIM domain of RIPK3 with RHIM-containing proteins allows autophosphorylation and activation of RIPK3&#46; Non-canonical RIPK3 activation is independent of the RHIM domain&#44; and it is mediated by osmotic stress-induced intracellular acidification through NHE1&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Juan Guerrero-Mauvecin, Miguel Fontecha-Barriuso, Ana M&#46; L&#243;pez-Diaz, Alberto Ortiz, Ana B&#46; Sanz"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "Juan"
              "apellidos" => "Guerrero-Mauvecin"
            ]
            1 => array:2 [
              "nombre" => "Miguel"
              "apellidos" => "Fontecha-Barriuso"
            ]
            2 => array:2 [
              "nombre" => "Ana M&#46;"
              "apellidos" => "L&#243;pez-Diaz"
            ]
            3 => array:2 [
              "nombre" => "Alberto"
              "apellidos" => "Ortiz"
            ]
            4 => array:2 [
              "nombre" => "Ana B&#46;"
              "apellidos" => "Sanz"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251423000755?idApp=UINPBA000064"
    "url" => "/20132514/0000004400000001/v1_202403090635/S2013251423000755/v1_202403090635/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
    "titulo" => "Renal diseases that course with hypomagnesemia&#46; Comments on a new hereditary hypomagnesemic tubulopathy"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "23"
        "paginaFinal" => "31"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "V&#237;ctor M&#46; Garcia-Nieto, F&#233;lix Claverie-Martin, Teresa Moraleda-Mesa, Ana Perdomo-Ram&#237;rez, Gloria M&#170; Fraga-Rodr&#237;guez, Mar&#237;a Isabel Luis-Yanes, Elena Ramos-Trujillo"
        "autores" => array:8 [
          0 => array:4 [
            "nombre" => "V&#237;ctor M&#46;"
            "apellidos" => "Garcia-Nieto"
            "email" => array:1 [
              0 => "vgarcianieto@gmail.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" => "F&#233;lix"
            "apellidos" => "Claverie-Martin"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Teresa"
            "apellidos" => "Moraleda-Mesa"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Ana"
            "apellidos" => "Perdomo-Ram&#237;rez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Gloria M&#170;"
            "apellidos" => "Fraga-Rodr&#237;guez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Mar&#237;a Isabel"
            "apellidos" => "Luis-Yanes"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          6 => array:3 [
            "nombre" => "Elena"
            "apellidos" => "Ramos-Trujillo"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          7 => array:1 [
            "colaborador" => "Grupo RenalTube"
          ]
        ]
        "afiliaciones" => array:4 [
          0 => array:3 [
            "entidad" => "Unidad de Nefrolog&#237;a Pedi&#225;trica&#44; Hospital Universitario Nuestra Se&#241;ora de Candelaria&#44; Santa Cruz de Tenerife&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Unidad de Investigaci&#243;n&#44; Hospital Universitario Nuestra Se&#241;ora de Candelaria&#44; Santa Cruz de Tenerife&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Nefrologia Pedi&#224;trica&#44; Hospital de la Santa Creu i Sant Pau&#44; Universitat Aut&#242;noma de Barcelona&#44; Barcelona&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Departamento de Medicina F&#237;sica y Farmacolog&#237;a&#44; Facultad de Medicina&#44; Universidad de la Laguna&#44; Santa Cruz de Tenerife&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
        ]
        "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" => "Enfermedades renales que cursan con hipomagnesemia&#46; Comentarios acerca de una nueva tubulopat&#237;a hipomagnes&#233;mica de origen gen&#233;tico"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:8 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1791
            "Ancho" => 3175
            "Tamanyo" => 511606
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Diagnostic algorithm for hypomagnesemias based on calcium and calciuria levels&#46; Abnormal transporters &#40;AD&#58; autosomal dominant&#59; ABB&#58; acid&#8211;base balance&#41; are shown in parentheses in most cases&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Renal tubules select the filtered solutes necessary to maintain body homeostasis&#46; Most solutes are reabsorbed and returned to the blood&#59; those that are not needed will be eliminated in the urine&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">In the first tubular regions the process of reabsorption is very intense &#40;for example&#44; 65&#37; of the sodium filtered is reabsorbed in the proximal tubule and 25&#37; in the ascending branch of the loop of Henle&#41;&#46; For this reason&#44; tubulopathies with intense damage in these segments &#40;Toni-Debr&#233;-Fanconi syndrome and Bartter syndrome&#44; for example&#41; can be very serious and difficult to treat due to the difficulty of compensating for the loss of solutes&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">It is therefore up to the distal tubule and collecting duct to fine-tune&#44; to put the finishing touches on recovering the solutes necessary for the body and therefore must not be lost in the urine&#46; This task is very complex and requires appropriate specialization&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Distal convoluted tubule</span><p id="par0020" class="elsevierStylePara elsevierViewall">To highlight its importance&#44; it is enough to recall the functional interest of the macula densa as a sensor of intratubular sodium concentration within the structure of the juxtaglomerular apparatus&#46; Suffice to emphasize that the distal tubule contains the only renal specific channel for calcium reabsorption &#40;ECaC&#41; whose function is modulated by various hormones and that the regulation of the thiazide-sensitive sodium chloride &#40;NaCl&#41; transporter is very complex&#44; as can be seen when studying the pathophysiology of Gordon&#8217;s syndrome&#46; In addition&#44; the distal tubule has an important functional involvement in calcium and magnesium reabsorption &#40;Mg<span class="elsevierStyleSup">2&#43;</span>&#41; and has the highest Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase activity of the nephron in the basolateral membrane and supplies the energy necessary for ionic transport in this segment&#46; The complexity of the regulation of tubular Mg reabsorption<span class="elsevierStyleSup">2&#43;</span> is manifested in the large number and diversity of hypomagnesemic tubulopathies&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Physiology of renal tubular handling of Mg<span class="elsevierStyleSup">2&#43;</span></span><p id="par0025" class="elsevierStylePara elsevierViewall">The ion Mg<span class="elsevierStyleSup">2&#43;</span> is filtered by the glomerulus&#46; In the proximal tubule&#44; 10&#37;&#8211;25&#37; of the initially filtered load is reabsorbed via a passive paracellular pathway that is poorly understood&#46; The ascending thick branch of the loop of Henle reabsorbs approximately 50&#37;&#8211;70&#37; of the filtered Mg load<span class="elsevierStyleSup">2&#43;</span> via passive paracellular transport&#46; The remaining 5&#37;&#8211;10&#37; of the filtered Mg<span class="elsevierStyleSup">2&#43;</span> is reabsorbed in the distal convoluted tubule via an active transcellular route&#46; Thus&#44; the causes of renal hypomagnesemia are in the loop of Henle and distal tubule&#46; In the end&#44; more than 96&#37; of the filtered Mg<span class="elsevierStyleSup">2&#43;</span> is reabsorbed along the nephron&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Historical description of the main causes of hypomagnesemia</span><p id="par0030" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">a&#41;</span><p id="par0035" class="elsevierStylePara elsevierViewall">In 1962&#44; Bartter et al&#46; reported clinical and biochemical data observed in two male patients aged 5 and 25 years respectively&#44; with a new disease characterized by growth retardation&#44; hyperplasia of the juxtaglomerular apparatus&#44; hyperaldosteronism&#44; normal blood pressure&#44; hypokalemic and hypochloremic metabolic alkalosis&#44; and defect in renal concentrating ability resistant to the action of pitresin&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It eventually became clear that the term <span class="elsevierStyleItalic">Bartter syndrome</span> refers to up to five diseases that share a defective reabsorption of salt&#44; potassium&#44; calcium and water in the ascending limb of the loop of Henle&#46; Two clinical patterns were established that allow distinguishing between a severe form of antenatal presentation &#40;neonatal Bartter corresponding to types 1 and 2&#41; and a form of later onset during the first years of life &#40;classic Bartter or type 3&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">b&#41;</span><p id="par0040" class="elsevierStylePara elsevierViewall">In 1966&#44; Gitelman et al&#46; published clinical data on three adult patients&#44; two of them brothers&#44; with hypokalemia&#44; hypomagnesemia and metabolic alkalosis&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> For many years&#44; patients with these features were misdiagnosed as a variant of Bartter syndrome&#46; The presence of hyperreninemia and hyperaldosteronism contributed to this confusion&#46; Clinical onset usually appears in adolescence&#44; generally with mild neuromuscular symptoms&#46; The spectrum of manifestations&#44; however&#44; is broad&#46; Thus&#44; the disease may be asymptomatic or manifest itself as mild and sometimes intermittent symptoms &#40;muscle weakness&#44; cramps&#44; fatigue&#44; polyuria&#44; nocturia or joint pain&#41; or more severe symptoms &#40;tetany&#44; convulsions&#41;&#46; Paresthesias occur frequently&#44; especially in the face&#46; Salt craving is common and blood pressure values are lower than in the general population&#46; Growth is usually unaffected&#44; although failure to thrive and short stature have been reported in a minority of cases&#46; Hypomagnesemia and hypokalemia prolong ventricular repolarization which predisposes to severe arrhythmias&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">c&#41;</span><p id="par0045" class="elsevierStylePara elsevierViewall">In 1968&#44; Paunier et al&#46; reported the case of a male infant who at six weeks of age presented with generalized seizures and tetany associated with hypomagnesemia and hypocalcemia&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The hypomagnesemia was associated with elevated fractional excretion of Mg<span class="elsevierStyleSup">2&#43;</span>&#46; Treatment with Mg<span class="elsevierStyleSup">2&#43;</span> corrected tetany and normalized calcium levels&#46; Renal biopsy showed hyalinization of some glomeruli&#44; interstitial fibrosis and calcium salt deposition&#46; This was the first case of what later became known as <span class="elsevierStyleItalic">hypomagnesemia with secondary hypocalcemia</span>&#46; Shortly thereafter&#44; another case was published in a five-month-old infant with tetany due to secondary hypomagnesemia and hypocalcemia&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Treatment with vitamin D corrected the hypocalcemia without changing the clinical situation&#46; The child died shortly thereafter&#59; biopsy showed calcinosis of the myocardium&#44; kidneys and in one of the cerebral arteries&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Later&#44; in another family&#44; the association with incomplete distal renal tubular acidosis was described&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> In the cases described later&#44; muscle cramps and convulsions coincided&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">d&#41;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Although some cases combining hypomagnesemia and nephrocalcinosis had been reported<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;8</span></a> previously&#44; the first article reporting the presence of hypomagnesemia and nephrocalcinosis was related to hypercalciuria and bilateral macular coloboma appeared in 1979&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The authors reported that the condition suffered by the two affected siblings could be included in a new variant of the oculorenal syndrome because it had some similarities with Lowe syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p></li></ul></p><p id="par0055" class="elsevierStylePara elsevierViewall">Subsequently&#44; some cases of isolated tubular hypomagnesemia of unknown origin were published&#46; Thus&#44; hypomagnesemias of renal tubular origin were not systematized well into the 1980s&#46; The Spanish pediatric nephrologist Juan Rodr&#237;guez Soriano and his collaborators described in 1987 in an anthological article that at least three hereditary diseases with hypomagnesemia should be considered&#44; caused by defects in renal tubular reabsorption of Mg<span class="elsevierStyleSup">2&#43;</span>&#44; namely&#44; familial isolated hypomagnesemia&#44; familial hypomagnesemia&#8211;hypokalemia or Gitelman syndrome and familial hypomagnesemia&#8211;hypercalciuria&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Of the latter&#44; at least 15 patients had been described&#44; to which the authors added three new cases&#46; The authors wrote that &#8220;Hypomagnesaemia is always accompanied by hypercalciuria and nephrocalcinosis&#46; Ocular abnormalities such as myopia and horizontal nystagmus are often present&#46; Hypermagnesiuria is of a greater degree than that observed in the previous entity and reflects a low &#91;maximal transport&#93; of Mg reabsorption&#46;&#8221; They further emphasized that&#44; &#8220;The defect must be situated at the level of the ascending limb of the loop of Henle and affects the transport of both calcium and Mg<span class="elsevierStyleSup">2&#43;</span>&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">In 1995&#44; Praga et al&#46;&#44; members of the Hospital 12 de Octubre in Madrid&#44; published clinical and biochemical data corresponding to eight patients belonging to five families with <span class="elsevierStyleItalic">familial hypomagnesemia&#8211;hypercalciuria</span>&#46; The authors found that&#44; in this autosomal recessive tubulopathy&#44; there is a progressive deterioration of renal glomerular function and that the tubular damage did not recur after transplantation&#46; The title of their article is the one that has passed to posterity and given the disease its name&#58; <span class="elsevierStyleItalic">familial hypomagnesemia with hypercalciuria and nephrocalcinosis</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Molecular genetics describes the etiology of the four tubulopathies mentioned above</span><p id="par0065" class="elsevierStylePara elsevierViewall">Since the mid-1990s and within seven years&#44; the etiology of the four causes of hypomagnesemia mentioned above was described&#46; Later&#44; other variants were discovered and have recently been reviewed by our group&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">a&#41;</span><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Bartter&#8217;s syndrome type 3</span> is caused by recessive mutations that result in a loss of function of the <span class="elsevierStyleItalic">CLCNKB</span> gene encoding a Cl channel<span class="elsevierStyleSup">&#8722;</span> &#40;ClC-Kb&#41; that is expressed in the basolateral membrane of the ascending thick branch cells of the loop of Henle and in the distal convoluted tubule<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Loss of ClC-Kb function alters the intracellular regulation of Cl- concentration which subsequently interferes with the generation of the lumen-positive potential resulting in salt loss and possibly hypomagnesemia&#46; Patients with this subtype develop reduced Mg levels<span class="elsevierStyleSup">2&#43;</span> during infancy or thereafter&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">b&#41;</span><p id="par0075" class="elsevierStylePara elsevierViewall">In patients with <span class="elsevierStyleItalic">Gitelman syndrome</span>&#44; the observation that the electrolyte abnormalities resembled the effects produced by chronic administration of thiazides&#44;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> as well as the results obtained in clearance studies&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> suggested that the defect must lie in the distal tubular transport of sodium and chloride sensitive to thiazides&#46; Indeed&#44; in 1996&#44; it was established that Gitelman syndrome is caused by a reduction in NaCl transport in the distal convoluted tubule due to mutations in the <span class="elsevierStyleItalic">SLC12A3</span> gene encoding the thiazide-sensitive NaCl cotransporter &#40;NCC&#41; located in the luminal membrane of the distal convoluted tubule cells<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; It has been suggested that hypomagnesemia in this disease is secondary to a reduction in the activity of the epithelial Mg channel<span class="elsevierStyleSup">2&#43;</span> TRPM6 also located in the apical membrane of the distal convoluted tubule<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">c&#41;</span><p id="par0080" class="elsevierStylePara elsevierViewall">In 2002&#44; two independent groups demonstrated that <span class="elsevierStyleItalic">hypomagnesemia with secondary hypocalcemia</span> is an autosomal recessive inherited entity caused by mutations in the <span class="elsevierStyleItalic">Transient receptor potential melastatin type 6</span> &#40;<span class="elsevierStyleItalic">TRPM6</span>&#41; gene&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;20</span></a> Soon after&#44; new mutations in this gene were described&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;22</span></a> The TRPM6 protein is a Ca2<span class="elsevierStyleSup">&#43;</span> and Mg<span class="elsevierStyleSup">2&#43;</span> permeable channel expressed in the luminal membranes of the intestinal epithelium and the cells of the distal convoluted tubule and the collecting duct &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Inactivating mutations of TRPM6 combine an impaired intestinal absorption of Mg<span class="elsevierStyleSup">2&#43;</span> and excessive renal loss of Mg&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The hypocalcemia that is associated with hypomagnesemia is primarily due to a decrease in parathormone synthesis and release because of decreased calcium-sensitive receptor &#40;CaSR&#41; activity&#44; as well as increased parathormone receptor resistance in bone tissue&#46; Thus&#44; parathormone levels are inappropriately low for the concentration of serum calcium&#46; Treatment requires high doses of oral Mg<span class="elsevierStyleSup">2&#43;</span> if tolerated&#44; as passive&#44; unsaturable paracellular transport of Mg<span class="elsevierStyleSup">2&#43;</span> at the level of the intestine is normal&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">d&#41;</span><p id="par0095" class="elsevierStylePara elsevierViewall">In 1999&#44; Simon et al&#46; described the existence of a protein&#44; paracellin-1&#44; which is necessary for paracellular tubular reabsorption of Mg<span class="elsevierStyleSup">2&#43;</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> This protein exists in the tight junction zones of the ascending thick branch cells of the loop of Henle&#46; This work established that mutations in the <span class="elsevierStyleItalic">PCLN-1</span> gene encoding paracellin-1 were the cause of <span class="elsevierStyleItalic">familial hypomagnesemia with hypercalciuria and nephrocalcinosis</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> When it was found that paracellin-1 is a member of the claudin family&#44; it was renamed claudin-16 &#40;<span class="elsevierStyleItalic">CLDN16</span> gene&#41;&#46; Shortly after&#44; it was observed that there were subjects with the disease who did not carry mutations in the <span class="elsevierStyleItalic">CLDN16 gene</span>&#46; In this regard&#44; it was striking that Spanish patients&#44; except for a very few&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> did not have mutations in the gene&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> In 2006&#44; Konrad et al&#46; resolved the issue by identifying subjects carrying mutations in a new gene&#44; <span class="elsevierStyleItalic">CLDN19</span>&#44; another member of the multigene family of claudins&#44; who had hypomagnesemia&#44; chronic kidney disease and severe ocular abnormalities&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> The gene product&#44; claudin-19&#44; performs its function&#44; like claudin-16&#44; at the tight junctions of the renal tubule and retina&#46; Under physiological conditions&#44; claudin-19 acts as a selective barrier to cations at tight junctions and regulates permeability to monovalent and divalent cations&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> In 2008&#44; Hou et al&#46; demonstrated that claudin-16 interacts with claudin-19&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> such that this association confers tight junctions the ability to contain a selective mechanism in cation reabsorption&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Our group demonstrated that most Spanish patients carry the same mutation &#40;p&#46;G20D&#41; located in the <span class="elsevierStyleItalic">CLDN19</span> gene&#44; which facilitates the molecular diagnosis of the disease in our country&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#8211;33</span></a></p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Basic biochemical patterns in renal tubular hypomagnesemias &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;</span><p id="par0100" class="elsevierStylePara elsevierViewall">At present&#44; clinicians know of more than 15 genetic causes of renal tubular hypomagnesemia&#46; According to biochemical criteria they can be classified into three subtypes<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a>&#58;</p><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Tubulopathies with hypokalemia and metabolic alkalosis</span></span>&#46; The anomalous protein can be in the thick ascending branch of the loop of Henle and&#47;or the distal convoluted tubule&#46; This subgroup includes&#44; among others&#44; <span class="elsevierStyleItalic">Bartter syndrome type 3</span>&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;13&#44;14</span></a> Gitelman syndrome&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;15&#8211;18</span></a> seizure syndrome&#44; sensorineural deafness&#44; ataxia&#44; intellectual disability&#44; tubulopathy &#40;EAST&#47;SeSAME&#41;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#8211;36</span></a> and HFN1&#946; nephropathy &#40;malformations of the urinary and genital tracts&#44; renal cysts&#44; gout&#44; urinary Mg<span class="elsevierStyleSup">2&#43;</span> loss&#44; elevated liver enzymes and juvenile diabetes type MODY&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#8211;39</span></a> Renal biochemical data of EAST&#47;SeSAME syndrome and HFN1&#946; nephropathy are similar to those of Gitelman syndrome&#44; including hypocalciuria&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Tubulopathies with hypercalciuria</span></span>&#46; This subgroup includes entities in which the abnormal proteins are expressed in the thick ascending branch of the loop of Henle&#46; We refer to the two variants of <span class="elsevierStyleItalic">familial hypomagnesemia with hypercalciuria and nephrocalcinosis</span><a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#8211;11&#44;24&#8211;33</span></a> and the heterozygous &#8220;gain-of-function&#8221; mutations in the <span class="elsevierStyleItalic">CASR</span> gene encoding the calcium-sensitive receptor CaSR that produce <span class="elsevierStyleItalic">autosomal dominant hypocalcemia with hypercalciuria</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">40&#44;41</span></a> In this case&#44; the parathyroid CaSR becomes more sensitive and will detect hypocalcemia as normal calcium and will not stimulate parathyroid hormone secretion&#46; Hypocalcemia is mild to moderate and may be symptomatic in about half of cases &#40;paresthesias&#44; carpopedal spasm and seizures&#41;&#46; Activation of CaSR present in the basolateral membrane of the ascending limb of Henle&#8217;s loop inhibits the activity of the luminal ROMK channel &#40;Kir 1&#46;1&#41; and produces a pseudo-Bartter&#8217;s syndrome&#46; Secondarily&#44; NaCl reabsorption and cation permeability of the claudin-16&#47;claudin-19 channel are reduced with the consequence of salt loss&#44; hypercalciuria&#44; hypermagnesuria and activation of the renin-angiotensin-aldosterone system&#46; Hypokalemic alkalosis may be present&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Tubulopathies without hypercalciuria or hypokalemic metabolic alkalosis</span></span>&#46; In this subgroup&#44; the abnormal proteins are expressed in the distal convoluted tubule&#46; They are rare isolated hypomagnesemias that&#44; in some cases&#44; present with neurological symptoms&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#8211;46</span></a> In addition to <span class="elsevierStyleItalic">hypomagnesemia with secondary hypocalcemia</span><a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5&#44;19&#8211;23</span></a> this subgroup includes&#44; among others&#44; <span class="elsevierStyleItalic">autosomal dominant hypomagnesemia with hypocalciuria</span> characterized by dysfunction of the &#611;-subunit of the Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase caused by mutations in the <span class="elsevierStyleItalic">FXYD2</span> gene&#44;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#44;43</span></a><span class="elsevierStyleItalic">autosomal recessive hypomagnesemia</span> caused by mutations in the epidermal growth factor &#40;EGF&#41; gene<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">44&#44;45</span></a> and <span class="elsevierStyleItalic">hypomagnesemia with seizures and</span> intellectual disability type 1 caused by mutations in the <span class="elsevierStyleItalic">CNNM2</span> gene encoding cyclin M2&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Multisystemic tubulopathies</span>&#46; This subgroup includes some diseases caused by mutations in mitochondrial genes in which there may also be urinary loss of Mg<span class="elsevierStyleSup">2&#43;</span>&#46; This is the case for Kearns-Sayre syndrome &#40;progressive external ophthalmoplegia&#44; retinitis pigmentosa&#44; hearing loss&#44; cerebellar ataxia and heart block with clinical debut before the age of 20 years&#41; and for HUPRA syndrome&#58; hyperuricemia &#40;HU&#41;&#44; pulmonary hypertension &#40;P&#41;&#44; renal failure &#40;R&#41; and metabolic alkalosis &#40;A&#41; &#40;<span class="elsevierStyleItalic">SARS2</span> gene&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows a diagnostic algorithm for hypomagnesemias constructed based on calcium and calciuria levels&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">Transport modalities and interaction between transporters involved in Mg<span class="elsevierStyleSup">2&#43;</span> reabsorption in the distal convoluted tubule &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Mg<span class="elsevierStyleSup">2&#43;</span><span class="elsevierStyleBold"><span class="elsevierStyleItalic">transporters</span></span>&#46; The main one is the epithelial Mg<span class="elsevierStyleSup">2&#43;</span> channel TRPM6 which&#44; as indicated&#44; is located in the apical membrane of the distal convoluted tubule and brings Mg<span class="elsevierStyleSup">2&#43;</span> from the tubular lumen into the cytosol&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#8211;23</span></a> Mg<span class="elsevierStyleSup">2&#43;</span> is thought to exit the cell through the action of the Mg<span class="elsevierStyleSup">2&#43;</span> exchanger<span class="elsevierStyleItalic">&#47;sodium solute carrier family 41&#44; member 1</span> &#40;SLC41A1&#41; in the basolateral membrane&#46; Mutations in the <span class="elsevierStyleItalic">SLC41A1</span> gene result in a <span class="elsevierStyleItalic">nephronophthisis-like</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#8211;49</span></a> Loss of Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase activity hinders the activity of the Mg<span class="elsevierStyleSup">2&#43;</span> exchanger -Na<span class="elsevierStyleSup">&#43;</span> as Mg<span class="elsevierStyleSup">2&#43;</span> extrusion on the basolateral side is dependent on the Na gradient<span class="elsevierStyleSup">&#43;</span>&#46; Cyclin M2 &#40;CNNM2&#41; is a candidate for basolateral Mg<span class="elsevierStyleSup">2&#43;</span> outflow or a regulator of Mg<span class="elsevierStyleSup">2&#43;</span> transport but has not yet been confirmed experimentally&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">A regulator of</span></span> Mg<span class="elsevierStyleSup">2&#43;</span><span class="elsevierStyleBold"><span class="elsevierStyleItalic">channel activity TRPM6</span></span>&#46; EGF encoded by the <span class="elsevierStyleItalic">EGF</span> gene<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">44&#44;45</span></a> binds with high affinity to its receptor EGFR &#40;encoded by the <span class="elsevierStyleItalic">EGFR</span> gene&#41; located on the basolateral membrane of the distal convoluted tubule thereby initiating a signaling cascade for Akt-mediated activation of Rac1&#44; resulting in an increase in TRPM6 channels&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Channels and proteins involved in</span> Mg<span class="elsevierStyleSup">2&#43;</span><span class="elsevierStyleItalic">transport by favoring</span> NaCl <span class="elsevierStyleItalic">reabsorption</span></span>&#46; Mg<span class="elsevierStyleSup">2&#43;</span> reabsorption benefits from the generation of a gradient in the apical membrane that enables the NCC cotransporter to transport sodium to the cytosol&#46; Conversely&#44; under pathological conditions&#44; if sodium outflow at the basolateral membrane is reduced&#44; the intracellular Na<span class="elsevierStyleSup">&#43;</span> concentration rises and the activity of the NCC transporter is inhibited and&#44; secondarily&#44; that of the Mg<span class="elsevierStyleSup">2&#43;</span> channel TRPM6 is reduced&#46; The Na<span class="elsevierStyleSup">&#43;</span> pump&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase&#44; the Cl channel&#8211; ClC-Kb and the heteromeric channel Kir4&#46;1&#47;Kir5&#46;1 &#40;Kir&#58; <span class="elsevierStyleItalic">inwardly rectifying potassium</span>&#41; are all involved in the basolateral membrane&#46; The proper function of the &#945;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> and &#611;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#44;43</span></a> subunits of the Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase pump is necessary for Mg<span class="elsevierStyleSup">2&#43;</span> reabsorption&#46; Kir4&#46;1&#47;Kir5&#46;1 is a rectifying channel of the intracellular potassium concentration that participates in a K<span class="elsevierStyleSup">&#43;</span> recycling mechanism together with the Na<span class="elsevierStyleSup">&#43;</span>&#8211;K<span class="elsevierStyleSup">&#43;</span>&#8211;ATPase &#40;&#8220;pump-leak coupling&#8221;&#41;&#46; An alteration in the function of Kir4&#46;1 favors the uncoupling of the K<span class="elsevierStyleSup">&#43;</span> recycling mechanism and reduces the activity of Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase&#44; with the consequent inhibition of the activity of the NCC cotransporter&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#8211;36</span></a> This is what occurs in EAST&#47;SeSAME syndrome&#46; Mutations have been described in the gene encoding Kir 5&#46;1 that cause the association of distal &#40;hypokalemia&#44; salt loss&#41; and proximal &#40;proximal renal tubular acidosis&#41; tubulopathy with sensorineural deafness&#59; only one of the patients studied had hypomagnesemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">51&#44;52</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">K<span class="elsevierStyleSup">&#43;</span> secretory channels directed toward the tubular lumen are in the apical membrane</span>&#46; Under physiological conditions&#44; potassium that enters the cell via the basolateral Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase and escapes the K<span class="elsevierStyleSup">&#43;</span> recycling mechanism mentioned above&#44; exits into the tubular lumina through the action of Kv1&#46;1 and ROMK channels &#40;Kir 1&#46;1&#41;&#46; The voltage-gated K<span class="elsevierStyleSup">&#43;</span> channel Kv1&#46;1 encoded by the <span class="elsevierStyleItalic">KCNA1</span> gene directly regulates the activity of the Mg<span class="elsevierStyleSup">2&#43;</span> channel TRPM6&#46; Thus&#44; when Kv1&#46;1 is non-functional the luminal membrane potential is lost and TRPM6<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">53&#44;54</span></a> activity is reduced&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">A transcription factor&#44; a dimerization cofactor and a transcriptional regulator</span></span>&#46; Hepatocyte nuclear transcription factor 1 &#40;HNF1&#946;&#41; encoded by the <span class="elsevierStyleItalic">hepatocyte nuclear factor-1&#946;</span> gene &#40;TCF2&#41;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#44;38</span></a> regulates the transcription of the <span class="elsevierStyleItalic">FXYD2</span> gene encoding the &#611; subunit of the Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase which&#44; on the basolateral side&#44; extracts Na<span class="elsevierStyleSup">&#43;</span> from the cell in exchange by K<span class="elsevierStyleSup">&#43;</span>&#46; It is a subunit that adapts the functional properties of this pump to the cellular requirements&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#44;43</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">The coactivator <span class="elsevierStyleItalic">pterin-4-alpha-carbinolamine dehydratase 1</span> &#40;PCBD1&#41; is an HNF1&#946; dimerization cofactor that increases the transcriptional activity of the Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase subunit&#947;&#46; Several mutations in the <span class="elsevierStyleItalic">PCBD1</span> gene cause reduced activity of the promoter of the <span class="elsevierStyleItalic">FXYD2</span> gene and lead to renal Mg<span class="elsevierStyleSup">2&#43;</span> loss and hypomagnesemia&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> Its association with transient neonatal hyperphenylalaninemia and primapterinuria has been described in a benign neonatal case without long-term sequelae&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">FAM111A&#44; a nuclear trypsin-like serine protease&#44; is involved in the regulation of PTH production&#44; calcium homeostasis and bone development and growth&#46; Its nuclear localization suggests that it may be involved in transcriptional regulation&#46; Heterozygous <span class="elsevierStyleItalic">missense</span> mutations in the <span class="elsevierStyleItalic">FAM111A</span> gene that cause <span class="elsevierStyleItalic">Kenny-Caffey syndrome type 2</span> result in hyperactivation of its intrinsic protein activity that may cause abnormal degradation of DNA-binding proteins&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">56&#44;57</span></a> Kenny-Caffey syndrome is a rare dysmorphological picture characterized by short proportionate stature with heights below 150&#8239;cm at adulthood&#44; cortical thickening and medullary stenosis of tubular bones&#44; delayed closure of the anterior fontanel&#44; ocular abnormalities&#44; hypomagnesemia&#44; hypoparathyroidism and hypocalcemia&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> Hypomagnesemia in patients with <span class="elsevierStyleItalic">Kenny-Caffey syndrome type 2</span> could be attributed to degradation of transcription factors involved in Mg<span class="elsevierStyleSup">2&#43;</span> homeostasis&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Description of a new hypomagnesemic tubulopathy</span><p id="par0170" class="elsevierStylePara elsevierViewall">TRPM6 interacts specifically with its closest homologue&#44; the Mg<span class="elsevierStyleSup">2&#43;</span>-permeable cation channel <span class="elsevierStyleItalic">Transient receptor potential melastatin 7</span> &#40;TRPM7&#41;&#44; resulting in the assembly of functional TRPM6&#47;TRPM7 complexes forming heterotetramers at the luminal cell membrane&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a> So far&#44; it had been reported that the TRPM7 channel promotes neuronal death by non-glutamate-dependent calcium overload during ischemic hypoxia injury&#46; Furthermore&#44; a model of cerebral ischemia in experimental animals<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> established the relationship between the TRPM7 channel and tissue injury&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">As indicated&#44; <span class="elsevierStyleItalic">hypomagnesemia with secondary hypocalcemia</span> of autosomal recessive inheritance is related to mutations in the <span class="elsevierStyleItalic">TRPM6</span> gene&#44; but&#44; until now&#44; no variants in the <span class="elsevierStyleItalic">TRPM7</span> gene had been described in patients with hypomagnesemia&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">In an international collaborative work&#44; our group has participated in the study of two families affected by hypomagnesemia and hypocalcemia that were not carriers of mutations in <span class="elsevierStyleItalic">TRPM6</span> in which it was demonstrated for the first time that they had mutations in the <span class="elsevierStyleItalic">TRPM7</span> gene&#46; The patients suffered seizures and muscle cramps associated with hypomagnesemia &#40;0&#46;25&#8211;0&#46;51&#8239;mmol&#47;L&#59; normal&#58; 0&#46;70&#8211;1&#8239;mmol&#47;L&#41; and hypocalcemia &#40;0&#46;94&#8211;1&#46;1&#8239;mmol&#47;L&#59; normal&#58; 2&#46;13&#8211;2&#46;55&#8239;mmol&#47;L&#41;&#46; In the first family&#44; a splice site variant induced the incorporation of intron 1 sequences into the <span class="elsevierStyleItalic">TRPM7</span> messenger RNA &#40;mRNA&#41; and generated a premature stop codon&#46; Fibroblasts from one of the patients showed reduced cell growth&#46; In the second family&#44; a heterozygous missense variant in the pore domain led to decreased TRPM7 channel activity&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">A few weeks later&#44; Lei et al&#46; confirmed our findings&#46; These authors studied a patient with recurrent hemiplegic migraine attacks accompanied by &#8220;intractable hypomagnesemia&#8221; &#40;0&#46;41&#8722;0&#46;54&#8239;mmol&#47;L&#41;&#46; The fractional urinary excretion of Mg<span class="elsevierStyleSup">2&#43;</span> was 9&#46;7 &#37; &#40;normal&#58; &#60;4&#37;&#41; and calcium levels were 1&#46;1&#8239;mmol&#47;L&#46; The authors located a heterozygous mutation in the <span class="elsevierStyleItalic">TRPM7</span> gene that produces a variant in the transmembrane region of the TRPM7 protein that is possibly crucial for the normal function of the ion channel&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> Both in this case and in the second family included in our publication these were <span class="elsevierStyleItalic">de novo</span> mutations&#46; Since both cases are heterozygous variants&#44; we believe that this is a new tubulopathy&#44; namely <span class="elsevierStyleItalic">hypomagnesemia with secondary hypocalcemia type 2</span>&#44; possibly of autosomal dominant inheritance&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Financing</span><p id="par0190" class="elsevierStylePara elsevierViewall">This work was funded by project PI20&#47;00652&#44; integrated in the <span class="elsevierStyleGrantSponsor" id="gs0005">National R&#38;D&#38;I Plan</span> 2013&#8211;2016 and co-funded by the <span class="elsevierStyleGrantSponsor" id="gs0010">ISCIII-Subdirectorate General for Evaluation and Promotion of Research</span> and the <span class="elsevierStyleGrantSponsor" id="gs0015">European Regional Development Fund</span> &#8220;A way to make Europe&#8221;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflict of interest</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:14 [
        0 => array:3 [
          "identificador" => "xres2103452"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1792422"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres2103453"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1792423"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Distal convoluted tubule"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Physiology of renal tubular handling of Mg"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Historical description of the main causes of hypomagnesemia"
        ]
        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Molecular genetics describes the etiology of the four tubulopathies mentioned above"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Basic biochemical patterns in renal tubular hypomagnesemias &#40;Fig&#46; 1&#41;"
        ]
        10 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Description of a new hypomagnesemic tubulopathy"
        ]
        11 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Financing"
        ]
        12 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Conflict of interest"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2023-01-26"
    "fechaAceptado" => "2023-02-15"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1792422"
          "palabras" => array:5 [
            0 => "Hypomagnesemia"
            1 => "Loop of Henle"
            2 => "Distal convoluted tubule"
            3 => "TRPM7 channel"
            4 => "Tubulopathies"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1792423"
          "palabras" => array:5 [
            0 => "Hipomagnesemia"
            1 => "Asa de Henle"
            2 => "Tubulo contorneado distal"
            3 => "Canal TRPM7"
            4 => "Tubulopathies"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Renal diseases associated with hypomagnesemia are a complex and diverse group of tubulopathies caused by mutations in genes encoding proteins that are expressed in the thick ascending limb of the loop of Henle and in the distal convoluted tubule&#46; In this paper&#44; we review the initial description&#44; the clinical expressiveness and etiology of four of the first hypomagnesemic tubulopathies described&#58; <span class="elsevierStyleItalic">type 3 Bartter and Gitelman diseases&#44; Autosomal recessive hypomagnesemia with secondary hypocalcemia and Familial hypomagnesemia with hypercalciuria and nephrocalcinosis</span>&#46; The basic biochemical patterns observed in renal tubular hypomagnesemias and the modalities of transport and interaction that occur between the transporters involved in the reabsorption of magnesium in the distal convoluted tubule are described below&#46; Finally&#44; the recent report of a new renal disease with hypomagnesemia&#44; type 2 <span class="elsevierStyleItalic">hypomagnesemia with secondary hypocalcemia</span> caused by reduced TRPM7 channel activity is described&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Las enfermedades renales que cursan con hipomagnesemia son un grupo complejo y variopinto de tubulopat&#237;as producidas por mutaciones en genes que codifican prote&#237;nas que se expresan en la rama gruesa ascendente del asa de Henle y en el t&#250;bulo contorneado distal&#46; En el presente art&#237;culo revisamos la descripci&#243;n inicial&#44; la expresividad cl&#237;nica y la etiolog&#237;a de cuatro de las primeras causas de tubulopat&#237;as hipomagnes&#233;micas que se describieron&#58; las <span class="elsevierStyleItalic">enfermedades de Bartter tipo 3 y Gitelman</span>&#44; la <span class="elsevierStyleItalic">hipomagnesemia con hipocalcemia secundaria autos&#243;mica recesiva</span> y la <span class="elsevierStyleItalic">hipomagnesemia familiar con hipercalciuria y nefrocalcinosis</span>&#46; A continuaci&#243;n&#44; se describen los patrones bioqu&#237;micos b&#225;sicos que se observan en las hipomagnesemias tubulares renales y las modalidades de transporte e interacci&#243;n que concurren entre los transportadores implicados en la reabsorci&#243;n de magnesio en el t&#250;bulo contorneado distal&#46; Finalmente&#44; se comunica la reciente descripci&#243;n de una nueva tubulopat&#237;a hipomagnes&#233;mica&#44; la <span class="elsevierStyleItalic">hipomagnesemia con hipocalcemia secundaria</span> tipo 2 causada por una reducci&#243;n de la actividad del canal TRPM7&#46;</p></span>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2185
            "Ancho" => 2508
            "Tamanyo" => 277362
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Physiological mechanisms of transport in the distal convoluted tubule&#46; Na<span class="elsevierStyleSup">&#43;</span> and Cl<span class="elsevierStyleSup">&#8722;</span> pass from the tubular lumen into the cell via the thiazide-sensitive NaCl cotransporter &#40;NCC&#41; &#40;mutations in the coding gene cause <span class="elsevierStyleItalic">Gitelman syndrome</span>&#41;&#46; Cl<span class="elsevierStyleSup">&#8722;</span> leaves the cell via the chloride channel ClC-Kb &#40;mutations in the gene lead to <span class="elsevierStyleItalic">Bartter syndrome type 3</span>&#41;&#46; Na<span class="elsevierStyleSup">&#43;</span> leaves the cell via Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase &#40;mutations in the gene encoding the &#611; subunit of Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase cause <span class="elsevierStyleItalic">autosomal dominant hypomagnesemia with hypocalciuria</span> and those encoding the &#945; subunit cause <span class="elsevierStyleItalic">hypomagnesemia with seizures</span> and type 2 intellectual disability&#41;&#46; Hepatocyte nuclear transcription factor 1 &#40;HNF1&#946;&#41; regulates transcription of the gene encoding the &#611;-subunit of the Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase &#40;mutations in the coding gene produce <span class="elsevierStyleItalic">HNF1</span>&#946; <span class="elsevierStyleItalic">nephropathy</span>&#41;&#46; The coactivator <span class="elsevierStyleItalic">pterin-4-alpha-carbinolamine dehydratase 1</span> &#40;PCBD1&#41; is a cofactor of HNF1&#946; and increases the transcriptional activity of the&#947; subunit of Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase &#40;mutations in the coding gene produce <span class="elsevierStyleItalic">transient neonatal hyperphenylalaninemia with primapterinuria</span>&#41;&#46; FAM111A is a regulator of certain nuclear transcription factors &#40;heterozygous missense mutations in the coding gene cause <span class="elsevierStyleItalic">Kenny-Caffey syndrome type 2</span> which can present with hypomagnesemia&#41;&#46; In the distal tubule&#44; the reabsorption of Mg<span class="elsevierStyleSup">2&#43;</span> is an active transport process by transcellular routes&#44; driven by the potential difference between the tubular lumen and the interior of the cell&#46; Mg<span class="elsevierStyleSup">2&#43;</span> ions pass from the tubular lumen to the cytosol via the apical TRPM6&#47;TRPM7 channel &#40;mutations in the TRPM6 and TRPM7 coding genes produce <span class="elsevierStyleItalic">hypomagnesemia with autosomal recessive secondary hypocalcemia type 1 and type 2&#44; respectively</span>&#41;&#46; Mg<span class="elsevierStyleSup">2&#43;</span> ions may exit the cell via CNNM2 &#40;mutations in the coding gene produce <span class="elsevierStyleItalic">hypomagnesemia with seizures and</span> intellectual disability type 1&#41; and the Mg<span class="elsevierStyleSup">2&#43;</span> exchanger&#47;Na<span class="elsevierStyleSup">&#43;</span> SLC41A1 &#40;mutations in the coding gene produce a nephronophthisis-like phenotype&#41;&#46; <span class="elsevierStyleItalic">Epidermal growth factor</span> &#40;EGF&#41; is an activator of the TRPM6 channel &#40;mutations in the coding gene produce <span class="elsevierStyleItalic">autosomal recessive hypomagnesemia</span>&#59; mutations in the EGF receptor &#91;EGFR&#93; produce <span class="elsevierStyleItalic">neonatal inflammatory skin and bowel disease type 2</span>&#41;&#46; The apical force required for Mg<span class="elsevierStyleSup">2&#43;</span> transport is created by the cooperative action of the basolateral Na<span class="elsevierStyleSup">&#43;</span>&#44; K<span class="elsevierStyleSup">&#43;</span>-ATPase&#44; the chloride channel ClC-Kb&#44; the heteromeric channel Kir4&#46;1&#47;Kir5&#46;1 that recycles K<span class="elsevierStyleSup">&#43;</span> &#40;mutations in the gene encoding Kir 4&#46;1 produce <span class="elsevierStyleItalic">EAST&#47;SeSAME</span> syndrome&#41;&#44; the NCC and K<span class="elsevierStyleSup">&#43;</span> extruding channels&#44; ROMK &#40;Kir1&#46;1&#41; &#40;mutations in the coding gene produce <span class="elsevierStyleItalic">Bartter syndrome type II</span>&#41; and Kv1&#46;1 &#40;mutations in the coding gene produce <span class="elsevierStyleItalic">autosomal dominant hypomagnesemia or episodic ataxia type 1&#41;</span>&#46; Note&#58; the names of the coding genes are not included here as they are given in the text&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1791
            "Ancho" => 3175
            "Tamanyo" => 511606
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Diagnostic algorithm for hypomagnesemias based on calcium and calciuria levels&#46; Abnormal transporters &#40;AD&#58; autosomal dominant&#59; ABB&#58; acid&#8211;base balance&#41; are shown in parentheses in most cases&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:62 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hyperplasia of the yuxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "F&#46;C&#46; Bartter"
                            1 => "P&#46; Pronove"
                            2 => "J&#46;R&#46; Gill Jr"
                            3 => "R&#46;C&#46; MacCardle"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/0002-9343(62)90214-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med"
                        "fecha" => "1962"
                        "volumen" => "33"
                        "paginaInicial" => "811"
                        "paginaFinal" => "828"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13969763"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A new familial disorder characterized by hypokalemia and hypomagnesemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H&#46;J&#46; Gitelman"
                            1 => "J&#46;B&#46; Graham"
                            2 => "L&#46;G&#46; Welt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Trans Assoc Am Physicians"
                        "fecha" => "1966"
                        "volumen" => "79"
                        "paginaInicial" => "221"
                        "paginaFinal" => "235"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5929460"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Primary hypomagnesemia with secondary hypocalcemia in an infant"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "L&#46; Paunier"
                            1 => "I&#46;C&#46; Radde"
                            2 => "S&#46;W&#46; Kooh"
                            3 => "P&#46;E&#46; Conen"
                            4 => "D&#46; Fraser"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatrics"
                        "fecha" => "1968"
                        "volumen" => "41"
                        "paginaInicial" => "385"
                        "paginaFinal" => "402"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5637791"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tetany due to hypomagnesaemia with secondary hypocalcaemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Vainsel"
                            1 => "G&#46; Vandevelde"
                            2 => "J&#46; Smulders"
                            3 => "M&#46; Vosters"
                            4 => "P&#46; Hubain"
                            5 => "H&#46; Loeb"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/adc.45.240.254"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Dis Child"
                        "fecha" => "1970"
                        "volumen" => "45"
                        "paginaInicial" => "254"
                        "paginaFinal" => "258"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5419995"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incomplete distal renal tubular acidosis in hypomagnesemia-dependent hypocalcemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46; Passer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Intern Med"
                        "fecha" => "1976"
                        "volumen" => "136"
                        "paginaInicial" => "462"
                        "paginaFinal" => "466"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1267554"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Magnesium losing nephropathy associated with hypomagnesemic tetany and nephrocalcinosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Alfrey"
                            1 => "D&#46; Jenkins"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Clin Res"
                        "fecha" => "1969"
                        "volumen" => "17"
                        "paginaInicial" => "128"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Decreased bicarbonate threshold and renal magnesium wasting in a sibship with distal renal tubular acidosis&#46; &#40;Evaluation of the pathophysiologic role of parathyroid hormone&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46;F&#46; Michelis"
                            1 => "A&#46;L&#46; Drash"
                            2 => "L&#46;G&#46; Linarelli"
                            3 => "F&#46;R&#46; De Rubertis"
                            4 => "B&#46;B&#46; Davis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/0026-0495(72)90025-x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Metabolism"
                        "fecha" => "1972"
                        "volumen" => "21"
                        "paginaInicial" => "905"
                        "paginaFinal" => "920"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5071957"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal magnesium wasting&#44; incomplete tubular acidosis&#44; hypercalciuria and nephrocalcinosis in siblings"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "F&#46; Manz"
                            1 => "K&#46; Sch&#228;rer"
                            2 => "P&#46; Janka"
                            3 => "J&#46; Lombeck"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/BF00496992"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Pediatr"
                        "fecha" => "1978"
                        "volumen" => "128"
                        "paginaInicial" => "67"
                        "paginaFinal" => "79"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/668721"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Idiopathic hypercalciuria with bilateral macular colobomata&#58; a new variant of oculo-renal syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "W&#46; Meier"
                            1 => "A&#46; Blumberg"
                            2 => "W&#46; Imahorn"
                            3 => "F&#46; De Luca"
                            4 => "H&#46; Wildberger"
                            5 => "O&#46; Oetliker"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Helv Paediatr Acta"
                        "fecha" => "1979"
                        "volumen" => "34"
                        "paginaInicial" => "257"
                        "paginaFinal" => "269"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/500385"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hypomagnesaemia of hereditary renal origin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Rodr&#237;guez-Soriano"
                            1 => "A&#46; Vallo"
                            2 => "M&#46; Garc&#237;a-Fuentes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/BF00849255"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Nephrol"
                        "fecha" => "1987"
                        "volumen" => "1"
                        "paginaInicial" => "465"
                        "paginaFinal" => "472"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3153319"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Familial hypomagnesemia with hypercalciuria and nephrocalcinosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Praga"
                            1 => "J&#46; Vara"
                            2 => "E&#46; Gonz&#225;lez-Parra"
                            3 => "A&#46; Andr&#233;s"
                            4 => "C&#46; &#193;lamo"
                            5 => "A&#46; Araque"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ki.1995.199"
                      "Revista" => array:5 [
                        "tituloSerie" => "Kidney Int"
                        "fecha" => "1995"
                        "volumen" => "47"
                        "paginaInicial" => "1419"
                        "paginaFinal" => "1425"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary kidney diseases associated with hypomagnesemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "F&#46; Claverie-Martin"
                            1 => "A&#46; Perdomo-Ramirez"
                            2 => "V&#46; Garcia-Nieto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.23876/j.krcp.21.112"
                      "Revista" => array:6 [
                        "tituloSerie" => "Kidney Res Clin Pract"
                        "fecha" => "2021"
                        "volumen" => "40"
                        "paginaInicial" => "512"
                        "paginaFinal" => "526"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34784661"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mutations in the chloride channel gene&#44; CLCNKB&#44; cause Bartter&#8217;s syndrome type III"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;B&#46; Simon"
                            1 => "R&#46;S&#46; Bindra"
                            2 => "T&#46;A&#46; Mansfield"
                            3 => "C&#46; Nelson-Williams"
                            4 => "E&#46; Mendonca"
                            5 => "R&#46; Stone"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ng1097-171"
                      "Revista" => array:5 [
                        "tituloSerie" => "Nat Genet"
                        "fecha" => "1997"
                        "volumen" => "17"
                        "paginaInicial" => "171"
                        "paginaFinal" => "178"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and genetic spectrum of Bartter syndrome type 3"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Seys"
                            1 => "O&#46; Andrini"
                            2 => "M&#46; Keck"
                            3 => "L&#46; Mansour-Hendili"
                            4 => "P&#46;Y&#46; Courand"
                            5 => "C&#46; Simian"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2016101057"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2017"
                        "volumen" => "28"
                        "paginaInicial" => "2540"
                        "paginaFinal" => "2552"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28381550"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanism of calcium transport stimulated by chlorothiazide in mouse distal convoluted tubule cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "F&#46;A&#46; Gesek"
                            1 => "P&#46;A&#46; Friedman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI115878"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "1992"
                        "volumen" => "90"
                        "paginaInicial" => "429"
                        "paginaFinal" => "438"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bartter&#8217;s syndrome&#58; evidence suggesting a distal tubular defect in a hypocalciuric variant of the syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46;A&#46;L&#46; Sutton"
                            1 => "V&#46; Marichak"
                            2 => "A&#46; Halebe"
                            3 => "G&#46;E&#46; Wilkins"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Miner Electrolyte Metab"
                        "fecha" => "1992"
                        "volumen" => "18"
                        "paginaInicial" => "43"
                        "paginaFinal" => "51"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1406504"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gitelman&#8217;s variant of Bartter&#8217;s syndrome&#44; inherited hypokalaemic alkalosis&#44; is caused by mutations in the thiazide-sensitive Na-Cl cotransporter"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;B&#46; Simon"
                            1 => "C&#46; Nelson-Williams"
                            2 => "M&#46;J&#46; Bia"
                            3 => "D&#46; Ellison"
                            4 => "F&#46;E&#46; Karet"
                            5 => "A&#46;M&#46; Molina"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ng0196-24"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Genet"
                        "fecha" => "1996"
                        "volumen" => "12"
                        "paginaInicial" => "24"
                        "paginaFinal" => "30"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8528245"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Enhanced passive Ca<span class="elsevierStyleSup">2&#43;</span> reabsorption and reduced Mg<span class="elsevierStyleSup">2&#43;</span> channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "T&#46; Nijenhuis"
                            1 => "V&#46; Vallon"
                            2 => "A&#46;W&#46; van der Kemp"
                            3 => "J&#46; Loffing"
                            4 => "J&#46;G&#46; Hoenderop"
                            5 => "R&#46;J&#46; Bindels"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI24134"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2005"
                        "volumen" => "115"
                        "paginaInicial" => "1651"
                        "paginaFinal" => "1658"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15902302"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6&#44; a new member of the TRPM gene family"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;P&#46; Schlingmann"
                            1 => "S&#46; Weber"
                            2 => "M&#46; Peters"
                            3 => "L&#46; Niemann Nejsum"
                            4 => "H&#46; Vitzthum"
                            5 => "K&#46; Klingel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ng889"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Genet"
                        "fecha" => "2002"
                        "volumen" => "31"
                        "paginaInicial" => "166"
                        "paginaFinal" => "170"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12032568"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;Y&#46; Walder"
                            1 => "D&#46; Landau"
                            2 => "P&#46; Meyer"
                            3 => "H&#46; Shalev"
                            4 => "M&#46; Tsolia"
                            5 => "Z&#46; Borochowitz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ng901"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Genet"
                        "fecha" => "2002"
                        "volumen" => "31"
                        "paginaInicial" => "171"
                        "paginaFinal" => "174"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12032570"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Novel TRPM6 mutations in 21 families with primary hypomagnesemia and secondary hypocalcemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;P&#46; Schlingmann"
                            1 => "M&#46;C&#46; Sassen"
                            2 => "S&#46; Weber"
                            3 => "U&#46; Pechmann"
                            4 => "K&#46; Kusch"
                            5 => "L&#46; Pelken"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2004110989"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2005"
                        "volumen" => "16"
                        "paginaInicial" => "3061"
                        "paginaFinal" => "3069"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hypomagnesemia with secondary hypocalcemia due to a missense mutation in the putative pore-forming region of TRPM6"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46; Chubanov"
                            1 => "K&#46;P&#46; Schlingmann"
                            2 => "J&#46; W&#228;ring"
                            3 => "J&#46; Heinzinger"
                            4 => "S&#46; Kaske"
                            5 => "S&#46; Waldegger"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.M611117200"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2007"
                        "volumen" => "282"
                        "paginaInicial" => "7656"
                        "paginaFinal" => "7667"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17197439"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A critical role of TRPM channel-kinase for human magnesium transport"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46;P&#46; Schlingmann"
                            1 => "T&#46; Gudermann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1113/jphysiol.2004.080200"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Physiol"
                        "fecha" => "2005"
                        "volumen" => "566"
                        "paginaInicial" => "301"
                        "paginaFinal" => "308"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15845589"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Paracellin-1&#44; a renal tight junction protein required for paracellular Mg<span class="elsevierStyleSup">2&#43;</span> resorption"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;B&#46; Simon"
                            1 => "Y&#46; Lu"
                            2 => "K&#46;A&#46; Choate"
                            3 => "H&#46; Vel&#225;zquez"
                            4 => "E&#46; Al-Sabban"
                            5 => "M&#46; Praga"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.285.5424.103"
                      "Revista" => array:6 [
                        "tituloSerie" => "Science"
                        "fecha" => "1999"
                        "volumen" => "285"
                        "paginaInicial" => "103"
                        "paginaFinal" => "106"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10390358"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A novel claudin 16 mutation associated with childhood hypercalciuria abolished binding to ZO-1 and results in lysosomal mistargeting"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; M&#252;ller"
                            1 => "J&#46; Kausalya"
                            2 => "F&#46; Claverie-Martin"
                            3 => "I&#46;C&#46; Meij"
                            4 => "P&#46; Eggert"
                            5 => "V&#46; Garc&#237;a-Nieto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/380418"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hum Genet"
                        "fecha" => "2003"
                        "volumen" => "73"
                        "paginaInicial" => "1293"
                        "paginaFinal" => "1301"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14628289"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Familial hypomagnesemia with hypercalciuria and nephrocalcinosis non associated to mutations in gene <span class="elsevierStyleItalic">CLDN16</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "V&#46; Garc&#237;a Nieto"
                            1 => "H&#46; Gonz&#225;lez Acosta"
                            2 => "M&#46;C&#46; Vega Hern&#225;ndez"
                            3 => "M&#46;I&#46; Luis Yanes"
                            4 => "L&#46; Espinosa"
                            5 => "F&#46; Claverie Mart&#237;n"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Pediatr Nephrol"
                        "fecha" => "2007"
                        "volumen" => "22"
                        "paginaInicial" => "1069"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mutations in the tight-junction gene claudin 19 &#40;<span class="elsevierStyleItalic">CLDN 19</span>&#41; are associated with renal magnesium wasting&#44; renal failure and severe ocular involvement"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Konrad"
                            1 => "A&#46; Schaller"
                            2 => "D&#46; Seelow"
                            3 => "A&#46;V&#46; Pandey"
                            4 => "S&#46; Waldegger"
                            5 => "A&#46; Lesslauer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/508617"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hum Genet"
                        "fecha" => "2006"
                        "volumen" => "79"
                        "paginaInicial" => "949"
                        "paginaFinal" => "957"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17033971"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Renal localization and function of the tight junction protein&#44; claudin-19"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Angelow"
                            1 => "R&#46; El-Husseini"
                            2 => "S&#46;A&#46; Kanzawa"
                            3 => "A&#46;S&#46; Yu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajprenal.00087.2007"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Physiol Renal Physiol"
                        "fecha" => "2007"
                        "volumen" => "293"
                        "paginaInicial" => "F166"
                        "paginaFinal" => "F177"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17389678"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Hou"
                            1 => "A&#46; Renigunta"
                            2 => "M&#46; Konrad"
                            3 => "A&#46;S&#46; Gomes"
                            4 => "E&#46;E&#46; Schneeberger"
                            5 => "D&#46;L&#46; Paul"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI33970"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2008"
                        "volumen" => "118"
                        "paginaInicial" => "619"
                        "paginaFinal" => "628"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18188451"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The biology of epithelial cell tight junctions in the kidney"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "B&#46;M&#46; Denker"
                            1 => "E&#46; Sabath"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2010090922"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2011"
                        "volumen" => "22"
                        "paginaInicial" => "622"
                        "paginaFinal" => "625"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21415157"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Claudin-19 mutations and clinical phenotype in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Claverie-Mart&#237;n"
                            1 => "V&#46; Garc&#237;a-Nieto"
                            2 => "C&#46; Loris"
                            3 => "G&#46; Ariceta"
                            4 => "I&#46; Nadal"
                            5 => "L&#46; Espinosa"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0053151"
                      "Revista" => array:4 [
                        "tituloSerie" => "PLoS One"
                        "fecha" => "2013"
                        "volumen" => "8"
                        "paginaInicial" => "e53151"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Haplotype analysis of CLDN19 single nucleotide polymorphisms in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "E&#46; Martin-Nu&#241;ez"
                            1 => "E&#46; Cordoba-Lanus"
                            2 => "H&#46; Gonzalez-Acosta"
                            3 => "A&#46; Oliet"
                            4 => "E&#46; Izquierdo"
                            5 => "F&#46; Claverie-Martin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12519-014-0528-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "World J Pediatr"
                        "fecha" => "2015"
                        "volumen" => "11"
                        "paginaInicial" => "272"
                        "paginaFinal" => "275"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25410674"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hipomagnesemia familiar con hipercalciuria y nefrocalcinosis&#46; Su historia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "V&#46;M&#46; Garc&#237;a Nieto"
                            1 => "F&#46; Claverie-Mart&#237;n"
                            2 => "C&#46; Loris Pablo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3265/Nefrologia.pre2013.Nov.12230"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nefrolog&#237;a"
                        "fecha" => "2014"
                        "volumen" => "34"
                        "paginaInicial" => "5"
                        "paginaFinal" => "10"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24463860"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "In vivo formation of a proton-sensitive K<span class="elsevierStyleSup">&#43;</span> channel by heteromeric subunit assembly of Kir5&#46;1 with Kir4&#46;1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Tanemoto"
                            1 => "N&#46; Kittaka"
                            2 => "A&#46; Inanobe"
                            3 => "Y&#46; Kurachi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1469-7793.2000.00587.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Physiol"
                        "fecha" => "2000"
                        "volumen" => "525"
                        "paginaInicial" => "587"
                        "paginaFinal" => "592"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10856114"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epilepsy&#44; ataxia&#44; sensorineural deafness&#44; tubulopathy&#44; and KCNJ10 mutations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Bockenhauer"
                            1 => "S&#46; Feather"
                            2 => "H&#46;C&#46; Stanescu"
                            3 => "S&#46; Bandulik"
                            4 => "A&#46;A&#46; Zdebik"
                            5 => "M&#46; Reichold"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa0810276"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2009"
                        "volumen" => "360"
                        "paginaInicial" => "1960"
                        "paginaFinal" => "1970"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19420365"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Seizures&#44; sensorineural deafness&#44; ataxia&#44; mental retardation&#44; and electrolyte imbalance &#40;SeSAME syndrome&#41; caused by mutations in KCNJ10"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "U&#46;I&#46; Scholl"
                            1 => "M&#46; Choi"
                            2 => "T&#46; Liu"
                            3 => "V&#46;T&#46; Ramaekers"
                            4 => "M&#46;G&#46; H&#228;usler"
                            5 => "J&#46; Grimmer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.0901749106"
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci USA"
                        "fecha" => "2009"
                        "volumen" => "106"
                        "paginaInicial" => "5842"
                        "paginaFinal" => "5847"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19289823"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mutation in hepatocyte nuclear factor-1&#946; gene &#40;TCF2&#41; associated with MODY"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Horikawa"
                            1 => "N&#46; Iwasaki"
                            2 => "M&#46; Hara"
                            3 => "H&#46; Furuta"
                            4 => "Y&#46; Hinokio"
                            5 => "B&#46;N&#46; Cockburn"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ng1297-384"
                      "Revista" => array:5 [
                        "tituloSerie" => "Nat Genet"
                        "fecha" => "1997"
                        "volumen" => "17"
                        "paginaInicial" => "384"
                        "paginaFinal" => "385"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mutations in the hepatocyte nuclear factor-1&#946; gene are associated with familial hypoplastic glomerulocystic kidney disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Bingham"
                            1 => "M&#46;P&#46; Bulman"
                            2 => "S&#46; Ellard"
                            3 => "L&#46;I&#46; Allen"
                            4 => "G&#46;W&#46; Lipkin"
                            5 => "W&#46;G&#46; Hoff"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/316945"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hum Genet"
                        "fecha" => "2001"
                        "volumen" => "68"
                        "paginaInicial" => "219"
                        "paginaFinal" => "224"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11085914"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nefropat&#237;a HNF1&#946;&#46; Otra causa de p&#233;rdida renal distal de cloro y potasio &#40;CC17&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46;L&#46; Luis Yanes"
                            1 => "P&#46; Tejera Carre&#241;o"
                            2 => "T&#46; Moraleda Mesa"
                            3 => "L&#46; Madariaga"
                            4 => "A&#46; Garc&#237;a Casta&#241;o"
                            5 => "V&#46;M&#46; Garcia Nieto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Vox Paediatrica"
                        "fecha" => "2019"
                        "volumen" => "26"
                        "numero" => "Supl 1"
                        "paginaInicial" => "165"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association between activating mutations of calcium-sensing receptor and Bartter&#8217;s syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Watanabe"
                            1 => "S&#46; Fukumoto"
                            2 => "H&#46; Chang"
                            3 => "Y&#46; Takeuchi"
                            4 => "Y&#46; Hasegawa"
                            5 => "R&#46; Okazaki"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(02)09842-2"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2002"
                        "volumen" => "360"
                        "paginaInicial" => "692"
                        "paginaFinal" => "694"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12241879"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Functional characterization of a calcium-sensing receptor mutation in severe autosomal dominant hypocalcemia with a Bartter-like syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Vargas-Poussou"
                            1 => "C&#46; Huang"
                            2 => "P&#46; Hulin"
                            3 => "P&#46; Houillier"
                            4 => "X&#46; Jeunemaitre"
                            5 => "M&#46; Paillard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.asn.0000025781.16723.68"
                      "Revista" => array:5 [
                        "tituloSerie" => "Am Soc Nephrol"
                        "fecha" => "2002"
                        "volumen" => "13"
                        "paginaInicial" => "2259"
                        "paginaFinal" => "2266"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dominant isolated renal magnesium loss is caused by misrouting of the Na&#40;&#43;&#41;K&#40;&#43;&#41;-ATPase gamma-subunit"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "I&#46;C&#46; Meij"
                            1 => "J&#46;B&#46; Koenderink"
                            2 => "H&#46; van Bokhoven"
                            3 => "K&#46;F&#46; Assink"
                            4 => "W&#46;T&#46; Groenestege"
                            5 => "J&#46;J&#46; de Pont"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/81543"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Genet"
                        "fecha" => "2000"
                        "volumen" => "26"
                        "paginaInicial" => "265"
                        "paginaFinal" => "266"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11062458"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recurrent FXYD2 p&#46;Gly41Arg mutation in patients with isolated dominant hypomagnesaemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;H&#46; de Baaij"
                            1 => "E&#46;M&#46; Dorresteijn"
                            2 => "E&#46;A&#46; Hennekam"
                            3 => "E&#46;J&#46; Kamsteeg"
                            4 => "R&#46; Meijer"
                            5 => "K&#46; Dahan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfv014"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2015"
                        "volumen" => "30"
                        "paginaInicial" => "952"
                        "paginaFinal" => "957"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25765846"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "W&#46;M&#46; Groenestege"
                            1 => "S&#46; Thebault"
                            2 => "J&#46; van der Wijst"
                            3 => "D&#46; van den Berg"
                            4 => "R&#46; Janssen"
                            5 => "S&#46; Tejpar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI31680"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2007"
                        "volumen" => "117"
                        "paginaInicial" => "2260"
                        "paginaFinal" => "2267"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "EGF increases TRPM6 activity and surface expression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Thebault"
                            1 => "R&#46;T&#46; Alexander"
                            2 => "W&#46;M&#46; Tiel Groenestege"
                            3 => "J&#46;G&#46; Hoenderop"
                            4 => "R&#46;J&#46; Bindels"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2008030327"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2009"
                        "volumen" => "20"
                        "paginaInicial" => "78"
                        "paginaFinal" => "85"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19073827"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CNNM2&#44; encoding a basolateral protein required for renal Mg<span class="elsevierStyleSup">2&#43;</span> handling&#44; is mutated in dominant hypomagnesemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Stuiver"
                            1 => "S&#46; Lainez"
                            2 => "C&#46; Will"
                            3 => "S&#46; Terryn"
                            4 => "D&#46; Gunzel"
                            5 => "H&#46; Debaix"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ajhg.2011.02.005"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hum Genet"
                        "fecha" => "2011"
                        "volumen" => "88"
                        "paginaInicial" => "333"
                        "paginaFinal" => "343"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21397062"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Human gene SLC41A1 encodes for the Na<span class="elsevierStyleSup">&#43;</span>&#47;Mg&#178;<span class="elsevierStyleSup">&#43;</span> exchanger"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Kolisek"
                            1 => "A&#46; Nestler"
                            2 => "J&#46; Vormann"
                            3 => "M&#46; Schweigel-R&#246;ntgen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajpcell.00289.2011"
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Physiol Cell Physiol"
                        "fecha" => "2012"
                        "volumen" => "302"
                        "paginaInicial" => "C318"
                        "paginaFinal" => "C326"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mutation of the Mg<span class="elsevierStyleSup">2&#43;</span> transporter SLC41A1 results in a nephronophthisis-like phenotype"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;W&#46; Hurd"
                            1 => "E&#46;A&#46; Otto"
                            2 => "E&#46; Mishima"
                            3 => "H&#46;Y&#46; Gee"
                            4 => "H&#46; Inoue"
                            5 => "M&#46; Inazu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2012101034"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2013"
                        "volumen" => "24"
                        "paginaInicial" => "967"
                        "paginaFinal" => "977"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23661805"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "SLC41A1 is essential for magnesium homeostasis in vivo"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46;J&#46; Arjona"
                            1 => "F&#46; Latta"
                            2 => "S&#46;G&#46; Mohammed"
                            3 => "M&#46; Thomassen"
                            4 => "E&#46; van Wijk"
                            5 => "R&#46;J&#46;M&#46; Bindels"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00424-018-2234-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pflugers Arch"
                        "fecha" => "2019"
                        "volumen" => "471"
                        "paginaInicial" => "845"
                        "paginaFinal" => "860"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30417250"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Germline de novo mutations in <span class="elsevierStyleItalic">ATP1A1</span> cause renal hypomagnesemia&#44; refractory seizures&#44; and intellectual disability"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;P&#46; Schlingmann"
                            1 => "S&#46; Bandulik"
                            2 => "C&#46; Mammen"
                            3 => "M&#46; Tarailo-Graovac"
                            4 => "R&#46; Holm"
                            5 => "M&#46; Baumann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ajhg.2018.10.004"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hum Genet"
                        "fecha" => "2018"
                        "volumen" => "103"
                        "paginaInicial" => "808"
                        "paginaFinal" => "816"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30388404"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The human inward rectifier K&#40;&#43;&#41; channel subunit kir5&#46;1 &#40;KCNJ16&#41; maps to chromosome 17q25 and is expressed in kidney and pancreas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Liu"
                            1 => "E&#46; McKenna"
                            2 => "D&#46;J&#46; Figueroa"
                            3 => "R&#46; Blevins"
                            4 => "C&#46;P&#46; Austin"
                            5 => "P&#46;B&#46; Bennett"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000015662"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cytogenet Cell Genet"
                        "fecha" => "2000"
                        "volumen" => "90"
                        "paginaInicial" => "60"
                        "paginaFinal" => "63"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11060447"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Defects in KCNJ16 cause a novel tubulopathy with hypokalemia&#46; Salt wasting&#44; disturbed acid-base homeostasis&#44; and sensorineural deafness"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;P&#46; Schlingmann"
                            1 => "A&#46; Renigunta"
                            2 => "E&#46;J&#46; Hoorn"
                            3 => "A&#46;L&#46; Forst"
                            4 => "V&#46; Renigunta"
                            5 => "V&#46; Atanasov"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2020111587"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2021"
                        "volumen" => "32"
                        "paginaInicial" => "1498"
                        "paginaFinal" => "1512"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33811157"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Episodic ataxia&#47;myokymia syndrome is associated with point mutations in the human potassium channel gene&#44; KCNA1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;L&#46; Browne"
                            1 => "S&#46;T&#46; Gancher"
                            2 => "J&#46;G&#46; Nutt"
                            3 => "E&#46;R&#46; Brunt"
                            4 => "E&#46;A&#46; Smith"
                            5 => "P&#46; Kramer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/ng1094-136"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Genet"
                        "fecha" => "1994"
                        "volumen" => "8"
                        "paginaInicial" => "136"
                        "paginaFinal" => "140"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7842011"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A missense mutation in the Kv1&#46;1 voltage-gated potassium channel-encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Glaudemans"
                            1 => "J&#46; van der Wijst"
                            2 => "R&#46;H&#46; Scola"
                            3 => "P&#46;J&#46; Lorenzoni"
                            4 => "A&#46; Heister"
                            5 => "A&#46;W&#46; van der Kemp"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI36948"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2009"
                        "volumen" => "119"
                        "paginaInicial" => "936"
                        "paginaFinal" => "942"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19307729"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mutations in PCBD1 cause hypomagnesemia and renal magnesium wasting"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Ferr&#232;"
                            1 => "J&#46;H&#46; de Baaij"
                            2 => "P&#46; Ferreira"
                            3 => "R&#46; Germann"
                            4 => "J&#46;B&#46; de Klerk"
                            5 => "M&#46; Lavrijsen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1681/ASN.2013040337"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Soc Nephrol"
                        "fecha" => "2014"
                        "volumen" => "25"
                        "paginaInicial" => "574"
                        "paginaFinal" => "586"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24204001"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "FAM111A mutations result in hypoparathyroidism and impaired skeletal development"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Unger"
                            1 => "M&#46;W&#46; G&#243;rna"
                            2 => "A&#46; Le B&#233;chec"
                            3 => "S&#46; Do Vale-Pereira"
                            4 => "M&#46;F&#46; Bedeschi"
                            5 => "S&#46; Geiberger"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ajhg.2013.04.020"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Hum Genet"
                        "fecha" => "2013"
                        "volumen" => "92"
                        "paginaInicial" => "990"
                        "paginaFinal" => "995"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23684011"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A recurrent de novo FAM111A mutation causes Kenny-Caffey syndrome type 2"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46; Isojima"
                            1 => "K&#46; Doi"
                            2 => "J&#46; Mitsui"
                            3 => "Y&#46; Oda"
                            4 => "E&#46; Tokuhiro"
                            5 => "A&#46; Yasoda"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jbmr.2091"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Bone Miner Res"
                        "fecha" => "2014"
                        "volumen" => "29"
                        "paginaInicial" => "992"
                        "paginaFinal" => "998"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23996431"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Estenosis tubular diafisaria &#40;s&#237;ndrome de Kenny-Caffey&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Sarr&#237;a"
                            1 => "F&#46; Toledo"
                            2 => "J&#46; Toledo"
                            3 => "M&#46;L&#46; Vega"
                            4 => "S&#46; L&#243;pez"
                            5 => "M&#46; Bueno"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "An Esp Pediatr"
                        "fecha" => "1980"
                        "volumen" => "13"
                        "paginaInicial" => "373"
                        "paginaFinal" => "380"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7406361"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Disruption of TRPM6&#47;TRPM7 complex formation by a mutation in the TRPM6 gene causes hypomagnesemia with secondary hypocalcemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "V&#46; Chubanov"
                            1 => "S&#46; Waldegger"
                            2 => "Mederos"
                            3 => "M&#46; Schnitzler"
                            4 => "H&#46; Vitzthum"
                            5 => "M&#46;C&#46; Sassen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1073/pnas.0305252101"
                      "Revista" => array:6 [
                        "tituloSerie" => "Proc Natl Acad Sci USA"
                        "fecha" => "2004"
                        "volumen" => "101"
                        "paginaInicial" => "2894"
                        "paginaFinal" => "2899"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14976260"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Electroacupuncture regulates TRPM7 expression through the trkA&#47;PI3K pathway after cerebral ischemia reperfusion in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "L&#46; Zhao"
                            1 => "Y&#46; Wang"
                            2 => "N&#46; Sun"
                            3 => "X&#46; Liu"
                            4 => "L&#46; Li"
                            5 => "J&#46; Shi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.lfs.2007.08.034"
                      "Revista" => array:6 [
                        "tituloSerie" => "Life Sci"
                        "fecha" => "2007"
                        "volumen" => "81"
                        "paginaInicial" => "1211"
                        "paginaFinal" => "1222"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17904584"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Possible role for rare TRPM7 variants in patients with hypomagnesemia with secondary hypocalcemia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Vargas-Poussou"
                            1 => "F&#46; Claverie-Martin"
                            2 => "C&#46; Prot-Bertoye"
                            3 => "V&#46; Carotti"
                            4 => "J&#46; van der Wijst"
                            5 => "A&#46; Perdomo-Ramirez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfac182"
                      "Revista" => array:3 [
                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2022"
                        "paginaInicial" => "gfac182"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Case report&#58; recurrent hemiplegic migraine attacks accompanied by intractable hypomagnesemia due to a <span class="elsevierStyleItalic">de novo TRPM7</span> gene variant"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Lei"
                            1 => "P&#46; Wang"
                            2 => "H&#46; Li"
                            3 => "X&#46; Liu"
                            4 => "J&#46; Shu"
                            5 => "Q&#46; Zhang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fped.2022.880242"
                      "Revista" => array:5 [
                        "tituloSerie" => "Front Pediatr"
                        "fecha" => "2022"
                        "volumen" => "10"
                        "paginaInicial" => "880242"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35712613"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/20132514/0000004400000001/v1_202403090635/S2013251424000452/v1_202403090635/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "35443"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Reviews"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/20132514/0000004400000001/v1_202403090635/S2013251424000452/v1_202403090635/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251424000452?idApp=UINPBA000064"
]

Información del artículo

ISSN: 20132514
Idioma original: Inglés

DOI:10.1016/j.nefroe.2024.02.003

Datos actualizados diariamente

año/Mes	Html	Pdf	Total

2024 Octubre	61	38	99
2024 Septiembre	115	60	175
2024 Agosto	99	96	195
2024 Julio	121	57	178
2024 Junio	125	74	199
2024 Mayo	154	78	232
2024 Abril	471	115	586
2024 Marzo	348	76	424
2024 Febrero	79	51	130

Indexada en:

Síguenos:

Estadísticas

Indexada en:

Síguenos:

Estadísticas

Suscríbase a la newsletter