Letter to the Editor
Alogliptin and tubulointerstitial nephritis: A potential complication
Alogliptina y nefritis tubulointersticial: una complicación potencial
Byron Chiliquinga Moralesa,
, Carmen Martin Varasa, Leonardo Calle Garcíaa, Astrid Rodríguez Gómeza, Carlos Santos Alonsoa, Pablo Sánchez Garrotea, Paulo García Gutiérreza, Nieves Losada de la Rosaa, María José Fernández-Reyes Luisa, Ana Saiz Gonzálezb, Angie Tenelanda Santillanb
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array:21 [ "pii" => "S2013251424001901" "issn" => "20132514" "doi" => "10.1016/j.nefroe.2024.10.008" "estado" => "S200" "fechaPublicacion" => "2024-10-31" "aid" => "1253" "copyrightAnyo" => "2024" "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "cor" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0211699524000286" "issn" => "02116995" "doi" => "10.1016/j.nefro.2024.03.006" "estado" => "S300" "fechaPublicacion" => "2024-09-01" "aid" => "1253" "copyright" => "Sociedad Española de Nefrología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Nefrologia. 2024;44:755-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Director</span>" "titulo" => "Alogliptina y nefritis tubulointersticial: una complicación potencial" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "755" "paginaFinal" => "757" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Alogliptin and tubulointerstitial nephritis: A potential complication" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 537 "Ancho" => 755 "Tamanyo" => 152336 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">En el intersticio se identifica prominente infiltrado inflamatorio polimorfo, constituido por abundantes leucocitos polimorfonucleares, linfocitos, células plasmáticas y ocasionales eosinófilos con imágenes de tubulitis. Parénquima renal con datos morfológicos compatibles con una nefropatía intersticial aguda y necrosis tubular aguda con cambios regenerativos. Tinción PAS (ácido peryódico de Schiff), ×400.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Byron Chiliquinga Morales, Carmen Martin Varas, Leonardo Calle Garcia, Astrid Rodríguez Gómez, Carlos Santos Alonso, Pablo Sánchez Garrote, Paulo Garcia Gutierrez, Nieves Losada de la Rosa, María José Fernández-Reyes Luis, Ana Saiz González, Angie Tenelanda Santillan" "autores" => array:11 [ 0 => array:2 [ "nombre" => "Byron" "apellidos" => "Chiliquinga Morales" ] 1 => array:2 [ "nombre" => "Carmen" "apellidos" => "Martin Varas" ] 2 => array:2 [ "nombre" => "Leonardo" "apellidos" => "Calle Garcia" ] 3 => array:2 [ "nombre" => "Astrid" "apellidos" => "Rodríguez Gómez" ] 4 => array:2 [ "nombre" => "Carlos" "apellidos" => "Santos Alonso" ] 5 => array:2 [ "nombre" => "Pablo" "apellidos" => "Sánchez Garrote" ] 6 => array:2 [ "nombre" => "Paulo" "apellidos" => "Garcia Gutierrez" ] 7 => array:2 [ "nombre" => "Nieves" "apellidos" => "Losada de la Rosa" ] 8 => array:2 [ "nombre" => "María José" "apellidos" => "Fernández-Reyes Luis" ] 9 => array:2 [ "nombre" => "Ana Saiz" "apellidos" => "González" ] 10 => array:2 [ "nombre" => "Angie" "apellidos" => "Tenelanda Santillan" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2013251424001901" "doi" => "10.1016/j.nefroe.2024.10.008" "estado" => "S200" "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/S2013251424001901?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699524000286?idApp=UINPBA000064" "url" => "/02116995/0000004400000005/v1_202409110539/S0211699524000286/v1_202409110539/es/main.assets" ] ] "itemAnterior" => array:18 [ "pii" => "S201325142300024X" "issn" => "20132514" "doi" => "10.1016/j.nefroe.2023.02.001" "estado" => "S200" "fechaPublicacion" => "2023-02-27" "aid" => "5004" "copyright" => "Sociedad Española de Nefrología" "documento" => "simple-article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "err" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:9 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Erratum</span>" "titulo" => "Erratum to “Recommendations for living donor kidney transplantation”" "tienePdf" => "en" "tieneTextoCompleto" => "en" "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fe de errores de “Recomendaciones para el trasplante renal de donante vivo”" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Miguel Ángel Frutos, Marta Crespo, María de la Oliva Valentín, Ángel Alonso-Melgar, Juana Alonso, Constantino Fernández, Gorka García-Erauzkin, Esther González, Ana M. 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[ "autoresLista" => "Byron Chiliquinga Morales, Carmen Martin Varas, Leonardo Calle García, Astrid Rodríguez Gómez, Carlos Santos Alonso, Pablo Sánchez Garrote, Paulo García Gutiérrez, Nieves Losada de la Rosa, María José Fernández-Reyes Luis, Ana Saiz González, Angie Tenelanda Santillan" "autores" => array:11 [ 0 => array:4 [ "nombre" => "Byron" "apellidos" => "Chiliquinga Morales" "email" => array:1 [ 0 => "byronchm94@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Carmen" "apellidos" => "Martin Varas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Leonardo" "apellidos" => "Calle García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" 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class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "María José" "apellidos" => "Fernández-Reyes Luis" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 9 => array:3 [ "nombre" => "Ana Saiz" "apellidos" => "González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 10 => array:3 [ "nombre" => "Angie" "apellidos" => "Tenelanda Santillan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital General de Segovia, Segovia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Ramón y Cajal, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Alogliptina y nefritis tubulointersticial: una complicación potencial" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 537 "Ancho" => 755 "Tamanyo" => 152336 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The interstitium shows a prominent polymorphous inflammatory infiltrate consisting of abundant polymorphonuclear leucocytes, lymphocytes, plasma cells and occasional eosinophils with images of tubulitis. Renal parenchyma with morphological data consistent with acute interstitial nephropathy and acute tubular necrosis with regenerative changes. PAS (periodic acid-schiff) stain, ×400.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Alogliptin is one of the dipeptidyl-peptidase 4 (DPP4) inhibitors used in the treatment of type 2 diabetes mellitus. Acute pancreatitis, as well as hypersensitivity reactions and allergic reactions such as rash or pruritus have been reported as side effects. However, there are very few reported cases of renal adverse effects. Renal adverse reactions include isolated cases of acute interstitial nephritis associated with DPP4 inhibitors.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 57-year-old female patient with a history of type 2 diabetes mellitus, being evaluated in the outpatient internal medicine department for constitutional syndrome of one and a half month duration. She was urgently admitted to the nephrology department after detecting creatinine levels of 5.1 mg/dl in a blood test carried out prior to the consultation. The patient exhibited no cardiovascular symptoms and was haemodynamically stable with a tendency to hypertension, 160/80 mmHg, heart rate 96 bpm and normal blood volume. In the Emergency room, impairement of renal function was confirmed, with potassium 4.6 mmol/l, sodium 138.6 mmol/l, pH 7.27, bicarbonate 18.4 mmol/l, pCO<span class="elsevierStyleInf">2</span> 40 mmHg and lactate 0.9 mmol/l. The patient’s urinalysis and urinary sediment were normal, with proteinuria of less than 0.3 g/24 h, suggestive of tubulointerstitial damage.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Investigation of impaired renal function (autoimmunity, serology, complement and immunoglobulins) was extended and all were negative. Renal biopsy confirmed morphological data consistent with acute tubulointerstitial nephropathy and acute tubular necrosis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). With these findings, pulses of 250 mg methylprednisolone were started for three days followed by oral prednisone at a tapering dose of 1 mg/kg. After ruling out other possible causes of tubulointerstitial nephritis and conducting a thorough review of the patient’s usual medication, we were able to relate the onset of symptoms and impaired renal function to the start of treatment with alogliptin. After starting corticosteroid therapy and discontinuing alogliptin, the patient’s renal function progressively improved, with Cr 2.5 mg/dl upon hospital discharge. She is currently on outpatient follow-up at our clinic; renal function has been restored to previous values, recording 1.2 mg/dl at the last creatinine check (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). We classified this adverse drug reaction as probable, according to the WHO causality criteria, as it had a reasonable time relationship between the clinical manifestations and drug intake, could not be attributed to other causes or medications, and responded favourably to drug withdrawal.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">In our patient’s case, the clinical presentation of tubulointerstitial nephritis was not classic, as she did not have skin rash, eosinophilia or joint pain.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–5</span></a> Our patient’s condition began with rapidly progressive renal failure accompanied by weight loss and asthenia. Other diseases and recent medication that could have triggered the condition were ruled out, with the most likely cause of tubulointerstitial nephritis being the initiation of alogliptin as an oral antidiabetic agent.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Reviewing the literature, there are very few reported cases of adverse reactions to alogliptin compared to other DPP4 inhibitors, such as sitagliptin. Evidence supports starting corticosteroid therapy when renal function does not improve despite drug withdrawal and while awaiting renal biopsy results.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> In our case, given the severity of the patient’s renal failure, it was decided to start corticosteroid therapy early<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a> after withdrawal of alogliptin and until the result was confirmed by the renal biopsy report. As a result, the patient experienced a marked clinical improvement and her renal function returned to its previous values.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Given that this is a rarely described adverse reaction and that these are commonly-used drugs, we believe it is important to consider the involvement of these drugs in patients presenting with acute renal failure in relation to tubulointerstitial nephritis.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "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" => 537 "Ancho" => 755 "Tamanyo" => 152336 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The interstitium shows a prominent polymorphous inflammatory infiltrate consisting of abundant polymorphonuclear leucocytes, lymphocytes, plasma cells and occasional eosinophils with images of tubulitis. Renal parenchyma with morphological data consistent with acute interstitial nephropathy and acute tubular necrosis with regenerative changes. PAS (periodic acid-schiff) stain, ×400.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The table shows changes in the patient’s renal function and treatment received in chronological order.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Month \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Creatinine (mg/dl) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">December 2022 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">February 2023 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alogliptin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">March 2023 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">May 2023 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Alogliptin discontinued \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Methylprednisolone 250 mg IV \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">June 2023 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prednisone 1 mg/kg PO \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">July 2023 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">October 2023 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3708962.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Changes in renal function.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rare allergic reaction of the kidney: sitagliptin-induced acute tubulointerstitial nephritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.A. 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