Letter to the Editor – Brief Case Reports
Ibuprofen-induced acute interstitial nephritis in the paediatric population
Nefritis intersticial aguda por ibuprofeno en población pediátrica
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"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" => 3462 "Ancho" => 2390 "Tamanyo" => 405309 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical course: laboratory data and treatment. Corticosteroid therapy was started with intravenous administration of methylprednisolone (1000<span class="elsevierStyleHsp" style=""></span>mg/day for 3 days) followed by oral prednisolone and an initial dosage of 60<span class="elsevierStyleHsp" style=""></span>mg/day. This dosage was maintained until the 53rd day after admission, with posterior tapering. Rituximab (arrows) was administered at a dose of 600<span class="elsevierStyleHsp" style=""></span>mg (375<span class="elsevierStyleHsp" style=""></span>mg/m2) on the 27th, 34th, 41st and 48th days after admission. Cyclophosphamide (arrowhead) was administered in a single dose of 1000<span class="elsevierStyleHsp" style=""></span>mg on the 61st day after admission (2nd day after readmission). Eculizumab was administered at a dose of 900<span class="elsevierStyleHsp" style=""></span>mg for a week for 4 weeks, started on the 158th day after admission, followed by a dosage of 1200<span class="elsevierStyleHsp" style=""></span>mg 1 week later an then a maintenance dose of 1200<span class="elsevierStyleHsp" style=""></span>mg every 2 weeks. This dosage is still being continued. We performed a total of 79 plasma exchange sessions. 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] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0211699515001599" "doi" => "10.1016/j.nefro.2015.08.008" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699515001599?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251416000249?idApp=UINPBA000064" "url" => "/20132514/0000003600000001/v2_201703300133/S2013251416000249/v2_201703300133/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor – Brief Case Reports</span>" "titulo" => "Ibuprofen-induced acute interstitial nephritis in the paediatric population" "tieneTextoCompleto" => true "saludo" => "To the Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "69" "paginaFinal" => "71" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Ana Belen Martínez-López, Olalla Álvarez Blanco, Augusto Luque de Pablos, María Dolores Morales San-José, Ana Rodríguez Sanchez de la Blanca" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Ana Belen" "apellidos" => "Martínez-López" "email" => array:1 [ 0 => "anabelen.martinez@salud.madrid.org" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Olalla" "apellidos" => "Álvarez Blanco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Augusto" "apellidos" => "Luque de Pablos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "María Dolores" "apellidos" => "Morales San-José" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Ana" "apellidos" => "Rodríguez Sanchez de la Blanca" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Sección de Nefrología Pediátrica, Servicio de Pediatría, Hospital General Universitario Gregorio Marañón, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Pediatría, Hospital General Universitario Gregorio Marañón, 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" => "Nefritis intersticial aguda por ibuprofeno en población pediátrica" ] ] "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" => 1951 "Ancho" => 1653 "Tamanyo" => 179260 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Changes over time in urea and creatinine levels.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acute tubulointerstitial nephritis (ATIN) leads to acute kidney damage; it has a low incidence in the paediatric population<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1,2</span></a> and is present in up to 15% of renal biopsies performed in adults for acute kidney damage.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Currently, the most common cause of ATIN is drugs. Other causes include infection, immunological disease (such as systemic lupus erythematosus or Sjögren's syndrome), and sometimes the cause is unknown.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> Several groups of drugs have been identified as ethiological agents: antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs), which are extensively used in routine clinical practice, are among the most frequently implicated in ATIN.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present 3 cases of paediatric patients with non-oliguric acute kidney damage, seen in our department between 2008 and 2010, with a working diagnosis of NSAID-induced (ibuprofen) ATIN.</p><p id="par0015" class="elsevierStylePara elsevierViewall">None of the children had a past history of kidney disease or other past medical history of relevance, and all had had blood tests in the previous months with normal creatinine levels and the estimated glomerular filtration rate according to the original Schwartz formula<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> were normal. On physical examination, there were no signs of dehydration, blood pressures were normal for the patients’ age, sex, and height, and there was no oedema. There were no features of obstructive uropathy or evidence of glomerulopathy (C3 and C4 complement study, immunoglobulins, and ANA were normal). The 3 patients had received ibuprofen before developing kidney damage. The patients’ clinical characteristics and laboratory results are presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">On admission, ibuprofen treatment was stopped in patients 1 and 3. Patient 2, who was referred from another hospital, had stopped the medication 2 days before admission to our department. Once a diagnosis of ATIN was suspected, treatment was started with intravenous methylprednisolone boluses (15<span class="elsevierStyleHsp" style=""></span>mg/kg/day for 3 consecutive days, accounting for 250–500<span class="elsevierStyleHsp" style=""></span>mg iv/day of methylprednisolone) followed by oral prednisolone (starting dose 1<span class="elsevierStyleHsp" style=""></span>mg/kg/day) at a reducing dose, which was then stopped at 8 weeks. None of the patients had adverse effects attributable to steroids. Urea and creatinine returned to normal levels during the first week in all 3 cases (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Urinary biochemistry and sediment returned to normal within 6 months.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Drug-induced ATIN is the result of a cell-mediated hypersensitivity reaction to a drug. It occurs independently of the route of administration (intravenous, intramuscular, oral, or rectal)<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> and the duration of treatment.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> Patients who have had drug-induced ATIN should avoid further exposure to the drug, as recurrence is possible.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The clinical manifestations are variable, and the severity of symptoms varies from asymptomatic urinary abnormalities to acute kidney damage (oliguric or non-oliguric), which may require extra-renal replacement therapy. The classic manifestations (fever, rash, and arthralgia) are present in only 10% of cases<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a>; the most common manifestations are non-specific symptoms such as abdominal pain, vomiting, anorexia, weakness, or fever.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Urinalysis may show proteinuria (generally in the non-nephrotic range and predominantly tubular), haematuria, leukocytes, granular hyaline casts, and eosinophils (which are less common in the NSAID-induced ATIN). There may also be other clinical manifestations of tubular injury abnormalities depending on the segment affected (such as glycosuria, bicarbonaturia, tubular acidosis, inability to concentrate urine). A normal sediment does not exclude ATIN.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Ultrasound of the urinary system may show enlarged kidneys and increased echogenicity in the cortex.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> The gold standard for diagnosis is renal biopsy, which shows inflammatory cell infiltration of the renal interstitium (T lymphocytes, monocytes, macrophages plasma cells, eosinophils) along with local oedema and, occasionally, fibrosis. There may be tubulitis, and the vessels and glomeruli are usually normal.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> The first step in treatment is to stop the drug responsible and provide adequate supportive treatment for the degree of established kidney damage. Use of corticosteroids as part of the treatment has been debated for years; however, recent publications support their use because they have been demonstrated to improve the prognosis of renal function recovery. Therefore, starting treatment early is the main prognostic marker.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">10,11</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Renal biopsy is the investigation of choice to confirm the diagnosis. However, none of our patients underwent biopsy, because they progressed well clinically and biochemically once the responsible agent was stopped (immediately after the diagnosis was suspected) and corticosteroid treatment was started. The corticosteroid protocol used, by González et al, is described above.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a> The 3 patients showed a rapid response to treatment, and the outcome has been excellent. However, renal biopsy should be considered in cases that are slow to resolve or in case of diagnostic uncertainty.</p><p id="par0050" class="elsevierStylePara elsevierViewall">It is important to explore the past drug history in patients with acute renal failure without previous renal disease or signs of dehydration, and in whom ultrasound of the urinary tract has ruled out obstructive causes. The first step in the treatment of ATIN is to stop the causative drug and provide adequate supportive therapy. Early administration of corticosteroids once a diagnosis is suspected is associated with early resolution of renal failure.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Martínez-López AB, Álvarez Blanco O, Luque de Pablos A, Morales San-José MD, Rodríguez Sanchez de la Blanca A. Nefritis intersticial aguda por ibuprofeno en población pediátrica. Nefrologia. 2016;36:69–71.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1951 "Ancho" => 1653 "Tamanyo" => 179260 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Changes over time in urea and creatinine levels.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case number \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years), gender \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4, male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12, female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12, female \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weight (kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Reason for taking NSAIDs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Urethroplasty \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Headache \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Appendicectomy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Duration of NSAID (days), dose \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5<br>5<span class="elsevierStyleHsp" style=""></span>mg/kg/8<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3<br>10<span class="elsevierStyleHsp" style=""></span>mg/kg/8<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4<br>10<span class="elsevierStyleHsp" style=""></span>mg/kg/8<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vomiting, abdominal pain, weakness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Macroscopic haematuria and fever \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nausea, vomiting, loss of appetite \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline serum creatinine (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.51 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline urea (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Maximum creatinine (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Maximum urea (mg/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">140 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">182 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Urinalysis</td><td class="td" title="table-entry " align="left" valign="top">Some isolated red cells and white cells. No eosinophils \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100+ red cells/field and granular casts. No eosinophils \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1–2 leucocytes and 5–10 red cells/field. No eosinophils \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proteinuria with P:Cr ratio of 1.3<span class="elsevierStyleHsp" style=""></span>mg/mg and tubular component. Osmo 262<span class="elsevierStyleHsp" style=""></span>mOsm/kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Proteinuria with P:Cr ratio 1.9<span class="elsevierStyleHsp" style=""></span>mg/mg and tubular component. Osmo 453<span class="elsevierStyleHsp" style=""></span>mOsm/kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P:Cr ratio 0.3<span class="elsevierStyleHsp" style=""></span>mg/mg. Osmo 303<span class="elsevierStyleHsp" style=""></span>mOsm/kg \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Renal ultrasound \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Kidneys mildly enlarged.<br>Cortical hyperechogenicity and increased corticomedullary differentiation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diffuse parenchymal hyperechogenicity of both kidneys with loss of corticomedullary differentiation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diffuse cortical hyperechogenicity \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1381843.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Clinical details and investigations.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute tubulointerstitial nephritis in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "V. 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| Year/Month | Html | Total | |
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| 2024 November | 15 | 12 | 27 |
| 2024 October | 73 | 43 | 116 |
| 2024 September | 88 | 21 | 109 |
| 2024 August | 99 | 69 | 168 |
| 2024 July | 74 | 34 | 108 |
| 2024 June | 75 | 43 | 118 |
| 2024 May | 98 | 26 | 124 |
| 2024 April | 82 | 31 | 113 |
| 2024 March | 78 | 37 | 115 |
| 2024 February | 61 | 43 | 104 |
| 2024 January | 66 | 41 | 107 |
| 2023 December | 70 | 28 | 98 |
| 2023 November | 126 | 41 | 167 |
| 2023 October | 80 | 42 | 122 |
| 2023 September | 71 | 30 | 101 |
| 2023 August | 61 | 39 | 100 |
| 2023 July | 113 | 46 | 159 |
| 2023 June | 102 | 34 | 136 |
| 2023 May | 116 | 57 | 173 |
| 2023 April | 74 | 58 | 132 |
| 2023 March | 105 | 46 | 151 |
| 2023 February | 90 | 30 | 120 |
| 2023 January | 97 | 36 | 133 |
| 2022 December | 106 | 35 | 141 |
| 2022 November | 86 | 41 | 127 |
| 2022 October | 90 | 50 | 140 |
| 2022 September | 53 | 38 | 91 |
| 2022 August | 127 | 71 | 198 |
| 2022 July | 96 | 58 | 154 |
| 2022 June | 111 | 57 | 168 |
| 2022 May | 92 | 46 | 138 |
| 2022 April | 115 | 66 | 181 |
| 2022 March | 156 | 58 | 214 |
| 2022 February | 94 | 52 | 146 |
| 2022 January | 110 | 45 | 155 |
| 2021 December | 96 | 44 | 140 |
| 2021 November | 83 | 43 | 126 |
| 2021 October | 127 | 45 | 172 |
| 2021 September | 102 | 36 | 138 |
| 2021 August | 117 | 39 | 156 |
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| 2021 May | 156 | 37 | 193 |
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| 2021 March | 166 | 43 | 209 |
| 2021 February | 174 | 20 | 194 |
| 2021 January | 101 | 29 | 130 |
| 2020 December | 78 | 18 | 96 |
| 2020 November | 87 | 20 | 107 |
| 2020 October | 68 | 24 | 92 |
| 2020 September | 84 | 22 | 106 |
| 2020 August | 83 | 15 | 98 |
| 2020 July | 82 | 12 | 94 |
| 2020 June | 74 | 22 | 96 |
| 2020 May | 84 | 10 | 94 |
| 2020 April | 98 | 22 | 120 |
| 2020 March | 92 | 19 | 111 |
| 2020 February | 86 | 34 | 120 |
| 2020 January | 103 | 20 | 123 |
| 2019 December | 162 | 26 | 188 |
| 2019 November | 86 | 28 | 114 |
| 2019 October | 105 | 15 | 120 |
| 2019 September | 73 | 20 | 93 |
| 2019 August | 78 | 19 | 97 |
| 2019 July | 81 | 27 | 108 |
| 2019 June | 68 | 15 | 83 |
| 2019 May | 95 | 17 | 112 |
| 2019 April | 95 | 29 | 124 |
| 2019 March | 83 | 31 | 114 |
| 2019 February | 58 | 21 | 79 |
| 2019 January | 81 | 34 | 115 |
| 2018 December | 165 | 44 | 209 |
| 2018 November | 224 | 30 | 254 |
| 2018 October | 246 | 41 | 287 |
| 2018 September | 144 | 21 | 165 |
| 2018 August | 168 | 23 | 191 |
| 2018 July | 105 | 11 | 116 |
| 2018 June | 132 | 24 | 156 |
| 2018 May | 156 | 11 | 167 |
| 2018 April | 128 | 7 | 135 |
| 2018 March | 142 | 8 | 150 |
| 2018 February | 81 | 9 | 90 |
| 2018 January | 84 | 9 | 93 |
| 2017 December | 103 | 8 | 111 |
| 2017 November | 82 | 23 | 105 |
| 2017 October | 95 | 12 | 107 |
| 2017 September | 46 | 8 | 54 |
| 2017 August | 47 | 11 | 58 |
| 2017 July | 42 | 8 | 50 |
| 2017 June | 68 | 17 | 85 |
| 2017 May | 65 | 14 | 79 |
| 2017 April | 51 | 7 | 58 |
| 2017 March | 42 | 3 | 45 |
| 2017 February | 72 | 11 | 83 |
| 2017 January | 17 | 10 | 27 |
| 2016 December | 41 | 5 | 46 |
| 2016 November | 58 | 22 | 80 |
| 2016 October | 73 | 13 | 86 |
| 2016 September | 127 | 11 | 138 |
| 2016 August | 83 | 3 | 86 |
| 2016 July | 150 | 3 | 153 |
| 2016 June | 112 | 0 | 112 |
| 2016 May | 140 | 0 | 140 |
| 2016 April | 92 | 0 | 92 |
| 2016 March | 72 | 0 | 72 |
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