Acute renal failure secondary to interstitial acute nephritis and Fanconi syndrome due to metamizole and gemfibrozil

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"referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "María José" "apellidos" => "Gutiérrez-Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Luis" "apellidos" => "Pedraza-Cezón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital del Tajo, Aranjuez, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Farmacia, Hospital del Tajo, Aranjuez, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fracaso renal agudo por nefritis intersticial aguda con síndrome de Fanconi en relación con metamizol y gemfibrozilo" ] ] "textoCompleto" => "We present a case of acute interstitial nephropathy (AIN) associated with Fanconi syndrome, resolving after early treatment with steroids.A 49-year-old man with a past medical history of alcoholic pancreatitis and liver disease, hypertriglyceridemia, and hypertension (HTN) treated with gemfibrozil and valsartan for over one year.Two months ago, he had undergone an umbilical hernia repair. At that time, plasma creatinine was 0.79mg/dl and urinalysis was normal. He received a cephalosporin, and 3 weeks of analgesia in the form of metamizole and paracetamol, with complete recovery. Two weeks later, metamizole was restarted at a dose of 575mg/8h orally for flu-like symptoms. He developed progressive weakness, abdominal pain, and nausea. Oral intake was reduced and BP control worsened, therefore the doses of valsartan and metamizole were increased, with additional paracetamol as required. His general condition worsened, therefore he attended the emergency department where BP was 135/85. Skin and mucous membranes were dry, he was afebrile, with no skin lesions, and no other physical findings. He had a high urine output (3.5L/day), which was macroscopically normal. Blood tests showed a full blood count with no eosinophilia, metabolic acidosis with normal lactic acid, normal CK, reduced glomerular filtration rate (GFR), hypouricemia, and a mixed proteinuria of 1.4g/24h. Urinalysis revealed an alkaline pH, glycosuria with normoglycaemia, microhaematuria, isosthenuria, and the presence of granular hyaline casts.<a class="elsevierStyleCrossRefs" href="#bib0065">4,5</a> There was reduced tubular reabsorption of phosphate, potassium, calcium, and uric acid, and generalised hyperaminoaciduria. Abdominal ultrasound showed kidneys measuring 146mm with preserved corticomedullary differentiation and no signs of hydronephrosis. There were no abnormalities of the bladder or prostate. Viral serology and tumour markers were negative. Immunology was normal, including complement, ANA, ANCA, anti-GBM, and protein electrophoresis and immunoglobulins. Intact parathyroid hormone, 72pg/mL; 25-OH-vitamin D, 6.0ng/mL; ACE, normal Mantoux negative; and CXR, normal (investigation results, <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Pre-renal factors were corrected, but with no improvement in GFR, therefore renal biopsy was performed. This showed 13 glomeruli with no abnormalities, interstitial oedema, an intense lymphoid infiltrate accompanied with polymorphonuclear neutrophils and eosinophils, no granuloma, acute tubular necrosis, normal arteries and arterioles, and no complement or immune-complex deposits on direct immunofluorescence. A diagnosis was made of acute renal failure due to tubular necrosis and acute interstitial nephritis (AIN) secondary to metamizole, and Fanconi syndrome. Treatment was started with methylprednisolone 250mg/day for 3 days and was then switched to prednisone 1mg/kg/day at a reducing dose until it was stopped 12 weeks later, once the GFR had recovered and the tubular abnormalities had resolved.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Acute interstitial nephritis comprises 15–27% of findings in renal biopsy.<a class="elsevierStyleCrossRef" href="#bib0050">1</a> Recent years have seen a change in the clinical pattern and causative agents.<a class="elsevierStyleCrossRef" href="#bib0055">2</a> The observed incidence of AIN secondary to metamizole is 10.48 cases per 10,000 patient/year.<a class="elsevierStyleCrossRef" href="#bib0050">1</a> Although previously described,<a class="elsevierStyleCrossRef" href="#bib0060">3</a> it is not common to find a Fanconi-type proximal tubulopathy.In this case, features of AIN were found (isothenuria, non-nephrotic proteinuria, rapid deterioration of GFR) along with features typical of a proximal tubulopathy (metabolic acidosis, glycosuria with normoglycaemia, hyperphosphaturia, hyperuricosuria, and generalised hyperaminoaciduria). The main mechanism was direct immune-mediated tubular toxicity related to metamizole. The second mechanism was tubular necrosis secondary to renal vasoconstriction caused by the inhibition of prostaglandins by metamizole (inhibition of the enzyme COX-3) and gemfibrozole (stimulation of the peroxisome prolipherator-activated receptor PPAR-α<a class="elsevierStyleCrossRefs" href="#bib0075">6,7</a>), and by the inhibition of angiotensin II by valsartan. As in other studies,<a class="elsevierStyleCrossRef" href="#bib0065">4</a> renal failure developed between 1 and 3 weeks after taking the drug, was nonoliguric, without eosinophilia, skin changes, or fever, and with characteristic abdominal pain and proteinuria of around 1g/day. The absence of deposits on DIF and the fact that the patient developed symptoms on the second exposure to the drug led us to think of an IgE-mediated type I hypersensitivity mechanism.Notably, there was an increased anion gap (AG), which was unexpected for a proximal renal tubular acidosis. We ruled out consumption of salicylates, ethanol, propylene glycol and ethylene glycol, methanol, toluene, and other causes that would explain l- and d-lactic acidosis. There was no evidence of rhabdomyolysis, and no measurable changes in plasma calcium, magnesium, or albumin levels. We did not find any evidence in the medical literature that metamizole, valsartan, or gemfibrozole increased AG by producing intermediate metabolites. It is possible that the consumption of paracetamol, by producing the metabolite 5-oxoproline, would explain the finding.<a class="elsevierStyleCrossRefs" href="#bib0085">8,9</a> In fact, the patients had consumed it prior admission, during his hospital admission and after discharge. The acquired accumulation of 5-oxyproline is found in long-term paracetamol users, and occurs with normal blood paracetamol levels. Predisposing circumstances are female sex, malnutrition, pregnancy, vegetarian diet, sepsis, chronic renal failure, liver disease (mainly alcoholic), and the use of certain antibiotics and anticonvulsants.The combined action of drugs that synergistically affect the distal tubule (valsartan) and proximal tubule (metamizole and genfibrozil<a class="elsevierStyleCrossRefs" href="#bib0060">3,7</a>) could increase the chances of renal damage. This should be taken into account at the time of prescribing them concurrently. It is worth considering the possibility that the fibrate might have played a role in the development of Fanconi syndrome, given its action on the proximal tubule, although the timing of the clinical presentation makes this less likely.FundingThe authors declare that they have received no funding for this work." "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Martín-Navarro JA, Petkov-Stoyanov V, Gutiérrez-Sánchez MJ, Pedraza-Cezón L. Fracaso renal agudo por nefritis intersticial aguda con síndrome de Fanconi en relación con metamizol y gemfibrozilo. Nefrologia. 2016;36:321–323." ] ] "multimedia" => array:1 [ 0 => 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">Values \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">Initial \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">Nadir \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">12 weeks \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">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">88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40 \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">FE urea (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.14 \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">ClCr (ml/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Estimated GFR using MDRD-IDMS >60 \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">BUN/Cr \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 \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">pH plasma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.35 \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">Bicarbonate (mEq/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin (g/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.3 \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">Anion gap (mMol/l) \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">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 \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">UAG (mEq/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+5 \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">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Calcium (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Phosphorus (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.6 \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></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Uric acid (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Potassium (mMol/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.7 \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">Ca/GFR (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \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">TRF (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54 \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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FE AU (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 \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">FE K+ (%) \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">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 \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">FE Na+ (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.5 \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">Urine pH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.0 \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 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99mg/dl \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.4g/24h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dipstick Neg. \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">Glycosuria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100mg/dl \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dipstick Neg. \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">Aminoaciduria \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Positive, generalised \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1393599.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Investigation results." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute interstitial nephritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. 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Letter to the Editor

Fracaso renal agudo por nefritis intersticial aguda con síndrome de Fanconi en relación con metamizol y gemfibrozilo

Juan Antonio Martín-Navarroa,

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juanmartinnav@hotmail.com

Corresponding author.

, Vladimir Petkov-Stoyanova, María José Gutiérrez-Sáncheza, Luis Pedraza-Cezónb

a Servicio de Nefrología, Hospital del Tajo, Aranjuez, Madrid, Spain

b Servicio de Farmacia, Hospital del Tajo, Aranjuez, Madrid, Spain

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He developed progressive weakness&#44; abdominal pain&#44; and nausea&#46; Oral intake was reduced and BP control worsened&#44; therefore the doses of valsartan and metamizole were increased&#44; with additional paracetamol as required&#46; His general condition worsened&#44; therefore he attended the emergency department where BP was 135&#47;85&#46; Skin and mucous membranes were dry&#44; he was afebrile&#44; with no skin lesions&#44; and no other physical findings&#46; He had a high urine output &#40;3&#46;5<span class="elsevierStyleHsp" style=""></span>L&#47;day&#41;&#44; which was macroscopically normal&#46; Blood tests showed a full blood count with no eosinophilia&#44; metabolic acidosis with normal lactic acid&#44; normal CK&#44; reduced glomerular filtration rate &#40;GFR&#41;&#44; hypouricemia&#44; and a mixed proteinuria of 1&#46;4<span class="elsevierStyleHsp" style=""></span>g&#47;24<span class="elsevierStyleHsp" style=""></span>h&#46; Urinalysis revealed an alkaline pH&#44; glycosuria with normoglycaemia&#44; microhaematuria&#44; isosthenuria&#44; and the presence of granular hyaline casts&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">4&#44;5</span></a> There was reduced tubular reabsorption of phosphate&#44; potassium&#44; calcium&#44; and uric acid&#44; and generalised hyperaminoaciduria&#46; Abdominal ultrasound showed kidneys measuring 146<span class="elsevierStyleHsp" style=""></span>mm with preserved corticomedullary differentiation and no signs of hydronephrosis&#46; There were no abnormalities of the bladder or prostate&#46; Viral serology and tumour markers were negative&#46; Immunology was normal&#44; including complement&#44; ANA&#44; ANCA&#44; anti-GBM&#44; and protein electrophoresis and immunoglobulins&#46; Intact parathyroid hormone&#44; 72<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#59; 25-OH-vitamin D&#44; 6&#46;0<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#59; ACE&#44; normal Mantoux negative&#59; and CXR&#44; normal &#40;investigation results&#44; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Pre-renal factors were corrected&#44; but with no improvement in GFR&#44; therefore renal biopsy was performed&#46; This showed 13 glomeruli with no abnormalities&#44; interstitial oedema&#44; an intense lymphoid infiltrate accompanied with polymorphonuclear neutrophils and eosinophils&#44; no granuloma&#44; acute tubular necrosis&#44; normal arteries and arterioles&#44; and no complement or immune-complex deposits on direct immunofluorescence&#46; A diagnosis was made of acute renal failure due to tubular necrosis and acute interstitial nephritis &#40;AIN&#41; secondary to metamizole&#44; and Fanconi syndrome&#46; Treatment was started with methylprednisolone 250<span class="elsevierStyleHsp" style=""></span>mg&#47;day for 3 days and was then switched to prednisone 1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day at a reducing dose until it was stopped 12 weeks later&#44; once the GFR had recovered and the tubular abnormalities had resolved&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Acute interstitial nephritis comprises 15&#8211;27&#37; of findings in renal biopsy&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Recent years have seen a change in the clinical pattern and causative agents&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> The observed incidence of AIN secondary to metamizole is 10&#46;48 cases per 10&#44;000 patient&#47;year&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Although previously described&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> it is not common to find a Fanconi-type proximal tubulopathy&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In this case&#44; features of AIN were found &#40;isothenuria&#44; non-nephrotic proteinuria&#44; rapid deterioration of GFR&#41; along with features typical of a proximal tubulopathy &#40;metabolic acidosis&#44; glycosuria with normoglycaemia&#44; hyperphosphaturia&#44; hyperuricosuria&#44; and generalised hyperaminoaciduria&#41;&#46; The main mechanism was direct immune-mediated tubular toxicity related to metamizole&#46; The second mechanism was tubular necrosis secondary to renal vasoconstriction caused by the inhibition of prostaglandins by metamizole &#40;inhibition of the enzyme COX-3&#41; and gemfibrozole &#40;stimulation of the peroxisome prolipherator-activated receptor PPAR-&#945;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">6&#44;7</span></a>&#41;&#44; and by the inhibition of angiotensin II by valsartan&#46; As in other studies&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> renal failure developed between 1 and 3 weeks after taking the drug&#44; was nonoliguric&#44; without eosinophilia&#44; skin changes&#44; or fever&#44; and with characteristic abdominal pain and proteinuria of around 1<span class="elsevierStyleHsp" style=""></span>g&#47;day&#46; The absence of deposits on DIF and the fact that the patient developed symptoms on the second exposure to the drug led us to think of an IgE-mediated type I hypersensitivity mechanism&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Notably&#44; there was an increased anion gap &#40;AG&#41;&#44; which was unexpected for a proximal renal tubular acidosis&#46; We ruled out consumption of salicylates&#44; ethanol&#44; propylene glycol and ethylene glycol&#44; methanol&#44; toluene&#44; and other causes that would explain <span class="elsevierStyleSmallCaps">l</span>- and <span class="elsevierStyleSmallCaps">d</span>-lactic acidosis&#46; There was no evidence of rhabdomyolysis&#44; and no measurable changes in plasma calcium&#44; magnesium&#44; or albumin levels&#46; We did not find any evidence in the medical literature that metamizole&#44; valsartan&#44; or gemfibrozole increased AG by producing intermediate metabolites&#46; It is possible that the consumption of paracetamol&#44; by producing the metabolite 5-oxoproline&#44; would explain the finding&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">8&#44;9</span></a> In fact&#44; the patients had consumed it prior admission&#44; during his hospital admission and after discharge&#46; The acquired accumulation of 5-oxyproline is found in long-term paracetamol users&#44; and occurs with normal blood paracetamol levels&#46; Predisposing circumstances are female sex&#44; malnutrition&#44; pregnancy&#44; vegetarian diet&#44; sepsis&#44; chronic renal failure&#44; liver disease &#40;mainly alcoholic&#41;&#44; and the use of certain antibiotics and anticonvulsants&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The combined action of drugs that synergistically affect the distal tubule &#40;valsartan&#41; and proximal tubule &#40;metamizole and genfibrozil<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">3&#44;7</span></a>&#41; 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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Mart&#237;n-Navarro JA&#44; Petkov-Stoyanov V&#44; Guti&#233;rrez-S&#225;nchez MJ&#44; Pedraza-Cez&#243;n L&#46; Fracaso renal agudo por nefritis intersticial aguda con s&#237;ndrome de Fanconi en relaci&#243;n con metamizol y gemfibrozilo&#46; Nefrologia&#46; 2016&#59;36&#58;321&#8211;323&#46;</p>"
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                  \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">Values&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Initial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Nadir&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">12 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urea &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FE urea &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ClCr &#40;ml&#47;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Estimated GFR using MDRD-IDMS &#62;60&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">pH plasma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bicarbonate &#40;mEq&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin &#40;g&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anion gap &#40;mMol&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">UAG &#40;mEq&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Calcium &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Phosphorus &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Uric acid &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Potassium &#40;mMol&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ca&#47;GFR &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TRF &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FE AU &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FE K&#43; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FE Na&#43; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Urine pH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proteinuria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">99<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;4<span class="elsevierStyleHsp" style=""></span>g&#47;24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dipstick Neg&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glycosuria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100<span class="elsevierStyleHsp" style=""></span>mg&#47;dl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dipstick Neg&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Aminoaciduria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Positive&#44; generalised&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Normal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                      "titulo" => "Acute interstitial nephritis"
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                        0 => array:2 [
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                          "autores" => array:2 [
                            0 => "M&#46; Praga"
                            1 => "E&#46; Gonz&#225;lez"
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                      "doi" => "10.1038/ki.2010.89"
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                        "tituloSerie" => "Kidney Int"
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                  "comentario" => "pii&#58;gfu326&#46; &#91;Epub ahead of print&#93;"
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                      "titulo" => "Changes in the aetiology&#44; clinical presentation and management of acute interstitial nephritis&#44; an increasingly common cause of acute kidney injury"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
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                    0 => array:2 [
                      "doi" => "10.1093/ndt/gfs152"
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                        "tituloSerie" => "Nephrol Dial Transplant"
                        "fecha" => "2014"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22773240"
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                            0 => "M&#46;D&#46; Redondo-Pach&#243;n"
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                            2 => "A&#46;E&#46; Sirvent"
                            3 => "I&#46; Mill&#225;n"
                            4 => "A&#46; Romero"
                            5 => "F&#46; Amor&#243;s"
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                        "tituloSerie" => "Saudi J Kidney Dis Transpl"
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                          "autores" => array:4 [
                            0 => "H&#46; Izzedine"
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                            3 => "G&#46; Deray"
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Article information

ISSN: 20132514
Original language: English

DOI:10.1016/j.nefroe.2015.06.012

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	6	3	9
2024 October	85	53	138
2024 September	119	36	155
2024 August	106	49	155
2024 July	77	37	114
2024 June	86	43	129
2024 May	103	60	163
2024 April	85	36	121
2024 March	76	28	104
2024 February	55	45	100
2024 January	55	28	83
2023 December	60	24	84
2023 November	79	34	113
2023 October	85	34	119
2023 September	90	22	112
2023 August	82	31	113
2023 July	78	35	113
2023 June	77	28	105
2023 May	86	52	138
2023 April	68	20	88
2023 March	89	22	111
2023 February	66	35	101
2023 January	73	18	91
2022 December	82	42	124
2022 November	105	74	179
2022 October	122	65	187
2022 September	65	35	100
2022 August	65	48	113
2022 July	56	51	107
2022 June	61	43	104
2022 May	76	38	114
2022 April	79	56	135
2022 March	73	73	146
2022 February	67	49	116
2022 January	66	41	107
2021 December	57	42	99
2021 November	67	43	110
2021 October	137	36	173
2021 September	84	46	130
2021 August	57	48	105
2021 July	49	44	93
2021 June	59	34	93
2021 May	61	48	109
2021 April	176	58	234
2021 March	84	43	127
2021 February	58	49	107
2021 January	52	28	80
2020 December	52	21	73
2020 November	60	17	77
2020 October	54	29	83
2020 September	47	21	68
2020 August	68	30	98
2020 July	40	13	53
2020 June	48	30	78
2020 May	81	16	97
2020 April	50	17	67
2020 March	63	13	76
2020 February	80	24	104
2020 January	82	23	105
2019 December	59	30	89
2019 November	53	27	80
2019 October	56	13	69
2019 September	102	21	123
2019 August	33	17	50
2019 July	45	29	74
2019 June	47	13	60
2019 May	65	27	92
2019 April	98	36	134
2019 March	65	25	90
2019 February	37	18	55
2019 January	39	25	64
2018 December	165	45	210
2018 November	256	23	279
2018 October	163	32	195
2018 September	95	15	110
2018 August	75	18	93
2018 July	63	13	76
2018 June	62	18	80
2018 May	79	18	97
2018 April	112	12	124
2018 March	62	9	71
2018 February	81	8	89
2018 January	56	6	62
2017 December	90	7	97
2017 November	65	19	84
2017 October	58	15	73
2017 September	42	10	52
2017 August	34	10	44
2017 July	48	15	63
2017 June	43	20	63
2017 May	45	14	59
2017 April	50	14	64
2017 March	35	12	47
2017 February	36	9	45
2017 January	52	6	58
2016 December	42	11	53
2016 November	58	26	84
2016 October	93	15	108
2016 September	120	10	130
2016 August	214	16	230
2016 July	160	13	173
2016 June	92	0	92
2016 May	135	0	135
2016 April	110	0	110
2016 March	75	0	75
2016 February	67	0	67
2016 January	53	0	53
2015 December	22	0	22

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