Letter to the Editor
Acute interstitial tubulo nephritis associated with statin treatment
Nefritis tubulointersticial aguda asociada al tratamiento con estatinas
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Está constituido principalmente por linfocitos (flechas azules). Focalmente el infiltrado afecta a los túbulos (tubulitis) (flechas verdes). Hematoxilina-eosina ×20. El color de las figuras solo puede apreciarse en la versión electrónica del artículo.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Miguel Ángel González Martínez, Dora Angélica Varillas Caso, María Ramírez Gómez, Mercedes Caba Molina" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Miguel Ángel" "apellidos" => "González Martínez" ] 1 => array:2 [ "nombre" => "Dora Angélica" "apellidos" => "Varillas Caso" ] 2 => array:2 [ "nombre" => "María" "apellidos" => "Ramírez Gómez" ] 3 => array:2 [ "nombre" => "Mercedes" "apellidos" => "Caba Molina" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S201325142400186X" "doi" => "10.1016/j.nefroe.2024.10.004" "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/S201325142400186X?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699524000250?idApp=UINPBA000064" "url" => "/02116995/0000004400000005/v1_202409110539/S0211699524000250/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. González-Rinne, Lluis Guirado, Alex Gutiérrez-Dalmau, Jorge Huguet, José Luis López del Moral, Mireia Musquera, David Paredes, Dolores Redondo, Ignacio Revuelta, Carlos J Van-der Hofstadt, Antonio Alcaraz, Ángel Alonso-Hernández, Manuel Alonso, Purificación Bernabeu, Gabriel Bernal, Alberto Breda, Mercedes Cabello, José Luis Caro-Oleas, Joan Cid, Fritz Diekmann, Laura Espinosa, Carme Facundo, Marta García, Salvador Gil-Vernet, Miquel Lozano, Beatriz Mahillo, María José Martínez, Blanca Miranda, Federico Oppenheimer, Eduard Palou, María José Pérez-Saez, Lluis Peri, Oscar Rodríguez, Carlos Santiago, Guadalupe Tabernero, Domingo Hernández, Beatriz Domínguez-Gil, Julio Pascual" "autores" => array:46 [ 0 => array:2 [ "nombre" => "Miguel Ángel" "apellidos" => "Frutos" ] 1 => array:2 [ "nombre" => "Marta" "apellidos" => "Crespo" ] 2 => array:2 [ "nombre" => "María de la Oliva" "apellidos" => "Valentín" ] 3 => array:2 [ "nombre" => "Ángel" "apellidos" => "Alonso-Melgar" ] 4 => array:2 [ "nombre" => "Juana" "apellidos" => "Alonso" ] 5 => array:2 [ "nombre" => "Constantino" "apellidos" => "Fernández" ] 6 => array:2 [ "nombre" => "Gorka" "apellidos" => "García-Erauzkin" ] 7 => array:2 [ "nombre" => "Esther" "apellidos" => "González" ] 8 => array:2 [ "nombre" => "Ana M." "apellidos" => "González-Rinne" ] 9 => array:2 [ "nombre" => "Lluis" "apellidos" => "Guirado" ] 10 => array:2 [ "nombre" => "Alex" "apellidos" => "Gutiérrez-Dalmau" ] 11 => array:2 [ "nombre" => "Jorge" "apellidos" => "Huguet" ] 12 => array:2 [ "nombre" => "José Luis López del" "apellidos" => "Moral" ] 13 => array:2 [ "nombre" => "Mireia" "apellidos" => "Musquera" ] 14 => array:2 [ "nombre" => "David" "apellidos" => "Paredes" ] 15 => array:2 [ "nombre" => "Dolores" "apellidos" => "Redondo" ] 16 => array:2 [ "nombre" => "Ignacio" "apellidos" => "Revuelta" ] 17 => array:2 [ "nombre" => "Carlos J Van-der" "apellidos" => "Hofstadt" ] 18 => array:2 [ "nombre" => "Antonio" "apellidos" => "Alcaraz" ] 19 => array:2 [ "nombre" => "Ángel" "apellidos" => "Alonso-Hernández" ] 20 => array:2 [ "nombre" => "Manuel" "apellidos" => "Alonso" ] 21 => array:2 [ "nombre" => "Purificación" "apellidos" => "Bernabeu" ] 22 => array:2 [ "nombre" => "Gabriel" "apellidos" => "Bernal" ] 23 => array:2 [ "nombre" => 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[ "autoresLista" => "Miguel Ángel González Martínez, Dora Angélica Varillas Caso, María Ramírez Gómez, Mercedes Caba Molina" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Miguel Ángel" "apellidos" => "González Martínez" "email" => array:1 [ 0 => "miguel.agm1505@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:4 [ "nombre" => "Dora Angélica" "apellidos" => "Varillas Caso" "email" => array:1 [ 0 => "varillascaso@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:4 [ "nombre" => "María" "apellidos" => "Ramírez Gómez" "email" => array:1 [ 0 => "marago87@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:4 [ "nombre" => "Mercedes" "apellidos" => "Caba Molina" "email" => array:1 [ 0 => "merchecabamolina2@gmail.com" ] "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 Universitario Clínico San Cecilio, Granada, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario Virgen Delas Nieves, Beiro, Granada, 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 tubulointersticial aguda asociada al tratamiento con estatinas" ] ] "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" => 1335 "Ancho" => 2601 "Tamanyo" => 694259 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Foci of inflammatory infiltrate are observed in the cortex, forming patches and also arranged in a dispersed manner. It is mainly composed of lymphocytes (blue arrows). Focally, the infiltrate affects the tubules (tubulitis) (green arrows). Hematoxylin-eosin ×20. The color of the figures can only be seen in the electronic version of the article.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acute tubulointerstitial nephropathy is a type of renal injury characterized by the presence of inflammatory infiltrates, edema, and tubulitis in the interstitial compartment, and it is often accompanied by acute failure.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It represents the third most frequent cause of acute renal function impairment in hospitalized patients,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> with an incidence of 5–27% in renal biopsies performed for diagnosis of acute renal failure.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> Its course may be subclinical or it may present progressive deterioration evolving into chronic renal failure. Its etiology is diverse, with immunoallergic reaction to drugs being the most frequent cause, with a prevalence of approximately 60–70%.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the clinical case of a patient with a pathological diagnosis of acute tubulointerstitial nephritis with hyaline arteriopathy secondary to treatment with statins.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The patient is a 69-year-old woman with a personal history of vascular risk factors: high blood pressure, mixed dyslipidemia on treatment with pravastatin, and ischemic heart disease that require a stent. She came to the emergency room with symptoms of asthenia, vomiting, and low blood pressure. These symptoms were accompanied by foamy urine with preserved diuresis, without dark urine or hematuria, of approximately two months' duration. Laboratory tests showed acute deterioration of renal function with creatinine 6.82 mg/dl (previously preserved renal function), metabolic acidosis (pH 7.28 with HCO3 15.5 mmol/l), hemoglobin 9.1 g/dl, and eosinophilia 7.2%. Finally, it was decided to admit her to the Nephrology department for study due to non-oliguric acute renal failure refractory to initial medical treatment and observation.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Due to the suspicion of a possible systemic disease with renal involvement, a study of secondary causes was performed, highlighting a normal autoimmune profile except for the presence of positive ANA values ​​(ANA 1/320, homogeneous pattern). Regarding the rest of the complementary tests, the proteinogram, immunoglobulins and complement were within normal range, as well as negative viral serologies. A renal ultrasound was performed, which reported normal-sized kidneys with preserved cortical thickness without urinary tract dilation. It was decided to administer 3 boluses of methylprednisolone 250 mg for the treatment of a probable acute interstitial nephropathy, with adequate renal response in the first 48 h after starting corticosteroid treatment (creatinine 4.42 mg/dl). Finally, an ultrasound-guided percutaneous renal biopsy was performed with a pathological result (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) of evolving tubulointerstitial nephritis (cytoplasmic acidophilia, nuclear pyknosis, loss of the brush border, flattening and detachment of the tubular epithelium) with moderate hyaline arteriopathy. The patient was subsequently discharged with follow-up by Nephrology, presenting stable renal function with creatinine of 3 mg/dl.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">However, the year after hospital admission, the patient again presented two clinical symptoms similar to those of the first admission (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). As a novelty, in the second admission she started treatment only with simvastatin/ezetimibe and the third admission she had started treatment with atorvastatin, presenting in addition with the deterioration of renal function a generalized skin rash. Progressive deterioration of renal function was notable (peak creatinine of 8.06 mg/dl). Finally, she responded on all occasions to corticosteroid therapy, thus the cause of acute renal failure in the last two admissions was associated with the use of statins. Allergy study was completed and currently she is being treated with alirocumab, maintaining lipid levels within the range (total cholesterol 145 mg/dl, HDL 49 mg/dl and LDL 38 mg/dl) and the renal function is preserved (creatinine 1.29 mg/dl).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Today, statins are one of the most prescribed drugs for the treatment of dyslipidemia. One of the side effects described in relation to the use of statins is rhabdomyolysis due to myotoxicity in 2–11% of patients,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> with the presence of myoglobinuria being attributed to the development of acute interstitial nephritis.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> However, acute interstitial nephropathy is a rare cause of acute renal failure.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The importance of this clinical case lies in the fact that it is essential to ask the patient about the recent medication received, changes in treatment or the introduction of new drugs, since in many cases it is difficult to establish the causal agent of the pathology. It should be taking into account that kidney damage does not always correlate directly with the initiation of the drug and the clinical manifestations can be variable.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical aspects</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols established in their work center to access the data of the patient's clinical history to be able write this manuscript aiming to be disseminated to the scientific community.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0045" class="elsevierStylePara elsevierViewall">This research has not received specific financial aid from public sector agencies, the commercial sector or non-profit entities.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical aspects" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2024-02-15" "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" => 1335 "Ancho" => 2601 "Tamanyo" => 694259 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Foci of inflammatory infiltrate are observed in the cortex, forming patches and also arranged in a dispersed manner. It is mainly composed of lymphocytes (blue arrows). Focally, the infiltrate affects the tubules (tubulitis) (green arrows). Hematoxylin-eosin ×20. The color of the figures can only be seen in the electronic version of the article.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1732 "Ancho" => 2583 "Tamanyo" => 208641 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Evolution of glomerular filtration rate expressed by CKD-EPI formula (ml/min) associated with the moments of administration of the statin, observing a decrease in glomerular filtration rate coinciding with the administration of such drug.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute kidney injury in interstitial nephritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F. 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