Letter to the Editor
Intravesical cidofovir, use in BK polyomavirus-associated haemorrhagic cystitis after haematopoietic stem cell transplantation: off-label
Cidofovir intravesical, uso en cistitis hemorrágica por poliomavirus bk tras un trasplante de progenitores hematopoyéticos: off-label
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=> array:2 [ "paginaInicial" => "79" "paginaFinal" => "80" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Alejandro Ferrer, María Micaela Viña, Elisa Pérez Limiñana, Javier Merino" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Alejandro" "apellidos" => "Ferrer" "email" => array:1 [ 0 => "Alefermac1989@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" => "María Micaela" "apellidos" => "Viña" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Elisa Pérez" "apellidos" => "Limiñana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Javier" "apellidos" => "Merino" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Farmacia Hospitalaria, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Enfermería, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, 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" => "Cidofovir intravesical, uso en cistitis hemorrágica por poliomavirus bk tras un trasplante de progenitores hematopoyéticos: <span class="elsevierStyleItalic">off-label</span>" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1652 "Ancho" => 2175 "Tamanyo" => 129235 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evolution of creatinine levels during hospital stay.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Haemorrhagic cystitis is defined as inflammation of the bladder mucosa that causes acute or subacute diffuse bleeding.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is caused by the inappropriate activation of proinflammatory cytokines, which destroy the mucosa and chorion through inflammatory apoptosis (pyroptosis), which leads to the opening of the microvessels to the bladder lumen. The main causes of bladder pyroptosis are bacterial or viral pathogens, ionising radiation or acrolein, a urinary metabolite of cyclophosphamide and ifosfamide.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The BK virus is one of the most important causes of late-onset haemorrhagic cystitis in patients undergoing haematopoietic cell transplantation (HCT). The evidence for the treatment of BK virus-associated haemorrhagic cystitis (BKV−HC) is limited, with cidofovir being one of the treatment options.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Cidofovir is a cytidine analogue that demonstrates in vitro and in vivo activity against human cytomegalovirus (HCMV) because it suppresses replication by selective inhibition of viral DNA synthesis.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The use of this drug in BKV−HC would be off-label.</p><p id="par0015" class="elsevierStylePara elsevierViewall">This is the case of a 53-year-old man with no known drug allergies and with a personal history of dyslipidaemia and arterial hypertension.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was diagnosed in 2016 with chronic myelomonocytic leukaemia (CML) and, after several cycles of chemotherapy (MAZE: amsacrine-azacitidine-etoposide; IDA-ARA-C: idarubicin-cytarabine), he underwent allogeneic haematopoietic stem cell transplantation (Allo-HSCT) in May 2018.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Two months later, the patient went to the haematology day unit (HDU) to receive treatment with foscarnet against cytomegalovirus (CMV), acquired after Allo-HSCT, having reported haematuria accompanied by dysuria and burning over the previous few days. With these symptoms, the patient was admitted and diagnosed with haemorrhagic cystitis.</p><p id="par0030" class="elsevierStylePara elsevierViewall">After several tests to discover the aetiology of the disease, copies of BK polyomavirus were detected in his urine. In light of these findings and after communication with the regional referral centre, it was proposed the use of intravenous cidofovir at a daily dose of 400<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h for 2 weeks (induction) and then every 15 days until virus eradication.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Renal function was assessed before starting treatment with cidofovir (>60<span class="elsevierStyleHsp" style=""></span>ml/min) and the treatment start date was set: 03/07/2018. To decrease renal toxicity, probenecid was co-administered with cidofovir.</p><p id="par0040" class="elsevierStylePara elsevierViewall">After the first dose of cidofovir, it was observed a significant increase in blood creatinine levels (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), so the haematology unit contacted the pharmacy to find a solution to the problem.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">As previously mentioned, the main toxicity associated with cidofovir is dose-dependent nephrotoxicity. The Spanish Agency of Medication ines and Health products (Agencia Española de Medicamentos y Productos Sanitarios — AEMPS) reports that the safety of cidofovir has not been evaluated in patients receiving other agents that are known to be potentially nephrotoxic (for example: tenofovir, aminoglycosides, amphotericin B, foscarnet, intravenous pentamidine, adefovir and vancomycin).<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In our case, the nephrotoxicity by cidofovir was exacerbated by the concomitant use of foscarnet, which could not be discontinued since the patient maintained positive CMV copies in plasma.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In light of the above, from the pharmacy department we conducted a literature search and found a systematic review that compared intravenous and intravesical administration of cidofovir in the treatment of BK polyomavirus-associated haemorrhagic cystitis after Allo-HSCT. It was found that the intravesical route gave a high rate of complete responses, but without renal toxicity.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Based on these information, the use of intravesical cidofovir was recommended at 5<span class="elsevierStyleHsp" style=""></span>mg/kg diluted in 60<span class="elsevierStyleHsp" style=""></span>ml of 0.9% physiological saline solution and instilled for one hour into the bladder, with changes in posture (supine position, left lateral position, prone position and right lateral position) every 15<span class="elsevierStyleHsp" style=""></span>min so that the drug could penetrate the entire mucosa of the bladder (nursing recommendation).</p><p id="par0060" class="elsevierStylePara elsevierViewall">The first dose of intravesical cidofovir was administered on 13/07/2018, after which an improvement in renal function was observed (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). After the first instillation of intravesical cidofovir, the urine PCR was repeated to detect copies of BK polyomavirus. The result was negative, so treatment with cidofovir was discontinued.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Our case shows that the use of intravesical cidofovir can be proposed as an effective alternative in patients with creatinine clearance ≤55<span class="elsevierStyleHsp" style=""></span>ml/min (the limit for contraindication of intravenous cidofovir).</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ferrer A, Viña MM, Limiñana EP, Merino J. Cidofovir intravesical, uso en cistitis hemorrágica por poliomavirus BK tras un trasplante de progenitores hematopoyéticos: off-label. Nefrologia. 2021;41:79–80.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1652 "Ancho" => 2175 "Tamanyo" => 129235 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Evolution of creatinine levels during hospital stay.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Manual terapéutico. 4ª ed. Corregida y ampliada" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. García Criado" 1 => "I. Corbacho Cambero" 2 => "V. Sánchez Moro" 3 => "A. Muñoz Galindo" 4 => "J.A. Sánchez Serrano" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2019" "editorial" => "Ediciones Universidad de Salamanca" "editorialLocalizacion" => "Salamanca" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cistitis hemorrágica: fisiopatología y conducta práctica" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Colombel" 1 => "H.L. Wallet" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "EMC - Urologia" "fecha" => "2019" "volumen" => "51" "paginaInicial" => "1" "paginaFinal" => "10" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "BK virus associated haemorrhagic cystitis. A systematic review of current prevention and treatment strategies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Aldiwani" 1 => "T. Tharakan" 2 => "A. Al-Hassani" 3 => "N. Gibbons" 4 => "J. Pavlu" 5 => "D. 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Krüger" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Transpl Infect Dis" "fecha" => "2018" "volumen" => "20" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000004100000001/v1_202103250823/S2013251421000079/v1_202103250823/en/main.assets" "Apartado" => array:4 [ "identificador" => "35436" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000004100000001/v1_202103250823/S2013251421000079/v1_202103250823/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251421000079?idApp=UINPBA000064" ]
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| 2024 February | 54 | 39 | 93 |
| 2024 January | 42 | 23 | 65 |
| 2023 December | 60 | 33 | 93 |
| 2023 November | 47 | 40 | 87 |
| 2023 October | 87 | 36 | 123 |
| 2023 September | 148 | 31 | 179 |
| 2023 August | 51 | 33 | 84 |
| 2023 July | 68 | 38 | 106 |
| 2023 June | 53 | 35 | 88 |
| 2023 May | 55 | 26 | 81 |
| 2023 April | 51 | 16 | 67 |
| 2023 March | 64 | 39 | 103 |
| 2023 February | 35 | 20 | 55 |
| 2023 January | 47 | 34 | 81 |
| 2022 December | 62 | 33 | 95 |
| 2022 November | 65 | 41 | 106 |
| 2022 October | 81 | 57 | 138 |
| 2022 September | 48 | 39 | 87 |
| 2022 August | 44 | 49 | 93 |
| 2022 July | 48 | 54 | 102 |
| 2022 June | 53 | 42 | 95 |
| 2022 May | 49 | 38 | 87 |
| 2022 April | 44 | 46 | 90 |
| 2022 March | 44 | 60 | 104 |
| 2022 February | 50 | 44 | 94 |
| 2022 January | 49 | 46 | 95 |
| 2021 December | 55 | 43 | 98 |
| 2021 November | 56 | 38 | 94 |
| 2021 October | 71 | 56 | 127 |
| 2021 September | 50 | 51 | 101 |
| 2021 August | 45 | 52 | 97 |
| 2021 July | 51 | 39 | 90 |
| 2021 June | 38 | 30 | 68 |
| 2021 May | 61 | 52 | 113 |
| 2021 April | 75 | 69 | 144 |
| 2021 March | 39 | 44 | 83 |
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