Letter to the Editor
Bile cast nephropathy associated with severe liver dysfunction caused by anabolic steroids
Nefropatía por cilindros biliares asociada a disfunción hepática severa causada por esteroides anabolizantes
Mónica Milla Castellanos
, Eduardo Gutiérrez Martínez, Ángel Sevillano Prieto, Paola Rodríguez Ramos, Manuel Praga Terente
Corresponding author
Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, Spain
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"total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0211699517300504?idApp=UINPBA000064" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251417301748?idApp=UINPBA000064" "url" => "/20132514/0000003800000002/v1_201803090444/S2013251417301748/v1_201803090444/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Bile cast nephropathy associated with severe liver dysfunction caused by anabolic steroids" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "221" "paginaFinal" => "223" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Mónica Milla Castellanos, Eduardo Gutiérrez Martínez, Ángel Sevillano Prieto, Paola Rodríguez Ramos, Manuel Praga Terente" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Mónica" "apellidos" => "Milla Castellanos" "email" => array:1 [ 0 => "monica.milla15@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Eduardo" "apellidos" => "Gutiérrez Martínez" ] 2 => array:2 [ "nombre" => "Ángel" "apellidos" => "Sevillano Prieto" ] 3 => array:2 [ "nombre" => "Paola" "apellidos" => "Rodríguez Ramos" ] 4 => array:2 [ "nombre" => "Manuel" "apellidos" => "Praga Terente" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Nefropatía por cilindros biliares asociada a disfunción hepática severa causada por esteroides anabolizantes" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1223 "Ancho" => 1649 "Tamanyo" => 209039 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Urine sediment in which a bilirubin cast can be seen using an optical microscope (x40).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acute kidney injury (AKI) is a common and significant complication in patients with liver failure (LF).<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> AKI related to increased bilirubin levels has been well known since the beginning of the <span class="elsevierStyleSmallCaps">20</span>th century. This condition has received different names: cholestatic nephropathy, jaundice-related nephropathy, bile cast nephropathy and bile nephropathy.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present an unusual case of AKI due to severe hyperbilirubinaemia caused by anabolic steroids (AS) used for body-building. This is a 40-year-old man, with no previous medical history of interest, who came to the clinics for symptoms of jaundice, hypocholia, choluria, itching and asthenia. The patient presented with no substance abuse and reported that he had been taking Animal-Pak<span class="elsevierStyleSup">®</span> and EA Havoc<span class="elsevierStyleSup">®</span> vitamin supplements the previous month.</p><p id="par0015" class="elsevierStylePara elsevierViewall">On physical examination, the only thing of note was a marked mucocutaneous jaundice. The tests on admission showed bilirubin: 30<span class="elsevierStyleHsp" style=""></span>mg/dl, GPT: 226<span class="elsevierStyleHsp" style=""></span>U/l, GOT: 89<span class="elsevierStyleHsp" style=""></span>U/l and alkaline phosphatase and gamma-GT within normal range. He did not show coagulopathy and renal function was normal. Viral serologies, alpha-1-antitrypsin, ceruloplasmin, copper, antibodies, immunoglobulins and complement were normal, as was the abdominal ultrasound.</p><p id="par0020" class="elsevierStylePara elsevierViewall">His clinical course showed a progressive increase in bilirubin to a peak of 39.9<span class="elsevierStyleHsp" style=""></span>mg/dl. A liver biopsy was performed, showing areas of periportal hepatitis, canalicular and parenchymal cholestasis and perisinusoidal fibrosis; findings consistent with drug-induced hepatitis. Bilirubin levels gradually improved, reaching a bilirubin concentration of 30<span class="elsevierStyleHsp" style=""></span>mg/dl at the time of discharge.</p><p id="par0025" class="elsevierStylePara elsevierViewall">A week after being discharged the patient was admitted for AKI with serum creatinine (SCr) of 4.5<span class="elsevierStyleHsp" style=""></span>mg/dl and bilirubin levels, which had increased, to 38<span class="elsevierStyleHsp" style=""></span>mg/dl (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In light of these findings, treatment started with fluid replacement therapy, ursodeoxycholic acid, cholestyramine resin and corticosteroids (1<span class="elsevierStyleHsp" style=""></span>mg/kg), the bilirubin levels decreased to 30<span class="elsevierStyleHsp" style=""></span>mg/dl, but with AKI persisted, so haemodialysis was started followed by <span class="elsevierStyleItalic">Molecular Adsorbents Recirculation System</span> (MARS) therapy and continuous venovenous haemodiafiltration (CVVHD).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">A complete renal evaluation was performed showing only the presence of abundant bilirubin casts in the sediment (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Subsequently, bilirubin levels gradually improved to 18.8<span class="elsevierStyleHsp" style=""></span>mg/dl in parallel with the treatment, and corticosteroids were gradually decreased and MARS and CVVHD were withdrawn. Kidney function improved to a SCr of 2.4<span class="elsevierStyleHsp" style=""></span>mg/dl at the time of discharge, so it was decided not to perform a renal biopsy. Four months after the onset of symptoms, the patient reached a SCr of 1.1<span class="elsevierStyleHsp" style=""></span>mg/dl with a bilirubin level of 1.3<span class="elsevierStyleHsp" style=""></span>mg/dl, with steroids being suspended two months after their introduction.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">AS are synthetic derivatives of testosterone and can cause liver toxicity (cholestasis, nodular regenerative hyperplasia, neoplasms, etc.) as they alter the canalicular excretion of conjugated bilirubin and its sinusoidal uptake, causing it to accumulate.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,5</span></a> The patient had been taking Havoc<span class="elsevierStyleSup">®</span>, which contains methylepitiostanol, a prohormone that is metabolised to produce the compound desoxymethyltestosterone. This compound can cause liver cholestasis, which is one of the reasons its sale has been banned.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">From a renal perspective, proteinuria associated with focal segmental glomerulosclerosis and AKI has been reported.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,5</span></a> Robles-Díaz et al. reported a series of 25 patients with hepatotoxicity due to AS, 31% of which developed AKI with full recovery of kidney function after the liver damage had been resolved without the need for renal biopsy.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Bilirubin increases in the sinusoid in LF which can cause direct tubular damage, and therefore AKI. It is known that the risk of tubular injury increases when the bilirubin levels are higher than 20<span class="elsevierStyleHsp" style=""></span>mg/dl.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2,5,8,9</span></a> Bilirubin is transported in the proximal tubule; when it is saturated it leads to the formation of casts which cause tubular damage, either from the direct toxicity of the bilirubin or from the intratubular obstruction of the casts.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,8</span></a> The mechanisms responsible for the tubular damage are the uncoupling of the mitochondrial phosphorylation, thereby decreasing ATPase activity, oxidative damage of the tubular cell membrane, and the inhibition of Na<span class="elsevierStyleSup">+</span>−H<span class="elsevierStyleSup">+</span>, Na<span class="elsevierStyleSup">+</span>−Cl− and Na<span class="elsevierStyleSup">+</span>−K<span class="elsevierStyleSup">+</span><a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,10</span></a> pumps.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Diagnosis requires clinical suspicion and a urinary sediment test needs to be carried out, which typically shows bilirubin casts and epithelial cells containing bilirubin.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Tubules full of degenerated epithelial cells and bile pigment casts together with dilation of the lumen and cytoplasmic vacuolisation with glomerular integrity are usually found in the kidney biopsy.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a> In the electron microscope study it is typical to find dilated mitochondrial cristae and an accumulation of bile acids within the lysosomes.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Treatment is not specific and is fundamentally supportive. Renal replacement therapy has no specific role except for the treatment of AKI, while plasmapheresis may have a use in reducing pro-inflammatory substances.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Other options aimed at reducing inflammatory cytokines and bilirubin are MARS, <span class="elsevierStyleItalic">Coupled Plasma Filtration Adsorption</span> (CPFA) and plasma filtration adsorption dialysis. Steroids, cholestyramine, ursodeoxycholic acid and lactulose have demonstrated minimal benefit.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> AS can cause these symptoms, so amateur athletes should be informed about their side-effects.</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: Milla Castellanos M, Gutiérrez Martínez E, Sevillano Prieto A, Rodríguez Ramos P, Praga Terente M. Nefropatía por cilindros biliares asociada a disfunción hepática severa causada por esteroides anabolizantes. Nefrologia. 2018;38:221–223.</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" => 1663 "Ancho" => 2678 "Tamanyo" => 195318 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Analytical evolution of bilirubin and creatinine.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1223 "Ancho" => 1649 "Tamanyo" => 209039 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Urine sediment in which a bilirubin cast can be seen using an optical microscope (x40).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bile cast nephropathy is a common pathologic finding for kidney injury associated with severe liver dysfunction" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C.M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 13 | 10 | 23 |
| 2024 October | 85 | 37 | 122 |
| 2024 September | 107 | 41 | 148 |
| 2024 August | 118 | 72 | 190 |
| 2024 July | 96 | 40 | 136 |
| 2024 June | 107 | 51 | 158 |
| 2024 May | 119 | 51 | 170 |
| 2024 April | 99 | 41 | 140 |
| 2024 March | 87 | 32 | 119 |
| 2024 February | 101 | 38 | 139 |
| 2024 January | 94 | 28 | 122 |
| 2023 December | 114 | 38 | 152 |
| 2023 November | 138 | 32 | 170 |
| 2023 October | 132 | 36 | 168 |
| 2023 September | 115 | 29 | 144 |
| 2023 August | 156 | 26 | 182 |
| 2023 July | 182 | 46 | 228 |
| 2023 June | 162 | 37 | 199 |
| 2023 May | 177 | 37 | 214 |
| 2023 April | 182 | 20 | 202 |
| 2023 March | 177 | 27 | 204 |
| 2023 February | 143 | 25 | 168 |
| 2023 January | 158 | 42 | 200 |
| 2022 December | 140 | 53 | 193 |
| 2022 November | 137 | 53 | 190 |
| 2022 October | 194 | 66 | 260 |
| 2022 September | 154 | 60 | 214 |
| 2022 August | 166 | 60 | 226 |
| 2022 July | 191 | 57 | 248 |
| 2022 June | 204 | 56 | 260 |
| 2022 May | 260 | 45 | 305 |
| 2022 April | 215 | 59 | 274 |
| 2022 March | 246 | 76 | 322 |
| 2022 February | 224 | 63 | 287 |
| 2022 January | 172 | 42 | 214 |
| 2021 December | 147 | 56 | 203 |
| 2021 November | 149 | 46 | 195 |
| 2021 October | 131 | 53 | 184 |
| 2021 September | 150 | 48 | 198 |
| 2021 August | 112 | 52 | 164 |
| 2021 July | 186 | 43 | 229 |
| 2021 June | 168 | 44 | 212 |
| 2021 May | 129 | 78 | 207 |
| 2021 April | 294 | 82 | 376 |
| 2021 March | 260 | 74 | 334 |
| 2021 February | 226 | 50 | 276 |
| 2021 January | 153 | 44 | 197 |
| 2020 December | 118 | 35 | 153 |
| 2020 November | 137 | 31 | 168 |
| 2020 October | 93 | 26 | 119 |
| 2020 September | 131 | 32 | 163 |
| 2020 August | 117 | 32 | 149 |
| 2020 July | 118 | 15 | 133 |
| 2020 June | 117 | 36 | 153 |
| 2020 May | 112 | 42 | 154 |
| 2020 April | 125 | 37 | 162 |
| 2020 March | 149 | 21 | 170 |
| 2020 February | 145 | 30 | 175 |
| 2020 January | 160 | 32 | 192 |
| 2019 December | 165 | 33 | 198 |
| 2019 November | 135 | 31 | 166 |
| 2019 October | 120 | 17 | 137 |
| 2019 September | 117 | 28 | 145 |
| 2019 August | 89 | 27 | 116 |
| 2019 July | 96 | 32 | 128 |
| 2019 June | 75 | 27 | 102 |
| 2019 May | 84 | 31 | 115 |
| 2019 April | 105 | 52 | 157 |
| 2019 March | 60 | 22 | 82 |
| 2019 February | 52 | 28 | 80 |
| 2019 January | 55 | 27 | 82 |
| 2018 December | 130 | 45 | 175 |
| 2018 November | 209 | 14 | 223 |
| 2018 October | 186 | 12 | 198 |
| 2018 September | 113 | 19 | 132 |
| 2018 August | 71 | 8 | 79 |
| 2018 July | 74 | 10 | 84 |
| 2018 June | 78 | 10 | 88 |
| 2018 May | 71 | 11 | 82 |
| 2018 April | 96 | 15 | 111 |
| 2018 March | 95 | 23 | 118 |
| 2018 February | 62 | 7 | 69 |
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