Letter to the Editor
Treatment with sodium thiosulfate in calciphylaxis of topical active renal transplant patient
Tratamiento con tiosulfato de sodio tópico en calcifilaxia de paciente con trasplante renal activo
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Ludivina Robles-Osorio, Ernesto Sabath" "autores" => array:2 [ 0 => array:2 [ "nombre" => "M. 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Martín Navarro, Luis A. Pedraza Cezón, M. Pilar de Pablos Martín, Esther González Monte, Natalia Polanco Fernández, M. José Gutiérrez Sánchez, Vladimir Petkov Stoyanov" "autores" => array:7 [ 0 => array:4 [ "nombre" => "Juan A." "apellidos" => "Martín Navarro" "email" => array:1 [ 0 => "juanmartinnav@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Luis A." "apellidos" => "Pedraza Cezón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "M. Pilar" "apellidos" => "de Pablos Martín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Esther" "apellidos" => "González Monte" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Natalia" "apellidos" => "Polanco Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 5 => array:3 [ "nombre" => "M. José" "apellidos" => "Gutiérrez Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Vladimir" "apellidos" => "Petkov Stoyanov" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Unidad de Nefrología, Hospital del Tajo, Aranjuez, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Farmacia Hospitalaria, Hospital del Tajo, Aranjuez, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital del Tajo, Aranjuez, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital 12 de Octubre, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento con tiosulfato de sodio tópico en calcifilaxia de paciente con trasplante renal activo" ] ] "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" => 771 "Ancho" => 1700 "Tamanyo" => 173688 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Left leg: left: before treatment; centre: after intravenous treatment; right: after topical treatment.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Calciphylaxis is a clinical problem with increasing incidence in elderly patients, patients with vascular disease and haemodialysis patients. The treatment of choice should be multidisciplinary.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> The main agent is intravenous sodium thiosulfate (ST); however, it may be poorly tolerated. Here we discuss the possibility of using ST adjuvant treatment.</p><p id="par0010" class="elsevierStylePara elsevierViewall">73-Year-old woman on chronic haemodialysis for end-stage renal failure (diabetic and chronic interstitial nephropathy). Hypertension, hypertensive heart disease, type 2 diabetes mellitus, diabetic neuropathy, chronic revascularised ischaemic heart disease, severe atheromatous of the aorta and visceral branches with mesenteric angina and microscopic colitis, transient ischaemic attack, peripheral vascular disease and severe hyperparathyroidism. Treated with carvedilol, clopidogrel, simvastatin, ezetimibe, omega 3 fatty acids, paricalcitol, cinacalcet, omeprazole, insulin, repaglinide, lanthanum carbonate, transdermal nitroglycerin, oral budesonide, calcifediol, erythropoietin and intravenous iron and carnitine.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Dialysed through a outer humeral gore-tex prosthesis with <span class="elsevierStyleItalic">online haemodiafiltration</span>, for 3<span class="elsevierStyleHsp" style=""></span>h, 4 times a week, with high-permeability polysulfone, anticoagulation with enoxaparin, and calcium bath 1.5<span class="elsevierStyleHsp" style=""></span>mEq/L.</p><p id="par0020" class="elsevierStylePara elsevierViewall">At 18 months she had a painful macular lesion in the distal third of the right leg, which became ulcerated. Diagnostic biopsy revealed atherosclerotic vascular disease, treated conservatively and stabilised. Five months later she received a kidney transplant hat was technically difficult due to severe calcification. Immunosuppression was induced with basiliximab, steroids, tacrolimus, and mycophenolic acid, and kidney function stabilised at Cr 1.2<span class="elsevierStyleHsp" style=""></span>mg/dL (MDRD-IDMS 55<span class="elsevierStyleHsp" style=""></span>ml/min). In the following weeks the ulcer worsened and 3 more lesions appeared on the legs, which were very painful, necrotic that rapidly worsened. A second biopsy showed calciphylaxis, and so oral bisphosphonate and intravenous ST at doses of 7.5<span class="elsevierStyleHsp" style=""></span>g/session/2 sessions per week for 4<span class="elsevierStyleHsp" style=""></span>h were started. She developed metabolic acidosis, severe gastrointestinal intolerance, low blood pressure and general deterioration. The dose of ST was reduced and bed-rest was indicated after each session. No improvement with bicarbonate or ondansetron supplements; so after 50 days of treatment, during which she received 135<span class="elsevierStyleHsp" style=""></span>g for 18 sessions, the ST iv was suspended and topical ST started (magistral formula: 25%, based on Beeler). Occlusive dressings every 12<span class="elsevierStyleHsp" style=""></span>h, alternating with debriding ointment (Dertrase<span class="elsevierStyleSup">®</span>) for 90 days. Now the patient is doing very well, with less pain and with the lesions resolving without significant complications (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Calciphylaxis, or uraemic gangrene or calcific uraemic arteriolopathy,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> is a necrosis of fat caused by hypoperfusion that primarily affects the proximal areas of the legs. The diagnosis was made by biopsy, in which we found necrosis of the epidermis, dermis and hypodermis, intimate fibrodysplasia, micro-thrombosis and calcium deposition in the small arterioles and panniculitis.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> She presented with livedo reticularis, subcutaneous nodules and plaques that lead to necrosis and cause deep necrotic ulcers.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The following are risk factors for their development<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a>: kidney failure (1–4% incidence in haemodialysis and 1.3–4.5% a year in advanced chronic kidney failure),<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> low blood pressure, abnormal calcium and phosphorus product, metabolic syndrome, female gender, Caucasian and treatment with vitamin D, calcium, warfarin or acenocumarol. It can be associated with cirrhosis, Crohn's disease, hyper- or hypoparathyroidism, kidney transplantation, autoimmune diseases, thrombophilia, intravenous iron overload, Hodgkin lymphoma and gastric bypass, among other conditions.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Treatment should be multidisciplinary, treating the infection early, ensuring adequate nutrition, suspending vitamin D and calcium, adding bisphosphonates and, for haemodialysis patients, using a low calcium bath and dialysing daily. Other measures include iloprost, cinacalcet, statins, non-calcium phosphorus chelating agents, common green bottle fly (Lucilia sericata) larvae,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> diltiazem, colchicine and ceftriaxone<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and ST, preferably intravenously.</p><p id="par0040" class="elsevierStylePara elsevierViewall">ST has been used intravenously since 2004 due to its vasodilator and antioxidant effects. It is dialysable (molecular weight: 248<span class="elsevierStyleHsp" style=""></span>Da) and has a half life of 15<span class="elsevierStyleHsp" style=""></span>min with preserved glomerular filtration rate (GFR). Renal clearance is 95% and bile clearance 2%<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a>; it generates acid metabolites (thiosulfuric acid) that last for hours. A dose of 25<span class="elsevierStyleHsp" style=""></span>g 3 times a week in haemodialysis and preserved GF, in a slow infusion, is recommended. For a GF less than 60<span class="elsevierStyleHsp" style=""></span>ml/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> the initial dose is 12.5<span class="elsevierStyleHsp" style=""></span>g/2 times a week.</p><p id="par0045" class="elsevierStylePara elsevierViewall">It may cause acidosis, gastrointestinal intolerance, headache, phlebitis, hypocalcaemia, hypoglycaemia, QT prolongation and abnormal bone mineralisation.</p><p id="par0050" class="elsevierStylePara elsevierViewall">There are reported cases of oral administration,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> intralesional injection<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> and occlusive dressing with emulsion-based zinc oxide, in other ailments,<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8,9</span></a> for 11–24 weeks, with cost saving and no complications.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In our case, the IV route was poorly tolerated, which meant a small cumulative dose (there are cases of 1268<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1555<span class="elsevierStyleHsp" style=""></span>g cumulative dose),<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> and therefore we had to explore other possibilities to prevent previous undesirable effects.</p><p id="par0060" class="elsevierStylePara elsevierViewall">We believe that administration of topical ST is an economical, safe treatment that should not be dismissed as an alternative in selected cases.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Martín Navarro JA, Pedraza Cezón LA, de Pablos Martín MP, González Monte E, Polanco Fernández N, Gutiérrez Sánchez MJ, et al. Tratamiento con tiosulfato de sodio tópico en calcifilaxia de paciente con trasplante renal activo. Nefrologia. 2016;36:579–581.</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" => 776 "Ancho" => 1700 "Tamanyo" => 147308 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Right leg: left: before treatment; centre: after intravenous treatment; right: after topical treatment.</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" => 771 "Ancho" => 1700 "Tamanyo" => 173688 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Left leg: left: before treatment; centre: after intravenous treatment; right: after topical treatment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Calciphylaxis: risk factors, diagnosis, and treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.U. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 1 | 7 | 8 |
| 2024 October | 59 | 40 | 99 |
| 2024 September | 91 | 27 | 118 |
| 2024 August | 83 | 49 | 132 |
| 2024 July | 67 | 29 | 96 |
| 2024 June | 119 | 37 | 156 |
| 2024 May | 75 | 34 | 109 |
| 2024 April | 94 | 29 | 123 |
| 2024 March | 77 | 29 | 106 |
| 2024 February | 70 | 32 | 102 |
| 2024 January | 78 | 30 | 108 |
| 2023 December | 74 | 32 | 106 |
| 2023 November | 81 | 42 | 123 |
| 2023 October | 91 | 32 | 123 |
| 2023 September | 109 | 37 | 146 |
| 2023 August | 112 | 32 | 144 |
| 2023 July | 98 | 36 | 134 |
| 2023 June | 94 | 28 | 122 |
| 2023 May | 122 | 46 | 168 |
| 2023 April | 85 | 30 | 115 |
| 2023 March | 129 | 47 | 176 |
| 2023 February | 103 | 18 | 121 |
| 2023 January | 96 | 31 | 127 |
| 2022 December | 111 | 33 | 144 |
| 2022 November | 103 | 36 | 139 |
| 2022 October | 169 | 41 | 210 |
| 2022 September | 90 | 59 | 149 |
| 2022 August | 124 | 47 | 171 |
| 2022 July | 71 | 39 | 110 |
| 2022 June | 89 | 35 | 124 |
| 2022 May | 120 | 38 | 158 |
| 2022 April | 114 | 50 | 164 |
| 2022 March | 133 | 44 | 177 |
| 2022 February | 135 | 54 | 189 |
| 2022 January | 114 | 33 | 147 |
| 2021 December | 90 | 47 | 137 |
| 2021 November | 80 | 44 | 124 |
| 2021 October | 95 | 48 | 143 |
| 2021 September | 89 | 44 | 133 |
| 2021 August | 100 | 44 | 144 |
| 2021 July | 95 | 47 | 142 |
| 2021 June | 52 | 32 | 84 |
| 2021 May | 78 | 48 | 126 |
| 2021 April | 208 | 112 | 320 |
| 2021 March | 130 | 56 | 186 |
| 2021 February | 128 | 45 | 173 |
| 2021 January | 73 | 23 | 96 |
| 2020 December | 58 | 21 | 79 |
| 2020 November | 72 | 20 | 92 |
| 2020 October | 56 | 29 | 85 |
| 2020 September | 76 | 25 | 101 |
| 2020 August | 108 | 18 | 126 |
| 2020 July | 82 | 22 | 104 |
| 2020 June | 84 | 26 | 110 |
| 2020 May | 122 | 18 | 140 |
| 2020 April | 62 | 28 | 90 |
| 2020 March | 114 | 19 | 133 |
| 2020 February | 93 | 25 | 118 |
| 2020 January | 99 | 25 | 124 |
| 2019 December | 118 | 40 | 158 |
| 2019 November | 108 | 37 | 145 |
| 2019 October | 133 | 18 | 151 |
| 2019 September | 140 | 27 | 167 |
| 2019 August | 109 | 31 | 140 |
| 2019 July | 95 | 18 | 113 |
| 2019 June | 114 | 33 | 147 |
| 2019 May | 77 | 24 | 101 |
| 2019 April | 155 | 39 | 194 |
| 2019 March | 105 | 31 | 136 |
| 2019 February | 68 | 26 | 94 |
| 2019 January | 93 | 26 | 119 |
| 2018 December | 187 | 59 | 246 |
| 2018 November | 233 | 26 | 259 |
| 2018 October | 287 | 40 | 327 |
| 2018 September | 126 | 20 | 146 |
| 2018 August | 122 | 20 | 142 |
| 2018 July | 107 | 27 | 134 |
| 2018 June | 107 | 13 | 120 |
| 2018 May | 119 | 16 | 135 |
| 2018 April | 128 | 15 | 143 |
| 2018 March | 163 | 7 | 170 |
| 2018 February | 103 | 7 | 110 |
| 2018 January | 96 | 8 | 104 |
| 2017 December | 136 | 4 | 140 |
| 2017 November | 87 | 18 | 105 |
| 2017 October | 60 | 3 | 63 |
| 2017 September | 48 | 14 | 62 |
| 2017 August | 29 | 5 | 34 |
| 2017 July | 40 | 14 | 54 |
| 2017 June | 44 | 18 | 62 |
| 2017 May | 58 | 5 | 63 |
| 2017 April | 41 | 18 | 59 |
| 2017 March | 25 | 22 | 47 |
| 2017 February | 86 | 7 | 93 |
| 2017 January | 27 | 13 | 40 |
| 2016 December | 16 | 4 | 20 |
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