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Salanova Villanueva, M. C. Sánchez González, J. A. Sánchez Tomero, P. Sanz" "autores" => array:4 [ 0 => array:4 [ "Iniciales" => "L." "apellidos" => "Salanova Villanueva" "email" => array:1 [ 0 => "laurasalanova@yahoo.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:3 [ "Iniciales" => "M. C." "apellidos" => "Sánchez González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 2 => array:3 [ "Iniciales" => "J. A." "apellidos" => "Sánchez Tomero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 3 => array:3 [ "Iniciales" => "P." "apellidos" => "Sanz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario de la Princesa, Madrid, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Sección de Nefrología, Hospital San Camilo, Madrid, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento exitoso con tiosulfato sódico en la arteriolopatía urémica calcificante" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10859_108_17671_en_f110859.jpg" "Alto" => 447 "Ancho" => 600 "Tamanyo" => 264736 ] ] "descripcion" => array:1 [ "en" => "Lesion on right leg prior to treatment with thiosulfate." ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">To the Editor, </span></p><p class="elsevierStylePara">A dermatological manifestation of chronic kidney disease (CKD) is calcific uraemic arteriolopathy (CUA) or calciphylaxis. It is an anatomopathological entity characterised by necrosis of the skin and adipose tissue due to incorrect calcium salt deposits.<span class="elsevierStyleSup">1</span> Morbidity and mortality of calciphylaxis is high due to the complications associated with it: sepsis and ischaemia. Different clinical entities can manifest calciphylaxis: rheumatoid arthritis, inflammatory bowel disease, neoplasias, CKD, systemic lupus erythematosus or HIV infection.<span class="elsevierStyleSup">1</span> Its treatment has to be aggressive. Sodium thiosulfate has shown improvements in skin lesions caused by calciphylaxis.</p><p class="elsevierStylePara">Our patient was a 78-year-old man with history of high blood pressure, diabetes mellitus type 2, dyslipidaemia, CKD of unknown origin treated with haemodialysis three times a week for 3hr, mineral and bone disorder associated with CKD (MBD-CKD), auricular fibrillation and ischaemic heart disease. His usual treatment was sevelamer, enalapril, aspirin, acenocumarol and insulin.</p><p class="elsevierStylePara">He was admitted to hospital for painful skin erythematous lesions with necrotic edges on both lower limbs, measuring 5x6cm. Physical examination: good general condition, body mass index: 23; blood pressure 150/63mm Hg; heart rate 64bpm; no fever. Cardiopulmonary and abdominal auscultation: painless. Lower limbs: normal pulse, with no sign of deep vein thrombosis and showing previously described lesions. Analyses: parathyroid hormone (PTH): 826.3pg/ml, calcium: 8.9mg/dl; phosphorus; 7.40; creatinine: 9.8mg/dl; albumin: 3g/dl; urea: 156mg/dl; C-reactive protein; 4.3. A cervical ultrasound and parathyroid gammagraphy were performed showing parathyroid hyperplasia free of adenomas. The radiological study (bone series and supra-aortic trunks Doppler) showed vascular calcifications on the ascending and descending aorta. Given the suspected calciphylaxis, we performed a biopsy of one of the lesions, with results compatible with calciphylaxis: lesion with abundant calcium deposits compared with the walls of small vascular structures. Swollen septa due to fibrosis (Figure 1). No signs of necrosis are observed. Lastly, we performed a technetium-99 gammagraphy which did not show that the calciphylaxis spread to the bones.</p><p class="elsevierStylePara">We considered MBD-CKD to be the cause of calciphylaxis and intensified the treatment for it: daily dialysis of 4hr was started with low calcium (2.5mEq/l) in the haemodialysis solution and high flux dialyser. The treatment was intensified with calcium-free phosphate-binders: lanthanum carbonate: 750mg/8hr and sevelamer: 1600mg/8hr, and PTH control with calcimimetics: 60mg/24hr. Acenocoumarol was withdrawn and treatment was started with 80ml of sodium thiosulfate at 25% (20g) following haemodialysis (three times per week). Lesions improved 2 months later (Figure 2). Analytical parameters upon discharge: P: 3.6mg/dl; total Ca: 8.9mg/dl; PTH: 406.90pg/ml.</p><p class="elsevierStylePara">CUA consists of a hydroxyapatite deposit in the skin and soft tissues with risk of necrosis. In CKD, CUA physiopathology is due to an alteration in phosphocalcic metabolism, uraemic state, increase in PTH (although there are CUA cases following parathyroidectomy)<span class="elsevierStyleSup">2</span>, calcium-based phosphate binders and a high calcium concentration in the dialysis solution.<span class="elsevierStyleSup">3</span> Phosphate and calcium are bound producing vascular, skin and organic calcifications.<span class="elsevierStyleSup">4</span></p><p class="elsevierStylePara">Other predisposing factors are: female sex, obesity,<span class="elsevierStyleSup">5</span> hypoalbuminaemia (<2g/dl), diabetes mellitus, C and S protein deficiency,<span class="elsevierStyleSup">6</span> oral anticoagulants (they inhibit synthesis of 4.8-gamma-carboxyglumate)<span class="elsevierStyleSup">7</span>, intravenous iron and vitamin D due to its intestinal action on calcium reabsorption.<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">Lesions caused by CUA are often on the abdomen and the calf area, given their abundance of subcutaneous tissue. The lesion is similar to <span class="elsevierStyleItalic">livedo reticularis </span>progressing to ulceration. Calcium deposits in skin are deposited in the dermis and subcutaneous tissue. Physio-pathogenitically, high levels of urea and phosphorus cause smooth muscle cells to convert into osteoblast cells that also increase osteopontin levels, which together with proinflammatory and free radical molecules, make it easier for phosphorus to adhere to calcium.<span class="elsevierStyleSup">1,7,9,10</span> This magma is mostly concentrated around calcium deposits that are also found in the arterioles<span class="elsevierStyleSup">1</span> and media of the vessels.</p><p class="elsevierStylePara">The diagnosis is essentially clinical. Lesion biopsy is not recommended given the risk of infection and ulceration.<span class="elsevierStyleSup">10</span> Gammagraphy with technetium-99 is used to diagnose whether it has spread to the bones.<span class="elsevierStyleSup">10</span> Calciphylaxis has a morbidity and mortality of 80% given the risk of infection and necrosis.</p><p class="elsevierStylePara">The CUA therapeutic approach must be aggressive, controlling its associated alterations (BMD-CKD control), avoiding agents that could strengthen it, and curing the lesion and infectious complications.<span class="elsevierStyleSup">2</span> BMD-CKD control will be performed using calcium-free phosphate binders, low calcium haemodialysis and peritoneal dialysis solutions (CUA can develop above 4mEq/l<span class="elsevierStyleSup">11</span>) and implementing daily haemodialysis. PTH control will be performed using calcimimetics and vitamin D, preferably vitamin D analogues given that they have a lower calcifying and hyperphosphatemic effect.<span class="elsevierStyleSup">2</span> Parathyroidectomy will be reserved for cases resistant to drug treatment.</p><p class="elsevierStylePara">Dermal CUA lesions that have no ulcerations improve with corticoids.<span class="elsevierStyleSup">10</span> However, for those with ulceration, the hyperbaric oxygen chamber is effective against anaerobic organims.<span class="elsevierStyleSup">11</span> The sodium thiosulfate (antidote against cynade, used in skin treatments for acne and pityriasis versicolor, and protection against carboplatin and cisplatin toxicity) has proven a successful therapeutic measure in CUA lessions.<span class="elsevierStyleSup">5,14</span> Sodium thiosulfate inhibits calcium salt precipitation and dissolves calcium deposits.<span class="elsevierStyleSup">12,13</span> It does not have any effects on levels of calcium, phosphorus or PTH. The recommended dose is 20g I.V., three times a week during a minimum of 6 months.<span class="elsevierStyleSup">2,14</span> Its administration could lead to metabolic acidosis, osteoclast activation, volume overload and hypotension.</p><p class="elsevierStylePara">In summary, CUA is a serious entity among our patients. Its treatment has to be aggressive. Sodium thiosulfate is a valid therapeutic agent for treating CUA lesions. It is safe to use and the benefits obtained mean that it can be considered a first-line drug for CUA lesions.</p><p class="elsevierStylePara"><a href="grande/10859_108_17671_en_f110859.jpg" class="elsevierStyleCrossRefs"><img src="10859_108_17671_en_f110859.jpg" alt="Lesion on right leg prior to treatment with thiosulfate."></img></a></p><p class="elsevierStylePara">Figure 1. Lesion on right leg prior to treatment with thiosulfate.</p><p class="elsevierStylePara"><a href="grande/10859_108_17672_en_f210859.jpg" class="elsevierStyleCrossRefs"><img src="10859_108_17672_en_f210859.jpg" alt="Lesion on right leg after two months of treatment with sodium thiosulfate."></img></a></p><p class="elsevierStylePara">Figure 2. 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Year/Month | Html | Total | |
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2024 October | 73 | 28 | 101 |
2024 September | 98 | 30 | 128 |
2024 August | 98 | 57 | 155 |
2024 July | 95 | 41 | 136 |
2024 June | 107 | 52 | 159 |
2024 May | 95 | 41 | 136 |
2024 April | 63 | 35 | 98 |
2024 March | 71 | 24 | 95 |
2024 February | 61 | 40 | 101 |
2024 January | 68 | 34 | 102 |
2023 December | 55 | 26 | 81 |
2023 November | 73 | 39 | 112 |
2023 October | 93 | 48 | 141 |
2023 September | 105 | 28 | 133 |
2023 August | 99 | 21 | 120 |
2023 July | 123 | 28 | 151 |
2023 June | 108 | 23 | 131 |
2023 May | 102 | 38 | 140 |
2023 April | 71 | 28 | 99 |
2023 March | 96 | 29 | 125 |
2023 February | 40 | 27 | 67 |
2023 January | 101 | 25 | 126 |
2022 December | 66 | 34 | 100 |
2022 November | 89 | 38 | 127 |
2022 October | 86 | 36 | 122 |
2022 September | 94 | 35 | 129 |
2022 August | 76 | 56 | 132 |
2022 July | 76 | 65 | 141 |
2022 June | 82 | 49 | 131 |
2022 May | 75 | 37 | 112 |
2022 April | 84 | 48 | 132 |
2022 March | 58 | 48 | 106 |
2022 February | 82 | 41 | 123 |
2022 January | 86 | 30 | 116 |
2021 December | 93 | 42 | 135 |
2021 November | 91 | 35 | 126 |
2021 October | 92 | 31 | 123 |
2021 September | 105 | 46 | 151 |
2021 August | 75 | 53 | 128 |
2021 July | 105 | 32 | 137 |
2021 June | 88 | 27 | 115 |
2021 May | 106 | 53 | 159 |
2021 April | 169 | 80 | 249 |
2021 March | 137 | 47 | 184 |
2021 February | 144 | 39 | 183 |
2021 January | 98 | 22 | 120 |
2020 December | 92 | 14 | 106 |
2020 November | 51 | 18 | 69 |
2020 October | 67 | 17 | 84 |
2020 September | 117 | 15 | 132 |
2020 August | 100 | 12 | 112 |
2020 July | 92 | 16 | 108 |
2020 June | 72 | 25 | 97 |
2020 May | 76 | 18 | 94 |
2020 April | 104 | 16 | 120 |
2020 March | 103 | 12 | 115 |
2020 February | 102 | 28 | 130 |
2020 January | 105 | 32 | 137 |
2019 December | 67 | 24 | 91 |
2019 November | 96 | 21 | 117 |
2019 October | 107 | 22 | 129 |
2019 September | 117 | 17 | 134 |
2019 August | 70 | 16 | 86 |
2019 July | 107 | 26 | 133 |
2019 June | 92 | 33 | 125 |
2019 May | 75 | 16 | 91 |
2019 April | 142 | 41 | 183 |
2019 March | 97 | 18 | 115 |
2019 February | 65 | 16 | 81 |
2019 January | 79 | 12 | 91 |
2018 December | 117 | 48 | 165 |
2018 November | 176 | 14 | 190 |
2018 October | 183 | 17 | 200 |
2018 September | 128 | 17 | 145 |
2018 August | 82 | 20 | 102 |
2018 July | 102 | 20 | 122 |
2018 June | 116 | 14 | 130 |
2018 May | 129 | 20 | 149 |
2018 April | 100 | 9 | 109 |
2018 March | 93 | 9 | 102 |
2018 February | 102 | 8 | 110 |
2018 January | 136 | 18 | 154 |
2017 December | 90 | 15 | 105 |
2017 November | 73 | 5 | 78 |
2017 October | 47 | 12 | 59 |
2017 September | 63 | 12 | 75 |
2017 August | 42 | 14 | 56 |
2017 July | 42 | 10 | 52 |
2017 June | 62 | 10 | 72 |
2017 May | 66 | 11 | 77 |
2017 April | 62 | 20 | 82 |
2017 March | 43 | 15 | 58 |
2017 February | 137 | 10 | 147 |
2017 January | 77 | 16 | 93 |
2016 December | 77 | 16 | 93 |
2016 November | 121 | 13 | 134 |
2016 October | 239 | 9 | 248 |
2016 September | 348 | 2 | 350 |
2016 August | 456 | 8 | 464 |
2016 July | 279 | 14 | 293 |
2016 June | 194 | 0 | 194 |
2016 May | 141 | 0 | 141 |
2016 April | 157 | 0 | 157 |
2016 March | 121 | 0 | 121 |
2016 February | 139 | 0 | 139 |
2016 January | 114 | 0 | 114 |
2015 December | 135 | 0 | 135 |
2015 November | 98 | 0 | 98 |
2015 October | 101 | 0 | 101 |
2015 September | 100 | 0 | 100 |
2015 August | 72 | 0 | 72 |
2015 July | 89 | 0 | 89 |
2015 June | 57 | 0 | 57 |
2015 May | 58 | 0 | 58 |
2015 April | 5 | 0 | 5 |