Letter to the Editor
Denosumab and chronic kidney disease: Severe life-threatening hypocalcaemia
Denosumab y enfermedad renal crónica avanzada: hipocalcemia severa con riesgo vital
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Fernández-Fresnedo" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Pilar" "apellidos" => "Monge Rafael" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Ángel Luis" "apellidos" => "Martin de Francisco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:4 [ "nombre" => "Gema" "apellidos" => "Fernández-Fresnedo" "email" => array:1 [ 0 => "nefffg@humv.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Endocrinología, Hospital Universitario Marqués de Valdecilla, Santander (Cantabria), Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla, Santander (Cantabria), 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" => "Denosumab y enfermedad renal crónica avanzada: hipocalcemia severa con riesgo vital" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A few months ago, we published a case report of asymptomatic severe hypocalcaemia following a dose of denosumab in a patient with advanced chronic kidney disease.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> We now report a new case, this time one that was life-threatening for the patient. We thought that it important to report this new case due to its severity and, to show that it does no longer seems to be so rare.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 62-year-old woman whose medical history included slight intellectual disability, diabetes mellitus, long-standing dyslipidaemia and hypertension; and colon neoplasm 3 years earlier. She had been diagnosed of chronic kidney disease likely related to nephroangiosclerosis secondary to hypertension, currently in stage 4. Her regular treatment consisted of olmesartan, repaglinide, insulin glargine, atorvastatin, escitalopram, bromazepam, quetiapine and pantoprazole. Six months earlier, she suffered a hip fracture following an accidental fall and underwent implantation of a total hip prosthesis. The Traumatologists started treatment with denosumab 60<span class="elsevierStyleHsp" style=""></span>mg every 6 months and 1500<span class="elsevierStyleHsp" style=""></span>mg of calcium carbonate with 1000<span class="elsevierStyleHsp" style=""></span>IU of cholecalciferol daily to treat osteoporosis. After 10 days of administering denosumab, the patient visited the Emergency Department due to signs and symptoms of general malaise, as well as neck and leg muscle contracture. The testing performed revealed severe hypocalcaemia<span class="elsevierStyleHsp" style=""></span>—<span class="elsevierStyleHsp" style=""></span>5.2<span class="elsevierStyleHsp" style=""></span>mg/dl. Following fluid and electrolyte replacement therapy, her laboratory parameters returned to normal and her signs and symptoms disappeared in 3 days. After a week, the patient visited the Emergency Department again due to new signs and symptoms of anorexia, watery diarrhoea, general malaise, muscle stiffness and hypotension. She had severe hypocalcaemia, hypomagnesaemia, metabolic acidosis and worsening of kidney function. She required admission to the Intensive Care Unit for intravenously managed fluid and electrolyte replacement therapy. She experienced clinical and laboratory improvement. When she was discharged from hospital, treatment was maintained with calcium carbonate, magnesium lactate and calcitriol (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The patient was a woman with osteoporosis. However, in addition, she had advanced chronic kidney disease. In such a situation, osteomineral metabolism abnormality has some distinct, more complex features, with abnormalities in both remodelling and mineralisation rate, with different combinations of these, leading to different patterns of osteomineral abnormality (fibrous osteitis, adynamic bone disease, osteomalacia).<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">2,3</span></a> A few months ago, we published a similar case of severe hypocalcaemia, although that time it was asymptomatic. The use of a powerful antiresorptive agent such as denosumab<a class="elsevierStyleCrossRef" href="#fn0005"><span class="elsevierStyleSup">1</span></a> interferes with these mechanisms. This may lead to hungry bone syndrome by inhibiting osteoclast activity and causing severe hypocalcaemia. We believe that the use of denosumab in patients with advanced chronic kidney disease requires from clinicians to weigh up the risk/benefit ratio and, should they need to administer it, perform a tight follow-up of their patients’ signs and symptoms as well as laboratory values.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Monge Rafael P, Martin de Francisco ÁL, Fernández-Fresnedo G. Denosumab y enfermedad renal crónica avanzada: hipocalcemia severa con riesgo vital. Nefrologia. 2018;38:97–98.</p>" ] 1 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Denosumab is a human monoclonal antibody (IgG2) that binds with great affinity and specificity to RANKL and blocks activation of RANK, its receptor, on the surfaces of osteoclasts and their precursors. This reduces their activity and causes a decrease in bone resorption in trabecular and cortical bone. It is used to treat osteoporosis and administered every 6 months. It is not necessary to adjust the dose in renal failure, but there is an increased risk of hypocalcaemia.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">4,5</span></a></p>" "identificador" => "fn0005" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Laboratory parameters \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Before treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Day 10 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Day 13 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Day 18 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Day 30 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Corrected calcium (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Phosphorus (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Magnesium (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">iPTH (pmol/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">317 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">25-OH Vitamin D (ng/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MDRD (ml/min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1672153.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Laboratory data at baseline and over time.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hipocalcemia severa tras la administración de una dosis de denosumab en un paciente con insuficiencia renal avanzada" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 14 | 13 | 27 |
| 2024 October | 85 | 52 | 137 |
| 2024 September | 71 | 40 | 111 |
| 2024 August | 115 | 74 | 189 |
| 2024 July | 91 | 42 | 133 |
| 2024 June | 137 | 45 | 182 |
| 2024 May | 96 | 36 | 132 |
| 2024 April | 104 | 46 | 150 |
| 2024 March | 87 | 30 | 117 |
| 2024 February | 76 | 46 | 122 |
| 2024 January | 128 | 29 | 157 |
| 2023 December | 66 | 27 | 93 |
| 2023 November | 68 | 38 | 106 |
| 2023 October | 178 | 70 | 248 |
| 2023 September | 188 | 58 | 246 |
| 2023 August | 120 | 44 | 164 |
| 2023 July | 132 | 47 | 179 |
| 2023 June | 76 | 41 | 117 |
| 2023 May | 122 | 49 | 171 |
| 2023 April | 94 | 29 | 123 |
| 2023 March | 147 | 36 | 183 |
| 2023 February | 124 | 29 | 153 |
| 2023 January | 89 | 42 | 131 |
| 2022 December | 105 | 51 | 156 |
| 2022 November | 127 | 46 | 173 |
| 2022 October | 140 | 52 | 192 |
| 2022 September | 125 | 47 | 172 |
| 2022 August | 124 | 56 | 180 |
| 2022 July | 124 | 54 | 178 |
| 2022 June | 122 | 43 | 165 |
| 2022 May | 103 | 36 | 139 |
| 2022 April | 135 | 51 | 186 |
| 2022 March | 161 | 68 | 229 |
| 2022 February | 152 | 48 | 200 |
| 2022 January | 173 | 59 | 232 |
| 2021 December | 127 | 50 | 177 |
| 2021 November | 170 | 46 | 216 |
| 2021 October | 209 | 56 | 265 |
| 2021 September | 183 | 48 | 231 |
| 2021 August | 155 | 45 | 200 |
| 2021 July | 188 | 48 | 236 |
| 2021 June | 168 | 29 | 197 |
| 2021 May | 172 | 54 | 226 |
| 2021 April | 531 | 90 | 621 |
| 2021 March | 281 | 35 | 316 |
| 2021 February | 273 | 43 | 316 |
| 2021 January | 263 | 53 | 316 |
| 2020 December | 195 | 17 | 212 |
| 2020 November | 203 | 25 | 228 |
| 2020 October | 190 | 27 | 217 |
| 2020 September | 148 | 33 | 181 |
| 2020 August | 139 | 19 | 158 |
| 2020 July | 164 | 20 | 184 |
| 2020 June | 161 | 23 | 184 |
| 2020 May | 180 | 24 | 204 |
| 2020 April | 133 | 24 | 157 |
| 2020 March | 183 | 22 | 205 |
| 2020 February | 256 | 28 | 284 |
| 2020 January | 277 | 34 | 311 |
| 2019 December | 275 | 39 | 314 |
| 2019 November | 337 | 39 | 376 |
| 2019 October | 422 | 32 | 454 |
| 2019 September | 599 | 35 | 634 |
| 2019 August | 353 | 29 | 382 |
| 2019 July | 213 | 42 | 255 |
| 2019 June | 203 | 18 | 221 |
| 2019 May | 181 | 32 | 213 |
| 2019 April | 271 | 59 | 330 |
| 2019 March | 149 | 37 | 186 |
| 2019 February | 123 | 30 | 153 |
| 2019 January | 116 | 26 | 142 |
| 2018 December | 144 | 44 | 188 |
| 2018 November | 211 | 24 | 235 |
| 2018 October | 116 | 12 | 128 |
| 2018 September | 82 | 15 | 97 |
| 2018 August | 69 | 13 | 82 |
| 2018 July | 48 | 15 | 63 |
| 2018 June | 44 | 8 | 52 |
| 2018 May | 47 | 13 | 60 |
| 2018 April | 44 | 8 | 52 |
| 2018 March | 62 | 11 | 73 |
| 2018 February | 64 | 8 | 72 |
| 2018 January | 51 | 12 | 63 |
| 2017 December | 42 | 11 | 53 |
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