Letter to the Editor
Kidney failure caused by tubular intersticial nephropathy with Fanconi syndrome after treatment with zoledronic acid
Insuficiencia renal por nefropatía tubulointersticial con tubulopatía proximal tipo Fanconi tras tratamiento con ácido zoledrónico
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José Gutiérrez Sánchez, Vladimir Petkov Stoyanov, Luis Pedraza Cezón, Juan A. Martín Navarro" "autores" => array:4 [ 0 => array:3 [ "nombre" => "M. José" "apellidos" => "Gutiérrez Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Vladimir" "apellidos" => "Petkov Stoyanov" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Luis" "apellidos" => "Pedraza Cezón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => 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" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad de Nefrología, Hospital del Tajo, Aranjuez (Madrid), Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Farmacia, Hospital del Tajo, Aranjuez (Madrid), 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" => "Insuficiencia renal por nefropatía tubulointersticial con tubulopatía proximal tipo Fanconi tras tratamiento con ácido zoledrónico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1506 "Ancho" => 1658 "Tamanyo" => 176965 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Blood chemistry evolution. FE UA: fractional excretion of uric acid (in %). Creatinine, uric acid, phosphataemia and proteinuria in mg/dl.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The relationship between kidney disease and bisphosphonates is illustrated in the medical literature<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a>: the vast majority of cases involve glomerulonephritis and acute tubular necrosis. We discuss a case of tubulopathy related to the administration of zoledronic acid. This association has been described, although infrequently.</p><p id="par0010" class="elsevierStylePara elsevierViewall">80-Year-old man with COPD and dyslipidaemia treated with inhaled indacaterol and aclidinium bromide, oral atorvastatin and omeprazole, who presented with acute kidney failure in October 2013 due to obstructive uropathy. He was diagnosed with Gleason score 10 prostate cancer and, after placement of urinary catheter, he recovered his baseline glomerular filtration rate (Cr: 1.1<span class="elsevierStyleHsp" style=""></span>mg/dl). An extension study showed osteoblastic metastasis in the iliac wing. He was treated by a transurethral resection of the prostate and hormonal therapy (bicalutamide and leuprolide), to which intravenous zoledronic acid was added at a dosage of 4<span class="elsevierStyleHsp" style=""></span>mg per month from November 2013. His glomerular filtration rate progressively deteriorated and he developed hypophosphataemia, hyperphosphaturia, hypouricaemia, hyperuricosuria, non-nephrotic range mixed proteinuria, metabolic acidosis with normal anion gap, and glycosuria with aminoaciduria, which was the reason for consultation. His accumulated dose of zoledronic acid was 116<span class="elsevierStyleHsp" style=""></span>mg over 29 months. With these findings, he was diagnosed with kidney failure due to interstitial nephritis with Fanconi syndrome. The zoledronic acid was discontinued and substituted by denosumab. After 6 months of follow-up, the aminoaciduria and glycosuria disappeared, the uricosuria was reduced and the phosphataemia was normalised. Proteinuria continued to decrease, however, he only partially recovered glomerular filtration rate (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Bisphosphonates are bene anti-reabsorbing agents used to treat corticosteroid-induced post-menopausal osteoporosis and to prevent pathological fractures in Paget's disease, prostate or lung cancer and multiple myeloma. Strong biphosphonates have a nitrogenous chain in their structure. They may be administered orally or intravenously. In the former, they do not tend to induce nephrotoxicity. Intravenous administration involves circumventing the hepatic metabolism, interaction with the P450 enzymatic system and its unaltered excretion in the kidney, through glomerular filtration and through active tubular secretion which would account for the tubular damage. The strongest are pamidronate and zoledronic acid. Both have been associated with focal segmental glomerulonephritis, with minimal changes, as well as with severe tubular damage. Zoledronic acid normally produces toxic acute tubular necrosis, in part due to by its long half-life in plasma (150–200 days) and low binding rate with plasma proteins (56%). In rats,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> a single dose of 1<span class="elsevierStyleHsp" style=""></span>mg/kg induces proximal tubulopathy, while a dose of 10<span class="elsevierStyleHsp" style=""></span>mg/kg provokes additional damage in the distal tubule. The ratio between the lowest lethal dosage and the minimal nephrotoxic dosage is 3.3.</p><p id="par0020" class="elsevierStylePara elsevierViewall">In humans, it may cause direct mitochondrial damage and podocyte injury, secondary to farnesyl diphosphate inhibition, with decrease in prenylated proteins in the proximal tubule and direct toxicity to the parietal epithelial cells.</p><p id="par0025" class="elsevierStylePara elsevierViewall">We have only found 3 cases of Fanconi syndrome described in the medical literature (PubMed dated 23 November 2016 with the keywords: Fanconi and zoledronic acid) attributed to zoledronic acid administration.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The first case<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> is a 54-year-old woman with breast cancer who, 12 years after diagnosis, presented with hepatic and bone metastases treated with docetaxel, trastuzumab and zoledronic acid at doses of 4<span class="elsevierStyleHsp" style=""></span>mg/month IV. After one year of treatment, she developed a proximal tubulopathy, with deterioration of glomerular filtration rate. Evidence of interstitial nephritis and tubulopathy were identified in the renal biopsy. After discontinuing the zoledronic acid, the glomerular filtration rate was recovered.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The second case<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> is that of a 61-year-old woman with breast cancer and bone and liver metastases, which required zoledronic acid to be added to her basic treatment at a dose of 4<span class="elsevierStyleHsp" style=""></span>mg/week. At the ninth week, (36<span class="elsevierStyleHsp" style=""></span>mg accumulated) she developed proximal tubulopathy with glomerular filtration rate deterioration, which she also recovered upon discontinuing the zoledronic acid.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The third case<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> is that of a 60-year-old woman with metastatic colon cancer undergoing treatment with FOLFOX-6 and bevacizumab together with zoledronic acid. She developed hypokalaemia, hypocalcaemia, hypophosphataemia and proximal tubulopathy, from which she recovered after zoledronic acid was discontinued and substituted by denosumab.</p><p id="par0045" class="elsevierStylePara elsevierViewall">To the best our knowledge, this is the fourth reported case of Fanconi syndrome related to the administration of zoledronic acid. We believe it is important to bear in mind that interstitial nephropathy presenting with Fanconi syndrome is an undesirable effect of zoledronic acid which requires the close monitoring of tubular function in patients with this treatment.</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: Gutiérrez Sánchez MJ, Petkov Stoyanov V, Pedraza Cezón L, Martín Navarro JA. Insuficiencia renal por nefropatía tubulointersticial con tubulopatía proximal tipo Fanconi tras tratamiento con ácido zoledrónico. Nefrologia. 2017;37:660–661.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1506 "Ancho" => 1658 "Tamanyo" => 176965 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Blood chemistry evolution. FE UA: fractional excretion of uric acid (in %). Creatinine, uric acid, phosphataemia and proteinuria in mg/dl.</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" => "Bisphosphonate nephrotoxicity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.A. Perazella" 1 => "G.S. 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Sato" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Gan To Kagaku Ryoho" "fecha" => "2015" "volumen" => "42" "paginaInicial" => "867" "paginaFinal" => "870" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26197752" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000003700000006/v1_201712030528/S2013251417301803/v1_201712030528/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/20132514/0000003700000006/v1_201712030528/S2013251417301803/v1_201712030528/en/main.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2013251417301803?idApp=UINPBA000064" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 9 | 15 |
| 2024 October | 54 | 38 | 92 |
| 2024 September | 68 | 42 | 110 |
| 2024 August | 101 | 64 | 165 |
| 2024 July | 69 | 35 | 104 |
| 2024 June | 77 | 44 | 121 |
| 2024 May | 63 | 43 | 106 |
| 2024 April | 70 | 36 | 106 |
| 2024 March | 47 | 36 | 83 |
| 2024 February | 67 | 42 | 109 |
| 2024 January | 39 | 22 | 61 |
| 2023 December | 32 | 32 | 64 |
| 2023 November | 72 | 40 | 112 |
| 2023 October | 59 | 36 | 95 |
| 2023 September | 50 | 46 | 96 |
| 2023 August | 67 | 41 | 108 |
| 2023 July | 55 | 44 | 99 |
| 2023 June | 85 | 26 | 111 |
| 2023 May | 107 | 43 | 150 |
| 2023 April | 51 | 22 | 73 |
| 2023 March | 43 | 17 | 60 |
| 2023 February | 31 | 20 | 51 |
| 2023 January | 51 | 30 | 81 |
| 2022 December | 73 | 34 | 107 |
| 2022 November | 44 | 40 | 84 |
| 2022 October | 59 | 39 | 98 |
| 2022 September | 59 | 39 | 98 |
| 2022 August | 56 | 51 | 107 |
| 2022 July | 49 | 57 | 106 |
| 2022 June | 34 | 51 | 85 |
| 2022 May | 74 | 42 | 116 |
| 2022 April | 76 | 62 | 138 |
| 2022 March | 108 | 58 | 166 |
| 2022 February | 70 | 61 | 131 |
| 2022 January | 78 | 44 | 122 |
| 2021 December | 69 | 47 | 116 |
| 2021 November | 62 | 46 | 108 |
| 2021 October | 46 | 45 | 91 |
| 2021 September | 69 | 47 | 116 |
| 2021 August | 67 | 52 | 119 |
| 2021 July | 83 | 43 | 126 |
| 2021 June | 69 | 32 | 101 |
| 2021 May | 77 | 60 | 137 |
| 2021 April | 153 | 68 | 221 |
| 2021 March | 72 | 53 | 125 |
| 2021 February | 68 | 37 | 105 |
| 2021 January | 47 | 27 | 74 |
| 2020 December | 46 | 21 | 67 |
| 2020 November | 43 | 16 | 59 |
| 2020 October | 38 | 23 | 61 |
| 2020 September | 50 | 21 | 71 |
| 2020 August | 50 | 16 | 66 |
| 2020 July | 48 | 21 | 69 |
| 2020 June | 71 | 25 | 96 |
| 2020 May | 55 | 11 | 66 |
| 2020 April | 48 | 33 | 81 |
| 2020 March | 61 | 17 | 78 |
| 2020 February | 52 | 22 | 74 |
| 2020 January | 60 | 31 | 91 |
| 2019 December | 67 | 25 | 92 |
| 2019 November | 85 | 32 | 117 |
| 2019 October | 60 | 15 | 75 |
| 2019 September | 62 | 26 | 88 |
| 2019 August | 32 | 22 | 54 |
| 2019 July | 39 | 27 | 66 |
| 2019 June | 39 | 28 | 67 |
| 2019 May | 68 | 43 | 111 |
| 2019 April | 79 | 43 | 122 |
| 2019 March | 49 | 35 | 84 |
| 2019 February | 34 | 20 | 54 |
| 2019 January | 39 | 24 | 63 |
| 2018 December | 120 | 50 | 170 |
| 2018 November | 165 | 38 | 203 |
| 2018 October | 193 | 21 | 214 |
| 2018 September | 101 | 23 | 124 |
| 2018 August | 63 | 17 | 80 |
| 2018 July | 65 | 16 | 81 |
| 2018 June | 77 | 15 | 92 |
| 2018 May | 84 | 8 | 92 |
| 2018 April | 81 | 12 | 93 |
| 2018 March | 56 | 11 | 67 |
| 2018 February | 40 | 5 | 45 |
| 2018 January | 51 | 7 | 58 |
| 2017 December | 58 | 9 | 67 |
| 2017 November | 46 | 4 | 50 |
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