Letters to the Editor
New information on phosphate binder interactions with vitamin K
Nueva información sobre interacciones de captores de fósforo con la vitamina K
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phosphate binder interactions with vitamin K" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">Dear Editor</span>," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "369" "paginaFinal" => "370" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Jordi Bover, Juan Francisco Navarro-González, Iara daSilva" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Jordi" "apellidos" => "Bover" "email" => array:1 [ 0 => "jbover@fundacio-puigvert.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Juan Francisco" "apellidos" => "Navarro-González" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Iara" "apellidos" => "daSilva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Nefrología y Unidad de Investigación, Hospital Universitario Nuestra Señora de la Candelaria, REDinREN, Santa Cruz de Tenerife, Tenerife, 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" => "Nueva información sobre interacciones de captores de fósforo con la vitamina K" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We recently published an editorial in the journal <span class="elsevierStyleSmallCaps">Nefrología</span> to draw attention to a little known aspect of phosphate binders, specifically their potential pharmacological interactions.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> In this article, we underlined that sevelamer can reduce the absorption of fat-soluble vitamins D, E and K and folic acid (according to the summary of product characteristics), although with debatable clinical impact. These data from the summary of product characteristics were obtained from experimental pre-clinical studies in rats and dogs and <span class="elsevierStyleItalic">in vitro</span> studies.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In recent years, the distinction between vitamin K<span class="elsevierStyleInf">1</span> (phylloquinone or phytomenadione) and vitamins K<span class="elsevierStyleInf">2</span> (menaquinones) has been emphasised and, in the nephrology community, these vitamins have gained importance as it has been recognised that vitamin K deficiency is very common in kidney patients, in particular those on renal replacement therapy.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> This vitamin K deficiency would limit the post-translational activation by carboxylation and phosphorylation of multiple proteins related to the inhibition of vascular calcification (<span class="elsevierStyleBold">K</span>-alcification) (osteocalcin, Bone-Gla protein, Matrix-Gla protein [MGP], among other vitamin K-dependent proteins), in addition to their effects on the classic coagulation pathways (<span class="elsevierStyleBold">K</span>-oagulation).<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Therefore, as vitamin K is an important cofactor for the activation of these proteins, its deficiency produces an increase in inactive forms (dephosphorylated-uncarboxylated),<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> with vitamin K<span class="elsevierStyleInf">2</span> being the preferred cofactor for the carboxylation of MGP (tissue inhibitor of vascular calcification).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> In this way, very recent studies (included in Figure 1 of the publication) have underlined that sevelamer (just like sucroferric oxyhydroxide [SOH] and in contrast to lanthanum carbonate) did not seem to have interactions with vitamin K<span class="elsevierStyleInf">2</span>.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> This information comes from the publication by Neradova et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> in which it was reported that SOH and sevelamer did not bind to vitamin K<span class="elsevierStyleInf">2</span><span class="elsevierStyleItalic">in vitro</span>, both in the presence and in the absence of phosphate in the solution.</p><p id="par0015" class="elsevierStylePara elsevierViewall">However, a subsequent study in patients with chronic kidney disease (CKD) (on haemodialysis, peritoneal dialysis and transplant patients)<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> has analysed the impact of phosphate binders on vitamin K status in humans for the first time. These authors measured dephosphorylated-uncarboxylated MGP (inactive MGP), with a validated and standardised technique that better reflects vitamin K status than “simple” measurement of uncarboxylated MGP.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> This study demonstrated an association between monotherapy with sevelamer and higher levels of dephosphorylated-uncarboxylated MGP (inactive) after adjusting for age, gender and use of vitamin K, suggesting a possible worsening of vitamin K status with this phosphate binder, with the potential negative impact on vascular calcification progression in these patients.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> However, as we have pointed out previously, these interactions with vitamins have a debatable clinical impact. For example, no significant interactions have been reported in any of the summary of product characteristics for sevelamer, lanthanum or SOH (in healthy volunteers at least) with warfarin (vitamin K antagonist, with acenocoumarol being our normal equivalent). Furthermore, several studies and/or meta-analyses report (although not uniformly) an attenuation in the progression of vascular/valvular calcification and improvements in survival on dialysis with the use of non-calcium chelating agents in general and sevelamer (for which the greatest and most extensive experience is available), in particular.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7–9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Given the growing awareness acquired with the frequent use of vitamin K antagonists such as anticoagulants in patients with CKD, the potential use of vitamin K in kidney patients<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> and/or the emergence, with possible advantages, of the novel oral anticoagulants (NOACs),<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> independent of vitamin K, we believe it is relevant to highlight that this new information could be clinically relevant in the choice of phosphate binders, the concomitant prescription with acenocoumarol and, indeed, it should also be taken into account in the design and assessment of both current and future clinical studies.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors declare that they have not received funding to carry out this work.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0030" class="elsevierStylePara elsevierViewall">J.B. has received fees for conferences from AbbVie, Amgen, Genzyme and Shire, as well as for consultations from AbbVie, Amgen, Vifor/Fresenius-Renal Pharma, Chugai, Medice and Genzyme/Sanofi. J.F.N.G. has received fees for conferences and/or consultations from AbbVie, Amgen, Astra-Zeneca, Boehringer-Ingelheim, Esteve, Genzyme, Sanofi, Servier, Shire and Vifor/Fresenius-Renal Pharma. I.D. has received fees for scientific collaboration with Vifor/Fresenius-Renal Pharma.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of interest" ] 2 => 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: Bover J, Navarro-González JF, daSilva I. Nueva información sobre interacciones de captores de fósforo con la vitamina K. Nefrologia. 2020;40:369–370.</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" => "Interacciones farmacológicas de los captores del fósforo" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Bover" 1 => "J.F. Navarro-González" 2 => "M.D. Arenas" 3 => "V. Torregrosa" 4 => "J. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 8 | 14 |
| 2024 October | 42 | 50 | 92 |
| 2024 September | 58 | 34 | 92 |
| 2024 August | 70 | 71 | 141 |
| 2024 July | 45 | 37 | 82 |
| 2024 June | 61 | 34 | 95 |
| 2024 May | 47 | 29 | 76 |
| 2024 April | 47 | 30 | 77 |
| 2024 March | 74 | 27 | 101 |
| 2024 February | 44 | 31 | 75 |
| 2024 January | 32 | 28 | 60 |
| 2023 December | 31 | 21 | 52 |
| 2023 November | 59 | 38 | 97 |
| 2023 October | 42 | 38 | 80 |
| 2023 September | 51 | 32 | 83 |
| 2023 August | 55 | 23 | 78 |
| 2023 July | 60 | 25 | 85 |
| 2023 June | 57 | 20 | 77 |
| 2023 May | 62 | 33 | 95 |
| 2023 April | 38 | 17 | 55 |
| 2023 March | 59 | 19 | 78 |
| 2023 February | 49 | 19 | 68 |
| 2023 January | 65 | 24 | 89 |
| 2022 December | 60 | 36 | 96 |
| 2022 November | 71 | 29 | 100 |
| 2022 October | 74 | 44 | 118 |
| 2022 September | 99 | 37 | 136 |
| 2022 August | 76 | 45 | 121 |
| 2022 July | 79 | 57 | 136 |
| 2022 June | 46 | 39 | 85 |
| 2022 May | 67 | 41 | 108 |
| 2022 April | 58 | 45 | 103 |
| 2022 March | 56 | 49 | 105 |
| 2022 February | 88 | 54 | 142 |
| 2022 January | 56 | 38 | 94 |
| 2021 December | 44 | 49 | 93 |
| 2021 November | 51 | 30 | 81 |
| 2021 October | 62 | 64 | 126 |
| 2021 September | 40 | 43 | 83 |
| 2021 August | 56 | 42 | 98 |
| 2021 July | 49 | 30 | 79 |
| 2021 June | 39 | 38 | 77 |
| 2021 May | 63 | 42 | 105 |
| 2021 April | 68 | 43 | 111 |
| 2021 March | 57 | 33 | 90 |
| 2021 February | 46 | 37 | 83 |
| 2021 January | 33 | 26 | 59 |
| 2020 December | 34 | 16 | 50 |
| 2020 November | 19 | 10 | 29 |
| 2020 October | 32 | 16 | 48 |
| 2020 September | 36 | 29 | 65 |
| 2020 August | 29 | 16 | 45 |
| 2020 July | 47 | 24 | 71 |
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