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          "en" => "– Relationship between therapies and baseline serum 25¿OH¿D3 levels&#46; Patients were divided in three groups according with the concomitant therapies&#44; and there were significant statistical differences between groups &#40;p <0 001 patients who were not receiving renin angiotensin system ras inhibitors or allopurinol n="30&#41;" presented lower 25 8209 oh d3 d levels than those and plus p <0 001 highest 25 8209 oh d3 levels 11 7 3 p="0&#46;005&#41;" were found in patients receiving ras inhibitors plus allopurinol without statins lowest 5 1 82 who only</0> </0>"
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introduction </span></p><p class="elsevierStylePara"> Over last decade&#44; interest in vitamin D physiopathology has increased greatly due to the discovery of additional biological actions of vitamin D out off its traditional role in bone and mineral metabolism&#46; These additional biological effects are&#58; suppression of renin¿angiotensin system<span class="elsevierStyleSup">1</span> &#40;RAS&#41;&#44; protection against cardiovascular event&#44;<span class="elsevierStyleSup">2</span> decrease in inflammatory markers&#44;<span class="elsevierStyleSup">3&#44;4</span> reduction of megalin and cubilin shedding&#44;<span class="elsevierStyleSup">5</span> improved systolic blood pressure in patients with type 2 diabetes&#44;<span class="elsevierStyleSup">6</span> and increases nephrin expression in podocytes in experimental data&#46;<span class="elsevierStyleSup">7</span></p><p class="elsevierStylePara"> On the other hand&#44; vitamin D deficiency is an emerging global health problem that is estimated to affect more than 1&#160;billion people worldwide&#46;<span class="elsevierStyleSup">8</span> It is very common in patients with chronic kidney disease &#40;CKD&#41;&#44; even at early stages&#44;<span class="elsevierStyleSup">9</span> and the severity of deficiency increases with the progression of kidney disease&#46;</p><p class="elsevierStylePara"> Vitamin D deficiency is partly caused by vitamin dysregulated D metabolism in kidney disease&#44; because the final activation step of synthesis of Vitamin D&#44; 1¿hydroxylation&#44; occurs primarily&#44; but not exclusively&#44; in the kidney&#46;</p><p class="elsevierStylePara"> CKD patients used to have a high comorbidity&#44; so are treated with a huge amount of drugs&#46;<span class="elsevierStyleSup">10&#44;11</span> Therefore medication¿ related problems are very common in CKD patients&#46; The possible collateral effect of these medications on vitamin D synthesis and metabolism had been previously described&#44;<span class="elsevierStyleSup">12&#44;13</span> but remains unclear&#46;</p><p class="elsevierStylePara"> We conducted an observational study to assess the characteristics of 25¿OH¿D3 deficient CKD patients&#44; including the possible role of different associated therapies&#44; as statins&#44; renin angiotensin system &#40;RAS&#41; inhibitors or Allopurinol&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Methods</span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Participants </span></p><p class="elsevierStylePara"> A transversal single¿center study was conducted including a sample of 137 incident patients referred to our CKD outpatient clinic&#46; Patients undergoing renal replacement therapy&#44; kidney transplant recipients&#44; and with recent hospital admission in last 3 months or with acute diseases&#44; were excluded&#46; We also excluded patients supplemented with any kind of vitamin D or analog in the last 3 months&#46; Medical records were consulted to obtain demographic&#44; anthropometric data and previous cardiovascular events&#46; Treatment was also recorded&#58; kind and number of antihypertensive drugs&#44; statin and allopurinol therapy&#46; Analytical values were collected at the same time including creatinine&#44; calcium&#44; phosphate&#44; parathormone &#40;PTH&#41;&#44; serum uric acid&#44; ultrasensible C¿reactive protein &#40;CRP&#41;&#44; proteinuria and urine albumin&#47;creatinine ratio&#46; To avoid seasonal changes&#44; serum 25¿OH¿D3 levels were determined in all patients between February and May&#46;</p><p class="elsevierStylePara"> Patients were divided in three groups according RAS inhibitors or allopurinol concomitant therapies into none &#40;n&#61;26&#41;&#44; RAS inhibitors or allopurinol &#40;n&#61;81&#41;&#44; and RAS inhibitors plus allopurinol &#40;n&#61;30&#41;&#59; with the aim to study the influence of statin therapy in these groups&#46;</p><p class="elsevierStylePara"> Laboratory measurements were made using standardized automated methods&#46; Daily urinary albumin excretion was measured with an immunonephelometric method&#46; Serum 25¿OH¿D3 levels and intact PTH were measured using standarized automated methods of chemiluminescence immunoassay &#40;Liaison<span class="elsevierStyleSup">&#174;</span> and Immulite 2000<span class="elsevierStyleSup">&#174;</span>&#44; respectively&#41;&#46;</p><p class="elsevierStylePara"> Estimated glomerular filtration rate &#40;eGFR&#41; was calculated using the MDRD¿4 formula&#46;<span class="elsevierStyleSup">14</span> Vitamin D deficiency was defined according with KDOQI 2008 guidelines as 25¿OH¿D3 levels less than 15 ng&#47;mL&#46;<span class="elsevierStyleSup">15 </span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Statistical analysis </span></p><p class="elsevierStylePara"> Normally distributed values are expressed as mean &#177;SD &#40;standard deviation&#41;&#59; non¿normally distributed values are expressed as median &#177;IQR &#40;interquartile range&#41;&#46; The differences in quantitative variables were examined using the chi¿square test for categorical variables and t test for continuous variables&#46; Analysis of variance was used to study the differences on 25¿OH¿D3 levels between the groups according concomitant therapies&#46; A linear model was accomplished to identify the relationship between different variables&#46; Multivariate analysis &#40;linear multivariate regression&#41; was performed to determine the independent risk factors for 25¿OH¿D3 deficiency including all the factors with p&#60;0&#46;1 in the univariate model and potential confounding factors &#40;as concomitant therapies&#44; age&#44; gender&#44; diabetes mellitus&#44; eGFR&#44; and prior history of congestive cardiac failure&#41;&#46; All statistical analyses were conducted using SPSS for Windows&#44; V 11 &#40;SPSS<span class="elsevierStyleSup">&#174;</span>&#44; Chicago&#44; Illinois&#44; USA&#41;&#46; Statistical significance was set at P&#60;0&#46;05&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Results </span></p><p class="elsevierStylePara"> Demographic data&#44; clinical and baseline biochemical characteristics are shown in Table 1&#46; Mean serum 25¿OH¿D3 levels were 8&#46;23&#177;4&#46;03 ng&#47;ml&#46; According with KDOQUI guidelines<span class="elsevierStyleSup">16</span> 86 patients &#40;62&#46;7&#37;&#41; had CKD stage 3&#44; 10&#46;2&#37; stages 1 and 2&#44; and 27&#37; presented eGFR&#60;30 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#46; Although male gender presented higher 25¿OH¿D3 levels &#40;8&#46;35 &#91;&#177;3&#46;40&#93; versus 7&#46;52 &#91;&#177;3&#46;06&#93; ng&#47;dl&#41; these differences are not significant&#46; Sixty¿one patients &#40;33&#46;2&#37;&#41; had a previous cardiovascular event &#40;CVE&#41;&#46; The most frequent was myocardial infarction with 14&#46;7&#37;&#46; Previous congestive cardiac failure &#40;CCF&#41; had been found in 18 patients &#40;9&#46;8&#37;&#41;&#46;</p><p class="elsevierStylePara"><img alt="Table 1 – Baseline characteristic of the patients" src="498v35n02-90412311fig1.jpg"></img></p><p class="elsevierStylePara"> Eighty¿eight patients &#40;64&#46;7&#37;&#41; were receiving 3 or more concomitant drugs&#46; Only 7 patients &#40;5&#46;1&#37;&#41; were not receiving any treatment&#46; Bone and mineral metabolism parameters and eGFR of the patients according concomitant medications are shown in Table 2&#46; Patients under RAS inhibitors and allopurinol treatment were associated with higher 25¿OH¿D3 levels&#46; However&#44; statin treatment&#44; diabetes mellitus and history of CCF was associated with lower levels of 25¿OH¿D3 levels&#46; Allopur inol¿taking patients presented higher ser um phosphate and PTH levels as well as and lower eGFR&#46; Patients treated with insulin&#44; erythropoiesis¿stimulating agents &#40;ESA&#41; and with history of CVE presented lower eGFR&#46; There are no differences between calcium levels according concomitant drugs&#46; Multivariate analysis adjusted by age&#44; gender&#44; eGFR&#44; serum calcium and PTH levels&#44; personal history of diabetes&#44; CVE or CCF showed that RAS inhibitors &#40;beta 1&#46;73&#44; p&#61;0&#46;013&#41;&#44; allopurinol treatment &#40;beta 1&#46;63&#44; p&#61;0&#46;011&#41; and statins treatment &#40;beta &#8211;1&#46;35 and p&#61;0&#46;029&#41; were independent predictors for lower serum 25¿OH¿D3 levels &#40;Table 3&#41;&#46;</p><p class="elsevierStylePara"><img alt="Table 2 – Analytical characteristic of the patients according with the therapies" src="498v35n02-90412311fig2.jpg"></img></p><p class="elsevierStylePara"><img alt="Table 3 – Linear Multivariate Regression &#40;adjusted by age&#44; eGFR and prior history of Congestive cardiac failure&#41;" src="498v35n02-90412311fig3.jpg"></img></p><p class="elsevierStylePara"> Patients who were not receiving RAS inhibitors or allopurinol presented lower 25¿OH¿D3 levels than those receiving RAS inhibitors or allopurinol&#44; and RAS inhibitors plus allopurinol &#40;p&#60;0&#46;001&#41; &#40;Fig&#46; 1&#41;&#46; Highest 25¿OH¿D3 levels &#40;11&#46;7&#177;3&#46;11&#160;ng&#47;mL&#41; of our cohort were found in patients receiving RAS inhibitors plus allopurinol without statins&#46; Lowest 25¿OH¿D3 levels of our cohort &#40;5&#46;7&#177;1&#46;82 ng&#47;mL&#41; were found in patients who receiving statins alone&#46; In the group without RAS inhibitors or Allopurinol patients under statins therapy presented lower serum vitamin D levels &#40;5&#46;7&#177;1&#46;82 ng&#47;mL vs&#46; 7&#46;8&#177;3&#46;4&#160;ng&#47;mL&#44; p&#61;0&#46;05&#41; compared with patient under RAS inhibitors or Allopurinol alone&#46; Similarly&#44; in the group with RAS inhibitors plus Allopurinol patients under statins therapy presented lower serum vitamin D levels &#40;11&#46;7&#177;3&#46;5 ng&#47;mL vs&#46; 8&#46;5&#177;2&#46;5 ng&#47;mL&#44; p&#61;0&#46;003&#41; than those with RAS inhibitors plus Allopurinol alone&#46; There were also statistical differences when we compared patients under statin treatment with and without RAS or allopurinol therapy &#40;5&#46;7&#177;1&#46;82 ng&#47;mL vs&#46; 7&#46;5&#177;3&#46;2 ng&#47;mL&#44; respectively p&#61;0&#46;015&#41; and comparing patients under statin treatment with RAS or allopurinol therapy with patients under RAS plus allopurinol therapy &#40;5&#46;7&#177;1&#46;82 ng&#47;mL vs&#46; 8&#46;5&#177;2&#46;3 ng&#47;mL&#44; p&#61;0&#46;02 respectively&#41;&#46; Similarly&#44; there were statistical differences comparing patients without statin treatment with RAS inhibitors or Allopurinol treatment vs&#46; RAS inhibitors plus Allopurinol &#40;7&#46;8&#177;3&#46;4 ng&#47;mL vs&#46; 11&#46;7&#177;3&#46;5 ng&#47;mL&#44; p&#61;0&#46;002&#41;&#46;</p><p class="elsevierStylePara"><img alt="Figure 1 – Relationship between therapies and baseline serum 25¿OH¿D3 levels&#46; Patients were divided in three groups according with the concomitant therapies&#44; and there were significant statistical differences between groups &#40;p&#60;0&#46;001&#41;&#46; Patients who were not receiving renin angiotensin system &#40;RAS&#41; inhibitors or allopurinol &#40;n&#61;26&#41; presented lower 25¿OH¿D3 D levels than those receiving RAS inhibitors or allopurinol &#40;n&#61;81&#41;&#44; and RAS inhibitors plus allopurinol &#40;n&#61;30&#41; &#40;p&#60;0&#46;001&#41;&#46; Highest 25¿OH¿D3 levels &#40;11&#46;7&#177;3&#46;11&#44; p&#61;0&#46;003&#41; were found in patients receiving RAS inhibitors plus allopurinol without statins&#46; Lowest 25¿OH¿D3 levels &#40;5&#46;7&#177;1&#46;82&#44; p&#61;0&#46;005&#41; were found in patients who only receiving statins&#46;" src="498v35n02-90412311fig4.jpg"></img></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Figure 1 &#8211; Relationship between therapies and baseline serum 25¿OH¿D<span class="elsevierStyleInf">3</span> levels&#46; Patients were divided in three groups according with the concomitant therapies&#44; and there were significant statistical differences between groups &#40;p&#60;0&#46;001&#41;&#46; Patients who were not receiving renin angiotensin system &#40;RAS&#41; inhibitors or allopurinol &#40;n&#61;26&#41; presented lower 25¿OH¿D<span class="elsevierStyleInf">3</span> D levels than those receiving RAS inhibitors or allopurinol &#40;n&#61;81&#41;&#44; and RAS inhibitors plus allopurinol &#40;n&#61;30&#41; &#40;p&#60;0&#46;001&#41;&#46; Highest 25¿OH¿D<span class="elsevierStyleInf">3</span> levels &#40;11&#46;7&#177;3&#46;11&#44; p&#61;0&#46;003&#41; were found in patients receiving RAS inhibitors plus allopurinol without statins&#46; Lowest 25¿OH¿D<span class="elsevierStyleInf">3</span> levels &#40;5&#46;7&#177;1&#46;82&#44; p&#61;0&#46;005&#41; were found in patients who only receiving statins&#46;</span></p><p class="elsevierStylePara"> Additionally&#44; we collected 25¿OH¿D3 levels in 23 CKD patients before &#40;17&#46;8 &#91;11&#46;9¿26&#46;45&#93;&#41; and 3 months after &#40;22&#46;0 &#91;13&#46;65¿27&#46;45&#93;&#41; RAS inhibitors introduction &#40;p&#60;0&#46;001&#41;&#44; and in 15&#160;patients before &#40;43&#46;3 &#91;14&#46;0¿76&#46;8&#93;&#41; and 3 months after &#40;25&#46;7 &#91;23&#46;2¿43&#46;3&#93;&#41; Allopurinol introduction &#40;p&#61;0&#46;66&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Discussion </span></p><p class="elsevierStylePara"> Our data suggest that concomitant treatment with allopurinol and RAS inhibitors is associated with high levels of 25¿OH¿D3 in CKD vitamin D deficient population&#46; On the other hand&#44; treatment with statins is associated with lower levels&#46;</p><p class="elsevierStylePara"> CKD patients used to have a high comorbidity and therefore are treated with a huge amount of drugs&#46; The possible collateral effect of these medications on vitamin D synthesis and metabolism had been previously described in some reports&#44; but remains unclear&#46;</p><p class="elsevierStylePara"> Although the interaction between Vitamin D and RAS is well known there are not previous reports about the effect of RAS inhibition on vitamin D levels&#46; Vitamin D is a down regulator of the RAS by supressing renin expression&#44;<span class="elsevierStyleSup">1&#44;17</span> and its deficiency can activate the local RAS in the kidney&#46;<span class="elsevierStyleSup">18</span> The renoprotective and antiatherogenic efficacy of the combination therapies of RAS inhibitors and vitamin D analogue has been reported in animal models&#46;<span class="elsevierStyleSup">19¿21</span> To provide biological plausibility to our finding&#44; we have 2 different arguments&#46; Firstly&#44; RAS inhibitors by decreasing glomerular proteinuria&#44; decrease the competition between proteins and vitamin D for receptor¿binding site to be reabsorbed by megalin¿cubilin complex in the proximal tubule&#46;<span class="elsevierStyleSup">22</span> That means that RAS inhibitors increase the free receptor¿binding sites for vitamin D reabsorption&#46; And secondly&#44; RAS inhibitors have a potent anti¿inflammatory effect<span class="elsevierStyleSup">23&#44;24</span> and the inflammatory status has been associated in many studies with vitamin D levels&#46;<span class="elsevierStyleSup">3¿5</span></p><p class="elsevierStylePara"> Patients treated with Allopurinol had higher 25¿OH¿D3 levels&#46; We did not find any association with serum uric acid levels&#46; Takahashi et al&#46; described a lower serum 1¿25 &#40;OH&#41; D3 levels in gout patients compared with control subjects&#44; and a significant increase in serum 1¿25 &#40;OH&#41; D3 after 1 year of administration of uric acid lowering agent&#46; In animal models had been found that uric acid and xanthine suppresses 1alpha¿hydroxylase activity and synthesis of 1¿25 &#40;OH&#41; D3 and also suppresses its clearance rate&#46;<span class="elsevierStyleSup">25</span> Moreover in the Vanholder et al&#46; small cohort of CKD patients had been reported an increase in 1¿25 &#40;OH&#41; D3 after allopurinol treatment&#44;<span class="elsevierStyleSup">26</span> which they mainly attributed to a decrease in clearance rate of 1¿25 &#40;OH&#41; D3&#46; On the other hand&#44; the anti¿inflammatory power of Allopurinol was found also in moderate CKD&#46;<span class="elsevierStyleSup">27</span> In our opinion&#44; the increase in 25¿OH¿D3 on allopurinol treated patients observed is due to decrease in anti¿inflammatory markers and suppression on 25¿OH¿D3 clearance rate&#46;</p><p class="elsevierStylePara"> Vitamin D is mainly produced by the endogenous pathway&#46; Seven¿ dehydrocholesterol is converted to vitamin D3 in the skin in response to ultraviolet B light exposure&#46;<span class="elsevierStyleSup">28</span> Statins reduce both cholesterol and 7¿DHC production&#44; and would be expected to reduce both cholesterol and vitamin D production&#46; Furthermore&#44; 25¿OH¿D3 before to be hydroxilated in the kidney&#44; need to be reabsorbed in the proximal tubules by megalin&#47;cubilin&#47;amnioless complex&#46; Megalin belongs to LDL receptor family&#46;<span class="elsevierStyleSup">29</span> This complex must be prenylated to be active&#46; Statins&#44; by inhibiting HMG¿CoA reductase&#44; reduce the amount of mevalonate&#44; a key intermediate in these preynilation&#46; Deficiency or dysfunction of the megalin&#8211; cubilin complex decreases vitamin D concentrations&#46;<span class="elsevierStyleSup">30</span> However the effect of statins in vitamin D metabolism is unclear and some studies suggested that statins may increase<span class="elsevierStyleSup">10</span> or not affect30 vitamin D levels&#44; maybe depending on their anti¿inflammatory power&#46;</p><p class="elsevierStylePara"> We did not find any association between some of the traditional risk factors for 25¿OH¿D3 deficiency&#44; as age&#44; female gender&#44; diabetes mellitus<span class="elsevierStyleSup">5</span> or proteinuria&#46;4 Possibly because we selected a very specific cohort&#44; CKD patients with severe deficiency of 25¿OH¿D3&#44; what means a proteinuric elderly male dominant cohort &#40;564&#46;0 &#91;&#177;994&#46;6&#93; mg&#47;g&#44; 70&#46;77 &#91;&#177;16&#46;1&#93; years and 53&#46;3 respectively&#41; with 40&#46;4&#37; of diabetics&#46;</p><p class="elsevierStylePara"> Although we found an increase in 25¿OH¿D3 levels after 3&#160;months of SRAA therapy in a small subanalysis group &#40;n&#61;23&#41; reassuring our previous findings&#44; we understand that the small sample size just allow us to highlight the possible association&#46;</p><p class="elsevierStylePara"> There are several limitations to our study&#46; Firstly&#44; the small number of patients&#46; Secondly&#44; 25¿OH¿D3 levels could be undervalued because we only made a single determination in spring &#40;February and May&#41;&#46; Thirdly&#44; we did not consider for how long the patients have been with the recorded therapy&#44; the reason&#44; the dose or the achievement of the therapeutic gold&#46; Finally this is just a transversal study&#44; therefore we only can point the associations that we found&#44; but not the causality&#46;</p><p class="elsevierStylePara"> In conclusion&#44; 25¿OH¿D3 deficiency and polypharmacy are a common problem over CKD patients&#46; Patients under RAS inhibitors or Allopurinol treatment had higher 25&#40;OH&#41; D levels&#44; however patients with statins treatment had lower vitamin D level&#46; Finally&#44; randomized controlled trials are required to confirm these findings&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Financial support </span></p><p class="elsevierStylePara"> None&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflict of interests </span></p><p class="elsevierStylePara"> The authors declare that they have no conflict of interests&#46;</p><hr></hr><p class="elsevierStylePara"> &#42; <span class="elsevierStyleItalic">Corresponding author&#46;<br></br></span>Claudia Yuste&#44; <br></br> Department of Nephrology&#44; <br></br> Gregorio Mara&#241;&#243;n University General Hospital&#44; Madrid&#44; Spain&#46; <br></br> Telephone number&#58; 0034915868319&#46; Fax number&#58; 0034915868683&#46;<br></br><span class="elsevierStyleItalic">E-mail&#58;</span><a href="mailto&#58;claudiayustelozano&#64;yahoo&#46;es" class="elsevierStyleCrossRefs">claudiayustelozano&#64;yahoo&#46;es</a></p>"
    "pdfFichero" => "498v35n02a90412311pdf001.pdf"
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            0 => "Vitamina D"
            1 => "Enfermedad renal cr&#243;nica"
            2 => "Alopurinol"
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            0 => "Vitamin D"
            1 => "Chronic kidney disease"
            2 => "Allopurinol"
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            4 => "RAS inhibitors"
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        "resumen" => "<p class="elsevierStylePara"> <span class="elsevierStyleItalic">Antecedentes&#58;</span> La deficiencia de vitamina D y la polifarmacia constituyen un problema com&#250;n en la poblaci&#243;n con enfermedad renal cr&#243;nica &#40;ERC&#41;&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Objetivos&#58;</span> Evaluar las caracter&#237;sticas cl&#237;nicas y anal&#237;ticas de los pacientes de ERC con deficiencia de 25¿OH¿D3 &#40;&#60;15 ng&#47;mL&#41;&#44; incluyendo la funci&#243;n posible de los f&#225;rmacos asociados&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">M&#233;todos&#58;</span> Se realiz&#243; una revisi&#243;n observacional en un &#250;nico centro&#44; de 137 pacientes incidentes remitidos a nuestra cl&#237;nica ambulatoria con diferentes estadios de ERC y 25¿OH¿D3&#60;15&#160;ng&#47;mL &#40;varones 53&#44;3&#37;&#44; edad media 70&#44;8 &#91;&#177;16&#44;1&#93; a&#241;o&#44; GFR medio &#40;MDRD¿4&#41; 43&#44;6 &#91;&#177;25&#44;5&#93; ml&#47;min&#47;1&#44;73 m<span class="elsevierStyleSup">2</span>&#41;&#46; Los valores de 25¿OH¿D3 se recolectaron en primavera&#46; Se registraron los datos bioqu&#237;micos y los f&#225;rmacos asociados&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Resultados&#58;</span> Los niveles medios de 25¿OH¿D3 fueron de 8&#44;23 &#91;&#177;4&#44;03&#93; ng&#47;ml&#46; Ochenta y ocho pacientes &#40;64&#44;7&#37;&#41; tomaban tres o m&#225;s f&#225;rmacos concomitantes&#46; &#218;nicamente siete pacientes &#40;5&#44;1&#37;&#41; no recib&#237;an medicaci&#243;n alguna&#46; Los pacientes fueron divididos en tres grupos&#44; conforme a las terapias&#58; ninguna &#40;n &#61; 26&#41;&#44; inhibidores RAS o Alopurinol &#40;n &#61; 81&#41;&#44; e inhibidores RAS m&#225;s alopurinol &#40;n &#61; 30&#41;&#44; a fin de estudiar la influencia de la terapia de estatinas&#46; Los pacientes sometidos a tratamiento de inhibidores de la renina¿angiotensina &#40;RAS&#41; o Alopurinol presentaron unos niveles considerablemente superiores de 25¿OH¿D3 &#40;p &#61; 0&#44;001 y p &#61; 0&#44;01 respectivamente&#41;&#44; y sin embargo los pacientes con tratamiento de estatinas presentaron unos menores niveles de 25¿OH¿D3 &#40;p &#61; 0&#44;039&#41;&#46; La presencia de diabetes&#44; episodios cardiovasculares u otras terapias no modificaron los niveles de 25¿OH¿D3&#44; ajustados por edad y eGFR&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Conclusiones&#58;</span> Los pacientes de ERC con deficiencia de vitamina D&#44; sometidos a tratamiento de inhibidores RAS o Alopurinol reflejaron unos niveles superiores de 25¿OH¿D3&#44; y sin embargo aquellos sometidos a tratamiento de estatinas reflejaron unos menores niveles de vitamina&#160;D&#46; Se precisan ensayos aleatorizados controlados para confirmar estos hallazgos&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"> <span class="elsevierStyleItalic">Background&#58;</span> Vitamin D deficiency and polypharmacy is a common problem over chronic kidney disease &#40;CKD&#41; population&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Objectives&#58;</span> To assess the clinical and analytical characteristics of CKD patients with 25¿OH¿D3 deficiency &#40;&#60;15 ng&#47;mL&#41;&#44; including the possible role of associated drugs&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Methods&#58;</span> A single center observational review of 137 incident patients referred to our outpatient clinic with different stages of CKD and 25¿OH¿D3&#60;15ng&#47;mL &#40;male gender 53&#46;3&#37;&#44; mean age 70&#46;8 &#91;&#177;16&#46;1&#93; years&#44; mean GFR &#40;MDRD¿4&#41; 43&#46;6 &#91;&#177;25&#46;5&#93; ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41;&#46; 25¿OH¿D3 levels were collected in spring&#46; Clinical and biochemical data and associated medications were recorded&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Results&#58;</span> Mean 25¿OH¿D3 levels were 8&#46;23 &#91;&#177;4&#46;03&#93; ng&#47;ml&#46; Eighty¿eight patients &#40;64&#46;7&#37;&#41; had 3 or more concomitant drugs&#46; Only 7 patients &#40;5&#46;1&#37;&#41; were not receiving any medication&#46; Patients were divided in three groups according the therapies into none &#40;n&#61;26&#41;&#44; RAS inhibitors or allopurinol &#40;n&#61;81&#41;&#44; and RAS inhibitors plus allopurinol &#40;n&#61;30&#41;&#59; with the aim to study the influence of statin therapy&#46; Patients under renin angiotensin &#40;RAS&#41; inhibitors or Allopurinol treatment presented significantly higher 25¿OH¿D3 levels &#40;p&#61;0&#46;001 and p&#61;0&#46;01 respectively&#41;&#44; however patients with Statins treatment had lower 25¿OH¿D3 level &#40;p&#61;0&#46;039&#41;&#46; Personal history of diabetes&#44; cardiovascular events or other therapies did not modify 25¿OH¿D3 levels&#44; adjusted by age and eGFR&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Conclusions&#58;</span> CKD patients with vitamin D deficiency who received RAS inhibitors or Allopurinol treatment had higher 25¿OH¿D3 levels&#44; however those with statins treatment had lower vitamin D levels&#46; Randomized controlled trials are required to confirm these findings&#46;</p>"
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The effect of some medications given to CKD patients on vitamin D levels
Efectos de algunos fármacos administrados a los pacientes de ERC sobre los niveles de vitamina D
Claudia Yustea, Borja Quirogaa, Soledad García de Vinuesaa, Maria Angeles Goicoecheaa, Daniel Barracaa, Ursula Verdallesa, Jose Luñoa
a Department of Nephrology. Gregorio Marañón University General Hospital. Madrid (Spain)
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          "en" => "– Relationship between therapies and baseline serum 25¿OH¿D3 levels&#46; Patients were divided in three groups according with the concomitant therapies&#44; and there were significant statistical differences between groups &#40;p <0 001 patients who were not receiving renin angiotensin system ras inhibitors or allopurinol n="30&#41;" presented lower 25 8209 oh d3 d levels than those and plus p <0 001 highest 25 8209 oh d3 levels 11 7 3 p="0&#46;005&#41;" were found in patients receiving ras inhibitors plus allopurinol without statins lowest 5 1 82 who only</0> </0>"
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Introduction </span></p><p class="elsevierStylePara"> Over last decade&#44; interest in vitamin D physiopathology has increased greatly due to the discovery of additional biological actions of vitamin D out off its traditional role in bone and mineral metabolism&#46; These additional biological effects are&#58; suppression of renin¿angiotensin system<span class="elsevierStyleSup">1</span> &#40;RAS&#41;&#44; protection against cardiovascular event&#44;<span class="elsevierStyleSup">2</span> decrease in inflammatory markers&#44;<span class="elsevierStyleSup">3&#44;4</span> reduction of megalin and cubilin shedding&#44;<span class="elsevierStyleSup">5</span> improved systolic blood pressure in patients with type 2 diabetes&#44;<span class="elsevierStyleSup">6</span> and increases nephrin expression in podocytes in experimental data&#46;<span class="elsevierStyleSup">7</span></p><p class="elsevierStylePara"> On the other hand&#44; vitamin D deficiency is an emerging global health problem that is estimated to affect more than 1&#160;billion people worldwide&#46;<span class="elsevierStyleSup">8</span> It is very common in patients with chronic kidney disease &#40;CKD&#41;&#44; even at early stages&#44;<span class="elsevierStyleSup">9</span> and the severity of deficiency increases with the progression of kidney disease&#46;</p><p class="elsevierStylePara"> Vitamin D deficiency is partly caused by vitamin dysregulated D metabolism in kidney disease&#44; because the final activation step of synthesis of Vitamin D&#44; 1¿hydroxylation&#44; occurs primarily&#44; but not exclusively&#44; in the kidney&#46;</p><p class="elsevierStylePara"> CKD patients used to have a high comorbidity&#44; so are treated with a huge amount of drugs&#46;<span class="elsevierStyleSup">10&#44;11</span> Therefore medication¿ related problems are very common in CKD patients&#46; The possible collateral effect of these medications on vitamin D synthesis and metabolism had been previously described&#44;<span class="elsevierStyleSup">12&#44;13</span> but remains unclear&#46;</p><p class="elsevierStylePara"> We conducted an observational study to assess the characteristics of 25¿OH¿D3 deficient CKD patients&#44; including the possible role of different associated therapies&#44; as statins&#44; renin angiotensin system &#40;RAS&#41; inhibitors or Allopurinol&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Methods</span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Participants </span></p><p class="elsevierStylePara"> A transversal single¿center study was conducted including a sample of 137 incident patients referred to our CKD outpatient clinic&#46; Patients undergoing renal replacement therapy&#44; kidney transplant recipients&#44; and with recent hospital admission in last 3 months or with acute diseases&#44; were excluded&#46; We also excluded patients supplemented with any kind of vitamin D or analog in the last 3 months&#46; Medical records were consulted to obtain demographic&#44; anthropometric data and previous cardiovascular events&#46; Treatment was also recorded&#58; kind and number of antihypertensive drugs&#44; statin and allopurinol therapy&#46; Analytical values were collected at the same time including creatinine&#44; calcium&#44; phosphate&#44; parathormone &#40;PTH&#41;&#44; serum uric acid&#44; ultrasensible C¿reactive protein &#40;CRP&#41;&#44; proteinuria and urine albumin&#47;creatinine ratio&#46; To avoid seasonal changes&#44; serum 25¿OH¿D3 levels were determined in all patients between February and May&#46;</p><p class="elsevierStylePara"> Patients were divided in three groups according RAS inhibitors or allopurinol concomitant therapies into none &#40;n&#61;26&#41;&#44; RAS inhibitors or allopurinol &#40;n&#61;81&#41;&#44; and RAS inhibitors plus allopurinol &#40;n&#61;30&#41;&#59; with the aim to study the influence of statin therapy in these groups&#46;</p><p class="elsevierStylePara"> Laboratory measurements were made using standardized automated methods&#46; Daily urinary albumin excretion was measured with an immunonephelometric method&#46; Serum 25¿OH¿D3 levels and intact PTH were measured using standarized automated methods of chemiluminescence immunoassay &#40;Liaison<span class="elsevierStyleSup">&#174;</span> and Immulite 2000<span class="elsevierStyleSup">&#174;</span>&#44; respectively&#41;&#46;</p><p class="elsevierStylePara"> Estimated glomerular filtration rate &#40;eGFR&#41; was calculated using the MDRD¿4 formula&#46;<span class="elsevierStyleSup">14</span> Vitamin D deficiency was defined according with KDOQI 2008 guidelines as 25¿OH¿D3 levels less than 15 ng&#47;mL&#46;<span class="elsevierStyleSup">15 </span></p><p class="elsevierStylePara"><span class="elsevierStyleItalic">Statistical analysis </span></p><p class="elsevierStylePara"> Normally distributed values are expressed as mean &#177;SD &#40;standard deviation&#41;&#59; non¿normally distributed values are expressed as median &#177;IQR &#40;interquartile range&#41;&#46; The differences in quantitative variables were examined using the chi¿square test for categorical variables and t test for continuous variables&#46; Analysis of variance was used to study the differences on 25¿OH¿D3 levels between the groups according concomitant therapies&#46; A linear model was accomplished to identify the relationship between different variables&#46; Multivariate analysis &#40;linear multivariate regression&#41; was performed to determine the independent risk factors for 25¿OH¿D3 deficiency including all the factors with p&#60;0&#46;1 in the univariate model and potential confounding factors &#40;as concomitant therapies&#44; age&#44; gender&#44; diabetes mellitus&#44; eGFR&#44; and prior history of congestive cardiac failure&#41;&#46; All statistical analyses were conducted using SPSS for Windows&#44; V 11 &#40;SPSS<span class="elsevierStyleSup">&#174;</span>&#44; Chicago&#44; Illinois&#44; USA&#41;&#46; Statistical significance was set at P&#60;0&#46;05&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Results </span></p><p class="elsevierStylePara"> Demographic data&#44; clinical and baseline biochemical characteristics are shown in Table 1&#46; Mean serum 25¿OH¿D3 levels were 8&#46;23&#177;4&#46;03 ng&#47;ml&#46; According with KDOQUI guidelines<span class="elsevierStyleSup">16</span> 86 patients &#40;62&#46;7&#37;&#41; had CKD stage 3&#44; 10&#46;2&#37; stages 1 and 2&#44; and 27&#37; presented eGFR&#60;30 ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#46; Although male gender presented higher 25¿OH¿D3 levels &#40;8&#46;35 &#91;&#177;3&#46;40&#93; versus 7&#46;52 &#91;&#177;3&#46;06&#93; ng&#47;dl&#41; these differences are not significant&#46; Sixty¿one patients &#40;33&#46;2&#37;&#41; had a previous cardiovascular event &#40;CVE&#41;&#46; The most frequent was myocardial infarction with 14&#46;7&#37;&#46; Previous congestive cardiac failure &#40;CCF&#41; had been found in 18 patients &#40;9&#46;8&#37;&#41;&#46;</p><p class="elsevierStylePara"><img alt="Table 1 – Baseline characteristic of the patients" src="498v35n02-90412311fig1.jpg"></img></p><p class="elsevierStylePara"> Eighty¿eight patients &#40;64&#46;7&#37;&#41; were receiving 3 or more concomitant drugs&#46; Only 7 patients &#40;5&#46;1&#37;&#41; were not receiving any treatment&#46; Bone and mineral metabolism parameters and eGFR of the patients according concomitant medications are shown in Table 2&#46; Patients under RAS inhibitors and allopurinol treatment were associated with higher 25¿OH¿D3 levels&#46; However&#44; statin treatment&#44; diabetes mellitus and history of CCF was associated with lower levels of 25¿OH¿D3 levels&#46; Allopur inol¿taking patients presented higher ser um phosphate and PTH levels as well as and lower eGFR&#46; Patients treated with insulin&#44; erythropoiesis¿stimulating agents &#40;ESA&#41; and with history of CVE presented lower eGFR&#46; There are no differences between calcium levels according concomitant drugs&#46; Multivariate analysis adjusted by age&#44; gender&#44; eGFR&#44; serum calcium and PTH levels&#44; personal history of diabetes&#44; CVE or CCF showed that RAS inhibitors &#40;beta 1&#46;73&#44; p&#61;0&#46;013&#41;&#44; allopurinol treatment &#40;beta 1&#46;63&#44; p&#61;0&#46;011&#41; and statins treatment &#40;beta &#8211;1&#46;35 and p&#61;0&#46;029&#41; were independent predictors for lower serum 25¿OH¿D3 levels &#40;Table 3&#41;&#46;</p><p class="elsevierStylePara"><img alt="Table 2 – Analytical characteristic of the patients according with the therapies" src="498v35n02-90412311fig2.jpg"></img></p><p class="elsevierStylePara"><img alt="Table 3 – Linear Multivariate Regression &#40;adjusted by age&#44; eGFR and prior history of Congestive cardiac failure&#41;" src="498v35n02-90412311fig3.jpg"></img></p><p class="elsevierStylePara"> Patients who were not receiving RAS inhibitors or allopurinol presented lower 25¿OH¿D3 levels than those receiving RAS inhibitors or allopurinol&#44; and RAS inhibitors plus allopurinol &#40;p&#60;0&#46;001&#41; &#40;Fig&#46; 1&#41;&#46; Highest 25¿OH¿D3 levels &#40;11&#46;7&#177;3&#46;11&#160;ng&#47;mL&#41; of our cohort were found in patients receiving RAS inhibitors plus allopurinol without statins&#46; Lowest 25¿OH¿D3 levels of our cohort &#40;5&#46;7&#177;1&#46;82 ng&#47;mL&#41; were found in patients who receiving statins alone&#46; In the group without RAS inhibitors or Allopurinol patients under statins therapy presented lower serum vitamin D levels &#40;5&#46;7&#177;1&#46;82 ng&#47;mL vs&#46; 7&#46;8&#177;3&#46;4&#160;ng&#47;mL&#44; p&#61;0&#46;05&#41; compared with patient under RAS inhibitors or Allopurinol alone&#46; Similarly&#44; in the group with RAS inhibitors plus Allopurinol patients under statins therapy presented lower serum vitamin D levels &#40;11&#46;7&#177;3&#46;5 ng&#47;mL vs&#46; 8&#46;5&#177;2&#46;5 ng&#47;mL&#44; p&#61;0&#46;003&#41; than those with RAS inhibitors plus Allopurinol alone&#46; There were also statistical differences when we compared patients under statin treatment with and without RAS or allopurinol therapy &#40;5&#46;7&#177;1&#46;82 ng&#47;mL vs&#46; 7&#46;5&#177;3&#46;2 ng&#47;mL&#44; respectively p&#61;0&#46;015&#41; and comparing patients under statin treatment with RAS or allopurinol therapy with patients under RAS plus allopurinol therapy &#40;5&#46;7&#177;1&#46;82 ng&#47;mL vs&#46; 8&#46;5&#177;2&#46;3 ng&#47;mL&#44; p&#61;0&#46;02 respectively&#41;&#46; Similarly&#44; there were statistical differences comparing patients without statin treatment with RAS inhibitors or Allopurinol treatment vs&#46; RAS inhibitors plus Allopurinol &#40;7&#46;8&#177;3&#46;4 ng&#47;mL vs&#46; 11&#46;7&#177;3&#46;5 ng&#47;mL&#44; p&#61;0&#46;002&#41;&#46;</p><p class="elsevierStylePara"><img alt="Figure 1 – Relationship between therapies and baseline serum 25¿OH¿D3 levels&#46; Patients were divided in three groups according with the concomitant therapies&#44; and there were significant statistical differences between groups &#40;p&#60;0&#46;001&#41;&#46; Patients who were not receiving renin angiotensin system &#40;RAS&#41; inhibitors or allopurinol &#40;n&#61;26&#41; presented lower 25¿OH¿D3 D levels than those receiving RAS inhibitors or allopurinol &#40;n&#61;81&#41;&#44; and RAS inhibitors plus allopurinol &#40;n&#61;30&#41; &#40;p&#60;0&#46;001&#41;&#46; Highest 25¿OH¿D3 levels &#40;11&#46;7&#177;3&#46;11&#44; p&#61;0&#46;003&#41; were found in patients receiving RAS inhibitors plus allopurinol without statins&#46; Lowest 25¿OH¿D3 levels &#40;5&#46;7&#177;1&#46;82&#44; p&#61;0&#46;005&#41; were found in patients who only receiving statins&#46;" src="498v35n02-90412311fig4.jpg"></img></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Figure 1 &#8211; Relationship between therapies and baseline serum 25¿OH¿D<span class="elsevierStyleInf">3</span> levels&#46; Patients were divided in three groups according with the concomitant therapies&#44; and there were significant statistical differences between groups &#40;p&#60;0&#46;001&#41;&#46; Patients who were not receiving renin angiotensin system &#40;RAS&#41; inhibitors or allopurinol &#40;n&#61;26&#41; presented lower 25¿OH¿D<span class="elsevierStyleInf">3</span> D levels than those receiving RAS inhibitors or allopurinol &#40;n&#61;81&#41;&#44; and RAS inhibitors plus allopurinol &#40;n&#61;30&#41; &#40;p&#60;0&#46;001&#41;&#46; Highest 25¿OH¿D<span class="elsevierStyleInf">3</span> levels &#40;11&#46;7&#177;3&#46;11&#44; p&#61;0&#46;003&#41; were found in patients receiving RAS inhibitors plus allopurinol without statins&#46; Lowest 25¿OH¿D<span class="elsevierStyleInf">3</span> levels &#40;5&#46;7&#177;1&#46;82&#44; p&#61;0&#46;005&#41; were found in patients who only receiving statins&#46;</span></p><p class="elsevierStylePara"> Additionally&#44; we collected 25¿OH¿D3 levels in 23 CKD patients before &#40;17&#46;8 &#91;11&#46;9¿26&#46;45&#93;&#41; and 3 months after &#40;22&#46;0 &#91;13&#46;65¿27&#46;45&#93;&#41; RAS inhibitors introduction &#40;p&#60;0&#46;001&#41;&#44; and in 15&#160;patients before &#40;43&#46;3 &#91;14&#46;0¿76&#46;8&#93;&#41; and 3 months after &#40;25&#46;7 &#91;23&#46;2¿43&#46;3&#93;&#41; Allopurinol introduction &#40;p&#61;0&#46;66&#41;&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Discussion </span></p><p class="elsevierStylePara"> Our data suggest that concomitant treatment with allopurinol and RAS inhibitors is associated with high levels of 25¿OH¿D3 in CKD vitamin D deficient population&#46; On the other hand&#44; treatment with statins is associated with lower levels&#46;</p><p class="elsevierStylePara"> CKD patients used to have a high comorbidity and therefore are treated with a huge amount of drugs&#46; The possible collateral effect of these medications on vitamin D synthesis and metabolism had been previously described in some reports&#44; but remains unclear&#46;</p><p class="elsevierStylePara"> Although the interaction between Vitamin D and RAS is well known there are not previous reports about the effect of RAS inhibition on vitamin D levels&#46; Vitamin D is a down regulator of the RAS by supressing renin expression&#44;<span class="elsevierStyleSup">1&#44;17</span> and its deficiency can activate the local RAS in the kidney&#46;<span class="elsevierStyleSup">18</span> The renoprotective and antiatherogenic efficacy of the combination therapies of RAS inhibitors and vitamin D analogue has been reported in animal models&#46;<span class="elsevierStyleSup">19¿21</span> To provide biological plausibility to our finding&#44; we have 2 different arguments&#46; Firstly&#44; RAS inhibitors by decreasing glomerular proteinuria&#44; decrease the competition between proteins and vitamin D for receptor¿binding site to be reabsorbed by megalin¿cubilin complex in the proximal tubule&#46;<span class="elsevierStyleSup">22</span> That means that RAS inhibitors increase the free receptor¿binding sites for vitamin D reabsorption&#46; And secondly&#44; RAS inhibitors have a potent anti¿inflammatory effect<span class="elsevierStyleSup">23&#44;24</span> and the inflammatory status has been associated in many studies with vitamin D levels&#46;<span class="elsevierStyleSup">3¿5</span></p><p class="elsevierStylePara"> Patients treated with Allopurinol had higher 25¿OH¿D3 levels&#46; We did not find any association with serum uric acid levels&#46; Takahashi et al&#46; described a lower serum 1¿25 &#40;OH&#41; D3 levels in gout patients compared with control subjects&#44; and a significant increase in serum 1¿25 &#40;OH&#41; D3 after 1 year of administration of uric acid lowering agent&#46; In animal models had been found that uric acid and xanthine suppresses 1alpha¿hydroxylase activity and synthesis of 1¿25 &#40;OH&#41; D3 and also suppresses its clearance rate&#46;<span class="elsevierStyleSup">25</span> Moreover in the Vanholder et al&#46; small cohort of CKD patients had been reported an increase in 1¿25 &#40;OH&#41; D3 after allopurinol treatment&#44;<span class="elsevierStyleSup">26</span> which they mainly attributed to a decrease in clearance rate of 1¿25 &#40;OH&#41; D3&#46; On the other hand&#44; the anti¿inflammatory power of Allopurinol was found also in moderate CKD&#46;<span class="elsevierStyleSup">27</span> In our opinion&#44; the increase in 25¿OH¿D3 on allopurinol treated patients observed is due to decrease in anti¿inflammatory markers and suppression on 25¿OH¿D3 clearance rate&#46;</p><p class="elsevierStylePara"> Vitamin D is mainly produced by the endogenous pathway&#46; Seven¿ dehydrocholesterol is converted to vitamin D3 in the skin in response to ultraviolet B light exposure&#46;<span class="elsevierStyleSup">28</span> Statins reduce both cholesterol and 7¿DHC production&#44; and would be expected to reduce both cholesterol and vitamin D production&#46; Furthermore&#44; 25¿OH¿D3 before to be hydroxilated in the kidney&#44; need to be reabsorbed in the proximal tubules by megalin&#47;cubilin&#47;amnioless complex&#46; Megalin belongs to LDL receptor family&#46;<span class="elsevierStyleSup">29</span> This complex must be prenylated to be active&#46; Statins&#44; by inhibiting HMG¿CoA reductase&#44; reduce the amount of mevalonate&#44; a key intermediate in these preynilation&#46; Deficiency or dysfunction of the megalin&#8211; cubilin complex decreases vitamin D concentrations&#46;<span class="elsevierStyleSup">30</span> However the effect of statins in vitamin D metabolism is unclear and some studies suggested that statins may increase<span class="elsevierStyleSup">10</span> or not affect30 vitamin D levels&#44; maybe depending on their anti¿inflammatory power&#46;</p><p class="elsevierStylePara"> We did not find any association between some of the traditional risk factors for 25¿OH¿D3 deficiency&#44; as age&#44; female gender&#44; diabetes mellitus<span class="elsevierStyleSup">5</span> or proteinuria&#46;4 Possibly because we selected a very specific cohort&#44; CKD patients with severe deficiency of 25¿OH¿D3&#44; what means a proteinuric elderly male dominant cohort &#40;564&#46;0 &#91;&#177;994&#46;6&#93; mg&#47;g&#44; 70&#46;77 &#91;&#177;16&#46;1&#93; years and 53&#46;3 respectively&#41; with 40&#46;4&#37; of diabetics&#46;</p><p class="elsevierStylePara"> Although we found an increase in 25¿OH¿D3 levels after 3&#160;months of SRAA therapy in a small subanalysis group &#40;n&#61;23&#41; reassuring our previous findings&#44; we understand that the small sample size just allow us to highlight the possible association&#46;</p><p class="elsevierStylePara"> There are several limitations to our study&#46; Firstly&#44; the small number of patients&#46; Secondly&#44; 25¿OH¿D3 levels could be undervalued because we only made a single determination in spring &#40;February and May&#41;&#46; Thirdly&#44; we did not consider for how long the patients have been with the recorded therapy&#44; the reason&#44; the dose or the achievement of the therapeutic gold&#46; Finally this is just a transversal study&#44; therefore we only can point the associations that we found&#44; but not the causality&#46;</p><p class="elsevierStylePara"> In conclusion&#44; 25¿OH¿D3 deficiency and polypharmacy are a common problem over CKD patients&#46; Patients under RAS inhibitors or Allopurinol treatment had higher 25&#40;OH&#41; D levels&#44; however patients with statins treatment had lower vitamin D level&#46; Finally&#44; randomized controlled trials are required to confirm these findings&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Financial support </span></p><p class="elsevierStylePara"> None&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflict of interests </span></p><p class="elsevierStylePara"> The authors declare that they have no conflict of interests&#46;</p><hr></hr><p class="elsevierStylePara"> &#42; <span class="elsevierStyleItalic">Corresponding author&#46;<br></br></span>Claudia Yuste&#44; <br></br> Department of Nephrology&#44; <br></br> Gregorio Mara&#241;&#243;n University General Hospital&#44; Madrid&#44; Spain&#46; <br></br> Telephone number&#58; 0034915868319&#46; Fax number&#58; 0034915868683&#46;<br></br><span class="elsevierStyleItalic">E-mail&#58;</span><a href="mailto&#58;claudiayustelozano&#64;yahoo&#46;es" class="elsevierStyleCrossRefs">claudiayustelozano&#64;yahoo&#46;es</a></p>"
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        "resumen" => "<p class="elsevierStylePara"> <span class="elsevierStyleItalic">Antecedentes&#58;</span> La deficiencia de vitamina D y la polifarmacia constituyen un problema com&#250;n en la poblaci&#243;n con enfermedad renal cr&#243;nica &#40;ERC&#41;&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Objetivos&#58;</span> Evaluar las caracter&#237;sticas cl&#237;nicas y anal&#237;ticas de los pacientes de ERC con deficiencia de 25¿OH¿D3 &#40;&#60;15 ng&#47;mL&#41;&#44; incluyendo la funci&#243;n posible de los f&#225;rmacos asociados&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">M&#233;todos&#58;</span> Se realiz&#243; una revisi&#243;n observacional en un &#250;nico centro&#44; de 137 pacientes incidentes remitidos a nuestra cl&#237;nica ambulatoria con diferentes estadios de ERC y 25¿OH¿D3&#60;15&#160;ng&#47;mL &#40;varones 53&#44;3&#37;&#44; edad media 70&#44;8 &#91;&#177;16&#44;1&#93; a&#241;o&#44; GFR medio &#40;MDRD¿4&#41; 43&#44;6 &#91;&#177;25&#44;5&#93; ml&#47;min&#47;1&#44;73 m<span class="elsevierStyleSup">2</span>&#41;&#46; Los valores de 25¿OH¿D3 se recolectaron en primavera&#46; Se registraron los datos bioqu&#237;micos y los f&#225;rmacos asociados&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Resultados&#58;</span> Los niveles medios de 25¿OH¿D3 fueron de 8&#44;23 &#91;&#177;4&#44;03&#93; ng&#47;ml&#46; Ochenta y ocho pacientes &#40;64&#44;7&#37;&#41; tomaban tres o m&#225;s f&#225;rmacos concomitantes&#46; &#218;nicamente siete pacientes &#40;5&#44;1&#37;&#41; no recib&#237;an medicaci&#243;n alguna&#46; Los pacientes fueron divididos en tres grupos&#44; conforme a las terapias&#58; ninguna &#40;n &#61; 26&#41;&#44; inhibidores RAS o Alopurinol &#40;n &#61; 81&#41;&#44; e inhibidores RAS m&#225;s alopurinol &#40;n &#61; 30&#41;&#44; a fin de estudiar la influencia de la terapia de estatinas&#46; Los pacientes sometidos a tratamiento de inhibidores de la renina¿angiotensina &#40;RAS&#41; o Alopurinol presentaron unos niveles considerablemente superiores de 25¿OH¿D3 &#40;p &#61; 0&#44;001 y p &#61; 0&#44;01 respectivamente&#41;&#44; y sin embargo los pacientes con tratamiento de estatinas presentaron unos menores niveles de 25¿OH¿D3 &#40;p &#61; 0&#44;039&#41;&#46; La presencia de diabetes&#44; episodios cardiovasculares u otras terapias no modificaron los niveles de 25¿OH¿D3&#44; ajustados por edad y eGFR&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Conclusiones&#58;</span> Los pacientes de ERC con deficiencia de vitamina D&#44; sometidos a tratamiento de inhibidores RAS o Alopurinol reflejaron unos niveles superiores de 25¿OH¿D3&#44; y sin embargo aquellos sometidos a tratamiento de estatinas reflejaron unos menores niveles de vitamina&#160;D&#46; Se precisan ensayos aleatorizados controlados para confirmar estos hallazgos&#46;</p>"
      ]
      "en" => array:1 [
        "resumen" => "<p class="elsevierStylePara"> <span class="elsevierStyleItalic">Background&#58;</span> Vitamin D deficiency and polypharmacy is a common problem over chronic kidney disease &#40;CKD&#41; population&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Objectives&#58;</span> To assess the clinical and analytical characteristics of CKD patients with 25¿OH¿D3 deficiency &#40;&#60;15 ng&#47;mL&#41;&#44; including the possible role of associated drugs&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Methods&#58;</span> A single center observational review of 137 incident patients referred to our outpatient clinic with different stages of CKD and 25¿OH¿D3&#60;15ng&#47;mL &#40;male gender 53&#46;3&#37;&#44; mean age 70&#46;8 &#91;&#177;16&#46;1&#93; years&#44; mean GFR &#40;MDRD¿4&#41; 43&#46;6 &#91;&#177;25&#46;5&#93; ml&#47;min&#47;1&#46;73 m<span class="elsevierStyleSup">2</span>&#41;&#46; 25¿OH¿D3 levels were collected in spring&#46; Clinical and biochemical data and associated medications were recorded&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Results&#58;</span> Mean 25¿OH¿D3 levels were 8&#46;23 &#91;&#177;4&#46;03&#93; ng&#47;ml&#46; Eighty¿eight patients &#40;64&#46;7&#37;&#41; had 3 or more concomitant drugs&#46; Only 7 patients &#40;5&#46;1&#37;&#41; were not receiving any medication&#46; Patients were divided in three groups according the therapies into none &#40;n&#61;26&#41;&#44; RAS inhibitors or allopurinol &#40;n&#61;81&#41;&#44; and RAS inhibitors plus allopurinol &#40;n&#61;30&#41;&#59; with the aim to study the influence of statin therapy&#46; Patients under renin angiotensin &#40;RAS&#41; inhibitors or Allopurinol treatment presented significantly higher 25¿OH¿D3 levels &#40;p&#61;0&#46;001 and p&#61;0&#46;01 respectively&#41;&#44; however patients with Statins treatment had lower 25¿OH¿D3 level &#40;p&#61;0&#46;039&#41;&#46; Personal history of diabetes&#44; cardiovascular events or other therapies did not modify 25¿OH¿D3 levels&#44; adjusted by age and eGFR&#46;</p> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Conclusions&#58;</span> CKD patients with vitamin D deficiency who received RAS inhibitors or Allopurinol treatment had higher 25¿OH¿D3 levels&#44; however those with statins treatment had lower vitamin D levels&#46; Randomized controlled trials are required to confirm these findings&#46;</p>"
      ]
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          "en" => "– Linear Multivariate Regression &#40;adjusted by age&#44; eGFR and prior history of Congestive cardiac failure&#41;"
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          "en" => "– Relationship between therapies and baseline serum 25¿OH¿D3 levels&#46; Patients were divided in three groups according with the concomitant therapies&#44; and there were significant statistical differences between groups &#40;p <0 001 patients who were not receiving renin angiotensin system ras inhibitors or allopurinol n="30&#41;" presented lower 25 8209 oh d3 d levels than those and plus p <0 001 highest 25 8209 oh d3 levels 11 7 3 p="0&#46;005&#41;" were found in patients receiving ras inhibitors plus allopurinol without statins lowest 5 1 82 who only</0> </0>"
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ISSN: 20132514
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Nefrología (English Edition)