Acute and sub-acute effect of ferric carboxymaltose on inflammation and adhesion molecules in patients with predialysis chronic renal failure
Efecto agudo y subagudo de la carboximaltosa férrica sobre la inflamación y moléculas de adhesión en pacientes con insuficiencia renal crónica prediálisis
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Rosa" "apellidos" => "Nogués" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 6 => array:3 [ "nombre" => "Manel" "apellidos" => "Jariod" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] 7 => array:3 [ "nombre" => "Marta" "apellidos" => "Romeu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 8 => array:3 [ "nombre" => "Alberto" "apellidos" => "Martínez-Vea" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Nefrología, Hospital Universitari Joan XXIII, Tarragona, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Unidad de Farmacología, Facultad de Medicina y Ciencias de la Salud. Universitat Rovira i Virgili, Reus, Tarragona, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] 2 => array:3 [ "entidad" => "Unidad de Sistemas de Información de la Gestión, Hospital Universitari Joan XXIII, Tarragona, " "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "affc" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Efecto agudo y subagudo de la carboximaltosa férrica sobre la inflamación y moléculas de adhesión en pacientes con insuficiencia renal crónica prediálisis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11774_16025_45486_en_t111774.jpg" "Alto" => 892 "Ancho" => 1058 "Tamanyo" => 232254 ] ] "descripcion" => array:1 [ "en" => "Clinical variables of the population" ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">Anaemia in chronic kidney disease (CKD) has a multifactorial origin with iron deficiency being one of the main mechanisms, and a prevalence of about 50% according to studies.<span class="elsevierStyleSup">1</span> This deficiency also implies a risk of arteriosclerosis,<span class="elsevierStyleSup">2,3 </span>since there is a defect in iron-containing protein production with antioxidant capacity.</p><p class="elsevierStylePara">It has been observed how iron-deficient patients have a higher level of adhesion molecules, which are <span class="elsevierStyleItalic">per se</span> a risk factor for developing arteriosclerosis<span class="elsevierStyleSup">4</span> and are independent factors of cardiovascular death.<span class="elsevierStyleSup">5</span> In CKD, inflammatory markers and adhesion molecules expression are increased and there is an inverse relationship with renal function: the lower the glomerular filtration (GF), the higher its expression.<span class="elsevierStyleSup">6</span> This relationship is maintained in haemodialysis.<span class="elsevierStyleSup">7</span> In the population with normal renal function, the correction of iron deficiency decreases the expression of these molecules,<span class="elsevierStyleSup">8</span> although there are no studies in predialysis CKD patients.</p><p class="elsevierStylePara">Treatment with intravenous iron is safe and effective in correcting anaemia in patients with CKD in which iron requirements are increased. However, there are some studies, especially on dialysis, that demonstrate that the aforementioned treatment increases the inflammatory state;<span class="elsevierStyleSup">9-11</span> however, in other studies that use different preparations at different doses and frequencies of administration, the aforementioned increase is not observed.<span class="elsevierStyleSup">12-16</span> There is little evidence of the action of iron on the expression of adhesion molecules. Experimental studies examining the effect of different iron molecules on mononuclear cells of patients on haemodialysis demonstrate there is a lesion and an activation of these cells.<span class="elsevierStyleSup">17,18</span></p><p class="elsevierStylePara">It has been suggested that differences in the pharmacological characteristics of iron preparations and administration dosage (dose and administration intervals) of the iron administered may involve variations in the inflammatory effect<span class="elsevierStyleSup">19-22</span> and on adhesion molecules.</p><p class="elsevierStylePara">Ferric carboxymaltose (FCM) is a new generation of non-dextran iron, which may be administered quickly and at high doses; it involves a controlled release of iron to the tissues and has minimal side effects.<span class="elsevierStyleSup">23-25</span> Due to these characteristics, it has been suggested that this iron molecule would have less effect on inflammation and adhesion molecules. In fact, in experiments, it has been shown that FCM, compared with other iron preparations with lower molecular weight, does not induce oxidative stress or increase inflammation.<span class="elsevierStyleSup">22</span></p><p class="elsevierStylePara">The aim of our study was to analyse the effect of FCM administration in predialysis CKD patients with iron deficiency on adhesion molecules and inflammation.<span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">METHODS</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Study population</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">50 patients were recruited from the Nephrology department’s outpatient service of the Hospital Universitari Joan XXIII in Tarragona. They were above 18 years of age, had predialysis CKD and presented the following inclusion criteria: serum haemoglobin <11g/dl, serum ferritin <100ng/ml and/or transferrin saturation index <20%. Patients excluded were those who in the previous three months had received oral iron or blood transfusion or who had bleeding, infection or active acute inflammatory process and a history of hypersensitivity to treatment with intravenous iron.</p><p class="elsevierStylePara">Of the initial 50 patients, 3 were excluded (2 due to gastrointestinal bleeding and 1 due to active infection during follow-up), and therefore, the final study population consisted of 47 patients.</p><p class="elsevierStylePara">This study was approved by the hospital ethics committee and all patients signed the informed consent.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Study design</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">This was a prospective study that lasted for 18 months (beginning in April 2010 and ending in October 2011). Patients received a single dose of FCM (Ferinject<span class="elsevierStyleSup">®</span>) at 15mg/kg (maximum 1g) diluted in 250cc of saline solution with an infusion time of 30 minutes.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Determination of clinical variables</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Some cardiovascular risk factors such as hypertension, dyslipidaemia and obesity were determined.</p><p class="elsevierStylePara">Arterial hypertension (HTN): blood pressure was determined on three occasions during the procedure (with three measurements in each of them) for assessment of haemodynamic tolerance during the process. We used a validated automatic device (Omron 705CP, Healthcare GmbH, Hamburg, Germany). HTN was defined as systolic blood pressure of 140 mmHg or higher, diastolic blood pressure of 90mmHg or higher, or treatment with antihypertensive drugs.</p><p class="elsevierStylePara">Obesity: body mass index (BMI) expressed as weight (kg)/height (square metre) was calculated. Obesity was defined as BMI>30kg/m<span class="elsevierStyleSup">2</span>.</p><p class="elsevierStylePara">Dyslipidaemia: was defined as total cholesterol greater than 240mg/dl or being on statin therapy.</p><p class="elsevierStylePara">Diabetes mellitus: was defined as fasting plasma glucose above 126mg/dl or patients treated with oral anti-diabetic drugs and/or insulin.</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Biochemical determinations</span> </p><p class="elsevierStylePara">At baseline, 60 minutes after administration of FCM (acute effect), and after 3 weeks and 3 months of treatment (sub-acute effect), the determination of haemoglobin (Hb) and ferrokinetic parameters (ferritin, transferrin saturation index [TSI] was carried out by conventional methods and inflammatory markers: ultrasensitive C-reactive protein (CRP), interleukin 6 (IL-6) and adhesion molecules: soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cellular adhesion molecule-1 (sVCAM-1). Levels of IL-6 were determined using the commercial kit Human IL-6 Quantikine HS High Sensitivity (R&D Systems, Lille, France). The N High Sensitivity CRP kit was used to determine CRP (Dade Bering, Newark, USA). Levels of ICAM and VCAM were determined by the Quantikine<span class="elsevierStyleSup">®</span> ELISA kit (R&D Systems, Minneapolis, USA).</p><p class="elsevierStylePara">In all patients, routine methods were used to determine levels of creatinine and GF through the formula MDRD-4.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">STATISTICAL ANALYSIS</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Statistical analysis was performed using the SPSS v. 15 software. Ultrasensitive CRP values were not distributed normally and were therefore transformed logarithmically. The verification or rejection of the hypothesis of normality of continuous variables was performed with the Shapiro-Wilk test. The association between nominal variables was studied by contingency tables and Fisher’s exact probability test. To analyse the association between a continuous variable and a nominal variable, the Mann-Whitney “U” test or the Kruskal-Wallis test were used in accordance with whether or not it was dichotomous. We used Spearman’s correlation coefficient to measure the linear association between two continuous variables. For analysis involving repeated measurements of continuous variables, we used analysis of the variance for repeated measurements with the criterion of Wilks' lambda. The level of statistical significance was set at <span class="elsevierStyleItalic">P</span><.05 in a two-tailed test.</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Population characteristics</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">This is an older population (mean age 72 years) with CKD: 13 patients in stage 3; 27 in stage 4 (57.4%) and 7 non-dialysis patients in stage 5 CKD. The aetiology of the CKD was of vascular origin (48.9%), followed by diabetic nephropathy (25.5%); other causes included: interstitial/polycystic kidney disease (6.4%), glomerular (4.3%) and unknown origin (14.9%).</p><p class="elsevierStylePara">All patients were hypertensive, overweight (mean BMI of 29kg/m<span class="elsevierStyleSup">2</span>), 75% were dyslipidaemic and 40% had diabetes.</p><p class="elsevierStylePara">The characteristics of the population are summarised in Table 1.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Effect of ferric carboxymaltose on anaemia</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">After treatment with FCM, we observed a significant increase in levels of Hb, ferritin and TSI (Table 2).</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Acute effect of ferric carboxymaltose on adhesion molecules and inflammation</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">No significant differences were observed between the baseline levels and levels after 60 minutes of VCAM and ICAM treatment, and no significant differences were observed in inflammatory markers (Table 3).</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Sub-acute effect of ferric carboxymaltose on adhesion molecules and inflammation</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">We did not observe any significant changes in adhesion molecules or inflammatory markers after 3 weeks or 3 months of treatment with FCM. In an analysis differentiated in accordance with the CKD stage: stage 3 vs. stage 4 + 5, no significant changes were observed in any of the markers analysed. Albumin levels remained unchanged throughout the study.</p><p class="elsevierStylePara">After adjusting the effect of treatment with FCM and various parameters such as the presence of diabetes mellitus, dyslipidaemia, the use of erythropoiesis stimulating agents, the use of angiotensin converting enzyme inhibitors and/or angiotensin II receptor antagonists and statins, we only observed that statin use changed the response of the adhesion molecules on treatment with FCM. VCAM levels were lower in patients treated with statins than in untreated patients (<span class="elsevierStyleItalic">P</span>=.02). In addition, they significantly increased in untreated patients, while they remained unchanged in treated patients (<span class="elsevierStyleItalic">P</span>=.02) (Table 4). No significant differences were perceived in ICAM levels.</p><p class="elsevierStylePara">Lastly, we examined the influence of treatment with paricalcitol on the effect of FCM on inflammatory markers and endothelial cells, without perceiving significant differences between treated and untreated patients.</p><p class="elsevierStylePara">The effect of FCM on adhesion molecules and inflammation is summarised in Table 3.</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">The relationship between anaemia, inflammatory markers and adhesion molecules</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">No correlation was observed between baseline levels of Hb, ferritin, CRP, IL-6, VCAM or ICAM, or between the percentage of change in levels of Hb, CRP, IL-6, VCAM and ICAM after 3 weeks and 3 months.</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The result of our study shows that in patients with predialysis CKD and iron deficiency anaemia, treatment with FCM does not induce inflammation or cause an increase in adhesion molecules.</p><p class="elsevierStylePara">Iron deficiency anaemia in CKD patients is a major problem because of its high prevalence and its contribution to the morbidity and mortality associated with CKD.<span class="elsevierStyleSup">5</span> It is considered one of the non-traditional cardiovascular risk factors<span class="elsevierStyleSup">24</span> and, although less well-known, it is also considered an independent risk factor in the development of arteriosclerosis, probably due to a defect in the production of other Fe<span class="elsevierStyleSup">2+</span>-containing proteins such as peroxidases, catalases involved in preventing the latter.<span class="elsevierStyleSup">25</span></p><p class="elsevierStylePara">Patients with iron deficiency anaemia have higher levels of adhesion molecules.<span class="elsevierStyleSup">8</span> These molecules are directly involved in the initiation and aggravation of arteriosclerotic lesions.<span class="elsevierStyleSup">26</span> In CKD, there is an overexpression of these molecules, which are higher the lower the GF, and they remain high in the population on renal replacement therapy. High levels of these molecules are associated with malnutrition, inflammation and cardiovascular disease; this suggests that there is a relationship between vascular activation, systemic inflammation and uraemic toxicity. Lastly, CKD is considered to be an inflammatory state involved in different complications of CKD, such as malnutrition and accelerated atherosclerosis.<span class="elsevierStyleSup">27-29</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Ferric carboxymaltose and inflammation</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">It has been suggested that treatment with parenteral iron could contribute to morbidity and mortality in patients with CKD due to increased oxidative stress and inflammation. In our study, treatment with FCM did not have an acute or a short-term proinflammatory effect.</p><p class="elsevierStylePara">One of the possible mechanisms responsible for the neutral effect of FCM on inflammation could be that correcting anaemia would improve or rather counteract the inflammatory stimulus of FCM. In fact, there are studies in patients with anaemia treated with erythropoiesis-stimulating agents in which, after an improvement in Hb figures, there is a decrease of inflammatory parameters,<span class="elsevierStyleSup">30</span> even if taking iron.<span class="elsevierStyleSup">31</span> By contrast, in our study, we did not find a correlation between changes in Hb levels and inflammatory parameters, which suggests that the neutral effect of treatment with FCM on inflammation would not be mediated by the improvement of anaemia.</p><p class="elsevierStylePara">Another possible explanation could be the characteristics of the FCM molecule. Iron preparations of low molecular weight and low thermokinetic stability (iron gluconate, iron sucrose) cause an abrupt rise in serum iron, with transferrin oversaturation and more free iron, which determines an increase in inflammatory molecules. By contrast, ferric carboxymaltose is a macromolecular carbohydrate-iron hydroxide complex, designed to allow a controlled release of iron in the cells of the reticuloendothelial system, minimising the risk of releasing large amounts of ionic iron in serum. In a study conducted in rats,<span class="elsevierStyleSup">22</span> we compared the effect of different iron preparations, including carboxymaltose, on inflammation and oxidative stress, concluding that the aforementioned molecule would induce less inflammation than other preparations.</p><p class="elsevierStylePara">Lastly, we must mention the lack of a proinflammatory effect of FCM with high doses of this molecule used in this study. In most publications, intravenous iron doses are low compared to those of our study, and some also advocate the slow administration of the product in order to minimise the aforementioned proinflammatory effect. We have not observed this effect despite using large doses (about 1 gram on average) in a short interval of time (maximum 30 minutes). However, given that there are no studies with a follow-up time longer than three months, the implications of long-term use of FCM on inflammatory status is unknown.</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Ferric carboxymaltose and adhesion molecules</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">There are few studies that analyse the effect of parenteral iron administration on adhesion molecules in patients with CKD and iron deficiency anaemia.</p><p class="elsevierStylePara">In the population with normal renal function, it has been observed that administration of oral iron causes a decrease in VCAM, but not ICAM.<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">Treatment with four intravenous iron preparations (ferric gluconate, iron sucrose, iron dextran and FCM) causes an increase in the expression of ICAM-1, reactive oxygen species and apoptosis in the mononuclear cells of patients with stage 5 CKD and in haemodialysis patients, regardless of the iron used. By contrast, in our study, treatment with FCM had no effect on the levels of adhesion molecules, as has been described with iron sucrose on endothelial function in patients on haemodialysis<span class="elsevierStyleSup">16</span> or peritoneal dialysis.<span class="elsevierStyleSup">15</span></p><p class="elsevierStylePara">The mechanism by which FCM would not produce endothelial lesion could also be related to the characteristics of the molecule itself, with a lower release of ionic iron in serum and lower endothelial lesion.</p><p class="elsevierStylePara">Lastly, we must note the effect of statins on adhesion molecules. The relationship between arteriosclerosis and inflammation is known,<span class="elsevierStyleSup">32</span> as well as that statins reduce systemic inflammation and improve endothelial function.<span class="elsevierStyleSup">33,34</span> In our study, we observed lower levels of VCAM in patients who were on lipid-lowering treatment, which suggests that statins may counteract the stimulation of treatment with FCM on the aforementioned adhesion molecule.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Limitations of the study</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">The number of patients included in the study was small and the follow-up time was short. Studies with larger numbers of patients and longer follow-up periods are necessary to confirm the lack of effect of FCM on inflammation and adhesion molecules in this population.</p><p class="elsevierStylePara">Our study did not evaluate endothelial function. However, plasma concentrations of adhesion molecules analysed correlate with the expression of these molecules in the surface of the endothelial cells,<span class="elsevierStyleSup">35</span> they reflect endothelial activation and vascular inflammation<span class="elsevierStyleSup">36</span> and are considered to be markers of endothelial dysfunction.</p><p class="elsevierStylePara">In conclusion, treatment with high doses of FCM in patients with predialysis CKD has no proinflammatory effect and does not change the levels of adhesion molecules in these patients. Concomitant treatment with statins is associated with a lower concentration of these molecules.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article.</p><p class="elsevierStylePara"><a href="grande/11774_16025_45486_en_t111774.jpg" class="elsevierStyleCrossRefs"><img src="11774_16025_45486_en_t111774.jpg" alt="Clinical variables of the population"></img></a></p><p class="elsevierStylePara">Table 1. Clinical variables of the population</p><p class="elsevierStylePara"><a href="grande/11774_16025_45487_en_t2117742.jpg" class="elsevierStyleCrossRefs"><img src="11774_16025_45487_en_t2117742.jpg" alt="Effect of ferric carboxymaltose on anaemia"></img></a></p><p class="elsevierStylePara">Table 2. Effect of ferric carboxymaltose on anaemia</p><p class="elsevierStylePara"><a href="grande/11774_16025_45488_en_t3117743.jpg" class="elsevierStyleCrossRefs"><img src="11774_16025_45488_en_t3117743.jpg" alt="Acute and sub-acute effect of ferric carboxymaltose on inflammatory markers and adhesion molecules"></img></a></p><p class="elsevierStylePara">Table 3. Acute and sub-acute effect of ferric carboxymaltose on inflammatory markers and adhesion molecules</p><p class="elsevierStylePara"><a href="grande/11774_16025_45489_en_t4117744.jpg" class="elsevierStyleCrossRefs"><img src="11774_16025_45489_en_t4117744.jpg" alt="Influence of treatment with statins in the response of adhesion molecules to ferric carboxymaltose"></img></a></p><p class="elsevierStylePara">Table 4. Influence of treatment with statins in the response of adhesion molecules to ferric carboxymaltose</p>" "pdfFichero" => "P1-E550-S4065-A11774-EN.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "es" => array:4 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec436055" "palabras" => array:1 [ 0 => "Insuficiencia renal crónica" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec436057" "palabras" => array:1 [ 0 => "Moléculas de adhesión" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec436059" "palabras" => array:1 [ 0 => "Carboximaltosa férrica" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec436061" "palabras" => array:1 [ 0 => "Inflamación" ] ] ] "en" => array:4 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec436056" "palabras" => array:1 [ 0 => "Chronic renal failure" ] ] 1 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec436058" "palabras" => array:1 [ 0 => "Adhesion molecules" ] ] 2 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec436060" "palabras" => array:1 [ 0 => "Ferric carboxymaltose" ] ] 3 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec436062" "palabras" => array:1 [ 0 => "Inflammation" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "es" => array:1 [ "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Antecedentes:</span> El tratamiento con hierro parenteral provoca estrés oxidativo, inflamación y disfunción endotelial. La carboximaltosa férrica (CMF) es un nuevo preparado de hierro no dextrano que, por sus características farmacocinéticas y estabilidad, podría inducir menor toxicidad que otras moléculas de hierro. El objetivo de este estudio fue analizar el efecto de la CMF sobre la inflamación y moléculas de adhesión en la enfermedad renal crónica (ERC). <span class="elsevierStyleBold">Métodos</span><span class="elsevierStyleBold">:</span> Cuarenta y siete pacientes con ERC prediálisis y anemia ferropénica recibieron una dosis única de CMF (15 mg/kg, dosis máxima 1 gramo). De forma basal, a los 60 minutos (efecto agudo), y a las 3 semanas y 3 meses (efecto subagudo), se determinaron marcadores de inflamación: proteína C reactiva (PCR) e interleucina 6 (IL-6), y de disfunción endotelial: moléculas de adhesión intercelular (ICAM) y vascular (VCAM). <span class="elsevierStyleBold">Resultados</span><span class="elsevierStyleBold">:</span> El tratamiento con CMF se asoció a un incremento significativo de los niveles de hemoglobina: 10 (0,7) vs. 11,4 (1,3) g/dl, p < 0,0001. Los niveles de PCR, IL-6, ICAM y VCAM no se correlacionaron con los niveles basales de hemoglobina ni ferritina, y no se observó ninguna relación entre los cambios en estos marcadores y los de hemoglobina después de la administración de CMF. No se observaron cambios significativos ni de forma aguda o subaguda en ninguno de los marcadores inflamatorios o endoteliales estudiados. El tratamiento con estatinas se asoció a menores concentraciones de VCAM. <span class="elsevierStyleBold">Conclusiones</span><span class="elsevierStyleBold">:</span> El tratamiento con dosis elevadas de CMF en pacientes con ERC prediálisis no tiene efecto proinflamatorio ni modifica los niveles de moléculas de adhesión ICAM y VCAM en esta población.</p>" ] "en" => array:1 [ "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Background</span></span><span class="elsevierStyleItalic">: Treatment with parenteral iron causes oxidative stress, inflammation and endothelial dysfunction. Ferric carboxymaltose (FCM) is a new preparation of non-dextran iron which, due to its pharmacokinetics and stability, may induce less toxicity than other iron molecules. The aim of this study was to analyse the effect of FCM on inflammation and adhesion molecules in chronic kidney disease (CKD). <span class="elsevierStyleBold">Methods</span>: Forty-seven patients with predialysis CKD and iron-deficiency anaemia received a single dose of FCM (15mg/kg, maximum dose 1 gram). At baseline and after 60 minutes (acute effect) and after 3 weeks and 3 months (sub-acute effect), we determined inflammatory markers: C-reactive protein (CRP), interleukin-6 (IL-6) and endothelial dysfunction: intercellular adhesion molecule (ICAM) and vascular adhesion molecule (VCAM). <span class="elsevierStyleBold">Results</span><span class="elsevierStyleBold">:</span> Treatment with FCM was associated with a significant increase in haemoglobin levels: 10 (0.7) vs. 11.4 (1.3)g/dl, p<.0001. CRP, IL-6, ICAM and VCAM levels did not correlate with baseline haemoglobin or ferritin levels and there was no relationship between changes in these markers and those of haemoglobin after administration of FCM. No significant, acute or sub-acute changes occurred in any of the inflammatory or endothelial markers studied. Statin therapy was associated with lower VCAM concentrations. <span class="elsevierStyleBold">Conclusions</span>: Treatment with high doses of FCM in patients with predialysis CKD has no proinflammatory effect and does not alter levels of adhesion molecules ICAM and VCAM in this population.</span></p>" ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Tab. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11774_16025_45486_en_t111774.jpg" "Alto" => 892 "Ancho" => 1058 "Tamanyo" => 232254 ] ] "descripcion" => array:1 [ "en" => "Clinical variables of the population" ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Tab. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11774_16025_45487_en_t2117742.jpg" "Alto" => 328 "Ancho" => 2165 "Tamanyo" => 135294 ] ] "descripcion" => array:1 [ "en" => "Effect of ferric carboxymaltose on anaemia" ] ] 2 => array:8 [ "identificador" => "fig3" "etiqueta" => "Tab. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11774_16025_45488_en_t3117743.jpg" "Alto" => 325 "Ancho" => 2184 "Tamanyo" => 175578 ] ] "descripcion" => array:1 [ "en" => "Acute and sub-acute effect of ferric carboxymaltose on inflammatory markers and adhesion molecules" ] ] 3 => array:8 [ "identificador" => "fig4" "etiqueta" => "Tab. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "11774_16025_45489_en_t4117744.jpg" "Alto" => 433 "Ancho" => 2168 "Tamanyo" => 162782 ] ] "descripcion" => array:1 [ "en" => "Influence of treatment with statins in the response of adhesion molecules to ferric carboxymaltose" ] ] ] ] "idiomaDefecto" => "en" "url" => "/20132514/0000003300000003/v0_201502091549/X2013251413003201/v0_201502091549/en/main.assets" "Apartado" => array:4 [ "identificador" => "35441" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Originals" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/20132514/0000003300000003/v0_201502091549/X2013251413003201/v0_201502091549/en/P1-E550-S4065-A11774-EN.pdf?idApp=UINPBA000064&text.app=https://revistanefrologia.com/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/X2013251413003201?idApp=UINPBA000064" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 10 | 11 | 21 |
| 2024 October | 84 | 65 | 149 |
| 2024 September | 75 | 55 | 130 |
| 2024 August | 85 | 74 | 159 |
| 2024 July | 65 | 54 | 119 |
| 2024 June | 94 | 57 | 151 |
| 2024 May | 81 | 50 | 131 |
| 2024 April | 63 | 42 | 105 |
| 2024 March | 55 | 20 | 75 |
| 2024 February | 43 | 41 | 84 |
| 2024 January | 33 | 47 | 80 |
| 2023 December | 37 | 40 | 77 |
| 2023 November | 43 | 58 | 101 |
| 2023 October | 49 | 57 | 106 |
| 2023 September | 42 | 53 | 95 |
| 2023 August | 49 | 38 | 87 |
| 2023 July | 43 | 45 | 88 |
| 2023 June | 60 | 36 | 96 |
| 2023 May | 72 | 53 | 125 |
| 2023 April | 32 | 37 | 69 |
| 2023 March | 39 | 35 | 74 |
| 2023 February | 32 | 36 | 68 |
| 2023 January | 39 | 32 | 71 |
| 2022 December | 51 | 40 | 91 |
| 2022 November | 49 | 54 | 103 |
| 2022 October | 51 | 58 | 109 |
| 2022 September | 43 | 62 | 105 |
| 2022 August | 38 | 50 | 88 |
| 2022 July | 37 | 61 | 98 |
| 2022 June | 29 | 39 | 68 |
| 2022 May | 45 | 34 | 79 |
| 2022 April | 35 | 46 | 81 |
| 2022 March | 35 | 56 | 91 |
| 2022 February | 40 | 46 | 86 |
| 2022 January | 45 | 50 | 95 |
| 2021 December | 45 | 59 | 104 |
| 2021 November | 38 | 42 | 80 |
| 2021 October | 64 | 63 | 127 |
| 2021 September | 72 | 59 | 131 |
| 2021 August | 39 | 41 | 80 |
| 2021 July | 38 | 49 | 87 |
| 2021 June | 40 | 26 | 66 |
| 2021 May | 65 | 41 | 106 |
| 2021 April | 115 | 41 | 156 |
| 2021 March | 82 | 32 | 114 |
| 2021 February | 57 | 32 | 89 |
| 2021 January | 34 | 20 | 54 |
| 2020 December | 63 | 25 | 88 |
| 2020 November | 25 | 20 | 45 |
| 2020 October | 26 | 18 | 44 |
| 2020 September | 19 | 10 | 29 |
| 2020 August | 51 | 18 | 69 |
| 2020 July | 50 | 11 | 61 |
| 2020 June | 34 | 21 | 55 |
| 2020 May | 51 | 15 | 66 |
| 2020 April | 27 | 17 | 44 |
| 2020 March | 34 | 20 | 54 |
| 2020 February | 69 | 22 | 91 |
| 2020 January | 58 | 19 | 77 |
| 2019 December | 71 | 27 | 98 |
| 2019 November | 45 | 19 | 64 |
| 2019 October | 32 | 12 | 44 |
| 2019 September | 44 | 27 | 71 |
| 2019 August | 23 | 8 | 31 |
| 2019 July | 40 | 34 | 74 |
| 2019 June | 29 | 15 | 44 |
| 2019 May | 48 | 12 | 60 |
| 2019 April | 35 | 27 | 62 |
| 2019 March | 40 | 26 | 66 |
| 2019 February | 36 | 22 | 58 |
| 2019 January | 29 | 18 | 47 |
| 2018 December | 93 | 40 | 133 |
| 2018 November | 89 | 15 | 104 |
| 2018 October | 84 | 18 | 102 |
| 2018 September | 68 | 18 | 86 |
| 2018 August | 59 | 30 | 89 |
| 2018 July | 51 | 18 | 69 |
| 2018 June | 66 | 18 | 84 |
| 2018 May | 49 | 17 | 66 |
| 2018 April | 76 | 11 | 87 |
| 2018 March | 55 | 14 | 69 |
| 2018 February | 65 | 7 | 72 |
| 2018 January | 62 | 14 | 76 |
| 2017 December | 86 | 14 | 100 |
| 2017 November | 63 | 11 | 74 |
| 2017 October | 66 | 14 | 80 |
| 2017 September | 56 | 6 | 62 |
| 2017 August | 59 | 24 | 83 |
| 2017 July | 33 | 17 | 50 |
| 2017 June | 40 | 8 | 48 |
| 2017 May | 46 | 15 | 61 |
| 2017 April | 40 | 8 | 48 |
| 2017 March | 37 | 12 | 49 |
| 2017 February | 49 | 23 | 72 |
| 2017 January | 26 | 17 | 43 |
| 2016 December | 70 | 11 | 81 |
| 2016 November | 94 | 10 | 104 |
| 2016 October | 106 | 12 | 118 |
| 2016 September | 144 | 7 | 151 |
| 2016 August | 234 | 6 | 240 |
| 2016 July | 187 | 8 | 195 |
| 2016 June | 153 | 0 | 153 |
| 2016 May | 161 | 0 | 161 |
| 2016 April | 134 | 0 | 134 |
| 2016 March | 116 | 0 | 116 |
| 2016 February | 141 | 0 | 141 |
| 2016 January | 120 | 0 | 120 |
| 2015 December | 141 | 0 | 141 |
| 2015 November | 115 | 0 | 115 |
| 2015 October | 114 | 0 | 114 |
| 2015 September | 91 | 0 | 91 |
| 2015 August | 84 | 0 | 84 |
| 2015 July | 78 | 0 | 78 |
| 2015 June | 47 | 0 | 47 |
| 2015 May | 76 | 0 | 76 |
| 2015 April | 18 | 0 | 18 |
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