Hypogonadism associated with muscle atrophy, physical inactivity and ESA hyporesponsiveness in men undergoing haemodialysis

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hyporesponsiveness in men undergoing haemodialysis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "54" "paginaFinal" => "60" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Gabriela Cobo, Paloma Gallar, Cristina Di Gioia, Concepción García Lacalle, Rosa Camacho, Isabel Rodriguez, Olimpia Ortega, Carmen Mon, Ana Vigil, Bengt Lindholm, Juan Jesús Carrero" "autores" => array:11 [ 0 => array:4 [ "nombre" => "Gabriela" "apellidos" => "Cobo" "email" => array:1 [ 0 => "gabriela.cobo@ki.se" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Paloma" "apellidos" => "Gallar" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Cristina" "apellidos" => "Di Gioia" "referencia" => 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"aff0005" ] ] ] 9 => array:3 [ "nombre" => "Bengt" "apellidos" => "Lindholm" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 10 => array:3 [ "nombre" => "Juan Jesús" "apellidos" => "Carrero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Nephrology, Hospital Severo Ochoa, Leganes, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Divisions of Renal Medicine and Baxter Novum, CLINTEC, Karolinska Institutet, Stockholm, Sweden" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Biochemistry, Hospital Severo Ochoa, Leganes, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hipogonadismo asociado a atrofia muscular, inactividad física e hiposensibilidad a FEE en varones sometidos a hemodiálisis" ] ] "textoCompleto" => "IntroductionChronic kidney disease (CKD) involves alterations in body homeostasis and metabolic disturbances (including hormone secretion disorders and altered response to hormones in target tissues), resulting in endocrine dysfunctions that may contribute to the increased mortality in CKD patients.<a class="elsevierStyleCrossRef" href="#bib0150">1</a> Hypogonadism, hallmarked by testosterone deficiency is a common endocrine disorder among men undergoing dialysis, with a prevalence ranging from 35 to 50% in recent studies.<a class="elsevierStyleCrossRefs" href="#bib0155">2–4</a> Various studies link hypogonadism with mortality risk among hemodialysis patients,<a class="elsevierStyleCrossRefs" href="#bib0170">5,6</a> but the pathways by which this risk may be mediated are not well known.The clinical implications of hypogonadism among dialysis patients are not well characterized. Testosterone is a steroid hormone that has an important anabolic function influencing among others muscle mass, increasing both strength and size.<a class="elsevierStyleCrossRef" href="#bib0180">7</a> In the general population, testosterone deficiency that accompanies aging has been linked to decreased physical performance and its consequent limitation of mobility.<a class="elsevierStyleCrossRef" href="#bib0185">8</a> In non-dialysis CKD patients, endogenous testosterone is a strong determinant of both muscle mass and strength.<a class="elsevierStyleCrossRef" href="#bib0190">9</a> It is unknown if this is still the case in individuals undergoing dialysis.Furthermore, testosterone induces erythrocytosis<a class="elsevierStyleCrossRefs" href="#bib0195">10,11</a> and testosterone deficiency has been associated with anemia and increased resistance to erythropoietin-stimulating agents (ESA) in dialysis patients.<a class="elsevierStyleCrossRef" href="#bib0155">2</a> However, this finding has, to date, not been confirmed. The objective of our study was to assess the prevalence of hypogonadism among men undergoing dialysis at our center. Further, we explored the clinical phenotype of hypogonadal patients. Based on the abovementioned preceding literature, we hypothesized that endogenous testosterone would associate with the percentage of muscle strength and physical activity, as well as with higher ESA requirements.Patients and methodsPatientsThis cross-sectional study comprised clinically stable male patients with CKD attending the hemodialysis (HD) program at Severo Ochoa Hospital, Leganes, Madrid, Spain. Only patients who had been on HD for more than three months and without hospital admissions in the month preceding the investigation were invited to participate. Patients with physical limitations (amputation) and neurological impairment were not considered because of the difficulty in assessing physical activity. From 75 eligible patients, 57 patients met the inclusion criteria and all accepted to participate. None of the patients was receiving testosterone replacement therapy. All participants gave their written consent. The study was approved by the Ethics Committee of the Severo Ochoa Hospital.Clinical data including co-morbiditiesEach patient's medical chart was reviewed to extract demographic and clinical data including comorbidities. Clinical history of cardiovascular disease (CVD) was defined as cardiac, cerebrovascular (including stroke) or peripheral vascular disease. Mean arterial pressure (MAP) was defined as [diastolic pressure+(systolic pressure−diastolic pressure)/3]. Dose of erythropoietin-stimulating agents (ESAs) for each patient was recorded as international units administered per week (U/week). Weekly doses of darbepoetin in micrograms were converted to international units of erythropoietin by multiplying with a conversion factor of 200. The median ESA equivalent dose was 6000 (0–15300) U/week, which was normalized for body weight and for hemoglobin levels and presented as U/kg/mg/mL Hb/week in the following analyses.Laboratory analysisBlood samples were collected before midweek dialysis session. The plasma was separated within 30min, and samples were kept frozen at −70°C if not analyzed immediately. Biochemical parameters were determined by standard laboratory techniques at the Biochemical Department of the Severo Ochoa Hospital. Interleukin-6 (IL-6) concentration was assessed on plasma lithium heparin by multiplexing in a Bioplex system (X-MAP technology, BioRad, Madrid, Spain) using commercial kits (R&D Systems Europe, Ltd, UK). The concentration was calculated by interpolation from the calibration performed with the corresponding recombinant proteins provided by the kit. Total testosterone was assessed in serum with a chemiluminescence assay (Advia-Centaur, Siemens) that has sensitivity, specificity, precision and linearity according to the requirements for usage in clinical practice. The normal reference range established by our laboratory for the male population is 241–827ng/dL.Body composition assessmentDry weight (based on clinical approach) in kilograms and height in meters of each participant was recorded. Body mass index (BMI) was calculated dividing weight in kilograms by height in square meters (kg/m2). Body composition was assessed by bioimpedance (Body Composition Monitor, Fresenius Medical Care, Bad Homburg, Germany). The measurement was performed immediately before the second dialysis session of the week. Lean body mass (LBM) and fat body mass (FBM) were expressed as percentages. Total body water (TBW), extracellular water (ECW), intracellular water (ICW) and the relation ECW/ICW were collected. Other parameters obtained were body cell mass (BCM) in kg and an estimated index of over-hydration (OH) in liters.Physical activity measurementPhysical activity (PA) was measured by a Geonaute-onstep-400® pedometer. Each patient was requested to wear the device for six consecutive days (two HD days, two HD-free midweek days, and two HD-free weekend days). Information on PA was obtained from the device memory. The data were recorded as number of steps per day. We used the pedometer-determined PA classification for healthy adults<a class="elsevierStyleCrossRef" href="#bib0205">12</a> as a benchmark of PA degree. This classification considered that more than 10000 steps per day is the goal for an active life<a class="elsevierStyleCrossRef" href="#bib0210">13</a> and participants with PA recorded below 5000 steps/day are considered sedentary.<a class="elsevierStyleCrossRef" href="#bib0215">14</a>Statistical analysisAll statistical analyses were performed using SPSS version 12 (SPSS Inc., Chicago, IL, USA). Data are expressed as mean±SD or median (range of 10th to 90th percentile) or percentage, as appropriate. Statistical significance was set at the level of p<0.05.Comparisons between two groups were assessed with the Kruskal–Wallis test for continuous variables and a χ2 test for nominal variables. Univariate analysis was performed using Spearman correlation. Different multivariate linear regression analyses were performed to test the independence of the association between testosterone and the three main dependent variables: ESA dose, percentage of lean body mass and physical activity (number of steps/day). All models were adjusted for a priori decided biological confounders. Because bioimpedance measurement was performed before the dialysis session, LBM% may have been overestimated due to overhydration. As a sensitivity analysis we tested further including OH in the studied multivariate regression models. Since the variable ESA dose had a non-normal distribution, the Loge of the variable was calculated and used in the multivariate analysis. Data are presented as standardized coefficient (β) and standard error (SE).ResultsBaseline characteristicsAmong the 57 patients included, the median age was 65 years (49–80) with a median dialysis vintage time of 30 (7–183) months. Twenty-two (39%) patients were diabetics and 36 (66%) patients had a history of cardiovascular disease (CVD). Mean arterial pressure (MAP) at inclusion was 91 (76–109) mmHg. The median body mass index (BMI) was 25 (20–29)kg/m2.Testosterone levels and clinical and laboratory dataThe mean testosterone level was 321±146ng/dL. Twenty patients (35%) had a testosterone concentration below the normal range established in our laboratory and were classified as having hypogonadism. The general characteristics of all patients, and when placed in two groups according to testosterone levels, are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Patients in the hypogonadism group were older and had lower MAP, higher IL-6, lower LBM and higher FBM. Other variables did not differ.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Testosterone and ESA doseThe required weekly dose of EPO (normalized by weight and by hemoglobin levels) was significantly higher in the group with lower testosterone levels (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). This negative association was also observed after adjustment for potential confounders in a multivariable regression analysis (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Additional adjustment for OH or dialysis vintage did not alter the results (sensitivity analysis not shown).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Testosterone, lean body mass and physical activityIn uni- and multivariate analysis, testosterone positively correlated with the percentage of LBM (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Additional adjustment for dialysis vintage and OH did not alter the results (data are not shown). The average PA registered in the group with normal testosterone levels was 4291±3225steps/day compared to an average of 2753±1784 (p=0.04) in the group of patients with hypogonadism. In multivariate regression models considering confounders, testosterone levels remained positively associated to physical activity (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>, physical activity adjusted model 1). However, when the percentage of lean body mass was further included in the model (presumed within the causal pathway), the association between testosterone and physical activity ceased to be statistically significant, reducing the regression coefficient of the association (β) by approximately 30% (from 0.33 to 0.22) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>, Physical activity adjusted model 2). No changes in the model were found when we additionally adjusted for dialysis vintage or OH (data not shown).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>DiscussionThis study shows that hypogonadism is rather common among men undergoing HD and that, independently of age and other potential confounders, lower levels of endogenous testosterone associate with higher doses of ESA, lower lean body mass and poorer physical activity.The observed prevalence of hypogonadism among male dialysis patients in our study (35% prevalence) is in line with recent reports,<a class="elsevierStyleCrossRefs" href="#bib0220">15,16</a> although larger dialysis cohorts document up to 70% of their population to present with testosterone deficient levels.<a class="elsevierStyleCrossRefs" href="#bib0165">4,17</a> Inconsistencies in this information may be affected by different inclusion criteria, age-ranges, different cut-off points for hypogonadism and overall, differences in clinical practice between countries.Recently, low testosterone levels have been associated with lower levels of hemoglobin in ESA-naïve CKD patients and with higher ESA dosages in hemodialysis patients.<a class="elsevierStyleCrossRef" href="#bib0235">18</a> These data are now corroborated by the findings of our study, where the prescribed dose for ESA was negatively associated with serum testosterone levels. Testosterone is known to stimulate erythropoiesis through the production of hematopoietic growth factors<a class="elsevierStyleCrossRef" href="#bib0240">19</a> and through the improvement of iron bioavailability via the hepcidin pathway.<a class="elsevierStyleCrossRef" href="#bib0200">11</a> Considering that male hypogonadism may represent a contributing factor to renal anemia, restoration of this deficiency could potentially be of value in the treatment of anemia.<a class="elsevierStyleCrossRefs" href="#bib0245">20–22</a>One of the most important actions of testosterone regards its effect on body composition and metabolism. In our study, we observed an independent direct association between testosterone levels and muscle mass, which agrees with community studies<a class="elsevierStyleCrossRefs" href="#bib0260">23,24</a> and expands to hemodialysis our previous observation in non-dialyzed men with CKD stages 3–5.<a class="elsevierStyleCrossRef" href="#bib0190">9</a> Testosterone increases muscle mass by multiple mechanisms; including, differentiation of pluripotent stem cells toward the myogenic lineage, as well as, stimulation of muscle protein synthesis and inhibition of muscle protein degradation.<a class="elsevierStyleCrossRef" href="#bib0180">7</a> A novel finding in our report is the, perhaps expected, positive and independent association between endogenous testosterone levels and physical activity as determined by number of steps per day. Because the relationship between physical activity and testosterone levels ceased to be significant when muscle mass was included in the model (adjustment in the causal pathway), it would seem congruent to speculate that this association appears to be explained by the association between testosterone and muscle mass status. It is not well known whether testosterone supplementation affects muscle function over and above its effects on muscle mass. Some interventions have tested the effects of supraphysiological dosages of testosterone supplementation in HD patients (both men and women) with normal or unknown testosterone levels, and described muscle growth effects.<a class="elsevierStyleCrossRefs" href="#bib0270">25,26</a> The study of Johanssen et al., however, did not see any measurable improvement in physical performance coupled to this anabolism. The intervention period, however (3 months) may have been too short to discern this. Nevertheless, no study has yet addressed the impact that restoration of hypogonadism could have in improving or maintaining muscle mass in this patient population subjected to a strong catabolic environment.<a class="elsevierStyleCrossRef" href="#bib0280">27</a>Our study has some limitations that should be pointed out, starting by a reduced sample size and a cross-sectional design, which does not allow establishing causal relationships. The diagnosis of hypogonadism was performed based on a single testosterone determination, and signs and symptoms of this condition were not considered. However, because most hypogonadal symptoms coincide with those of uremia, reliance on testosterone levels in the setting of chronic diseases such as CKD is indicated by some guidelines.<a class="elsevierStyleCrossRef" href="#bib0285">28</a> The use of total rather than free testosterone concentrations might result in under-diagnosis because the concentration of sex-hormone binding globulin increases with age. We collected samples before the dialysis session, with some patients attending the afternoon rounds. Because testosterone has a certain circadian variation, this may have influenced our findings, however, toward the null. On the other hand, performing the bioimpedance measurement before the dialysis session could introduce a bias on the value of LBM due to overhydration, in order to reduce this possible bias the OH value was included in the different models without finding any modification on the results.To conclude, we show that hypogonadism is common among our population of men undergoing hemodialysis and it is related to higher doses of ESA, reduced muscle mass and poorer physical activity. Conceivably, these associations reflect inadequate erythropoiesis and low muscle protein synthesis due to low levels of circulating testosterone, while the observed link between low testosterone levels and physical inactivity is most likely explained by reduced muscle mass due to hypogonadism. The results of the current study can be of value to raise the awareness of male hypogonadism in CKD and increase interest on the potential of treating this endocrine deficiency. Although pharmacokinetics of testosterone administration seem unaffected in dialysis patients<a class="elsevierStyleCrossRef" href="#bib0290">29</a> and we are proposing restoration of clinical deficiencies rather than supraphysiological administration, safety of this therapy should not be taken for granted and needs to be confirmed by randomized controlled trials.Support and financial disclosuresGabriela Cobo is a beneficiary of a PhD scholarship from the Ecuadorian Government. This work also received a publication aid granted by the Spanish Nephrology Society. Bengt Lindholm is employed by Baxter Healthcare. Baxter Novum is the result of a grant from Baxter Healthcare to Karolinska Institutet. Juan Jesus Carrero is co-investigator of an ongoing investigator-driven randomized trial on testosterone restoration in dialysis patients that is partially funded by Bayer, the manufacturer of Nebido©.Conflict of interestNone of the other authors declare any conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres818637" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec815687" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres818636" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec815688" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Clinical data including co-morbidities" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Laboratory analysis" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Body composition assessment" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Physical activity measurement" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Baseline characteristics" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Testosterone levels and clinical and laboratory data" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Testosterone and ESA dose" ] 3 => array:2 [ "identificador" => "sec0065" "titulo" => "Testosterone, lean body mass and physical activity" ] ] ] 7 => array:2 [ "identificador" => "sec0070" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0075" "titulo" => "Support and financial disclosures" ] 9 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflict of interest" ] 10 => array:2 [ "identificador" => "xack274704" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-09-22" "fechaAceptado" => "2016-04-28" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec815687" "palabras" => array:3 [ 0 => "Haemodialysis" 1 => "Physical activity" 2 => "Testosterone" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec815688" "palabras" => array:3 [ 0 => "Hemodiálisis" 1 => "Actividad física" 2 => "Testosterona" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundTestosterone deficiency (hypogonadism) is common among men undergoing haemodialysis, but its clinical implications are not well characterized. Testosterone is an anabolic hormone that induces erythrocytosis and muscle synthesis. We hypothesized that testosterone deficiency would be associated with low muscle mass, physical inactivity and higher dosages of erythropoietin-stimulating agents (ESA). MethodsSingle-center cross-sectional study of 57 male haemodialysis patients. None of the patients was undergoing testosterone replacement therapy. Total testosterone was measured in serum. Body composition (by bioelectrical impedance analysis) and physical activity (by the use of pedometers) were assessed. Patients with testosterone levels below the normal range were considered hypogonadal. ResultsMean testosterone level was 321±146ng/dL; 20 patients (35%) were hypogonadal. Hypogonadal patients were older and had lower mean arterial blood pressure, higher interleukin-6 levels, lower lean body mass and higher fat body mass. A negative association between testosterone and normalized ESA dose was found in uni- and multivariate regression analyses. Testosterone levels directly correlated with lean body mass regardless of confounders. Hypogonadal patients had lower physical activity than their counterparts [2753±1784 vs. 4291±3225steps/day (p=0.04)]. The relationship between testosterone and physical activity was independent of age, comorbidities and inflammatory markers, but dependent on the proportion of muscle mass. ConclusionHypogonadism is common in our male haemodialysis population and is associated with higher ESA doses, reduced muscle mass and lower physical activity. The link between low testosterone levels and physical inactivity may conceivably relate to reduced muscle mass due to inadequate muscle protein synthesis." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "AntecedentesLa deficiencia de testosterona (hipogonadismo) es frecuente en varones en hemodiálisis, pero sus consecuencias clínicas no se han caracterizado satisfactoriamente. La testosterona es una hormona anabólica que provoca eritrocitosis y síntesis muscular. Nos planteamos la hipótesis de que la deficiencia de testosterona pudiera estar asociada a una masa muscular baja, a la inactividad física y a dosis más altas de fármacos estimulantes de la eritropoyesis (FEE). MétodosEstudio transversal de un solo centro de 57 pacientes varones en hemodiálisis. Ninguno de ellos estaba recibiendo tratamiento sustitutivo con testosterona. La cantidad total de testosterona se midió en el suero. Se evaluaron la composición corporal (mediante un análisis de impedancia bioeléctrica) y la actividad física (mediante el uso de podómetros). Los pacientes con concentraciones séricas de testosterona por debajo de los límites de normalidad se consideraron hipogonadales. ResultadosLa concentración media de testosterona fue de 321±146ng/dl; 20 pacientes (35%) se consideraron hipogonadales. Los pacientes hipogonadales eran de edad avanzada y presentaban una presión arterial media más baja, concentraciones más altas de interleucina 6, masa corporal magra más baja y masa corporal grasa más alta. Se observó una asociación negativa entre la dosis de testosterona y de FEE normalizada en análisis de regresión univariante y multivariante. Las concentraciones de testosterona estaban directamente correlacionadas con la masa corporal magra, independientemente de los factores de confusión. Los pacientes hipogonadales presentaban una actividad física más baja que sus homólogos (2.753±1.784 frente a 4.291±3.225 pasos/día; p=0,04). La relación entre la actividad física y la testosterona fue independiente de la edad, las comorbilidades y los marcadores de inflamación, pero dependían de la proporción de masa muscular. ConclusiónEl hipogonadismo es frecuente en la población de varones en hemodiálisis y está asociado a dosis más altas de FEE, masa muscular reducida y actividad física baja. El vínculo entre las concentraciones bajas de testosterona y la inactividad física está posiblemente relacionado con la masa muscular reducida debido a una síntesis de proteínas musculares insuficiente." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "BMI: body mass index, MAP: mean arterial pressure, TBW: total body water, ECW: extracellular water, ICW: intracellular water, LBM lean body mass, FBM: fat body mass, BCM: body cell mass." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">All patients n=57 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Hypogonadism Testosterone<241ng/dL n=20 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Normal Testosterone>241ng/dL n=37 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age, years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65 (49–80) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72 (52–84) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63 (48–78) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI, kg/m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 (20–29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 (21–30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 (19–29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MAP, mmHg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91 (76–109) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">87 (73–99) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96 (78–113) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22 (39%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (40%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (38%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cardiovascular disease, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 (63%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 (75%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 (57%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vintage, months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 (7–183) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 (7–152) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 (4–199) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine, mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.0 (5.2–11.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.9 (5.2–9.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.1 (5.2–12.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin, g/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.0 (3.6–4.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.9 (3.3–4.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.0 (3.7–4.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hemoglobin, g/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.4 (11.2–13.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.2 (11.2–13.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.4 (11.2–13.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ESA dose, UI/kg/mg/dL/week<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.1 (0–17.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.6 (4.3–36.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.0 (0–15.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><0.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IL-6, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.6 (1.5–13.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.7 (1.5–27.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.3 (1.2–10.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TBW (L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 (28–44) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 (26–47) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32 (28–44) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ECW/ICW \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.93 (0.82–1.15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.95 (0.83–1.18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.92 (0.77–1.07) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.07 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LBM (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 (35–61) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 (31–54) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 (39–65) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FBM (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 (27–46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 (31–48) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 (25–43) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BCM (kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17.1 (10.7–27.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.2 (9.5–27.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17.6 (11.2–27.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1375965.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "ESA (erythropoiesis-stimulating agent) normalized by kg of body weight and by Hb level." ] ] ] "descripcion" => array:1 [ "en" => "General characteristics of 57 prevalent male HD patients and stratified according to the presence of hypogonadism (median and range of 10th to 90th percentile)." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "BMI: body mass index, CVD: cardiovascular disease." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Univariate</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Multivariate analysis</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rho \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">β (SE) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Testosterone, ng/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.37 (0.001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.012 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age, years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.09 (0.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI, kg/m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.24 (0.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CVD (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 (0.25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.007 (0.21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin, g/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.24 (0.38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.09 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ferritin, ng/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.05 (0.001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IL-6, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.13 (0.006) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1375964.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Univariate y linear regression multivariate models for weekly ESA dose normalized by weight and by hemoglobin level (loge, UI/kg/week) (R2 0.27)." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Dashes indicate not included. CVD: cardiovascular disease, LBM: lean body mass." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Lean Body Mass (%)</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Physical Activity (Steps/day)</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Univariate \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Multivariate analysis \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Univariate \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Multivariate analysis</th></tr><tr title="table-row"><th class="td" title="table-head " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable</th><th class="td" title="table-head " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rho (p value)</th><th class="td" title="table-head " align="left" valign="top" scope="col">Adjusted Model 1 (R2 0.26, p=0.02) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rho (P value)</th><th class="td" title="table-head " align="left" valign="top" scope="col">Adjusted Model 1 (R2 0.48, p<0.001) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Adjusted Model 2 (R2 0.57, p<0.001) \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Beta (p value) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Beta (p value) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Beta (p value) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Testosterone, ng/dl \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.29 (0.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.33 (0.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.26 (0.07) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.33 (0.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.22 (0.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age, years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.33 (0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.32 (0.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.44 (0.002) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.30 (0.04) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.19 (0.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CVD (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.23 (0.09) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 (0.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.49(<0.001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.23 (0.09) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.26 (0.04) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.01 (0.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.15 (0.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.22 (0.14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.32 (0.02) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.27 (0.04) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IL-6, pg/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.38 (0.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.13 (0.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.32 (0.03) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.17 (0.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.13 (0.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LBM, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.59 (<0.001) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.34 (0.01) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1375963.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Linear regression model for lean body mass (percentage) and physical activity (number of steps/day)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0150" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic kidney disease and hypothalamic-pituitary axis dysfunction: the chicken or the egg" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.L. 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Hipogonadismo asociado a atrofia muscular, inactividad física e hiposensibilidad a FEE en varones sometidos a hemodiálisis

Gabriela Coboa,b,

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gabriela.cobo@ki.se

Corresponding author.

, Paloma Gallara, Cristina Di Gioiaa, Concepción García Lacallec, Rosa Camachoa, Isabel Rodrigueza, Olimpia Ortegaa, Carmen Mona, Ana Vigila, Bengt Lindholmb, Juan Jesús Carrerob

a Department of Nephrology, Hospital Severo Ochoa, Leganes, Madrid, Spain

b Divisions of Renal Medicine and Baxter Novum, CLINTEC, Karolinska Institutet, Stockholm, Sweden

c Department of Biochemistry, Hospital Severo Ochoa, Leganes, Madrid, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic kidney disease &#40;CKD&#41; involves alterations in body homeostasis and metabolic disturbances &#40;including hormone secretion disorders and altered response to hormones in target tissues&#41;&#44; resulting in endocrine dysfunctions that may contribute to the increased mortality in CKD patients&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">1</span></a> Hypogonadism&#44; hallmarked by testosterone deficiency is a common endocrine disorder among men undergoing dialysis&#44; with a prevalence ranging from 35 to 50&#37; in recent studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">2&#8211;4</span></a> Various studies link hypogonadism with mortality risk among hemodialysis patients&#44;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">5&#44;6</span></a> but the pathways by which this risk may be mediated are not well known&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The clinical implications of hypogonadism among dialysis patients are not well characterized&#46; Testosterone is a steroid hormone that has an important anabolic function influencing among others muscle mass&#44; increasing both strength and size&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a> In the general population&#44; testosterone deficiency that accompanies aging has been linked to decreased physical performance and its consequent limitation of mobility&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a> In non-dialysis CKD patients&#44; endogenous testosterone is a strong determinant of both muscle mass and strength&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">9</span></a> It is unknown if this is still the case in individuals undergoing dialysis&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Furthermore&#44; testosterone induces erythrocytosis<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">10&#44;11</span></a> and testosterone deficiency has been associated with anemia and increased resistance to erythropoietin-stimulating agents &#40;ESA&#41; in dialysis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">2</span></a> However&#44; this finding has&#44; to date&#44; not been confirmed&#46; The objective of our study was to assess the prevalence of hypogonadism among men undergoing dialysis at our center&#46; Further&#44; we explored the clinical phenotype of hypogonadal patients&#46; Based on the abovementioned preceding literature&#44; we hypothesized that endogenous testosterone would associate with the percentage of muscle strength and physical activity&#44; as well as with higher ESA requirements&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0020" class="elsevierStylePara elsevierViewall">This cross-sectional study comprised clinically stable male patients with CKD attending the hemodialysis &#40;HD&#41; program at Severo Ochoa Hospital&#44; Leganes&#44; Madrid&#44; Spain&#46; Only patients who had been on HD for more than three months and without hospital admissions in the month preceding the investigation were invited to participate&#46; Patients with physical limitations &#40;amputation&#41; and neurological impairment were not considered because of the difficulty in assessing physical activity&#46; From 75 eligible patients&#44; 57 patients met the inclusion criteria and all accepted to participate&#46; None of the patients was receiving testosterone replacement therapy&#46; All participants gave their written consent&#46; The study was approved by the Ethics Committee of the Severo Ochoa Hospital&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Clinical data including co-morbidities</span><p id="par0025" class="elsevierStylePara elsevierViewall">Each patient&#39;s medical chart was reviewed to extract demographic and clinical data including comorbidities&#46; Clinical history of cardiovascular disease &#40;CVD&#41; was defined as cardiac&#44; cerebrovascular &#40;including stroke&#41; or peripheral vascular disease&#46; Mean arterial pressure &#40;MAP&#41; was defined as &#91;diastolic pressure<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>&#40;systolic pressure<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>diastolic pressure&#41;&#47;3&#93;&#46; Dose of erythropoietin-stimulating agents &#40;ESAs&#41; for each patient was recorded as international units administered per week &#40;U&#47;week&#41;&#46; Weekly doses of darbepoetin in micrograms were converted to international units of erythropoietin by multiplying with a conversion factor of 200&#46; The median ESA equivalent dose was 6000 &#40;0&#8211;15<span class="elsevierStyleHsp" style=""></span>300&#41; U&#47;week&#44; which was normalized for body weight and for hemoglobin levels and presented as U&#47;kg&#47;mg&#47;mL Hb&#47;week in the following analyses&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Laboratory analysis</span><p id="par0030" class="elsevierStylePara elsevierViewall">Blood samples were collected before midweek dialysis session&#46; The plasma was separated within 30<span class="elsevierStyleHsp" style=""></span>min&#44; and samples were kept frozen at &#8722;70<span class="elsevierStyleHsp" style=""></span>&#176;C if not analyzed immediately&#46; Biochemical parameters were determined by standard laboratory techniques at the Biochemical Department of the Severo Ochoa Hospital&#46; Interleukin-6 &#40;IL-6&#41; concentration was assessed on plasma lithium heparin by multiplexing in a Bioplex system &#40;X-MAP technology&#44; BioRad&#44; Madrid&#44; Spain&#41; using commercial kits &#40;R&#38;D Systems Europe&#44; Ltd&#44; UK&#41;&#46; The concentration was calculated by interpolation from the calibration performed with the corresponding recombinant proteins provided by the kit&#46; Total testosterone was assessed in serum with a chemiluminescence assay &#40;Advia-Centaur&#44; Siemens&#41; that has sensitivity&#44; specificity&#44; precision and linearity according to the requirements for usage in clinical practice&#46; The normal reference range established by our laboratory for the male population is 241&#8211;827<span class="elsevierStyleHsp" style=""></span>ng&#47;dL&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Body composition assessment</span><p id="par0035" class="elsevierStylePara elsevierViewall">Dry weight &#40;based on clinical approach&#41; in kilograms and height in meters of each participant was recorded&#46; Body mass index &#40;BMI&#41; was calculated dividing weight in kilograms by height in square meters &#40;kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46; Body composition was assessed by bioimpedance &#40;Body Composition Monitor&#44; Fresenius Medical Care&#44; Bad Homburg&#44; Germany&#41;&#46; The measurement was performed immediately before the second dialysis session of the week&#46; Lean body mass &#40;LBM&#41; and fat body mass &#40;FBM&#41; were expressed as percentages&#46; Total body water &#40;TBW&#41;&#44; extracellular water &#40;ECW&#41;&#44; intracellular water &#40;ICW&#41; and the relation ECW&#47;ICW were collected&#46; Other parameters obtained were body cell mass &#40;BCM&#41; in kg and an estimated index of over-hydration &#40;OH&#41; in liters&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Physical activity measurement</span><p id="par0040" class="elsevierStylePara elsevierViewall">Physical activity &#40;PA&#41; was measured by a Geonaute-onstep-400<span class="elsevierStyleSup">&#174;</span> pedometer&#46; Each patient was requested to wear the device for six consecutive days &#40;two HD days&#44; two HD-free midweek days&#44; and two HD-free weekend days&#41;&#46; Information on PA was obtained from the device memory&#46; The data were recorded as number of steps per day&#46; We used the pedometer-determined PA classification for healthy adults<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">12</span></a> as a benchmark of PA degree&#46; This classification considered that more than 10<span class="elsevierStyleHsp" style=""></span>000 steps per day is the goal for an active life<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">13</span></a> and participants with PA recorded below 5000 steps&#47;day are considered sedentary&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">All statistical analyses were performed using SPSS version 12 &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; USA&#41;&#46; Data are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD or median &#40;range of 10th to 90th percentile&#41; or percentage&#44; as appropriate&#46; Statistical significance was set at the level of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Comparisons between two groups were assessed with the Kruskal&#8211;Wallis test for continuous variables and a <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test for nominal variables&#46; Univariate analysis was performed using Spearman correlation&#46; Different multivariate linear regression analyses were performed to test the independence of the association between testosterone and the three main dependent variables&#58; ESA dose&#44; percentage of lean body mass and physical activity &#40;number of steps&#47;day&#41;&#46; All models were adjusted for a priori decided biological confounders&#46; Because bioimpedance measurement was performed before the dialysis session&#44; LBM&#37; may have been overestimated due to overhydration&#46; As a sensitivity analysis we tested further including OH in the studied multivariate regression models&#46; Since the variable ESA dose had a non-normal distribution&#44; the Log<span class="elsevierStyleInf">e</span> of the variable was calculated and used in the multivariate analysis&#46; Data are presented as standardized coefficient &#40;<span class="elsevierStyleItalic">&#946;</span>&#41; and standard error &#40;SE&#41;&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Baseline characteristics</span><p id="par0055" class="elsevierStylePara elsevierViewall">Among the 57 patients included&#44; the median age was 65 years &#40;49&#8211;80&#41; with a median dialysis vintage time of 30 &#40;7&#8211;183&#41; months&#46; Twenty-two &#40;39&#37;&#41; patients were diabetics and 36 &#40;66&#37;&#41; patients had a history of cardiovascular disease &#40;CVD&#41;&#46; Mean arterial pressure &#40;MAP&#41; at inclusion was 91 &#40;76&#8211;109&#41; mmHg&#46; The median body mass index &#40;BMI&#41; was 25 &#40;20&#8211;29&#41;<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Testosterone levels and clinical and laboratory data</span><p id="par0060" class="elsevierStylePara elsevierViewall">The mean testosterone level was 321<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>146<span class="elsevierStyleHsp" style=""></span>ng&#47;dL&#46; Twenty patients &#40;35&#37;&#41; had a testosterone concentration below the normal range established in our laboratory and were classified as having hypogonadism&#46; The general characteristics of all patients&#44; and when placed in two groups according to testosterone levels&#44; are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Patients in the hypogonadism group were older and had lower MAP&#44; higher IL-6&#44; lower LBM and higher FBM&#46; Other variables did not differ&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Testosterone and ESA dose</span><p id="par0065" class="elsevierStylePara elsevierViewall">The required weekly dose of EPO &#40;normalized by weight and by hemoglobin levels&#41; was significantly higher in the group with lower testosterone levels &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; This negative association was also observed after adjustment for potential confounders in a multivariable regression analysis &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; Additional adjustment for OH or dialysis vintage did not alter the results &#40;sensitivity analysis not shown&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Testosterone&#44; lean body mass and physical activity</span><p id="par0070" class="elsevierStylePara elsevierViewall">In uni- and multivariate analysis&#44; testosterone positively correlated with the percentage of LBM &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Additional adjustment for dialysis vintage and OH did not alter the results &#40;data are not shown&#41;&#46; The average PA registered in the group with normal testosterone levels was 4291<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3225<span class="elsevierStyleHsp" style=""></span>steps&#47;day compared to an average of 2753<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1784 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41; in the group of patients with hypogonadism&#46; In multivariate regression models considering confounders&#44; testosterone levels remained positively associated to physical activity &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#44; physical activity adjusted model 1&#41;&#46; However&#44; when the percentage of lean body mass was further included in the model &#40;presumed within the causal pathway&#41;&#44; the association between testosterone and physical activity ceased to be statistically significant&#44; reducing the regression coefficient of the association &#40;<span class="elsevierStyleItalic">&#946;</span>&#41; by approximately 30&#37; &#40;from 0&#46;33 to 0&#46;22&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#44; Physical activity adjusted model 2&#41;&#46; No changes in the model were found when we additionally adjusted for dialysis vintage or OH &#40;data not shown&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">This study shows that hypogonadism is rather common among men undergoing HD and that&#44; independently of age and other potential confounders&#44; lower levels of endogenous testosterone associate with higher doses of ESA&#44; lower lean body mass and poorer physical activity&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The observed prevalence of hypogonadism among male dialysis patients in our study &#40;35&#37; prevalence&#41; is in line with recent reports&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">15&#44;16</span></a> although larger dialysis cohorts document up to 70&#37; of their population to present with testosterone deficient levels&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">4&#44;17</span></a> Inconsistencies in this information may be affected by different inclusion criteria&#44; age-ranges&#44; different cut-off points for hypogonadism and overall&#44; differences in clinical practice between countries&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Recently&#44; low testosterone levels have been associated with lower levels of hemoglobin in ESA-na&#239;ve CKD patients and with higher ESA dosages in hemodialysis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">18</span></a> These data are now corroborated by the findings of our study&#44; where the prescribed dose for ESA was negatively associated with serum testosterone levels&#46; Testosterone is known to stimulate erythropoiesis through the production of hematopoietic growth factors<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">19</span></a> and through the improvement of iron bioavailability via the hepcidin pathway&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a> Considering that male hypogonadism may represent a contributing factor to renal anemia&#44; restoration of this deficiency could potentially be of value in the treatment of anemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">20&#8211;22</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">One of the most important actions of testosterone regards its effect on body composition and metabolism&#46; In our study&#44; we observed an independent direct association between testosterone levels and muscle mass&#44; which agrees with community studies<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">23&#44;24</span></a> and expands to hemodialysis our previous observation in non-dialyzed men with CKD stages 3&#8211;5&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">9</span></a> Testosterone increases muscle mass by multiple mechanisms&#59; including&#44; differentiation of pluripotent stem cells toward the myogenic lineage&#44; as well as&#44; stimulation of muscle protein synthesis and inhibition of muscle protein degradation&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a> A novel finding in our report is the&#44; perhaps expected&#44; positive and independent association between endogenous testosterone levels and physical activity as determined by number of steps per day&#46; Because the relationship between physical activity and testosterone levels ceased to be significant when muscle mass was included in the model &#40;adjustment in the causal pathway&#41;&#44; it would seem congruent to speculate that this association appears to be explained by the association between testosterone and muscle mass status&#46; It is not well known whether testosterone supplementation affects muscle function over and above its effects on muscle mass&#46; Some interventions have tested the effects of supraphysiological dosages of testosterone supplementation in HD patients &#40;both men and women&#41; with normal or unknown testosterone levels&#44; and described muscle growth effects&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">25&#44;26</span></a> The study of Johanssen et al&#46;&#44; however&#44; did not see any measurable improvement in physical performance coupled to this anabolism&#46; The intervention period&#44; however &#40;3 months&#41; may have been too short to discern this&#46; Nevertheless&#44; no study has yet addressed the impact that restoration of hypogonadism could have in improving or maintaining muscle mass in this patient population subjected to a strong catabolic environment&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">27</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Our study has some limitations that should be pointed out&#44; starting by a reduced sample size and a cross-sectional design&#44; which does not allow establishing causal relationships&#46; The diagnosis of hypogonadism was performed based on a single testosterone determination&#44; and signs and symptoms of this condition were not considered&#46; However&#44; because most hypogonadal symptoms coincide with those of uremia&#44; reliance on testosterone levels in the setting of chronic diseases such as CKD is indicated by some guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">28</span></a> The use of total rather than free testosterone concentrations might result in under-diagnosis because the concentration of sex-hormone binding globulin increases with age&#46; We collected samples before the dialysis session&#44; with some patients attending the afternoon rounds&#46; Because testosterone has a certain circadian variation&#44; this may have influenced our findings&#44; however&#44; toward the null&#46; On the other hand&#44; performing the bioimpedance measurement before the dialysis session could introduce a bias on the value of LBM due to overhydration&#44; in order to reduce this possible bias the OH value was included in the different models without finding any modification on the results&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">To conclude&#44; we show that hypogonadism is common among our population of men undergoing hemodialysis and it is related to higher doses of ESA&#44; reduced muscle mass and poorer physical activity&#46; Conceivably&#44; these associations reflect inadequate erythropoiesis and low muscle protein synthesis due to low levels of circulating testosterone&#44; while the observed link between low testosterone levels and physical inactivity is most likely explained by reduced muscle mass due to hypogonadism&#46; The results of the current study can be of value to raise the awareness of male hypogonadism in CKD and increase interest on the potential of treating this endocrine deficiency&#46; Although pharmacokinetics of testosterone administration seem unaffected in dialysis patients<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a> and we are proposing restoration of clinical deficiencies rather than supraphysiological administration&#44; safety of this therapy should not be taken for granted and needs to be confirmed by randomized controlled trials&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Support and financial disclosures</span><p id="par0105" class="elsevierStylePara elsevierViewall">Gabriela Cobo is a beneficiary of a PhD scholarship from the Ecuadorian Government&#46; This work also received a publication aid granted by the Spanish Nephrology Society&#46; Bengt Lindholm is employed by Baxter Healthcare&#46; Baxter Novum is the result of a grant from Baxter Healthcare to Karolinska Institutet&#46; Juan Jesus Carrero is co-investigator of an ongoing investigator-driven randomized trial on testosterone restoration in dialysis patients that is partially funded by Bayer&#44; the manufacturer of Nebido<span class="elsevierStyleSup">&#169;</span>&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflict of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">None of the other authors declare any conflict of interest&#46;</p></span></span>"
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              "titulo" => "Testosterone and ESA dose"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Testosterone deficiency &#40;hypogonadism&#41; is common among men undergoing haemodialysis&#44; but its clinical implications are not well characterized&#46; Testosterone is an anabolic hormone that induces erythrocytosis and muscle synthesis&#46; We hypothesized that testosterone deficiency would be associated with low muscle mass&#44; physical inactivity and higher dosages of erythropoietin-stimulating agents &#40;ESA&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Single-center cross-sectional study of 57 male haemodialysis patients&#46; None of the patients was undergoing testosterone replacement therapy&#46; Total testosterone was measured in serum&#46; Body composition &#40;by bioelectrical impedance analysis&#41; and physical activity &#40;by the use of pedometers&#41; were assessed&#46; Patients with testosterone levels below the normal range were considered hypogonadal&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Mean testosterone level was 321<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>146<span class="elsevierStyleHsp" style=""></span>ng&#47;dL&#59; 20 patients &#40;35&#37;&#41; were hypogonadal&#46; Hypogonadal patients were older and had lower mean arterial blood pressure&#44; higher interleukin-6 levels&#44; lower lean body mass and higher fat body mass&#46; A negative association between testosterone and normalized ESA dose was found in uni- and multivariate regression analyses&#46; Testosterone levels directly correlated with lean body mass regardless of confounders&#46; Hypogonadal patients had lower physical activity than their counterparts &#91;2753<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1784 vs&#46; 4291<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3225<span class="elsevierStyleHsp" style=""></span>steps&#47;day &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#41;&#93;&#46; The relationship between testosterone and physical activity was independent of age&#44; comorbidities and inflammatory markers&#44; but dependent on the proportion of muscle mass&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Hypogonadism is common in our male haemodialysis population and is associated with higher ESA doses&#44; reduced muscle mass and lower physical activity&#46; The link between low testosterone levels and physical inactivity may conceivably relate to reduced muscle mass due to inadequate muscle protein synthesis&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La deficiencia de testosterona &#40;hipogonadismo&#41; es frecuente en varones en hemodi&#225;lisis&#44; pero sus consecuencias cl&#237;nicas no se han caracterizado satisfactoriamente&#46; La testosterona es una hormona anab&#243;lica que provoca eritrocitosis y s&#237;ntesis muscular&#46; Nos planteamos la hip&#243;tesis de que la deficiencia de testosterona pudiera estar asociada a una masa muscular baja&#44; a la inactividad f&#237;sica y a dosis m&#225;s altas de f&#225;rmacos estimulantes de la eritropoyesis &#40;FEE&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio transversal de un solo centro de 57 pacientes varones en hemodi&#225;lisis&#46; Ninguno de ellos estaba recibiendo tratamiento sustitutivo con testosterona&#46; La cantidad total de testosterona se midi&#243; en el suero&#46; Se evaluaron la composici&#243;n corporal &#40;mediante un an&#225;lisis de impedancia bioel&#233;ctrica&#41; y la actividad f&#237;sica &#40;mediante el uso de pod&#243;metros&#41;&#46; Los pacientes con concentraciones s&#233;ricas de testosterona por debajo de los l&#237;mites de normalidad se consideraron hipogonadales&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La concentraci&#243;n media de testosterona fue de 321<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>146<span class="elsevierStyleHsp" style=""></span>ng&#47;dl&#59; 20 pacientes &#40;35&#37;&#41; se consideraron hipogonadales&#46; Los pacientes hipogonadales eran de edad avanzada y presentaban una presi&#243;n arterial media m&#225;s baja&#44; concentraciones m&#225;s altas de interleucina 6&#44; masa corporal magra m&#225;s baja y masa corporal grasa m&#225;s alta&#46; Se observ&#243; una asociaci&#243;n negativa entre la dosis de testosterona y de FEE normalizada en an&#225;lisis de regresi&#243;n univariante y multivariante&#46; Las concentraciones de testosterona estaban directamente correlacionadas con la masa corporal magra&#44; independientemente de los factores de confusi&#243;n&#46; Los pacientes hipogonadales presentaban una actividad f&#237;sica m&#225;s baja que sus hom&#243;logos &#40;2&#46;753<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;784 frente a 4&#46;291<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;225 pasos&#47;d&#237;a&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;04&#41;&#46; La relaci&#243;n entre la actividad f&#237;sica y la testosterona fue independiente de la edad&#44; las comorbilidades y los marcadores de inflamaci&#243;n&#44; pero depend&#237;an de la proporci&#243;n de masa muscular&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El hipogonadismo es frecuente en la poblaci&#243;n de varones en hemodi&#225;lisis y est&#225; asociado a dosis m&#225;s altas de FEE&#44; masa muscular reducida y actividad f&#237;sica baja&#46; El v&#237;nculo entre las concentraciones bajas de testosterona y la inactividad f&#237;sica est&#225; posiblemente relacionado con la masa muscular reducida debido a una s&#237;ntesis de prote&#237;nas musculares insuficiente&#46;</p></span>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index&#44; MAP&#58; mean arterial pressure&#44; TBW&#58; total body water&#44; ECW&#58; extracellular water&#44; ICW&#58; intracellular water&#44; LBM lean body mass&#44; FBM&#58; fat body mass&#44; BCM&#58; body cell mass&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">All patients<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Hypogonadism<br><span class="elsevierStyleItalic">Testosterone</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#60;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">241</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ng&#47;dL</span><br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Normal<br><span class="elsevierStyleItalic">Testosterone</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#62;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">241</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ng&#47;dL</span><br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age&#44; years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65 &#40;49&#8211;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72 &#40;52&#8211;84&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63 &#40;48&#8211;78&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI&#44; kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;20&#8211;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;21&#8211;30&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24 &#40;19&#8211;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">MAP&#44; mmHg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">91 &#40;76&#8211;109&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">87 &#40;73&#8211;99&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">96 &#40;78&#8211;113&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22 &#40;39&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;40&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;38&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cardiovascular disease&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36 &#40;63&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15 &#40;75&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21 &#40;57&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vintage&#44; months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30 &#40;7&#8211;183&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29 &#40;7&#8211;152&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30 &#40;4&#8211;199&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine&#44; mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;0 &#40;5&#46;2&#8211;11&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;9 &#40;5&#46;2&#8211;9&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;1 &#40;5&#46;2&#8211;12&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin&#44; g&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;0 &#40;3&#46;6&#8211;4&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;9 &#40;3&#46;3&#8211;4&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;0 &#40;3&#46;7&#8211;4&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hemoglobin&#44; g&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;4 &#40;11&#46;2&#8211;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;2 &#40;11&#46;2&#8211;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;4 &#40;11&#46;2&#8211;13&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ESA dose&#44; UI&#47;kg&#47;mg&#47;dL&#47;week<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;1 &#40;0&#8211;17&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;6 &#40;4&#46;3&#8211;36&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;0 &#40;0&#8211;15&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IL-6&#44; pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;6 &#40;1&#46;5&#8211;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;7 &#40;1&#46;5&#8211;27&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;3 &#40;1&#46;2&#8211;10&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TBW &#40;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32 &#40;28&#8211;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33 &#40;26&#8211;47&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32 &#40;28&#8211;44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ECW&#47;ICW&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;93 &#40;0&#46;82&#8211;1&#46;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;95 &#40;0&#46;83&#8211;1&#46;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;92 &#40;0&#46;77&#8211;1&#46;07&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LBM &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48 &#40;35&#8211;61&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45 &#40;31&#8211;54&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48 &#40;39&#8211;65&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FBM &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37 &#40;27&#8211;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39 &#40;31&#8211;48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36 &#40;25&#8211;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BCM &#40;kg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;1 &#40;10&#46;7&#8211;27&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;2 &#40;9&#46;5&#8211;27&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;6 &#40;11&#46;2&#8211;27&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Variable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Univariate</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Multivariate analysis</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rho&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">&#946;</span> &#40;SE&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Testosterone&#44; ng&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;37 &#40;0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age&#44; years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;09 &#40;0&#46;01&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BMI&#44; kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;24 &#40;0&#46;03&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CVD &#40;presence&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;08 &#40;0&#46;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes &#40;presence&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;007 &#40;0&#46;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Albumin&#44; g&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;24 &#40;0&#46;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ferritin&#44; ng&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;05 &#40;0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IL-6&#44; pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;13 &#40;0&#46;006&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;26 &#40;0&#46;07&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;33 &#40;0&#46;03&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;22 &#40;0&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;32 &#40;0&#46;04&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;44 &#40;0&#46;002&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;23 &#40;0&#46;09&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;04 &#40;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;15 &#40;0&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;22 &#40;0&#46;14&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;27 &#40;0&#46;04&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IL-6&#44; pg&#47;mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;38 &#40;0&#46;01&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;13 &#40;0&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;32 &#40;0&#46;03&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;17 &#40;0&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;13 &#40;0&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LBM&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;59 &#40;&#60;0&#46;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;34 &#40;0&#46;01&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                      "titulo" => "Endogenous testosterone and mortality in male hemodialysis patients&#58; is it the result of aging&#63;"
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                          "autores" => array:6 [
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                            1 => "F&#46; Kircelli"
                            2 => "J&#46;J&#46; Carrero"
                            3 => "G&#46; Asci"
                            4 => "H&#46; Toz"
                            5 => "E&#46; Tatar"
                          ]
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Article information

ISSN: 20132514
Original language: English

DOI:10.1016/j.nefroe.2016.12.008

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Year/Month	Html	Pdf	Total

2024 November	3	3	6
2024 October	46	33	79
2024 September	32	16	48
2024 August	62	65	127
2024 July	38	29	67
2024 June	39	33	72
2024 May	65	28	93
2024 April	44	32	76
2024 March	42	23	65
2024 February	40	34	74
2024 January	28	18	46
2023 December	17	22	39
2023 November	44	27	71
2023 October	42	23	65
2023 September	32	27	59
2023 August	39	21	60
2023 July	44	28	72
2023 June	27	16	43
2023 May	36	30	66
2023 April	30	12	42
2023 March	40	27	67
2023 February	40	21	61
2023 January	30	20	50
2022 December	54	19	73
2022 November	53	34	87
2022 October	47	37	84
2022 September	34	24	58
2022 August	41	40	81
2022 July	35	44	79
2022 June	33	23	56
2022 May	48	33	81
2022 April	41	35	76
2022 March	38	35	73
2022 February	46	36	82
2022 January	56	28	84
2021 December	41	36	77
2021 November	40	35	75
2021 October	42	27	69
2021 September	33	31	64
2021 August	40	40	80
2021 July	33	31	64
2021 June	30	29	59
2021 May	40	52	92
2021 April	97	91	188
2021 March	65	44	109
2021 February	49	22	71
2021 January	46	12	58
2020 December	34	22	56
2020 November	51	16	67
2020 October	33	25	58
2020 September	45	20	65
2020 August	43	12	55
2020 July	51	12	63
2020 June	34	14	48
2020 May	50	17	67
2020 April	46	22	68
2020 March	26	14	40
2020 February	42	23	65
2020 January	57	22	79
2019 December	56	24	80
2019 November	78	18	96
2019 October	44	11	55
2019 September	38	12	50
2019 August	25	17	42
2019 July	40	19	59
2019 June	34	19	53
2019 May	50	29	79
2019 April	63	35	98
2019 March	50	30	80
2019 February	26	15	41
2019 January	22	23	45
2018 December	222	50	272
2018 November	345	19	364
2018 October	254	22	276
2018 September	104	24	128
2018 August	48	13	61
2018 July	36	15	51
2018 June	49	15	64
2018 May	56	11	67
2018 April	113	16	129
2018 March	93	6	99
2018 February	111	6	117
2018 January	78	8	86
2017 December	121	4	125
2017 November	59	16	75
2017 October	37	5	42
2017 September	35	6	41
2017 August	46	8	54
2017 July	41	5	46
2017 June	46	5	51
2017 May	52	12	64
2017 April	20	5	25
2017 March	14	3	17

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