Background: Testosterone 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). Methods: Single-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. Results: Mean testosterone level was 321 ± 146 ng/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 uniand 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 ± 3225 steps/day (p = 0.04)]. The relationship between testosterone and Please cite this article in press as: Cobo G, et al. Hypogonadism associated with muscle atrophy, physical inactivity and ESA hyporesponsiveness in men undergoing haemodialysis. Nefrologia. 2016. http://dx.doi.org/10.1016/j.nefro.2016.04.009 physical activity was independent of age, comorbidities and inflammatory markers, but dependent on the proportion of muscle mass. Conclusion: Hypogonadism is common in our male haemodialysis population and is associated with higher ESA doses, reduced muscle mass and lower physical activity. The link ∗ Corresponding author. E-mail address: gabriela.cobo@ki.se (G. Cobo). ttp://dx.doi.org/10.1016/j.nefro.2016.04.009 211-6995/© 2016 Sociedad Española de Nefrologı́a. Published by Elsevier España, S.L.U. This is an open access article under the CC Y-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ARTICLE IN PRESS NEFRO-214; No. of Pages 7 2 n e f r o l o g i a 2 0 1 6;x x x(x x):xxx–xxx between low testosterone levels and physical inactivity may conceivably relate to reduced muscle mass due to inadequate muscle protein synthesis. © 2016 Sociedad Española de Nefrologı́a. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/). Hipogonadismo asociado a atrofia muscular, inactividad física e hiposensibilidad a FEE en varones sometidos a hemodiálisis Palabras clave: Hemodiálisis Actividad física Testosterona r e s u m e n Antecedentes: La 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). Métodos: Estudio 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. Resultados: La concentración media de testosterona fue de 321 ± 146 ng/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. Conclusión: El 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. © 2016 Sociedad Española de Nefrologı́a. Publicado por Elsevier España, S.L.U. Este es un artı́culo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/

Background: Chronic fluid overload is frequent in hemodialysis patients (P) and it associates with hypertension, left ventricular hypertrophy (LVH) and higher mortality. Moreover, echocardiographic data assessing fluid overload is limited. Our aim was to evaluate the relationship between fluid overload measured by bioimpedance spectroscopy (BIS) and different echocardiographic parameters. Methods: Cross-sectional observational study including 76 stable patients. Dry weight was clinically assessed. BIS and echocardiography were performed. Weekly time-averaged fluid overload (TAFO) and relative fluid overload (FO/ECW) were calculated using BIS measurements. Results: Based on TAFO three groups were defined: A- dehydrated, TAFO 1.5 l: 18 (24%). We found significant correlation between TAFO and left atrial volume index (LAVI) (r: 0.29; p=0.013) but not with FO/ECW (r 0.06; p=0.61). TAFO, but not FO/ECW kept a significant relationship with LAVI (p=0.03) using One-Way ANOVA test and linear regression methods. LVH was present in 73.7% (concentric 63.2%, eccentric in 10.5%). No differences between groups in the presence of LVH or left ventricular mass index were found. Conclusions: We found that left atrial volume index determined by echocardiographic Area-length method, but not left ventricle hypertrophy or dimensions of cavities, are related on hydration status based on bioimpedance measured time-averaged fluid overload (TAFO), and not with FO/ECW.

Background: Testosterone 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). Methods: Single-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. Results: Mean testosterone level was 321 ± 146 ng/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 ± 3225 steps/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. Conclusion: Hypogonadism 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.

Background. Predicting the progression of kidney failure in patients with chronic kidney disease is difficult. The aim of this study was to assess the predictors of rapid kidney decline in a cohort of patients referred to a single outpatient nephrology clinic. Design. Longitudinal, prospective cohort study with a median follow-up of 3.39 years. Methods. Data were obtained from 306 patients with chronic renal failure based on serum creatinine-estimated glomerular filtration rate (eGFRcreat) < 90 mL/min/1.73 m 2 . After excluding patients who died (n=30) and those who developed end-stage renal failure (n=6), 270 patients were included. This population was grouped according to the rate of kidney function decline. Rapid kidney function decline was defined as an annual eGFRcreat loss > 4 mL/min/1.73 m 2 . We recorded nonfatal cardiovascular events at baseline and during follow-up in addition to biochemical parameters. Results. The mean loss in renal function was 1.22 mL/min/1.73 m 2 per year. The mean age was 75 ± 8.8 years old, and the mean baseline eGFRcreat was 42 ± 14 mL/min/1.73 m 2 . Almost one-fourth of the sample (23.3% [63 patients]) suffered a rapid decline in renal function. In a logistic regression model with rapid decline as the outcome, baseline characteristics, lower serum albumin (OR: 0.313, 95% CI: 0.114–0.859), previous cardiovascular disease (OR: 1.903 95% CI: 1.028–3.523), and higher proteinuria (g/24 h) (OR: 1.817 CI 95%: 1.213–2.723) were the main predictors of rapid kidney decline. On multivariate analysis, including baseline and follow-up data, we obtained similar adjusted associations of rapid kidney decline with baseline serum albumin and proteinuria. The follow-up time was also shorter in the group with rapid rates of decline in renal function. Conclusion. Renal function remained stable in the majority of our population. Previous cardiovascular disease and cardiovascular incidents, lower serum albumin, and higher proteinuria at baseline were the main predictors of rapid kidney decline in our population.

OBJECTIVES:The phenotype associated to reduced physical activity (PA) in dialysis patients is poorly documented. We here evaluate weekly PA in two independent cohorts.METHODS:Cross-sectional study with PA assessed by the number of steps/day measured by pedometer in two cohorts of prevalent dialysis patients: (1) peritoneal dialysis (PD) patients (n = 64; 62 ± 14 years; 70 % men) from Stockholm, Sweden using the pedometer for 7 consecutive days; (2) hemodialysis (HD) patients (n = 78; 63 ± 12 years; 65% men) from a single center in Madrid, Spain using the pedometer for 6 consecutive days: 2 HD days, 2 non-HD midweek days and 2 non-HD weekend days. In both cohorts, comorbidities, body composition, nutritional status, and related biomarkers were assessed. Cohorts were not merged; instead data were analyzed separately serving as reciprocal replication analyses.RESULTS:Most patients (63% of PD and 71% of HD) were considered sedentary (<5,000 steps/day). PD patients had on average 4,839 ± 3,313 steps/day. HD patients had 3,767 ± 3,370 steps/day on HD-free days, but fewer steps/day on HD days (2,274 ± 2,048 steps/day; p < 0.0001). In both cohorts, and across increasing PA tertiles, patients were younger and had less comorbidities. Higher PA was also accompanied by better nutritional status (depicted by albumin, pre-albumin, creatinine and normalized protein catabolic rate in HD, and by albumin and subjective global assessment [SGA] in PD), higher lean body mass, and lower fat body mass (bioimpedance and/or dual-energy X-ray absorptiometry [DEXA]). Higher levels of PA were accompanied by lower levels of C-reactive protein in PD. Age and lean body mass were the strongest multivariate predictors of PA in both cohorts.CONCLUSION:There is a high prevalence of sedentary behavior in dialysis patients. Better physical activity was consistently associated with younger age, lower presence of comorbidities and better nutritional status. Pedometers represent a simple and inexpensive tool to objectively evaluate physical activity in this patient population.

Background: Mycophenolate (MF) is effective as induction and maintenance treatment in patients with lupus nephritis (LN). This study evaluates the efficacy and safety of MF in patients with refractory and relapsing LN. Methods: Data were retrospectively obtained for 85 patients (35 refractory and 50 relapsing) from 11 nephrology departments in Spain. The primary endpoints were the incidence and cumulative number of renal responses and relapses and their relationship with baseline clinical and analytical data. The secondary endpoint was the appearance of side effects. Results: The main clinical and analytical variables were similar both in refractory and relapsing LN. Most of the patients had received cyclophosphamide, and all of them switched to MF. 74 patients (87%) achieved a response (69% partial, 31% complete). Age at starting MF, gender, pathological classification, body mass index, blood pressure, baseline renal function, and proteinuria were not associated with achieving response. After stopping MF, 3 of 19 patients (15.7%) relapsed, all at 6 months of follow-up. No differences were found between clinical and analytical variables and number of relapses. Side effects were unremarkable, except for 1 patient, who died of thrombocytopenia and ovarian hemorrhage. Conclusions: Switching to MF from other immunosuppressive treatments is effective and safe in refractory and relapsing LN.

Background. We examine whether cystatin C, a surrogate marker of renal function, could identify patients with chronic kidney disease (CKD) with an increased risk of renal disease progression, death, or cardiovascular events. Methods. Data were obtained for 180 patients, with a diagnosis of chronic renal failure based on serum creatinine estimated glomerular filtration rate (eGFR(creat)) <90 mL/min/1.73m(2). This population was grouped in tertiles according to cystatin C and creatinine values at baseline. Cardiovascular events and overall mortality were estimated for each tertile. Predictors of overall mortality and for the development of renal disease progression were analyzed. Results. The median age was 75 years (interquartile range 69-82) and the median eGFR(creat) 38 mL/min m(2) (interquartile range 33-49). Overall mortality was lower on the first and on the second tertiles of cystatin C than on the third one (HR = 0.060; 95% CI: 0.008-0.447 and HR = 0.094; 95% CI: 0.022-0.406, resp.). Deaths related to the creatinine tertiles followed the same pattern, but differences were not as large. Cardiovascular mortality was lower on the second than on the third cystatin C tertile (HR = 0.198; 95% CI: 0.040-0.987), but it did not show differences on the first and the second creatinine tertiles compared with the third one (HR = 0.126; 95% CI: 0.013-1.265 and HR = 0.403; 95% CI: 0.093-1.740). The only independent predictors of mortality during followup were baseline cystatin C (OR = 0.100; 95% CI: 0.021-0.463) and baseline uric acid (OR = 1.377; 95% CI: 1.070-1.773). Conclusion. Cystatin C may be an alternative to creatinine for detecting a high risk of death and cardiovascular events in a population with CKD.

Background: Overhydration, inflammation and protein-energy wasting have been related to all-cause mortality in dialysis patients, being lean mass loss, a poor prognostic factor. Objective: to monitor body composition changes (BCC) in hemodialysis (HD) patients and to relate BCC to mortality. Methods: Prospective follow up study: Bioimpedance spectroscopy (BIS) and nutritional parameters were performed every 6 months during three years. Results : Overall data show a significant loss of weight at 12m, 24m, and 36m, with decrease of lean tissue index and phase angle (PA) in each period measured. Fat tissue index (FTI) diminished in the third year's measurements. End of first year, 41 % of patients gain weight, them at baseline had lower age, higher serum albumin, lower Extracelular/intracellular water index (ECW/ICW) and higher PA, showing a significant FTI increase. Higher baseline PA was gain weight predictor by binary logistic regression. Cox regression analyses: Age, diabetes, HD technique, albumin, ECW/ICW, and PA were mortality predictors in univariate analysis; being PA the main mortality predictor in multivariate analysis. BCC were not associated with mortality. ROC curve: PA higher than 4.85° is protective for mortality. Conclusions: Lean mass loss was the most important change during follow up; we have not observed association between BCC with mortality. PA was the main mortality predictor.

Background/Aims: Lower serum sodium levels have been associated with increased mortality among patients with chronic kidney disease (CKD). Our aim was to analyze the independent factors associated with lower sodium levels among nondialysis patients with advanced CKD and to evaluate the evolution of these patients in comparison to those with higher plasma sodium over a 1-year period. Methods: We included 72 patients with CKD stages 4 and 5 without clinically evident cardiopathy or liver disease. Bioelectrical impedance and echocardiography were performed to analyze the possible relation between plasma sodium and volume status and subclinical left ventricular (LV) dysfunction. During follow-up, we compared the evolution of patients with lower baseline plasma sodium (low quartile: <138 mEq/l) with that of patients with higher levels over a 1-year period. Results: At baseline, the independent predictors of lower plasma sodium were C-reactive protein (CRP; OR 0.96; 95% CI 0.91-0.99) and body mass index (OR 0.89; 95% CI 0.78-0.99). An inverse correlation between plasma sodium and CRP was observed (r = -0.32; p = 0.01). Plasma sodium did not correlate with extracellular water and was not different between patients with or without echocardiographic data of LV dysfunction (p = 0.7). During follow-up, patients with lower sodium at baseline showed persistently lower sodium values (p = 0.04), higher CRP (p = 0.05), lower serum albumin (p < 0.01) and higher erythropoietin-stimulating agent resistance index (p = 0.05). Conclusions: Our results suggest an association between lower plasma sodium and a microinflammatory state among patients with advanced CKD. Inflammation could be an underlying confounding factor explaining the increased mortality in these patients.

In patients older than 75 years with advanced chronic kidney disease (CKD), the decision between treatment with dialysis [intention to treat with dialysis (ITD)] or conservative care (CC) is a challenge. Geriatric assessment can be helpful. The aim was to identify which factors had had an influence on decision-making. Methods: We recruited 56 patients. At baseline we analyzed age, frailty (defined following the criteria of Fried et al. [J Gerontol A Biol Sci Med Sci 2001;56:146-156]), dependence for activities of daily living (ADL), cognitive impairment, depression, comorbidity, cardiovascular disease, and diabetes. After full information about prognosis and treatment options, the preferences of the patients and families were taken into consideration as determinants in the decision-making process. During the follow-up, we evaluated clinical and laboratory parameters, hospitalization, mortality and reevaluated frailty. Results: Twenty patients opted for CC, and 36 patients opted for ITD. On univariate analysis, the predictive factors of the election of CC were age, prefrailty, cognitive impairment, and dependence for ADL. In the multivariate analysis, age and prefrailty remained as predictors for the choice of CC. Hospitalizations were more frequent in CC. Survival was similar in both groups (p = 0.098). Conclusions: Frailty assessment could be useful for decision-making about the treatment in elderly patients with CKD. CC may be a good treatment option.