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In patients with advanced chronic kidney disease (CKD), the accumulation of uremic toxins, caused by a combination of decreased excretion secondary to reduced kidney function and increased generation secondary to aberrant expression of metabolite genes, interferes with different biological functions of cells and organs, contributing to a state of chronic inflammation and other adverse biologic effects that may cause tissue damage. Several uremic toxins have been implicated in severe vascular smooth muscle cells (VSMCs) changes and other alterations leading to vascular calcification (VC) and early vascular ageing (EVA). The above mentioned are predominant clinical features of patients with CKD, contributing to their exceptionally high cardiovascular mortality. Herein, we present an update on pathophysiological processes and mediators underlying VC and EVA induced by uremic toxins. Moreover, we discuss their clinical impact, and possible therapeutic targets aiming at preventing or ameliorating the harmful effects of uremic toxins on the vasculature.

Objective: Hypogonadism is a common endocrine disorder in men with chronic kidney disease (CKD), but its pathophysiology is poorly understood. We here explore the plausible contribution of abdominal adiposity and leptin hyperproduction to testosterone deficiency in this patient population., Design: Cross-sectional analysis with all men included the Malnutrition, Inflammation and Vascular Calcification cohort, which enrolled consecutive nondialyzed patients with CKD stages 3-5., Subjects: A total of 172 men with CKD stages 3-5 nondialysis (median age 61 [45-75] years, median glomerular filtration rate 24 [9-45] mL/min/1.73 m 2 ). In them, serum levels of total testosterone, estrogen, sex hormone binding globulin, and leptin were quantified, together with visceral adipose tissue (VAT) by thoracic and abdominal CT scan., Intervention: None, observational study., Main Outcome Measure: Total testosterone, hypogonadism., Results: The median level of total testosterone was 11.7 (7.3-18.4) nmol/L, with hypogonadism (<10 nmol/L) present in 52 (30%) patients. Testosterone-deficient patients presented with significantly higher body mass index, waist circumference, and VAT. An inverse correlation between testosterone and VAT (rho = -0.25, P = .001) or waist circumference (rho = -0.20, P = .008) was found, also after multivariate adjustment including sex hormone binding globulin and estrogen. Total testosterone was inversely correlated with serum leptin (rho = -0.22, P = .003), and the ratio of leptin/VAT, an index of leptin hyperproduction, was strongly and independently associated with the prevalence of hypogonadism in multivariable regression analyses., Conclusion: Visceral adiposity independently associated with lower testosterone levels among men with CKD stage 3-5 nondialysis. The observed link between hyperleptinemia and hypogonadism is in line with previous evidence on direct effects of leptin on testosterone production., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

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 <-0.25 L 32 P (42%); B- normohydrated, TAFO between -0.25 and 1.5 l: 26 (34%); C- overhydrated, 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., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Sex and gender differences are of fundamental importance in most diseases, including chronic kidney disease (CKD). Men and women with CKD differ with regard to the underlying pathophysiology of the disease and its complications, present different symptoms and signs, respond differently to therapy and tolerate/cope with the disease differently. Yet an approach using gender in the prevention and treatment of CKD, implementation of clinical practice guidelines and in research has been largely neglected. The present review highlights some sex- and gender-specific evidence in the field of CKD, starting with a critical appraisal of the lack of inclusion of women in randomized clinical trials in nephrology, and thereafter revisits sex/gender differences in kidney pathophysiology, kidney disease progression, outcomes and management of haemodialysis care. In each case we critically consider whether apparent discrepancies are likely to be explained by biological or psycho-socioeconomic factors. In some cases (a few), these findings have resulted in the discovery of disease pathways and/or therapeutic opportunities for improvement. In most cases, they have been reported as merely anecdotal findings. The aim of the present review is to expose some of the stimulating hypotheses arising from these observations as a preamble for stricter approaches using gender for the prevention and treatment of CKD and its complications., (© 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

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.

Unlabelled: 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., (© 2014 S. Karger AG, Basel.)