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

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±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. 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.

Clinical determinants of reduced physical activity in hemodialysis and peritoneal dialysis patients.

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.

Cystatin C as a predictor of mortality and cardiovascular events in a population with chronic kidney disease.

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 (eGFRcreat) <90 mL/min/1.73 m(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 eGFRcreat 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.