Hypogonadism associated with muscle atrophy, physical inactivity and ESA hyporesponsiveness in men undergoing haemodialysis / Hipogonadismo asociado a atrofia muscular, inactividad física e hiposensibilidad a FEE en varones sometidos a hemodiálisis

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 (AU)

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±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. 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 (AU)

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.

Lower plasma sodium is associated with a microinflammatory state among patients with advanced chronic kidney disease.

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.

Lack of influence of serum magnesium levels on overall mortality and cardiovascular outcomes in patients with advanced chronic kidney disease.

Background. Low serum magnesium has been associated with an increased cardiovascular risk in the general population and in dialysis patients. Our aim was to analyze the influence of serum magnesium on overall mortality and cardiovascular outcomes in patients with advanced CKD not yet on dialysis. Methods. Seventy patients with CKD stages 4 and 5 were included. After a single measurement of s-magnesium, patients were followed a mean of 11 months. Primary end-point was death of any cause, and secondary end-point was the occurrence of fatal or nonfatal CV events. Results. Basal s-magnesium was within normal range (2.1 ± 0.3 mg/dL), was lower in men (P = 0.008) and in diabetic patients (P = 0.02), and was not different (P = 0.2) between patients with and without cardiopathy. Magnesium did not correlate with PTH, calcium, phosphate, albumin, inflammatory parameters (CRP), and cardiac (NT-proBNP) biomarkers but correlated inversely (r = -0.23; P = 0.052) with the daily dose of loop diuretics. In univariate and multivariate Cox proportional hazard models, magnesium was not an independent predictor for overall mortality or CV events. Conclusions. Our results do not support that serum magnesium can be an independent predictor for overall mortality or future cardiovascular events among patients with advanced CKD not yet on dialysis.

End-stage renal disease and its treatment in Latin America in the twenty-first century.

The Latin American Society of Nephrology and Arterial Hypertension's Dialysis and Transplant Registry was chartered in 1991. It collects information on ESRD and its treatment in 20 countries of the region. The prevalence of patients on renal replacement therapy (RRT) increased from 129 pmp in 1992 to 447 pmp in 2004; in 2004, 56% of the patients were on hemodialysis, 23% on peritoneal dialysis, and 21% had a functioning kidney graft. The highest rates of prevalence were reported in Puerto Rico (1027 pmp), Chile (686 pmp), and Uruguay (683 pmp). Hemodialysis was widely used, except in El Salvador, Mexico, Guatemala, Nicaragua, and the Dominican Republic, where peritoneal dialysis predominated. Incidence rate increased from 27.8 pmp to 147 pmp in the same period of observation; the lowest rate was reported in Guatemala (11.4 pmp) and the highest in Puerto Rico (337.4 pmp). Diabetes mellitus was the leading cause of renal failure in incident patients; the highest rates were reported in Puerto Rico (62.2%) and Mexico (60%). Forty-four percent of the incident population were older than 65 years. Access to renal replacement therapy was universal in Argentina, Brazil, Chile, Cuba, Puerto Rico, Uruguay, and Venezuela, while was restricted in other countries. Main causes of death in dialysis were cardiovascular (44%) and infectious disease (26%). The rate of renal transplantation increased from 3.7 pmp in 1987 to 14.5 in 2004; fifty-three percent of the organs came from cadavers. Overall, donation rate was 5.9 pmp. In conclusion, the prevalence and incidence rates have increased over the years, and diabetes mellitus has emerged as the leading cause of kidney disease in the region. Although the rate of kidney transplantation has increased, the number remains insufficient to match the growing demand. The implementation of renal health programs in the region is urgently needed.

The Latin American Dialysis and Transplantation Registry (RLDT) annual report 2004.

INTRODUCTION: The Latin American Dialysis and Transplantation Registry (RLDT) includes 20 national affiliates. Data are provided annually by delegates designated by the national affiliate or by the Registry's Coordinating Committee. RESULTS: Prevalence of persons on renal replacement therapy (RRT) has increased from 192 patients per million population (pmp) in 1992 to 424 pmp in 2003, a 10% annual increment. Fifty-six percent were on hemodialysis, 23% on peritoneal dialysis, and 21% had a functioning graft. The highest prevalence was observed in Puerto Rico, and the lowest in Ecuador. Hemodialysis was the preferred treatment modality, except in El Salvador, Mexico, and Guatemala. Incidence rates varied widely; they were high in Puerto Rico (336 pmp) and Mexico (275 pmp) and low in Costa Rica (24 pmp) and Ecuador (14 pmp). Diabetes was the main reported cause of endstage renal disease (ESRD); it caused from 21% (Uruguay) to 65% (Puerto Rico) of cases. Forty percent of incident patients were > 65 years old. Access to RRT is universal in Argentina, Brazil, Cuba, Puerto Rico, Uruguay, and Venezuela but restricted in countries like Mexico and Paraguay. Main causes of death on dialysis were cardiovascular (44%) and infection (26%). Transplantation rates increased from 3.7 pmp in 1987 to 13.7 pmp in 2003, mostly from living donors (55%). The number of transplants reached 69,181 grafts. CONCLUSION: Prevalence of RRT has increased over the years; diabetes has become the main cause of ESRD, and cardiovascular disease is the leading cause of death on dialysis. Transplantation rates, although increasing, have not matched the growing population on dialysis. Programs to promote renal health in the region are urgently needed.

The Latin American Dialysis and Renal Transplantation Registry Annual Report 2002.

Latin America is a conglomerate of adjacent countries having in common a Latin extraction and language (Spanish or Portuguese) and exhibiting extreme variations in socioeconomic status. The Latin American Society of Nephrology and Hypertension Dialysis and Renal Transplantation Registry was created in 1991. Annual data are sent by local societies in 3 forms: patient, center, and country. The prevalence of renal replacement therapy (RRT) (all modalities) increased from 119 patients per million population (pmp) in 1991 to 349 pmp in 2001; the acceptance rate was 91.7 pmp in 2001. Dialysis prevalence was 277 pmp; hemodialysis was the predominant modality, except in Mexico (86% on peritoneal dialysis). The highest dialysis prevalence and acceptance rates were reported by Puerto Rico, Uruguay, and Chile. Among incident patients, diabetic nephropathy (33%) and nephroangioesclerosis (32%) were the primary causes; 38% were older than 65 years old. Renal transplants increased from 3.7 pmp in 1987 to 13.7 pmp in 2001. In 2003, 6357 transplants were performed (55% living donor); the cumulative number performed since 1987 reached 55,947. Prevalence and incidence are low because not all patients with end-stage renal disease have access to RRT because of restricted availability, difficulties in referral, and inequities in coverage. The annual increase in the number of patients on RRT (8%-10%) is higher, proportionally, than the annual growth of the Latin American population in general (1.5%). Efforts must be focused on prevention and treatment of chronic kidney disease, especially in diabetic and older patients, and in implementing better organ donation programs to improve the pool of cadaveric donors.