1.
Muscle wasting in hemodialysis patients: new therapeutic strategies for resolving an old problem.
Chen, CT, Lin, SH, Chen, JS, Hsu, YJ
TheScientificWorldJournal. 2013;:643954
Abstract
Muscle wasting has long been recognized as a major clinical problem in hemodialysis (HD) patients. In addition to its impact on quality of life, muscle wasting has been proven to be associated with increased mortality rates. Identification of the molecular mechanisms underlying muscle wasting in HD patients provides opportunities to resolve this clinical problem. Several signaling pathways and humeral factors have been reported to be involved in the pathogenic mechanisms of muscle wasting in HD patients, including ubiquitin-proteasome system, caspase-3, insulin/insulin-like growth factor-1 (IGF-1) signaling, endogenous glucocorticoids, metabolic acidosis, inflammation, and sex hormones. Targeting the aforementioned crucial signaling and molecules to suppress protein degradation and augment muscle strength has been extensively investigated in HD patients. In addition to exercise training, administration of megestrol acetate has been proven to be effective in improving anorexia and muscle wasting in HD patients. Correction of metabolic acidosis through sodium bicarbonate supplements can decrease muscle protein degradation and hormone therapy with nandrolone decanoate has been reported to increase muscle mass. Although thiazolidinedione has been shown to improve insulin sensitivity, its role in the treatment of muscle wasting remains unclear. This review paper focuses on the molecular pathways and potential new therapeutic approaches to muscle wasting in HD patients.
2.
Influence of megestrol acetate on nutrition, inflammation and quality of life in dialysis patients.
Gołębiewska, JE, Lichodziejewska-Niemierko, M, Aleksandrowicz-Wrona, E, Majkowicz, M, Lysiak-Szydłowska, W, Rutkowski, B
International urology and nephrology. 2012;(4):1211-22
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Abstract
AIM: Malnutrition is a common clinical problem in dialysis patients. The objective of this study was to evaluate the efficacy and safety of megestrol acetate in malnourished dialysis patients. Thirty-two hypoalbuminemic dialysis patients took 160 mg of megestrol acetate daily for up to 6 months. METHODS We measured height, dry weight, BMI, modified Subjective Global Assessment (SGA) score, and serum albumin, triglycerides, total cholesterol, hsCRP, IL-1β and IL-6 concentrations. We used validated questionnaires to evaluate selected dimensions of the quality of life. RESULTS Only 12 patients completed the study. All patients reported improved appetite, and there were concurrent statistically significant increases in weight, BMI, SGA and albumin concentration (P < 0.05). For the 12 patients who completed 6 months of treatment the increase in these parameters was from 63.26 ± 13.04 to 65.58 ± 12.53 kg, from 23.5 ± 3.8 to 24.66 ± 4.23 kg/m(2), from 5.16 ± 0.94 to 6.16 ± 0.72 points, and from 36.45 ± 1.82 to 40.33 ± 2.71 g/l, respectively. However, there were no significant changes in the levels of inflammatory markers and in quality of life. Side effects included overhydration, excessive weight gain and hyperglycaemia. CONCLUSION Megestrol acetate may be effective in reversing poor appetite in carefully selected maintenance dialysis patients, but it might not reduce inflammation or improve the quality of life. Because of the potential side effects, close monitoring is essential.
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Effects of megestrol acetate in patients with cancer anorexia-cachexia syndrome--a systematic review and meta-analysis.
Leśniak, W, Bała, M, Jaeschke, R, Krzakowski, M
Polskie Archiwum Medycyny Wewnetrznej. 2008;(11):636-44
Abstract
INTRODUCTION Anorexia-cachexia syndrome (ACS) often occurs in patients with advanced cancer. OBJECTIVES To review the effect of megestrol acetate (MA) in patients with ACS. PATIENTS AND METHODS To identify eligible studies, systematic review by Lopez et al. (2004) was used, electronic databases (MEDLINE, EMBASE and CENTRAL) were searched and reference lists of included studies were reviewed. The studies were included in the review if they were randomized, enrolled patients with non-hormone-sensitive cancer and ACS and assessed the effects of MA compared with placebo, other drugs or different doses of MA. RESULTS The study population is characterized by high mortality and progressive weight loss irrespective of the treatment. Compared to placebo, the effect of MA on survival is similar, but MA increases appetite (number needed to treat [NNT]: 3) and leads to weight gain (NNT: 8) in more patients. The data on other aspects of the quality of life are limited. The comparison of MA and glucocorticosteroids showed no statistical difference in their effect on appetite and weight. CONCLUSIONS Compared to placebo, MA reduces the symptoms of ACS, with no effect on survival. The beneficial effect of MA on the overall quality of life has not been confirmed. In identified studies the effect of MA and glucocorticosteroids on anorexia and cachexia is similar. The estimation of the treatment utility in ACS depends on the weight attributed to discomfort caused by symptoms, adverse effects of the drugs and the treatment cost. Because of the low quality of the included studies a new randomized controlled trial is needed for valid assessment of the effects of MA.