Background: Anorexia is frequently found in end-stage renal disease and is a reliable predictor of morbidity and mortality in hemodialysis (HD) patients. The pathogenesis of anorexia is complex and the appetite-modulating hormone ghrelin could be involved. Two forms of circulating ghrelin have been described: acylated ghrelin (<10% of circulating ghrelin) which promotes food intake, and des-acyl ghrelin which induces a negative energy balance. The aim of this cross-sectional study is to clarify whether anorexia and body weight change in HD patients relate to plasma des-acyl ghrelin levels. Methods: 34 HD patients and 15 healthy controls were studied. The presence of anorexia was assessed by a questionnaire. Serum des-acyl ghrelin was measured in HD patients and in 15 body mass index-, sex- and age-matched controls by ELISA. Energy intake was assessed by a 3-day dietary diary, and fat-free mass (FFM) was evaluated by body impedance analysis. Data have been statistically analyzed and are presented as mean ± SD. Results: 14 patients (41%) were found to be anorexic, and 20 patients (59%) non-anorexic. Energy intake (kcal/day) was significantly lower in anorexic than in non-anorexic patients (1,682 ± 241 vs. 1,972.50 ± 490; p < 0.05). FFM (%) was lower in anorexic than in non-anorexic patients (65.8 ± 4.4 vs. 70.9 ± 8.7; p = 0.05). Plasma des-acyl ghrelin levels (fmol/ml) were significantly higher in HD patients than in controls (214.88 ± 154.24 vs. 128.93 ± 51.07; p < 0.05), and in anorexic HD patients than in non-anorexic (301.7 ± 162.4 vs. 159.1 ± 115.5; p < 0.01). Conclusion: Anorexia is highly prevalent among HD patients and des-acyl ghrelin could be involved in its pathogenesis.

Physical inactivity is highly prevalent among patients on HD and BAIBA correlates with barriers to physical activity reported by inactive patients.

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Rationale: Low physical activity is frequent in end stage renal disease. We evaluated the longitudinal change in physical activity and its barriers in hemodialysis (HD) patients and the association between the patterns of physical activity change, body composition, and beta-aminoisobutyric acid (BAIBA), as circulating myokine. Methods: This is an observational study, where HD patients were considered in a 24-month follow-up. We assessed overtime the change of physical inactivity and its barriers by validated questionnaires, body composition by bioimpedance analysis, muscle strength by hand-dynamometer, and plasma BAIBA levels by liquid chromatography spectrometry. Parametric and non-parametric analyses were performed, as appropriate. Results: Out of the 49 patients studied at baseline, 39 completed the first-year follow-up, and 29 completed the second year. At month 12, active patients had higher intracellular water (ICW) ( P = 0.001) and cellular mass ( P < 0.001), as well as at month 24 ( P = 0.012, P = 0.002; respectively) with respect to inactive. A significant reduction in ICW was shown at month 12 ( P = 0.011) and month 24 ( P = 0.014) in all patients. The barrier “reduced walking ability” was more frequent in inactive patients with respect to active at month 12 ( P = 0.003) and at month 24 ( P = 0.05). At month 24, plasma BAIBA levels were higher among active patients with respect to inactive ( P = 0.043) and a correlation was seen between muscle strength and ICW ( r = 0.51, P = 0.005); normalizing BAIBA per body mass index, we found it lower with respect to baseline ( P = 0.004), as well as after correcting per ICW ( P = 0.001), as marker of muscle mass. Conclusion: A high prevalence of physical inactivity persisted during a 24-month follow-up in this cohort. We found an association between physical activity and a decline in marker of muscularity and reduced plasma BAIBA levels.

Fatigue is a frequent symptom in hemodialysis (HD), and the indolamine-2,3-dioxygenase (IDO) metabolic trap has been hypothesized in the pathogenesis of fatigue. The association between IDO activity according to fatigue and its relationship with muscle mass and function in HD patients was verified. Chronic HD patients were considered, and fatigue was assessed. The plasma kynurenines and tryptophan ratio (Kyn/Trp), as surrogate of IDO activity, and interleukin (IL)-6 were measured. Muscularity was assessed by BIA and muscle strength by hand-grip dynamometer. 50 HD patients were enrolled, and fatigue was present in 24% of the cohort. Patients with fatigue showed higher Kyn/Trp (p = 0.005), were older (p = 0.007), and IL-6 levels resulted higher than in non-fatigue patients (p < 0.001). HD patients with fatigue showed lower intracellular water (surrogate of muscle mass) (p < 0.001), as well as lower hand grip strength (p = 0.02). The Kyn/Trp ratio positively correlated with IL-6 and ECW/ICW (p = 0.004 and p = 0.014). By logistic regression analysis, higher ICW/h2 was associated with lower odds of fatigue (OR, 0.10; 95% CI, 0.01 to 0.73). In conclusion, our cohort fatigue was associated with a higher Kyn/Trp ratio, indicating a modulation of IDO activity. The Kyn/Trp ratio correlated with IL-6, suggesting a potential role of IDO and inflammation in inducing fatigue and changes in muscularity.