Muscle wasting in patients with end‐stage renal disease or early‐stage lung cancer: common mechanisms at work

Abstract Background Loss of muscle mass worsens many diseases such as cancer and renal failure, contributes to the frailty syndrome, and is associated with an increased risk of death. Studies conducted on animal models have revealed the preponderant role of muscle proteolysis and in particular the activation of the ubiquitin proteasome system (UPS). Studies conducted in humans remain scarce, especially within renal deficiency. Whether a shared atrophying programme exists independently of the nature of the disease remains to be established. The aim of this work was to identify common modifications at the transcriptomic level or the proteomic level in atrophying skeletal muscles from cancer and renal failure patients. Methods Muscle biopsies were performed during scheduled interventions in early‐stage (no treatment and no detectable muscle loss) lung cancer (LC), chronic haemodialysis (HD), or healthy (CT) patients (n = 7 per group; 86% male; 69.6 ± 11.4, 67.9 ± 8.6, and 70.2 ± 7.9 years P > 0.9 for the CT, LC, and HD groups, respectively). Gene expression of members of the UPS, autophagy, and apoptotic systems was measured by quantitative real‐time PCR. A global analysis of the soluble muscle proteome was conducted by shotgun proteomics for investigating the processes altered. Results We found an increased expression of several UPS and autophagy‐related enzymes in both LC and HD patients. The E3 ligases MuRF1 (+56 to 78%, P 1700 proteins, and principal component analysis revealed three differential proteomes that matched to the three groups of patients. Orthogonal partial least square discriminant analysis created a model, which distinguished the muscles of diseased patients (LC or HD) from those of CT subjects. Proteins that most contributed to the model were selected. Functional analysis revealed up to 238 proteins belonging to nine metabolic processes (inflammatory response, proteolysis, cytoskeleton organization, glucose metabolism, muscle contraction, oxidant detoxification, energy metabolism, fatty acid metabolism, and extracellular matrix) involved in and/or altered by the atrophying programme in both LC and HD patients. This was confirmed by a co‐expression network analysis. Conclusions We were able to identify highly similar modifications of several metabolic pathways in patients exhibiting diseases with different aetiologies (early‐stage LC vs. long‐term renal failure). This strongly suggests that a common atrophying programme exists independently of the disease in human

Day and night changes in energy expenditure of patients on automated peritoneal dialysis

International audienceRationale: Automated peritoneal dialysis (APD) treatment for end-stage kidney disease affords patients a degree of autonomy in everyday life. Clinical investigations of their energy expenditure (EE) are usually based on resting EE, which could mask day and night variations in EE. The aim of this study, therefore, was to compare the components of EE in APD patients and healthy control (C) subjects.& nbsp; Material and method: Patients treated with APD for more than 3 months were compared with C volunteers matched for age and lean body mass (LBM). Biochemical analyses were performed and body composition was determined by DEXA to adjust EE to LBM. Total EE, its different components and respiratory quotients (RQ) were measured by a gas exchange method in calorimetric chambers. Spontaneous total and activity-related EE (AEE) were also measured in free-living conditions over 4 days by a calibrated accelerometer and a heart rate monitor.& nbsp; Results: APD (n = 7) and C (n = 7) patients did not differ in age and body composition. REE did not differ between the two groups. However, prandial increase in EE adjusted for dietary energy intake was higher in APD patients (+57.5 +/- 12.71 kcal/h) than in C subjects (+33.8 +/- 10.5 kcal/h, p = 0.003) and nocturnal decrease in EE tended to be lower in APD patients undergoing dialysis sessions (- 4.53 +/- 8.37 kcal/h) than in subjects (- 11.8 +/- 7.69 kcal/h, p = 0.059). Resting RQ (0.91 +/- 0.09 vs 0.81 +/- 0.04, p = 0.032) and nocturnal RQ (0.91 +/- 0.09 vs 0.81 +/- 0.04, p = 0.032) were significantly higher in APD patients, indicating a preferential use of glucose substrate potentially absorbed across the peritoneum. AEE was lower in APD patients (595.9 +/- 383.2 kcal/d) than in C subjects (1205.2 +/- 370.5 kcal/d, p = 0.011). In contrast, energy intakes were not significantly different (1986 +/- 465 vs 2083 +/- 377 kcal/d, p = 0.677).& nbsp; Conclusion: Although the two groups had identical resting EE, APD patients had a higher prandial increase in EE, a lower activity-related EE and higher resting and nocturnal RQ than healthy subjects. (C)& nbsp;2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolis