Skeletal muscle atrophy in clinical and preclinical models of chronic kidney disease: A systematic review and meta-analysis.

Patients with chronic kidney disease (CKD) are often regarded as experiencing wasting of muscle mass and declining muscle strength and function, collectively termed sarcopenia. The extent of skeletal muscle wasting in clinical and preclinical CKD populations is unclear. We evaluated skeletal muscle atrophy in preclinical and clinical models of CKD, with multiple sub-analyses for muscle mass assessment methods, CKD severity, sex and across the different preclinical models of CKD. We performed a systematic literature review of clinical and preclinical studies that measured muscle mass/size using the following databases: Ovid Medline, Embase and Scopus. A random effects meta-analysis was utilized to determine standard mean difference (SMD; Hedges' g) between healthy and CKD. Heterogeneity was evaluated using the I2 statistic. Preclinical study quality was assessed via the Systematic Review Centre for Laboratory Animal Experimentation and clinical studies quality was assessed via the Newcastle-Ottawa Scale. This study was registered in PROSPERO (CRD42020180737) prior to initiation of the search. A total of 111 studies were included in this analysis using the following subgroups: 106 studies in the primary CKD analysis, 18 studies that accounted for diabetes and 7 kidney transplant studies. Significant atrophy was demonstrated in 78% of the preclinical studies and 49% of the clinical studies. The random effects model demonstrated a medium overall SMD (SMD = 0.58, 95% CI = 0.52-0.64) when combining clinical and preclinical studies, a medium SMD for the clinical population (SMD = 0.48, 95% CI = 0.42-0.55; all stages) and a large SMD for preclinical CKD (SMD = 0.95, 95% CI = 0.76-1.14). Further sub-analyses were performed based upon assessment methods, disease status and animal model. Muscle atrophy was reported in 49% of the clinical studies, paired with small mean differences. Preclinical studies reported significant atrophy in 78% of studies, with large mean differences. Across multiple clinical sub-analyses such as severity of CKD, dialysis modality and diabetes, a medium mean difference was found. Sub-analyses in both clinical and preclinical studies found a large mean difference for males and medium for females suggesting sex-specific implications. Muscle atrophy differences varied based upon assessment method for clinical and preclinical studies. Limitations in study design prevented conclusions to be made about the extent of muscle loss with disease progression, or the impact of dialysis. Future work would benefit from the use of standardized measurement methods and consistent clinical staging to improve our understanding of atrophy changes in CKD progression, and analysis of biological sex differences.

Tumor necrosis factor-α, TNF receptor, and soluble TNF receptor responses to aerobic exercise in the heat.

The purpose of this study was to evaluate the effects of aerobic exercise in the heat on circulating concentrations of tumor necrosis factor (TNF)-α, soluble TNF receptors (STNFR1&2), and surface expression of TNFR1&2 on monocyte subpopulations. Twelve recreationally active Caucasian men (24.4 ± 3.4 yrs.; 180.0 ± 6.8 cm; 81.5 ± 8.0 kg; 47.2 ± 4.8 mL·kg-1·min-1) completed an exercise protocol in three environmental conditions: high temperature/low humidity [HTLH; 35 °C, 20% relative humidity (RH)]; high temperature/moderate humidity (HTMH; 35 °C, 45%RH); and moderate temperature/moderate humidity (MTMH; 22 °C, 45%RH). Each protocol consisted of a 60-minute cycling trial at 60% VO2max, a 15-minute rest, and a time-to-exhaustion trial at 90% VO2max (TTE). Blood was sampled before (PRE), immediately after (POST) the 60-minute trial, immediately post-TTE (PTTE), and one-hour post-TTE (REC). Circulating TNF-α and STNFR1&2 were assayed. TNFR1&2 expression on monocyte subsets was measured by flow cytometry on a subset of participants (n = 8). TNF-α area under the curve with respect to increase (AUCi) was greater during HTMH compared to MTMH and HTLH. STNFR1 concentration was greater during HTMH compared to MTMH. With all trials combined, STNFR1 concentration increased from PRE to POST, PTTE, and REC. TNFR1 expression on non-classical monocytes was greater during HTMH compared to HTLH while TNFR2 expression was lower during HTLH compared to both MTMH and HTMH. Data suggest that exercise in the heat increases circulating TNF-α and STNFR1 concentration concomitantly. Furthermore, non-classical monocyte expression of TNFRs are impacted by temperature and humidity during exercise.

Tumor necrosis factor-alpha and soluble TNF-alpha receptor responses in young vs. middle-aged males following eccentric exercise.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) has been shown to be implicated in both muscle regeneration and muscle wasting. However, it remains unclear whether TNF-α is responsible for the age-related losses in muscle size and function. Also, due to the high clearance rate of TNF-α from circulation, analyzing the circulating levels of soluble TNF-α receptors 1 and 2 (STNFR1 and STNFR2) may provide a better indication of inflammatory events. The aim of this study was to examine changes in circulating concentrations of TNF-α, STNFR1, and STNFR2 following acute eccentric exercise in young (YA) and middle-aged (MA) men. METHODS AND MATERIALS: Nine YA (N=9, 21.8±2.2y, 179.5±4.9cm, 91.2±12.2kg, 21.8±4.3% body fat) and ten MA (N=10, 47.0±4.4y, 176.8±7.6cm; 96.0±21.5kg, 25.4±5.3% body fat) men completed an acute muscle damaging protocol (MDP). Blood samples were obtained at baseline (BL), immediately (IP), 30-minute (30P), 60-minute (60P), 120-minute (120P), 24-hour (24H), and 48-hour (48H) post-MDP. Lower body performance was assessed via isokinetic dynamometer at BL, IP, 120P, 24H, and 48H. RESULTS: YA displayed higher values of peak torque (p=0.023) and mean torque (p=0.036) at BL. No significant group differences were observed for markers of muscle damage or TNF-α. Plasma concentrations of TNF-α were unchanged following MDP. STNFR1 concentrations were significantly higher in the YA group compared to MA (p=0.036). Significant time effects were observed for STNFR1 (p<0.001) and STNFR2 (p=0.001). With both groups combined, serum STNFR1 was decreased at 30P (p=0.001), while STNFR2 was decreased at 30P (p=0.008), 60P (p=0.003), and 120P (p=0.002) relative to BL. CONCLUSIONS: The pro-inflammatory response to muscle damage does not appear to decline at middle age when individuals are recreationally trained. However, young men showed significantly higher serum STNFR1 concentrations than middle age men. This may suggest that natural inhibitors of TNF-α decline as early as middle age.

Comparisons in the Recovery Response From Resistance Exercise Between Young and Middle-Aged Men.

Gordon, JA III, Hoffman, JR, Arroyo, E, Varanoske, AN, Coker, NA, Gepner, Y, Wells, AJ, Stout, JR, and Fukuda, DH. Comparisons in the recovery response from resistance exercise between young and middle-aged men. J Strength Cond Res 31(12): 3454-3462, 2017-The purpose of this study was to compare the effects of a bout of high-volume isokinetic resistance exercise protocol (HVP) on lower-body strength and markers of inflammation and muscle damage during recovery between young and middle-aged adult men. Nineteen recreationally trained men were classified as either a young adult (YA: 21.8 ± 2.0 years; 90.7 ± 11.6 kg) or a middle-aged adult (MA: 47.0 ± 4.4 years; 96.0 ± 21.5 kg) group. The HVP consisted of 8 sets of 10 repetitions, with 1 minute of rest between each set, performed on an isokinetic dynamometer at 60°·s. Maximal voluntary isometric contractions and isokinetic peak torque (PKT) and average torque (AVGT) (measured at 240° and 60°·s, respectively) were assessed at baseline (BL), immediately post (IP), 120 minutes, 24, and 48 hours after HVP. Blood was obtained at BL, IP, 30, 60, 120 minute, 24, and 48 hours after HVP to assess muscle damage and inflammation. All performance data were analyzed using repeated measures analysis of covariance, whereas all inflammatory and muscle damage markers were analyzed using a 2-way (time × group) repeated measures analysis of variance. Results revealed no between-group differences for PKT, AVGT, or rate of torque development at 200 ms (RTD200). No between-group differences in myoglobin, creatine kinase, C-reactive protein, or interleukin-6 were observed. Although BL differences in muscle performance were observed between YA and MA, no between-group differences were noted in performance recovery measures from high-volume isokinetic exercise in recreationally trained men. These results also indicate that the inflammatory and muscle damage response from high-volume isokinetic exercise is similar between recreationally trained, young, and middle-aged adult men.

Comparison of the recovery response from high-intensity and high-volume resistance exercise in trained men.

PURPOSE: The purpose of this study was to compare the physiological responses of a high-volume (HV; 8 sets of 10 repetitions) versus high-intensity (HI; 8 sets of 3 repetitions) exercise protocol in resistance-trained men. METHODS: Twelve men (24.5 ± 4.2 years; 82.3 ± 8.4 kg; 175.2 ± 5.5 cm) with 6.3 ± 3.4 years of resistance training experience performed each protocol in a counterbalanced, randomized order. Performance [counter movement jump peak power (CMJP), isokinetic (ISOK) and isometric leg extension (MVIC), isometric mid-thigh pull (IMTP), and isometric squat (ISQ)] and muscle morphological [cross-sectional area (CSA) of vastus lateralis] assessments were performed at baseline (BL), 30-min (P-30 min), 24-h (P-24 h), 48-h (P-48 h), and 72-h (P-72 h) post-exercise for each testing session. In addition, endocrine (testosterone and cortisol), inflammatory [interleukin-6 (IL-6) and C-reactive protein (CRP)], and markers of muscle damage [creatine kinase (CK), lactate dehydrogenase (LDH), and myoglobin (Mb)] were assessed at the same time points. RESULTS: Significantly greater reductions in CMJP (p < 0.001), and peak torque during both ISOK (p = 0.003) and MVIC (p = 0.008) at P-30 min were detected in HV compared to HI protocol. MVIC was still impaired at P-72 h following the HV protocol, while no differences were noted following HI. Markers of muscle damage (LDH, CK, and Mb) were significantly elevated following both HV and HI (p < 0.05), while cortisol and IL-6 concentrations were significantly elevated at P-30 min following HV only (p < 0.001 and p < 0.05, respectively). CONCLUSIONS: Results indicate that high-volume resistance exercise results in greater performance deficits, and a greater extent of muscle damage, than a bout of high-intensity resistance exercise.