Analysis of the rate of force development reveals high neuromuscular fatigability in elderly patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) induces muscle wasting and a reduction in the maximum voluntary force (MVF). Little is known about the neuromuscular fatigability in CKD patients, defined as the reduction of muscle force capacities during exercise. Neuromuscular fatigability is a crucial physical parameter of the daily living. The quantification of explosive force has been shown to be a sensitive means to assess neuromuscular fatigability. Thus, our study used explosive force estimates to assess neuromuscular fatigability in elderly CKD patients. METHODS: Inclusion criteria for CKD patients were age ≥ 60 years old and glomerular filtration rate (GFR) < 45 mL/min/1.73 m2 not on dialysis, and those for controls were GFR > 60 mL/min/1.73 m2 , age and diabetes matched. The fatigability protocol focused on a handgrip task coupled with surface electromyography (sEMG). Scalars were extracted from the rate of force development (RFD): absolute and normalized time periods (50, 75, 100, 150 and 200 ms, RFD50 , RFD75 , RFD100 , RFD150 and RFD200 , respectively), peak RFD (RFDpeak in absolute; NRFDpeak normalized), time-to-peak RFD (t-RFDpeak ) and the relative force at RFDpeak (MVF-RFDpeak ). A statistical parametric mapping approach was performed on the force, impulse and RFD-time curves. The integrated sEMG with time at 0-30, 0-50, 0-100 and 0-200 ms time intervals relative to onset of sEMG activity was extracted and groups were compared separately for each sex. RESULTS: The cohort of 159 individuals had a median age of 69 (9IQR ) years and body mass index was 27.6 (6.2IQR ) kg/m2 . Propensity-score-matched groups balanced CKD patients and controls by gender with 66 males and 34 females. In scalar analysis, CKD patients manifested a higher decrement than controls in the early phase of contraction, regarding the NRFDpeak (P = 0.009; η2 p  = 0.034) and RFD75 and RFD100 (for both P < 0.001; η2 p  = 0.068 and 0.064). The one-dimensional analysis confirmed that CKD males manifest higher and delayed neuromuscular fatigability, especially before 100 ms from onset of contraction. sEMG was lower in CKD patients than controls in the 0-100 ms (at rest: P = 0.049, Cohen's d = 0.458) and 0-200 ms (at rest: P = 0.016, Cohen's d = 0.496; during exercise: P = 0.006, Cohen's d = 0.421) time windows. Controls showed greater decrease of sEMG than CKD patients in the 0-30 ms (P = 0.020, Cohen's d = 0.533) and 0-50 ms (P = 0.010, Cohen's d = 0.640) time windows. As opposite to females, males showed almost the same differences between groups. CONCLUSIONS: Our study is the first to show that CKD patients have higher fatigability than controls, which may be associated with an impaired motor-unit recruitment, highlighting a neural drive disturbance with CKD. Further studies are needed to confirm these findings.

Neural Drive Impairment in Chronic Kidney Disease Patients Is Associated with Neuromuscular Fatigability and Fatigue.

INTRODUCTION: Chronic kidney disease (CKD) patients have a high degree of fatigue relating to neuromuscular symptoms. There is a lack of evidence regarding the etiology of neuromuscular fatigability in elderly CKD patients. METHODS: Inclusion criteria are as follows: age ≥60 yr, glomerular filtration rate (GFR) <45 mL·min -1 per 1.73 m 2 in CKD patients, and GFR >60 mL·min -1 ·1.73 m -2 in controls. The fatigability protocol consisted in a submaximal handgrip task at 40% peak force. Fatigue was assessed using the Multidimensional Fatigue Inventory-20 items (MFI-20) and the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaires. Peak rate of force development (RFD peak , normalized: NRFD peak ) and rate of EMG rise (RER) were measured during explosive contractions; peak force and mean surface EMG were measured during maximum voluntary contractions. Multilevel models tested neuromuscular parameters adjusted for clinical and Multidimensional Fatigue Inventory-20 items subscales. Neuromuscular fatigability contribution to fatigue description was tested using model comparison. RESULTS: The study included 102 participants; 45 CKD patients and 57 controls. CKD mainly affected the mental and the reduced motivation subscales of fatigue. CKD was associated with greater neuromuscular fatigability assessed using NRFD peak (group-time interaction, -16.7 % MVF·s -1 , P = 0.024), which increased with fatigue severity ( P = 0.018) and with a higher rate of decrement in RER compared with controls (RER at 50 ms: ß = -121.2 µV·s -1 , P = 0.016, and ß = -48.5 µV·s -1 , P = 0.196, respectively). Furthermore, these patients show an association between the reduced motivation subscale and the RER (e.g., 30 ms: ß = -59.8% EMG peak ·s -1 , P < 0.001). Only peak force fatigability contributed to fatigue variance, whereas RFD peak did not. CONCLUSIONS: In CKD patients, the neuromuscular fatigability assessed using RFD peak is related to an impairment in motor-unit recruitment or discharge rates, whereas only peak force fatigability was related to fatigue. This suggests that targeting exercise interventions might lessen fatigue and improve quality of life in CKD patients.

Pedobarographic Statistical Parametric Mapping may identify specific plantar pressure patterns in patients with diabetes mellitus among different degrees of peripheral neuropathy: A pilot study.

AIMS: Peripheral neuropathy (PN) in patients with diabetes can lead to changes in the distribution of plantar pressure during walking, which can be recorded with pedobarography. Compared to traditional spatial data reduction analysis, the pedobarographic Statistical Parametric Mapping (pSPM) allows comparison of the footprints with the advantage that sub-regions do not need to be defined a priori. Aim of the study was to test the potential of pSPM in identifying specific distribution of spatial pressure in different stages of PN. METHODS: PN was defined according to usual tools (i.e., tendon reflexes and sensory tests). Four groups were compared: patients with diabetes without PN (n = 24; 239 steps); with signs of mild PN (n = 12; 117 steps); with signs of severe PN (n = 6; 52 steps) and a control group without diabetes (n = 12; 124 steps). Traditional spatial data reduction and pSPM were performed to compare plantar pressures in the different groups. RESULTS: In patients with PN, traditional spatial data reduction analysis showed lower plantar pressures with PN severity. pSPM analysis is able to better define the initial changes: mild PN patients presents higher pressures on the anterior side of the metatarsal heads compared to patients without neuropathy. Patients with severe PN are characterised by higher pressures under the medial foot arch compared to other groups. CONCLUSIONS: pSPM may identify specific features of plantar pressure distribution during walking in patients with mild PN and may become a useful screening tool for a timely identification of this complication.

PhysIOpathology of NEuromuscular function rElated to fatigue in chronic Renal disease in the elderly (PIONEER): study protocol.

BACKGROUND: Chronic Kidney Disease (CKD) is associated with reduced muscular strength resulting in profound fatigue. The physiopathology of these changes, their prevalence and evolution are still debated. Moreover, we have little data on elderly CKD patients. The present study protocol aims to 1) quantify the prevalence of low muscle strength (dynapenia) in a cohort of elderly patients with advanced CKD and to 2) characterize their force production coupled with electromyographic features and the symptoms of fatigue compared to a matched control group. METHODS: This is a case-control, prospective, interventional study. INCLUSION CRITERIA: age ≥ 60 years; CKD Stage 3b-5; clinical stability (i.e. no hospitalization and ≤ 25% in creatinine increase in the previous 3 months). Controls with normal kidney function will be matched in terms of age, gender and diabetes mellitus (requisite: estimated glomerular filtration rate ≥ 60 ml/min/1.73m2 available in the last 6 months). Exclusion criteria for cases and controls: neuromuscular disease, life expectancy < 3 months. The handgrip strength protocol is an intermittent test consisting in 6 series of 9 repetitions of 3-s sub-maximum contractions at 40% of the maximum voluntary contraction (MVC) and 2 s of resting time between contractions. Each series is separated by one fast sub-maximum contraction and one MVC. Strength is assessed with a high-frequency handgrip dynamometer paired with surface electromyography. Symptoms of fatigue are assessed using MFI-20 and FACIT-F questionnaires. In order to reach a statistical power of 96%, we plan to enroll 110 subjects in each group. DISCUSSION: The novelty of this study resides in the application of an already validated set of tests in a population in which this combination (dynamometer, electromyography and questionnaires) has not previously been explored. We expect a high prevalence of dynapenia and a higher fatigability in CKD patients. A positive correlation is expected between reported fatigue and fatigability. Better appreciation of the prevalence and the relationship between fatigability and a sensation of fatigue can help us target interventions in CKD patients to improve quality of life and survival. TRIAL REGISTRATION: The study was approved by Ethical Committee EST III n°20.03.01 and was recorded as a Clinical Trial (NCT04330807) on April 2, 2020.