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

Abstract

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: β = -121.2 μV·s -1 , P = 0.016, and β = -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: β = -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.

FIGURE 1

Description of the neuromuscular fatigability protocol. Gray arrows represent explosive contractions, black lines represent maximal voluntary contractions, and the gridded boxes represent submaximal contractions.

FIGURE 2

Evolution of the MVF (A), RFD (B), and NRFD (C) during the fatigability protocol. Gray bars represent CKD patients, and black bars represent controls with the 95% CI.

FIGURE 3

Continuous wavelet transform analysis of the first and last explosive contractions within groups and degrees of fatigue. Onsets of contractions are symbolized with a dashed line at time 0, and the dotted lines represent the time period considered for ifmed analysis. The left panel represents the first 300 ms from the onset of the explosive contractions at rest, the middle panel shows the last explosive contraction, and the right panel maps differences (blue represents a higher decrease in energy with fatigability protocol).