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. Inclusion criteria for CKD patients were age≥60years old and glomerular filtration rate (GFR)<45mL/min/1.73m2 not on dialysis, and those for controls were GFR>60mL/min/1.73m2 , 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 200ms, 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 0-200ms time intervals relative to onset of sEMG activity was extracted and groups were compared separately for each sex. 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 100ms from onset of contraction. sEMG was lower in CKD patients than controls in the 0-100ms (at rest: P=0.049, Cohen's d=0.458) and 0-200ms (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 0-30ms (P=0.020, Cohen's d=0.533) and 0-50ms (P=0.010, Cohen's d=0.640) time windows. As opposite to females, males showed almost the same differences between groups. 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.
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