Hemodynamic and neuromuscular basis of reduced exercise capacity in patients with end-stage renal disease

The present study aimed to characterize the exercise-induced neuromuscular fatigue and its possible links with cerebral and muscular oxygen supply and utilization to provide mechanistic insights into the reduced exercise capacity characterizing patients with end-stage renal disease (ESRD).

Thirteen patients with ESRD and thirteen healthy males (CTR group) performed a constant-force sustained isometric contraction at 50% of their maximal voluntary isometric contraction (MVC) until exhaustion. Quadriceps muscle activation during exercise was estimated from vastus lateralis, vastus medialis, and rectus femoris EMG. Central and peripheral fatigue were quantified via changes in pre- to postexercise quadriceps voluntary activation (ΔVA) and quadriceps twitch force (ΔQ_tw,pot) evoked by supramaximal electrical stimulation, respectively. To assess cerebral and muscular oxygenation, throughout exercise, near-infrared spectroscopy allowed investigation of changes in oxyhemoglobin (∆O₂Hb), deoxyhemoglobin (∆HHb), and total hemoglobin (∆THb) in the prefrontal cortex and in the vastus lateralis muscle.

ESRD patients demonstrated lower exercise time to exhaustion than that of CTR (88.8 ± 15.3 s and 119.9 ± 14.6 s, respectively, P < 0.01). Following the exercise, MVC, Q_tw,pot, and VA reduction were similar between the groups (P > 0.05). There was no significant difference in muscle oxygenation (∆O₂Hb) between the two groups (P > 0.05). Cerebral and muscular blood volume (∆THb) and oxygen extraction (∆HHb) were significantly blunted in the ESRD group (P < 0.05). A significant positive correlation was observed between time to exhaustion and cerebral blood volume (∆THb) in both groups (r² = 0.64, P < 0.01).

These findings support cerebral hypoperfusion as a factor contributing to the reduction in exercise capacity characterizing ESRD patients.