Vascular and Inflammatory Response Patterns Across Fixed-Sequence Handgrip Exercise Conditions in Hemodialysis Patients: An Exploratory Clinical Study with Complementary Experimental Findings

Patients undergoing hemodialysis (HD) frequently exhibit endothelial dysfunction and limited exercise capacity, but vascular and inflammatory responses to different handgrip exercise intensities remain unclear. Male Wistar rats with or without chronic kidney disease (CKD) underwent 4 weeks of forelimb exercise or no exercise (n = 5/group). In the clinical study, eight HD and eight non-HD participants completed fixed-sequence 2-week handgrip exercise conditions at 40%, 60%, and 80% of maximal voluntary contraction (MVC), separated by 2-week washouts. Peripheral arterial tonometry (PAT), inflammatory markers, and muscle strength were assessed. In rats, CKD was associated with lower body weight and spontaneous activity; exercise was not associated with significant differences in systolic blood pressure, serum creatinine trajectories, or inflammatory cytokines. Clinically, PAT showed a significant group-by-intensity interaction (p = 0.0035), with the largest mean numerical increase from rest in HD after 60% MVC. Tumor necrosis factor-α (TNF-α) showed a significant interaction (p < 0.001), whereas interleukin-6 (IL-6) did not (p = 0.396). Muscle strength showed no consistent changes across exercise-intensity conditions. Heterogeneous vascular and inflammatory response patterns were observed across the fixed-sequence handgrip exercise conditions in HD. The non-HD participants were not age-matched to the HD group and were therefore treated as a reference group. These exploratory findings should not be interpreted as demonstrating a causal intensity-dependent effect and warrant confirmation in randomized studies.