Distinct Heart Rate Variability Signatures Characterize Uremic Pruritus in Adults and Children

Uremic pruritus is a common and debilitating complication of end-stage kidney disease (ESKD). Although autonomic dysfunction is prevalent in kidney failure, its relationship with chronic itch remains poorly understood. We conducted a cross-sectional study to investigate autonomic function in 354 kidney transplant candidates with ESKD (250 adults and 104 children) and 59 healthy controls using linear and nonlinear heart rate variability (HRV) analyses. Pruritus severity was assessed with validated clinical scales. Compared with healthy controls, patients with ESKD exhibited significant autonomic dysfunction, characterized by reduced overall HRV and altered nonlinear HRV parameters. Multivariable analyses identified distinct age-dependent HRV signatures associated with uremic pruritus. In adults, the root mean square of successive differences (RMSSD) and detrended fluctuation analysis alpha-2 (DFA α2) emerged as independent correlates of pruritus. In children, RMSSD and the low-frequency power/high-frequency power (LF/HF) were independently associated with pruritus. RMSSD showed the strongest and most consistent relationship with pruritus, correlating significantly with itch severity across all clinical scales in both age groups. DFA α2 was uniquely associated with pruritus in adults, whereas LF/HF was specific to pediatric cases. These findings identify autonomic dysregulation as a feature of uremic pruritus and reveal age-dependent autonomic signatures associated with itch.