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. 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 end-stage kidney disease (250 adults and 104 children) and 59 healthy controls using linear and nonlinear heart rate variability analyses. Pruritus severity was assessed using validated clinical scales. Compared with healthy controls, patients with end-stage kidney disease exhibited significant autonomic dysfunction, characterized by reduced overall heart rate variability and altered nonlinear heart rate variability parameters. Multivariable analyses identified distinct age-dependent heart rate variability signatures associated with uremic pruritus. In adults, the root mean square of successive differences and detrended fluctuation analysis alpha-2 emerged as independent correlates of pruritus. In children, root mean square of successive differences and the low-frequency power/high-frequency power ratio were independently associated with pruritus. Root mean square of successive differences showed the strongest and most consistent relationship with pruritus, correlating significantly with itch severity across all clinical scales in both age groups. Detrended fluctuation analysis alpha-2 was uniquely associated with pruritus in adults, whereas low-frequency power/high-frequency power 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.