Haemodialysis-Associated Pruritus
Severe itching experienced by patients undergoing haemodialysis for chronic kidney disease. The condition is undertreated and significantly impairs sleep and quality of life. Difelikefalin is administered intravenously after each dialysis session to control itching without the central side effects of traditional opioids.
Technical Context
CKD-associated pruritus (CKD-aP) in haemodialysis patients is often severe, chronic, and refractory to conventional antihistamines (because histamine is not the primary mediator). Pathophysiology: multifactorial — uraemic toxin accumulation (particularly protein-bound toxins not efficiently cleared by standard dialysis), systemic micro-inflammation (elevated CRP, IL-6, IL-31), peripheral neuropathy (C-fibre dysfunction), xerosis (dry skin from sweat gland atrophy), and altered endogenous opioid balance. Impact: sleep disturbance (reported in >60% of patients with moderate-severe pruritus), depression, reduced quality of life, and increased mortality risk (independent of other CKD factors). Difelikefalin dosing: 0.5μg/kg IV bolus into the venous blood line at the end of each haemodialysis session (3× weekly). This timing exploits the dialysis access for drug administration and synchronises dosing with the treatment schedule. SC difelikefalin formulation is in development for non-dialysis CKD-aP and other pruritic conditions.