Difelikefalin for Uraemic Pruritus — RACP Adult Medicine MCQ

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HardNephrologyDifelikefalin for Uraemic PruritusRACP Adult Medicine

A 55-year-old woman with CKD stage 5 on haemodialysis develops intense generalised pruritus refractory to emollients, antihistamines, and gabapentin. She has elevated phosphate (2.5 mmol/L) and PTH (800 pg/mL). What emerging therapy has demonstrated efficacy for uraemic pruritus?

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Correct answer: B — Difelikefalin (kappa-opioid receptor agonist)

Difelikefalin is a selective peripheral kappa-opioid receptor agonist that has demonstrated significant efficacy for moderate-to-severe uraemic pruritus in haemodialysis patients (KALM-1 and KALM-2 trials). It is administered IV post-dialysis. Unlike mu-opioid agonists, it does not cross the blood-brain barrier and has no CNS effects or abuse potential. It received TGA provisional approval in 2024 for this indication. Other options include UV-B phototherapy (effective but logistically difficult for dialysis patients) and optimisation of CKD-MBD management.

Reference: KDIGO – 2024 – Uraemic Pruritus; AMH – 2025 – Difelikefalin