Uremic Pruritus in Hemodialysis: Mechanisms, Burden, and Emerging Therapies

<b>Background/Objectives:</b> Uremic pruritus is a common complication in patients with end-stage kidney disease undergoing maintenance hemodialysis. Despite its high prevalence and substantial impact on sleep, psychological well-being, and overall quality of life, its pathophysiology remains multifactorial and incompletely understood. This narrative review summarizes contemporary evidence (2015-2025) on therapeutic strategies for uremic pruritus, with an emphasis on emerging treatments and evolving mechanistic insights. <b>Methods:</b> A PubMed search was conducted for original clinical studies published between 1 January 2015, and 31 October 2025, evaluating treatments for uremic pruritus in adult hemodialysis patients. Eligible study designs included randomized controlled trials and observational interventional studies. Non-English articles, pediatric studies, peritoneal dialysis studies, reviews, case reports, and studies of mixed-etiology pruritus were excluded. Earlier literature was reviewed to contextualize epidemiology and pathophysiology. <b>Results:</b> The review identifies multiple interacting mechanisms-including uremic toxins, immune dysregulation, mineral abnormalities, xerosis, neuropathic changes, and dysregulated opioid signaling-contributing to itch generation. Topical therapies, especially emollients and humectants, consistently improved symptoms with excellent safety profiles. Optimization of dialysis adequacy and membrane selection showed benefit in selected patients. Among systemic therapies, gabapentinoids demonstrated the most robust efficacy but required cautious dosing. Sertraline, nalbuphine, and difelikefalin showed significant antipruritic effects in controlled trials. Emerging therapies, including AST-120, omega-3 fatty acids, and the biologic dupilumab, demonstrated promising but preliminary results. <b>Conclusions:</b> Management of uremic pruritus requires a multifaceted, individualized approach integrating skin-directed therapies, dialysis optimization, and targeted systemic treatments. Ongoing research is needed to identify reliable biomarkers and to develop safer, more effective, mechanism-based therapies.