biostudies-literatureUnknown27(2)Dragos FThis systematic review examines chronic kidney disease-associated pruritus (CKD-aP) as a complex clinical manifestation in patients undergoing hemodialysis. Traditionally considered a secondary symptom of end-stage renal disease, emerging evidence now positions CKD-aP as a multidimensional disorder with substantial pathogenic influence on patient outcomes. Using the PRISMA 2020 methodology, we critically evaluated 54 peer-reviewed studies published between 2020 and 2025. Our synthesis highlights a convergence of five mechanistic frameworks underpinning CKD-aP: elevated levels of uremic toxins originating from gut microbial dysbiosis, immune activation driven by IL-31 and other pro-inflammatory cytokines, heightened peripheral and central neural sensitization, dysregulation of endogenous opInternational journal of molecular sciences851https://www.ebi.ac.uk/biostudies/studies/S-EPMC12840920biostudies-literatureChronic Kidney Disease-Associated Pruritus in Hemodialysis: Unraveling Mechanisms and Emerging Therapeutic Targets-A Systematic Review.PMC12840920Dragos FGabriel PFTatiana CLuana AFlorentin PMBogdan CTony HIulian MMihaela MLGeorgeta Camelia CAdrian NRLiliana-Ana TAndreea ALivia SIIuliana-Cezara TFlorin-Daniel EDaria AMStere PfalseChronic Kidney Disease-Associated Pruritus in Hemodialysis: Unraveling Mechanisms and Emerging Therapeutic Targets-A Systematic Review.This systematic review examines chronic kidney disease-associated pruritus (CKD-aP) as a complex clinical manifestation in patients undergoing hemodialysis. Traditionally considered a secondary symptom of end-stage renal disease, emerging evidence now positions CKD-aP as a multidimensional disorder with substantial pathogenic influence on patient outcomes. Using the PRISMA 2020 methodology, we critically evaluated 54 peer-reviewed studies published between 2020 and 2025. Our synthesis highlights a convergence of five mechanistic frameworks underpinning CKD-aP: elevated levels of uremic toxins originating from gut microbial dysbiosis, immune activation driven by IL-31 and other pro-inflammatory cytokines, heightened peripheral and central neural sensitization, dysregulation of endogenous op2026-01-01T00:00:00Z2026 Jan2026-06-09T03:17:56.378Z2026-06-09T03:11:43.242ZS-EPMC128409204159650010.3390/ijms27020851