IJMS, Vol. 27, Pages 851: Chronic Kidney Disease-Associated Pruritus in Hemodialysis: Unraveling Mechanisms and Emerging Therapeutic Targets—A Systematic Review

International Journal of Molecular Sciences doi: 10.3390/ijms27020851

Authors:
Fasie Dragos
Suliman Ioana Livia
Panculescu Florin Gabriel
Cimpineanu Bogdan
Alexandru Andreea
Alexandrescu Luana
Alexandrescu Maria Daria
Popescu Stere
Enache Florin-Daniel
Manac Iulian
Mihai Lavinia Mihaela
Popa Marius Florentin
Tudor Iuliana-Cezara
Nitu Radu Adrian
Chisnoiu Tatiana
Cozaru Georgeta Camelia
Hangan Tony
Tuta Liliana-Ana

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 opioid receptor pathways favoring μ-receptor activation, and xerosis-related epidermal barrier dysfunction. These mechanisms contribute to a systemic cycle of microinflammation, pruritogenic signaling, and neural hyperexcitability. We also identified and compared validated assessment tools—including the NRS, VAS, Skindex-10, and the UP-Dial scale—that facilitate standardized quantification of disease burden. While available treatments such as gabapentinoids and phototherapy offer partial relief, targeted therapies—including κ-opioid receptor agonists—represent a major advancement, although long-term effectiveness and accessibility remain under investigation. Growing scientific consensus establishes CKD-aP as a priority therapeutic target in hemodialysis care, underscoring the need for integrated, mechanism-based management strategies to improve quality of life and clinical outcomes. This work represents a narrative systematic review, integrating evidence from mechanistic, translational, and clinical studies to critically examine the biological pathways underlying CKD-associated pruritus.

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Fasie Dragos www.mdpi.com