Düll M, Kremer A (2026)
Publication Type: Authored book
Publication year: 2026
Publisher: Elsevier
ISBN: 9780443341724
DOI: 10.1016/B978-0-443-34172-4.00031-8
Pruritus is a frequent and burdensome symptom in individuals with chronic liver and kidney diseases. It is typically nonhistaminergic, does not respond to antihistamines, and often occurs in the absence of visible skin lesions, making diagnosis and management challenging. Recent advances have uncovered distinct molecular, neuronal, and immunological pathways that contribute to pruritus in these conditions. In chronic kidney disease-associated pruritus, disturbances in the calcium/phosphate homeostasis, accumulation of uremic toxins such as indoxyl sulfate and allantoin, cutaneous microinflammation, altered cutaneous innervation, and dysregulation of the opioid system have been implicated. The kappa-opioid receptor agonist difelikefalin has proven therapeutic efficacy in this setting. In liver disease-associated pruritus, bile acids, heme and progesterone metabolites, endogenous opioids, lysophosphatidic acid, and cytokines have emerged as major pruritogens. Mas-related G protein-coupled receptors (MRGPRs), particularly MRGPRX4 and MRGPRD, mediate nonhistaminergic itch, with bile acid subspecies and allantoin identified as respective agonists. Current treatment strategies focus on reducing bile acids, inhibiting bile acid transport, and targeting MRGPRs. This chapter provides an in-depth review of these mechanisms and their implications for developing novel treatment approaches to pruritus of chronic kidney and liver diseases.
APA:
Düll, M., & Kremer, A. (2026). Cholestatic and uremic itch. Elsevier.
MLA:
Düll, Miriam, and Andreas Kremer. Cholestatic and uremic itch. Elsevier, 2026.
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