Abstract
Chronic kidney disease-associated pruritus (CKD-aP) is a prevalent and challenging symptom in patients with CKD and end-stage renal disease (ESRD). The aim of this review is to update existing evidence on the pathogenesis and treatments of pruritus in CKD and to shed light on areas that hold promise. The uncertain pathogenesis, and thus seemingly miscellaneous causes, identifies chronic itch as an important challenge in health care. A complex interaction of uremic toxin accumulation, micro and systemic inflammation, dysregulation of the opioid system, and mast cell activation may each contribute to the pathophysiology of CKD-aP. No highly satisfactory antipruritic therapeutics are available. Difelikefalin, considered to be a peripherally acting highly selective kappa-opioid receptor agonist, has been shown to have a positive impact on CKD-aP. Approved by the FDA in 2021 for intravenous administration, difelikefalin remains the most recent drug available. A developing area is that altered hemoglobin metabolism may lead to the activation of mas-related G protein-coupled receptors (MRGPRs). As this family of receptors is associated with itch, it is possible that drugs that target certain MRGPRs may be of future benefit in CKD-aP.