Chronic kidney disease-associated pruritus (CKD-aP) is a debilitating condition that affects nearly half of patients undergoing dialysis, significantly impairing their quality of life (QoL), and requires multidisciplinary care, suggests a Singapore study.
“A stepwise, algorithmic approach—including screening, exclusion, and patient-reported outcome measures (PROM)-based severity assessment—can enhance physician awareness and support personalized management plans,” said lead author Dr Sye Nee Tan, Renal Medicine Department, Sengkang General Hospital, Singapore, and colleagues.
Due to lack of awareness and diagnostic guidelines, CKD-aP often goes unnoticed. Experts in Singapore then proposed a three-step, simplified diagnostic algorithm: screening, diagnosis, and severity assessment. [Clin Kidney J 2021;14:i8-i15; Clin Kidney J 2021;14:i16-i22]
Assessment
Screening may begin with a single question, such as “Do you itch?” or “Have you experienced itch recently?” This approach facilitates early symptom recognition since it is easy to understand among patients and to use by healthcare professionals. [Kidney Med 2021;3:42-53.e1]
“It encourages multidisciplinary involvement in symptom monitoring as it can be readily adopted not only by busy physicians in polyclinics but also by nephrologist in ward round and dialysis nurses in dialysis centres,” Tan and colleagues said.
During diagnosis, attending physicians can exclude other potential causes through a thorough clinical history and physical examination. They must be able to rule out conditions including primary dermatological disorders (xerosis, atopic dermatitis), or secondary causes including hepatic disorders, and neuropathic or psychogenic pruritus. [Proc Singap Healthc 2026;doi:10.1177/20101058261451643]
Finally, assessing CKD-aP severity must include validated PROMs to measure both itch intensity and its impact on QoL. [Kidney Int Rep 2020;5:1387-1402; J Dermatol 2021;48:e399-e413]
“Their main clinical utility is to facilitate the monitoring and treatment response,” according to Tan and colleagues. [J Clin Med 2023;12:4505]
Treatment
For the treatment of CKD-aP, a stepwise approach is currently being followed by physicians. This strategy begins with topical emollients and antihistamine for mild cases, followed by systemic agents such as gabapentinoids or κ-opioid receptor (KOR) agonists (eg, difelikefalin) for moderate-severe pruritic cases, and progressing to adjunctive options (eg, phototherapy or acupuncture) for treatment-resistant cases.
“CKD-aP may be partly reversible, as successful renal transplantation has been shown to significantly reduce its prevalence,” wrote Tan and colleagues. [J Pain Symptom Manag 2012;44:229-238]
The KOR agonist difelikefalin delivers pruritus relief with no adverse effect typically associated with mu-opioid stimulation. It is the first treatment approved by the US Food and Drug Administration, the European Medicines Agency, and the Health Sciences Authority of Singapore for moderate-to-severe CKD-aP. [Kidney Med 2022;4:100512]
“While effective therapies like difelikefalin exist, their use is limited by cost and unfamiliarity,” the authors said.
“Interdisciplinary collaboration in optimizing patient-centred care via a combination of pharmacological and nonpharmacological interventions remains the cornerstone of CKD-aP management,” they added.
Pathophysiology
One of the potential causes of CKD-aP is the accumulation of uraemic toxins. Pruritogenic toxins like aluminium, phosphorus, and vitamin A deposit in the skin, resulting in local inflammation and pruritus. In haemodialysis patients, the main contributor to pruritus intensity is inadequate dialysis clearance. [Kidney Res Clin Pract 2022;42:39-52; PLoS One 2013;8:e71404]
Peripheral neuropathy, in which damaged small nerve fibres are activated out of proportion, is another possible causative factor. With an impaired autonomic regulation, pruritic stimuli appeared to be enhanced through central and peripheral mechanisms. [Kidney Int Rep 2020;5:1387-1402; Exp Dermatol 2002;11:12-24]
Another potential factor is inflammatory dysregulation, wherein elevated levels of interleukin (IL)-31, IL-4, and IL-13 activate pruritogenic pathways. [Kidney Int Rep 2020;5:1387-1402; Exp Dermatol 2002;11:12-24]
“Lastly, a recent and crucial discovery in the pathogenesis of CKD-aP involves dysfunction of the opioid receptor system, which has led to the development of targeted KOR agonists,” Tan and colleagues said. “KOR which has antipruritic effect are reduced, while mu-opioid receptors … are overstimulated.” [J Eur Acad Dermatol Venereol 2020;34:2368-2372]
Study details
This narrative review was conducted using the databases of PubMed, Scopus, and Google Scholar. The researchers selected studies based on clinical relevance, methodological rigor, and focus on validated PROMs and therapeutic trials, particularly those involving gabapentinoids and KOR agonists.
Both nephrology and dermatology specialists reviewed key topics and collaborated to develop a synthesized management algorithm and treatment summary table through expert discussions.
“Future priorities should include improving access, comparing available treatments, exploring alternative drug delivery routes, and integrating QoL assessments into routine care,” wrote Tan and colleagues.