Have We Just Scratched the Surface? A Narrative Review of Uremic Pruritus in 2020

Abstract

Purpose of review: Uremic pruritus is a highly prevalent and debilitating symptom in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD). The purpose of this review is to examine current evidence on the mechanisms and treatments of pruritus in CKD and highlight promising areas for future research. Sources of information: Published literature, including randomized controlled trials, cohort studies, case reports, and review articles, was searched for evidence pertaining to the pathophysiology and treatment of uremic pruritus. Methods: A comprehensive narrative review was conducted to explore the molecular mechanisms underlying uremic pruritus, as well as the evidence (or lack thereof) supporting pharmacological and nonpharmacological treatments for uremic pruritus. The potential role of patient sex in the pathophysiology and management of uremic pruritus is also discussed. Key findings: The pathophysiology of uremic pruritus involves a complex interplay of uremic toxins, systemic inflammation, mast cell activation, and imbalance of opioid receptors. Classic treatment strategies for uremic pruritus include optimization of dialysis parameters, amelioration of CKD-related mineral and bone disease, topical emollients and analgesics, antihistamines, the anticonvulsant medications gabapentin and pregabalin, and ultraviolet light B (UV-B) phototherapy. Strong data to support many of these classical treatments for uremic pruritus are limited. Newly evolving treatment approaches for uremic pruritus include opioid receptor modulators, neurokinin-1 inhibitors, and cannabinoids. Further studies regarding their efficacy, pharmacodynamics, and safety in the CKD and ESKD population are needed before these agents are accepted into widespread use. Additional nonpharmacological strategies aimed at treating uremic pruritus include psychotherapy, acupuncture, omega-3 fatty acids, and exercise. Finally, sex differences may exist regarding uremic pruritus, but studies directly addressing sex-specific mechanisms of uremic pruritus remain absent. Limitations: High-quality evidence in the management of uremic pruritus remains lacking. Most recommendations are based on expert opinion or studies involving small numbers of patients. In addition, our understanding of the pathophysiological mechanisms behind uremic pruritus is incomplete and continues to evolve over time. Implications: Uremic pruritus is a common symptom which reduces quality of life in CKD and ESKD. The identification of novel targeted treatment approaches may ease the burden of uremic pruritus in the future.

Epidemiology and burden of chronic kidney disease-associated pruritus

“…Chronic kidney disease–associated pruritus (CKD-aP) is defined as itch secondary to kidney disease, unexplained by alternate causes. Differential diagnoses such as hypersensitivity reactions, primary dermatological disorders, infection, haematological malignancies and cholestasis must be excluded [ 1 ]. The nomenclature has recently shifted away from ‘uraemic pruritus’ due to the non-linear relationship between itch and the degree of uraemia [ 2 ].…”

“…Several factors are thought to contribute to CKD-aP, including an immune-mediated response and nociceptive stimulation. However, its complex pathophysiology remains poorly understood [ 1 ]. CKD-aP is reported to affect up to 80% of patients with end-stage kidney disease (ESKD), with 40% experiencing moderate to severe itch [ 3 ].…”

“…The approach to therapy typically includes a combination of topical treatments, gabapentinoids, µ-opioid receptor antagonists and κ-agonists, antidepressants, alterations to dialysis and phototherapy. However, treatment responses to these therapies are variable [ 1 , 7 ].…”

The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

“…The prevalence of chronic renal insufficiency associated with pruritus (uremic pruritus) is high, affecting up to half of the patients undergoing dialysis [194]. The pathophysiology of uremic pruritus is unclear and multifactorial [195]. Therefore, multiple therapies have been used, including gabapentin, pregabalin, MC stabilizers, phototherapy, hemodialysis modifications, and multiple other systemic and topical treatments.…”

Chronic Intractable Pruritus in Chronic Kidney Disease Patients: Prevalence, Impact, and Management Challenges — A Narrative Review

“…[158][159][160][161] In addition, aromatherapy, stress-reduction techniques, psychotherapy, and physical exercises can be considered support strategies. 162 It is vital to emphasize that in no way can these alternative methods be currently regarded as the basic or only antipruritic modality in the CDK-aP population.…”