Recent Advances in the Treatment of Uremic Pruritus

Aaron J. Trachtenberg; David Collister; Claudio Rigatto


Curr Opin Nephrol Hypertens. 2020;29(5):465-470. 

In This Article

Epidemiology and Outcomes

The exact prevalence of uremic pruritus is challenging to define because of the heterogeneity of definitions and measurement tools used to assess it. Our recent systematic review identified this heterogeneity of uremic pruritus definition/measurement as a major barrier to effectively summarizing the evidence and strongly recommended the use of standardized itch scales, preferably used together with tools to measure concomitant impacts of itch on function and quality of life, in future research.[7] Acknowledging this limitation, it is nevertheless still possible to estimate the approximate prevalence of uremic pruritus in kidney disease states. A systematic review and metaanalysis published in 2018, which included 42 cross-sectional studies comprising 11 800 patients with ESKD on dialysis across 16 different countries, estimated the prevalence of uremic pruritus to be 55% (95% confidence interval (CI): 49–61), albeit with significant heterogeneity between studies (range 18–98%) attributed to differing patient populations, differing definitions of uremic pruritus, and different measurement tools across studies.[12] Despite the heterogeneity, subgroup analyses were consistent across sex and modality categories: hemodialysis versus peritoneal dialysis.[12] Some reports suggest that hemodialysis patients tend to have higher rates of uremic pruritus than peritoneal dialysis patients,[13] which is consistent with our own clinical observations. Interestingly, countries such as China, Japan, and Pakistan report the highest rates of uremic pruritus, whereas Germany reports the lowest.[2,12,14–16] The reasons for this geographic variation are unknown.

Physicians often underestimate the prevalence and severity of uremic pruritus, partly because of patient underreporting.[2,17] A qualitative study recently identified lack of patient understanding about the link between CKD and itch, patient and physician attitudes minimizing the importance of itch as a symptom, and lack of prompts for itch assessment during clinical interactions, as key factors influencing underreporting of uremic pruritus.[18] It is important to remember that even for nondialysis CKD patients, pruritus is an important issue, with 24% of patients experiencing moderate to severe itch that impacts their sleep, mood, and overall quality of life.[1,2]

Several studies have shown an association between uremic pruritus and poor patient outcomes, including increased mortality.[5,16,19] A large cohort study using administrative data in over 75 000 Taiwanese patients found a modest increase in overall mortality (hazard ratio (HR) 1.05; 95% CI: 1.03, 1.07) cardiovascular mortality (HR 1.06; 95% CI: 1.02, 1.09), and infection-related death (HR 1.08; 95% CI: 1.05, 1.11) in dialysis patients with uremic pruritus; however, reliance on a treatment-based definition of uremic pruritus was an acknowledged limitation.[20] A retrospective cohort study of over 800 maintenance hemodialysis patients found a three-fold higher risk of cardiovascular mortality in patients with uremic pruritus after adjusting for important covariates, although the associations with overall and infection-related death were not significant.[21] Finally, a small prospective cohort study of 85 peritoneal dialysis patients demonstrated that a higher visual analog scale (VAS) score for pruritus was associated with an increased composite outcome of peritoneal dialysis technique failure or death.[22] A follow-up to the German Epidemiological Hemodialysis Itch Study also found that higher mean itch intensity on VAS was associated with increased mortality, although the association only persisted after adjustment for covariates in those patients with visible secondary scratch lesions on their skin.[16]

The association between itch and death may be mediated by insomnia and poor sleep quality.[19,23] There is mounting evidence that uremic pruritus impairs sleep, decreases quality of life, and worsens depressive symptoms in patients with CKD and ESKD.[1,24,25] One group has demonstrated a three-way correlation between uremic pruritus, impaired mental health, and elevated markers of systemic inflammation including C-reactive protein and IL-6,[26] suggesting a potential mechanism linking itch, its psychological effects, and mortality. Although a causal link between uremic pruritus and death is not yet established, routine assessment of itch with careful attention to modifiable cardiovascular risk factors in patients with uremic pruritus is probably reasonable.