Pruritus is a common symptom among patients with advanced chronic kidney disease (CKD), particularly those undergoing dialysis. Self-reported prevalence is 25% among individuals with nondialysis-dependent CKD and 40% among those receiving dialysis. The restlessness and discomfort that accompany pruritus make it a leading research priority for patients with advanced CKD.
However, characterization of pruritus burden is lacking, as is identification of populations at risk. Most previous research focuses on patients receiving hemodialysis (HD) rather than peritoneal dialysis (PD) and relies on self-reporting of symptoms.
Anne-Laure Faucon, MD, PhD, and colleagues studied a large cohort of patients receiving maintenance dialysis in Stockholm, Sweden, to quantify the population at risk for pruritus, their clinical determinants, and associated adverse health outcomes. The results were published in the American Journal of Kidney Diseases.
Their observational study incorporated data from the Stockholm Creatinine Measurement (SCREAM) study, a health care use cohort of the total population of the Stockholm area. The study included all patients initiating or receiving maintenance dialysis (HD or PD) from 2005 to 2021. The date of the first registered annual visit recorded in the Swedish Renal Registry was denoted as the index date (baseline) and the start of follow-up.
The study comprises two analyses. The outcome of the first analysis was clinically recognized pruritus, and the authors evaluated its prevalence, incidence, and primary baseline determinants. The second analysis considered pruritus to be a time-varying exposure and analyzed the association between prevalent or new-onset pruritus and a variety of adverse health outcomes (all-cause mortality, severe infection–related hospitalizations, de novo anxiety and depression, and sleep disorders).
The researchers assessed the baseline clinical determinants of prevalent pruritus using multivariable logistic regression. They used a multivariable cause-specific hazards model to evaluate new-onset pruritus overall and by dialysis modality. They then analyzed the association between pruritus and adverse health outcomes using time-varying cause-specific hazards models. Subgroup analyses were conducted to evaluate the consistency of results by age, sex, presence or absence of cardiovascular disease, diabetes, and dialysis modality. Sensitivity analysis was also performed.
A total of 3,281 patients receiving maintenance dialysis during 2005-2021 were identified. Of these patients, 77% had been receiving dialysis for less than one year at baseline. The median age of patients was 64 years, 66% were men, 69% were receiving HD, and the mean dialysis duration was 2.2 years.
At baseline, 456 (13.9%) patients had clinically recognized pruritus. Of those patients, 14.8% were receiving HD and 12.0% were receiving PD. International Classification of Diseases, Tenth Revision (ICD-10) codes were used to identify 36% of pruritus cases, and the other 64% were identified by initiation of pruritus treatment. Patients with pruritus were more often receiving HD, were older, were more likely to be women, and had a higher prevalence of cardiovascular disease, anxiety or depression, sleep disorders, and skin infections than patients without pruritus.
Median follow-up was 3.3 years (interquartile range, 1.3-9.2), during which 539 (19.1%) patients who did not have pruritus at baseline (21.2% of patients receiving HD and 14.4% receiving PD) developed the condition. Total period prevalence of pruritus was 33%, and it was higher among patients receiving HD than those receiving PD (36.0% vs 26.4%; P<.01). Overall, 19.3% of incident cases were identified through ICD-10 codes, and the remainder were identified by initiation of pruritus treatment.
Clinical determinants of both prevalent and new-onset pruritus included older age; female sex; higher levels of C-reactive protein, serum calcium, and phosphate; and a lower level of serum albumin. Diabetes, however, was associated only with prevalent pruritus. Determinants were consistent across dialysis modality and dialysis vintage, although confidence intervals were broad.
During the follow-up period, 1,532 deaths, 949 infection-related hospitalizations, 328 new cases of anxiety or depression, and 485 new cases of sleep disorders occurred. Pruritus was not associated with the risk of all-cause mortality. However, pruritus was associated with higher risks of de novo anxiety and depression (adjusted hazard ratio [aHR], 1.56; 95% CI, 1.23-1.98) and sleep disorders (aHR, 1.96; 95% CI, 1.60-2.39) and with the risk of subsequent severe infections (aHR, 1.36; 95% CI, 1.18-1.57).
The results were consistent across subgroups by age, sex, diabetes, cardiovascular disease, and dialysis modality. Pruritus was associated with adverse health outcomes even when patients with prevalent pruritus at enrollment were excluded or the study population was limited to patients receiving incident dialysis. When pruritus was defined strictly by ICD-10 codes or by initiation of pruritus treatment, similar trends occurred.
The authors acknowledge limitations of the study, including its observational nature, which may result in residual time-varying confounding; potential misclassification bias if pruritus is unreported or unrecognized or because medications for pruritus are nonspecific; and the lack of assessment of pruritus intensity and severity, the relationship between pruritus and the type of vascular access, and validation of the approach to identifying pruritus.
In summary, this study highlights the prevalence of pruritus among patients receiving dialysis, identifies at-risk patient populations, and demonstrates that pruritus is linked to a high risk of adverse health outcomes. The findings support periodic pruritus screening, particularly among high-risk patients, and personalized management, which may include “optimization of dialysis, treatment of CKD-associated mineral and bone disease, extemporaneous compounded topical preparations, systemic pharmacological treatments, UV therapy, and, in HD, difelikefalin, a recently introduced selective agonist of κ-opioid receptors.”
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