The incidence of chronic itch in patients on haemodialysis and associated factors

Dear Editor, Chronic itch (CI) is a frequent symptom in many skin diseases and also occurs in a number of systemic diseases, such as chronic kidney disease. CI is very bothersome for patients on haemodialysis (HD) in particular, and this symptom is still not well understood and can be difficult to treat.1, 2 Today there are few treatment options, and these have a moderate effect on CI in patients on HD.3 However, difelikefalin, a selective κ-opioid receptor agonist, was positively evaluated in a recent placebo-controlled phase III trial for the treatment of CI in patients on HD.4 A previous study that investigated patients in 12 Western countries has reported that up to 45% of all patients on HD were bothered by itch, at least to a moderate degree.5 The German Epidemiological Hemodialysis Study (GEHIS) was initiated in 2013 in order to assess the prevalence of CI together with associated factors. It was the first prospective cross-sectional observational study worldwide to determine the prevalence of CI in a geographically representative cohort using standardized prevalence measures. Overall, 860 patients on HD were investigated in 25 randomly selected German dialysis units. CI was defined as itch lasting 6 weeks or longer. A follow-up study on the patients of the GEHIS population was performed in 2017. We assessed several factors including sociodemographic criteria, status of the skin, health-related quality of life, general health status, comorbidities, dialysis characteristics and laboratory values at follow-up, together with the number of incident CI cases in patients on HD. Of the 626 baseline patients from the GEHIS population without CI in 2013, 263 patients (42.0%) had died, 31 patients (5.0%) had received a kidney transplant, 36 patients (5.8%) had changed HD unit, 10 patients (1.6%) refused to participate again, six patients (0.9%) were unable to participate owing to cognitive limitations and 15 patients (2.4%) were not included for other reasons (e.g. hospitalization). The remaining 265 patients were surveyed. The mean patient age was 68.2 years (SD 13.4) and 41.1% of the sample were female. The patients were on HD treatment for a mean duration of 54 months (SD 52). Overall, 47 patients on HD developed CI in the 3 years between baseline and follow-up study visit, resulting in a 3-year cumulative incidence of 17.7% (95% confidence interval 13.2–22.3). None of the demographic characteristics assessed were associated with the incidence of CI in the previous 3 years, except for the number of patients with a college or university degree, which was slightly increased in the group with incident CI. Incident CI was not associated with the occurrence of any skin disease or any secondary scratch lesions. CI in patients on HD was not associated with atopy (atopic dermatitis, hay fever, allergic rhinitis), dry skin or any of the comorbidities assessed at baseline (Table 1). The occurrence of CI was associated with slightly lower calcium serum levels (2.2 vs. 2.1 mmol L−1) and with higher serum alanine transaminase (ALT) levels at baseline investigation in 2013 (17.1 vs. 20.9 U L−1). At follow-up, ALT values were higher in patients with incident CI and mean alkaline phosphatase serum levels were also increased in patients on HD with incident CI (93.7 vs. 122.8 mmol L−1). The difference in calcium levels found in 2013 was no longer significant in 2017. When intraindividual paired t-tests were performed, patients with incident CI showed a significant decrease in parathormone levels at follow-up (−108.8 ng L−1), while potassium levels increased in these patients (+0.36 mmol L−1); these effects were not seen in patients without incident CI (+11.7 ng L−1 and +0.007 mmol L−1, respectively). With respect to the patient-reported outcomes, higher anxiety scores in 2013 (5.7 vs. 4.2) were associated with the incidence of CI (P < 0.05). There was no association between incident CI and depression or anxiety, nor was there an association between incident CI and the 12-Item Short Form Survey score. Our follow-up study showed that the 3-year cumulative incidence of CI in patients on HD is 17.7%. This result is of great importance because CI in HD is impairing (e.g. sleep), severe and long-lasting; 50% of those patients are affected by CI for longer than 3 years,6 which highlights the need for improved treatment of CI in patients on HD. Some limitations need to be considered when interpreting our results. Owing to the high mortality in this sample, it is likely that some incident cases had died prior to follow-up. Another limitation is the 3-year retrospective assessment of incident CI; recall bias may have influenced the results, especially in a group of chronically ill patients such as patients on HD. Younger patients have a higher chance of receiving a kidney transplant and are therefore more likely to have droppped out at our follow-up. The high incidence of CI in patients on HD, as documented in this study, should encourage nephrologists and dermatologists to intensify research activities in this field. Upcoming studies should focus on a narrow monitoring of laboratory values in patients on HD in order to further explore their association with the incidence of CI. Acknowledgments: Open Access funding enabled and organized by Projekt DEAL Robert Ofenloch: Formal analysis (equal); investigation (equal); methodology (equal); software (equal); validation (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal). Katarzyna Grochulska: Data curation (equal); investigation (equal); project administration (equal); writing – review and editing (equal). Thomas Mettang: Investigation (equal); supervision (equal); validation (equal); writing – review and editing (equal). Elke Weisshaar: Conceptualization (equal); data curation (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); supervision (equal); validation (equal); writing – review and editing (equal).