Association of pruritus with comorbidities and survival in chronic kidney disease: a narrative review of the pre-difelikefalin era literature

Pruritus is a frequent and distressing symptom in chronic kidney disease (CKD). This study aimed to evaluate the association between pruritus and comorbidities or survival in CKD before the approval of difelikefalin (DFK), a novel treatment for CKD-associated pruritus (CKD-aP). A systematic literature review was conducted using PubMed and Embase, including studies published between January 2000 and August 2022 that examined the link between CKD-aP and morbidity or survival in CKD. We analyzed 5,867 title/abstracts (3,541 from Pubmed, 2,313 from Embase, and nine additional articles) and excluded 5,721 references. Thirty-seven of the 146 articles that were eligible for full reading were included in the analysis. Thus, 18 identified a statistically significant association between CKD-aP and mortality. However, this association lost significance in 3 studies after adjusting for sleep. Two additional studies found no association between CKD-aP and mortality. In terms of sleep disturbance, 14 out of 15 studies reported a significant link with CKD-aP. Moreover, six studies demonstrated relationship between CKD-aP and cardiovascular events, which remained robust even after adjusting for diabetes. The connection between CKD-aP and mental health and depressive symptoms was investigated in 20 studies, with 18 confirming a significant association between the outcomes. Finally, six studies indicated that healthcare costs were higher in CKD-aP compared to those without. Pruritus appears to be associated with increased mortality, cardiovascular events, depressive symptoms, and healthcare costs in CKD patients. Early detection and treatment, particularly with new drugs like DFK, may improve patients' quality of life and reduce CKD-aP related.