CKD-Associated Pruritus and Clinical Outcomes in Nondialysis CKD

Rationale & Objective Itching is a frequent symptom experienced by people with chronic kidney disease (CKD). We investigated the associations of CKD-associated pruritus (CKD-aP) with clinical outcomes. Study Design Longitudinal cohort study. Setting & Participants Patients from Brazil, France, and United States (US) enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) from 2013-2021, an international prospective cohort study of adults with non-dialysis dependent CKD and an eGFR <60 mL/min/1.73m2. Exposure CKD-aP was self-reported by response to the question : During the past 4 weeks, to what extent were you bothered by itchy skin? Outcomes CKD progression, kidney replacement therapy (KRT) initiation, mortality, hospitalization, cardiovascular events, infection events. Analytical Approach Associations with time-to-event outcomes were investigated using Cox proportional hazards models adjusted for potential confounders. Results There were 4410 patients from 91 clinics with a median age of 69 years and median eGFR at patient questionnaire completion of 29 (21-38) mL/min/1.73m2. The proportion of patients not at all, somewhat, moderately, very much, and extremely bothered by itchy skin was 49%, 27%, 13%, 7%, and 3%, respectively. Patients with more advanced stages of CKD, older age, and greater comorbidity burden were more likely bothered by itchy skin. Among patients at least moderately bothered, 23% were prescribed at least one pharmacotherapy – 35% in US, 19% in France, 4% in Brazil – including antihistamine (10%), gabapentin (6%), topical corticosteroids (4%), pregabalin (3%), or sedating antihistamine (3%). The hazard ratio (95% CI) for patients extremely (vs. not at all) bothered was 1.74 (1.11, 2.73) for all-cause mortality, 1.56 (1.11, 2.18) for all-cause hospitalization, and 1.84 (1.22, 2.75) for cardiovascular events. As CKD-aP severity increased, patients also had higher rates of infection events (p=0.04); CKD-aP severity was not associated with KRT initiation (p=0.20) or CKD progression (p=0.87). Limitations 25% non-response; recall bias; residual confounding Conclusions These results demonstrate a strong association between severe itch and clinical outcomes, providing the nephrology community new insights into the possible adverse consequences of CKD-aP in individuals with non-dialysis CKD, and warrant further exploration.