Supplementary Material for: Association between antihistamine use and clinical outcomes in patients on maintenance hemodialysis

Introduction: H1-antihistamines are frequently used to treat pruritus in patients on dialysis, but their safety remains unclear. This study aimed to evaluate the effects of H1-antihistamine use on outcomes in patients undergoing maintenance hemodialysis (HD). Methods: This retrospective cohort study included adult patients undergoing HD identified through national HD quality assessment programs. Patients were grouped by H1-antihistamine use over 6 months: No prescription, Short (<60 days), and Long (≥60 days) groups. Outcomes included all-cause mortality, cardiovascular events (CVE), atrial fibrillation (AF), dementia, and Parkinson’s disease. Cox regression was used to estimate hazard ratios (HRs). Results: Among 71,540 patients, 22.9%, 34.4%, and 42.6% were classified into the No prescription, Short, and Long groups, respectively. H1-antihistamine use was associated with higher risks of adverse outcomes, with significantly greater HRs in the Long group than in the Short group. Compared to the No prescription group, the adjusted HRs (95% confidence interval) in the Long group were 1.12 (1.08–1.15) for all-cause mortality, 1.17 (1.12–1.23) for CVE, 1.06 (1.01–1.12) for AF, 1.31 (1.23–1.41) for dementia, and 1.47 (1.30–1.67) for Parkinson’s disease. These associations remained consistent irrespective of insomnia status, except for AF, where increased risk was only observed in patients without insomnia. First-generation antihistamines were linked to greater risks of all-cause mortality, CVE, and dementia, but not for AF and Parkinson’s disease, compared to second-generation agents. Conclusions: H1-antihistamine use, particularly long-term use and first-generation agents was associated with increased risks of adverse outcomes in patients undergoing HD. These findings suggest that antihistamine use may represent a potential risk marker in this population; however, the observed associations may reflect the presence or severity of pruritus rather than that of a direct causal effect.