Abstract
BACKGROUND: Vitamin D deficiency (VDD) is prevalent in patients with secondary hyperparathyroidism (SHPT) undergoing dialysis and may attenuate the efficacy of calcimimetic therapy, which is designed to reduce parathyroid hormone (PTH) levels and improve clinical outcomes. This study aimed to investigate the impact of vitamin D status on all-cause mortality, major adverse cardiovascular events (MACEs), fractures, and hypocalcemia in dialysis patients receiving calcimimetics. METHODS: This retrospective cohort study utilized the TriNetX database to identify dialysis patients treated with calcimimetics between 2010 and 2024. Patients were classified into VDD (<20 ng/mL) and vitamin D-adequate (VDA, ≥30 ng/mL) groups. Propensity score matching (1:1) was performed on 95 covariates to minimize confounding. Outcomes, including all-cause mortality, MACEs, fractures, hypocalcemia, and PTH suppression (≤300 pg/mL), were compared between groups over a 3-year follow-up. Multiple comparisons were adjusted using the Bonferroni-Holm correction. RESULTS: All-cause mortality was significantly higher in the VDD group (25.4%) compared to the VDA group (20.9%), with an adjusted odds ratio (OR) of 1.29 (95% CI: 1.10-1.51, p = 0.002, corrected α = 0.007). While initial analyses suggested associations between VDD and the increased risks of MACEs, fractures, and hypocalcemia, these results did not remain significant after correction. Subgroup analysis indicated that comorbidities, such as obesity, dyslipidemia, and depression, amplified these risks in the VDD group. No significant differences were observed for PTH suppression (≤300 pg/mL) between groups. CONCLUSIONS: VDD is independently associated with increased all-cause mortality in dialysis patients with SHPT, even after multiple comparison adjustments. While risks for MACEs, fractures, and hypocalcemia showed non-significant trends, their observed patterns suggest potential clinical relevance. Optimizing vitamin D status may enhance clinical outcomes in this high-risk population, warranting further investigation through randomized controlled trials.