Supplementary Material for: Association of Sevelamer Initiation with Gastrointestinal Bleeding Hospitalization in Individuals Requiring Hemodialysis

Introduction
Case reports have suggested a causative role between sevelamer use and subsequent gastrointestinal bleeding (GIB), but no large observational studies have evaluated this association.

Methods
Using the United States Renal Data System database from 2015 to 2019, we examined the association between initiation of sevelamer (versus non-sevelamer containing phosphate binders) and GIB hospitalization as well as all-cause mortality among individuals on hemodialysis. We emulated a target trial using Cox regression models and inverse probability of treatment weights to estimate the adjusted hazard ratios (HR) across outcomes and subgroups.

Results
Among 21,354 new users of phosphate binders (11,276 sevelamer and 10,078 non-sevelamer) with baseline lab data (calcium, phosphorus, hemoglobin, and albumin), there were 2,811 GIB hospitalizations and 5,920 deaths after a median follow-up of 1.3 years. Compared with the initiation of non-sevelamer binders, sevelamer was not associated with an increased risk of GIB hospitalization (89 vs. 90 events per 1000 person-years; IPTW-HR 0.98, 95% CI 0.91 – 1.06) or all-cause mortality (220 vs. 224 events per 1000 person-years; IPTW-HR 0.98 95% CI 0.93 – 1.03). Subgroup analyses (such as diabetes and anti-coagulation use) were generally consistent, and there was no association between sevelamer dose and GIB hospitalization.

Conclusion
Among patients requiring hemodialysis, sevelamer (vs non-sevelamer) containing phosphate binders was not associated with increased risk of GIB hospitalization.