Association of Sevelamer Initiation with Gastrointestinal Bleeding Hospitalization in Individuals Requiring Hemodialysis

Am J Nephrol. 2024;55(4):450-462. doi: 10.1159/000538253. Epub 2024 Mar 29.

Abstract

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 (vs. 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 1,000 person-years; IPTW-HR: 0.98, 95% CI: 0.91-1.06) or all-cause mortality (220 vs. 224 events per 1,000 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.

Keywords: Crystals; Dialysis; End-stage renal disease; Gastrointestinal bleed; Hemorrhage; Phosphate binders; Sevelamer.

MeSH terms

  • Aged
  • Chelating Agents* / adverse effects
  • Chelating Agents* / therapeutic use
  • Female
  • Gastrointestinal Hemorrhage* / epidemiology
  • Gastrointestinal Hemorrhage* / etiology
  • Hospitalization* / statistics & numerical data
  • Humans
  • Hyperphosphatemia / drug therapy
  • Hyperphosphatemia / etiology
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / mortality
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Renal Dialysis* / adverse effects
  • Sevelamer* / administration & dosage
  • Sevelamer* / adverse effects
  • Sevelamer* / therapeutic use

Substances

  • Sevelamer
  • Chelating Agents