Navdeep Tangri1, Dana C Miskulin2, Jing Zhou3, Karen Bandeen-Roche4, Wieneke M Michels5, Patti L Ephraim6, Aidan McDermott4, Deidra C Crews7, Julia J Scialla8, Stephen M Sozio7, Tariq Shafi7, Bernard G Jaar9, Klemens Meyer2, L Ebony Boulware10. 1. Division of Nephrology, Seven Oaks General Hospital, University of Manitoba, Winnipeg Manitoba, Canada. 2. Division of Nephrology, Tufts University School of Medicine, Boston, MA, USA. 3. Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA. 4. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 5. Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA Division of Nephrology, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 6. Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 7. Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 8. Division of Nephrology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. 9. Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA Nephrology Center of Maryland, Baltimore, MD, USA. 10. Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Abstract
BACKGROUND: Intravenous iron use in hemodialysis patients has greatly increased over the last decade, despite limited studies on the safety of iron. METHODS: We studied the association of receipt of intravenous iron with hospitalizations in an incident cohort of hemodialysis patients. We examined 9544 patients from Dialysis Clinic, Inc. (DCI). We ascertained intravenous iron use from DCI electronic medical record and USRDS data files, and hospitalizations through Medicare claims. We examined the association between iron exposure accumulated over 1-, 3- or 6-month time windows and incident hospitalizations in the follow-up period using marginal structural models accounting for time-dependent confounders. We performed sensitivity analyses including recurrent events models for multiple hospitalizations and models for combined outcome of hospitalization and death. RESULTS: There were 22 347 hospitalizations during a median follow-up of 23 months. Higher cumulative dose of intravenous iron was not associated with all-cause, cardiovascular or infectious hospitalizations [HR 0.97 (95% CI: 0.77-1.22) for all-cause hospitalizations comparing >2100 mg versus 0-900 mg of iron over 6 months]. Findings were similar in models examining the risk of hospitalizations in 1- and 3-month windows [HR 0.88 (95% CI: 0.79-0.99) and HR 0.88 (95% CI: 0.74-1.03), respectively] or the risk of combined outcome of hospitalization and death in the 6-month window [HR 0.98 (95% CI: 0.78-1.23)]. CONCLUSIONS: Higher cumulative dose of intravenous iron may not be associated with increased risk of hospitalizations in hemodialysis patients. While clinical trials are needed, employing higher iron doses to reduce erythropoiesis-stimulating agents does not appear to increase morbidity in routine clinical care.
BACKGROUND: Intravenous iron use in hemodialysis patients has greatly increased over the last decade, despite limited studies on the safety of iron. METHODS: We studied the association of receipt of intravenous iron with hospitalizations in an incident cohort of hemodialysis patients. We examined 9544 patients from Dialysis Clinic, Inc. (DCI). We ascertained intravenous iron use from DCI electronic medical record and USRDS data files, and hospitalizations through Medicare claims. We examined the association between iron exposure accumulated over 1-, 3- or 6-month time windows and incident hospitalizations in the follow-up period using marginal structural models accounting for time-dependent confounders. We performed sensitivity analyses including recurrent events models for multiple hospitalizations and models for combined outcome of hospitalization and death. RESULTS: There were 22 347 hospitalizations during a median follow-up of 23 months. Higher cumulative dose of intravenous iron was not associated with all-cause, cardiovascular or infectious hospitalizations [HR 0.97 (95% CI: 0.77-1.22) for all-cause hospitalizations comparing >2100 mg versus 0-900 mg of iron over 6 months]. Findings were similar in models examining the risk of hospitalizations in 1- and 3-month windows [HR 0.88 (95% CI: 0.79-0.99) and HR 0.88 (95% CI: 0.74-1.03), respectively] or the risk of combined outcome of hospitalization and death in the 6-month window [HR 0.98 (95% CI: 0.78-1.23)]. CONCLUSIONS: Higher cumulative dose of intravenous iron may not be associated with increased risk of hospitalizations in hemodialysis patients. While clinical trials are needed, employing higher iron doses to reduce erythropoiesis-stimulating agents does not appear to increase morbidity in routine clinical care.
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