Intravenous Iron Exposure and Mortality in Patients on Hemodialysis

Abstract

Background and objectives Clinical trials assessing effects of larger cumulative iron exposure with outcomes are lacking, and observational studies have been limited by assessment of short-term exposure only and/or failure to assess cause-specific mortality. The associations between short-and long-term iron exposure on all-cause and cause-specific mortality were examined.Design, setting, participants, & measurements The study included 14,078 United States patients on dialysis initiating dialysis between 2003 and 2008. Intravenous iron dose accumulations over 1-, 3-, and 6-month rolling windows were related to all-cause, cardiovascular, and infection-related mortality in Cox proportional hazards models that used marginal structural modeling to control for time-dependent confounding.Results Patients in the 1-month model cohort (n=14,078) were followed a median of 19 months, during which there were 27.6% all-cause deaths, 13.5% cardiovascular deaths, and 3% infection-related deaths. A reduced risk of all-cause mortality with receipt of .150-350 (hazard ratio, 0.78; 95% confidence interval, 0.64 to 0.95) or .350 mg (hazard ratio, 0.79; 95% confidence interval, 0.62 to 0.99) intravenous iron compared with .0-150 mg over 1 month was observed. There was no relation of 1-month intravenous iron dose with cardiovascular or infectionrelated mortality and no relation of 3-or 6-month cumulative intravenous iron dose with all-cause or cardiovascular mortality. There was a nonstatistically significant increase in infection-related mortality with receipt of .1050 mg intravenous iron in 3 months (hazard ratio, 1.69; 95% confidence interval, 0.87 to 3.28) and .2100 mg in 6 months (hazard ratio, 1.59; 95% confidence interval, 0.73 to 3.46).Conclusions Among patients on incident dialysis, receipt of #1050 mg intravenous iron in 3 months or 2100 mg in 6 months was not associated with all-cause, cardiovascular, or infection-related mortality. However, nonstatistically significant findings suggested the possibility of infection-related mortality with receipt of .1050 mg in 3 months or .2100 mg in 6 months. Randomized clinical trials are needed to assess the safety of exposure to greater cumulative intravenous iron doses.

Intravenous Iron Exposure and Outcomes in Patients on Hemodialysis

“…The study by Miskulin et al (14) also raises concern with respect to intravenous iron and infection. Iron is a key nutrient for microorganisms.…”

“…A relatively underpowered study of Taiwanese patients on dialysis found that intravenous iron doses .800 mg over 6 months were associated with a higher risk of mortality compared with lower doses (13). In this issue of CJASN, Miskulin et al (14) report on patients on hemodialysis treated at Dialysis Clinic Inc. facilities. The study used robust statistical methods to account for time-varying confounding (14).…”

“…In this issue of CJASN, Miskulin et al (14) report on patients on hemodialysis treated at Dialysis Clinic Inc. facilities. The study used robust statistical methods to account for time-varying confounding (14). The large number of subjects lost to follow-up or excluded might somewhat bias the results (14).…”

“…The study used robust statistical methods to account for time-varying confounding (14). The large number of subjects lost to follow-up or excluded might somewhat bias the results (14). In addition, the time period used for study (2003)(2004)(2005)(2006)(2007)(2008) was one where the use of intravenous iron was somewhat lower, with mean serum ferritin in this study approximately 30% lower than current United States mean values.…”

Iatrogenic iron overload and its potential consequences in patients on hemodialysis

“…Data from epidemiological studies [65][66][67][68]. On the contrary, three other epidemiological studies with longer follow-up (1 to 2 years) showed that excessive IV iron might be associated with increased mortality and cardiovascular events in hemodialysis patients [12][13][14].…”