Miskulin Dana C, Tangri Navdeep, Bandeen-Roche Karen, Zhou Jing, McDermott Aidan, Meyer Klemens B, Ephraim Patti L, Michels Wieneke M, Jaar Bernard G, Crews Deidra C, Scialla Julia J, Sozio Stephen M, Shafi Tariq, Wu Albert W, Cook Courtney, Boulware L Ebony
Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
Clin J Am Soc Nephrol. 2014 Nov 7;9(11):1930-9. doi: 10.2215/CJN.03370414. Epub 2014 Oct 15.
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.
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 infection-related 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).
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.
缺乏评估更大累积铁暴露对预后影响的临床试验，且观察性研究仅局限于短期暴露评估和/或未能评估特定病因死亡率。本研究对短期和长期铁暴露与全因死亡率及特定病因死亡率之间的关联进行了探究。
设计、地点、参与者及测量方法：本研究纳入了2003年至2008年间开始透析的14078例美国透析患者。在Cox比例风险模型中，采用边际结构模型控制时间依赖性混杂因素，将1个月、3个月和6个月滚动窗口内的静脉铁剂量累积与全因、心血管及感染相关死亡率进行关联分析。
1个月模型队列中的患者（n = 14078）中位随访时间为19个月，在此期间全因死亡率为27.6%，心血管死亡率为13.5%以及感染相关死亡率为3%。与1个月内静脉铁剂量>0 - 150 mg相比，接受>150 - 350 mg（风险比，0.78；95%置信区间，0.64至0.95）或>350 mg（风险比，0.79；95%置信区间，0.62至0.99）静脉铁的患者全因死亡率风险降低。1个月静脉铁剂量与心血管或感染相关死亡率无关，3个月或6个月累积静脉铁剂量与全因或心血管死亡率无关。3个月内接受>1050 mg静脉铁（风险比，1.69；95%置信区间，0.87至3.28）和6个月内接受>2100 mg静脉铁（风险比，1.59；95%置信区间，0.73至3.46）时，感染相关死亡率有非统计学意义的增加。
在新发透析患者中，3个月内接受≤1050 mg静脉铁或6个月内接受≤2100 mg静脉铁与全因、心血管或感染相关死亡率无关。然而，非统计学意义的结果提示3个月内接受>1050 mg或6个月内接受>2100 mg静脉铁可能存在感染相关死亡风险。需要进行随机临床试验来评估更大累积静脉铁剂量暴露的安全性。
