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Safety of Dynamic Intravenous Iron Administration Strategies in Hemodialysis Patients.

ABSTRACT: BACKGROUND AND OBJECTIVES:Intravenous iron therapy for chronic anemia management is largely driven by dosing protocols that differ in intensity with respect to dosing approach (i.e., dose, frequency, and duration). Little is known about the safety of these protocols. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Using clinical data from a large United States dialysis provider linked to health care utilization data from Medicare, we constructed a cohort of patients with ESKD aged ?65 years who initiated and continued center-based hemodialysis for ?90 days between 2009 and 2012, and initiated at least one of the five common intravenous iron administration strategies; ranked by intensity (the amount of iron given at moderate-to-high iron indices), the order of strategies was 3 (least intensive), 2 (less intensive), 1 (reference), 4 (more intensive), and 5 (most intensive). We estimated the effect of continuous exposure to these strategies on cumulative risks of mortality and infection-related events with dynamic Cox marginal structural models. RESULTS:Of 13,249 eligible patients, 1320 (10%) died and 1627 (12%) had one or more infection-related events during the 4-month follow-up. The most and least commonly initiated strategy was strategy 2 and 5, respectively. Compared with the reference strategy 1, more intensive strategies (4 and 5) demonstrated a higher risk of all-cause mortality (e.g., most intensive strategy 5: 60-day risk difference: 1.3%; 95% confidence interval [95% CI], 0.8% to 2.1%; 120-day risk difference: 3.1%; 95% CI, 1.0% to 5.6%). Similarly, higher risks were observed for infection-related morbidity and mortality among more intensive strategies (e.g., strategy 5: 60-day risk difference: 1.8%; 95% CI, 1.2% to 2.6%; 120-day risk difference: 4.3%; 95% CI, 2.2% to 6.8%). Less intensive strategies (2 and 3) demonstrated lower risks of all-cause mortality and infection-related events. CONCLUSIONS:Among dialysis patients surviving 90 days, subsequent intravenous iron administration strategies promoting more intensive iron treatment at moderate-to-high iron indices levels are associated with higher risks of mortality and infection-related events.

SUBMITTER: Li X

PROVIDER: S-EPMC6500950 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Safety of Dynamic Intravenous Iron Administration Strategies in Hemodialysis Patients.

Li Xiaojuan X Cole Stephen R SR Kshirsagar Abhijit V AV Fine Jason P JP Stürmer Til T Brookhart M Alan MA

Clinical journal of the American Society of Nephrology : CJASN 20190415 5

<h4>Background and objectives</h4>Intravenous iron therapy for chronic anemia management is largely driven by dosing protocols that differ in intensity with respect to dosing approach (<i>i.e.</i>, dose, frequency, and duration). Little is known about the safety of these protocols.<h4>Design, setting, participants, & measurements</h4>Using clinical data from a large United States dialysis provider linked to health care utilization data from Medicare, we constructed a cohort of patients with ESKD ...[more]

PMID: 30988164

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Project description:Background and objectivesClinical 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, & measurementsThe 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.ResultsPatients 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).ConclusionsAmong 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.

Project description:Background and objectivesAnemia guidelines for CKD recommend withholding intravenous iron in the setting of active infection, although no data specifically support this recommendation. This study aimed to examine the association between intravenous iron and clinical outcomes among hemodialysis patients hospitalized for infection.Design, setting, participants, & measurementsThis was a retrospective observational cohort study using data from the US Renal Data System of 22,820 adult Medicare beneficiaries on in-center hemodialysis who had received intravenous iron in the 14 days preceding their first hospitalization for bacterial infection in 2010. In multivariable analyses, the association between receipt of intravenous iron at any point from the day of hospital admission to discharge and all-cause 30-day mortality, mortality in 2010, length of hospital stay, and readmission for infection or death within 30 days of discharge was evaluated.ResultsThere were 2463 patients (10.8%) who received intravenous iron at any point from the day of admission to discharge. Receipt of intravenous iron was not associated with age, dialysis vintage, or comorbidities. There were 2618 deaths within 30 days of admission and 6921 deaths in 2010 (median follow-up 173 days; 25th and 75th percentiles, 78-271 days). The median length of stay was 7 days (25th and 75th percentiles, 5-12 days). Receipt of intravenous iron was not associated with higher 30-day mortality (odds ratio, 0.86; 95% confidence interval [95% CI], 0.74 to 1.00), higher mortality in 2010 (hazard ratio, 0.92; 95% CI, 0.85 to 1.00), longer mean length of stay (10.1 days [95% CI, 9.7 to 10.5] versus 10.5 days [95% CI, 10.3 to 10.7]; P=0.05), or readmission for infection or death within 30 days of discharge (odds ratio, 1.08; 95% CI, 0.96 to 1.22) compared with no receipt of intravenous iron.ConclusionsThis analysis does not support withholding intravenous iron upon admission for bacterial infection in hemodialysis patients, although clinical trials are required to make definitive recommendations.

Project description:Anaemia in chronic kidney disease (CKD) is managed primarily with erythropoiesis-stimulating agents (ESAs) and iron therapy. Following concerns around ESA therapy, intravenous (IV) iron is being administered more and more worldwide. However, it is still unclear whether this approach is safe at very high doses or in the presence of very high ferritin levels. Some observational studies have shown a relationship between either high ferritin level or high iron dose and increased risk of death, cardiovascular events, hospitalization or infection. Others have not been able to confirm these findings. However, they suffer from indication biases. On the other hand, the majority of randomized clinical trials have only a very short follow-up (and thus drug exposure) and are inadequate to assess the mortality risk. None of them have tested the role of different iron doses on hard end points. With the lack of clear evidence coming from well-designed and large-scale studies, several data suggest that excessive iron therapy may be toxic in several aspects, ranging from iron overload to tissue damage from labile iron. A number of experimental and clinical data suggest that either excessive iron therapy or iron overload may be a possible culprit of atherogenesis. The process seems to be mediated by oxidative stress. Iron therapy should also be used cautiously in the presence of active infections, since iron is essential for bacterial growth. Recently, the European Medicines Agency officially raised concerns about rare hypersensitivity reactions following IV iron administration. The balance has been in favour of benefits. In several European countries, this has created a lot of confusion and somewhat slowed the run towards excessive use. Altogether, IV iron remains a mainstay of anaemia treatment in CKD patients. However, in our opinion, its excessive use should be avoided, especially in patients with high ferritin levels and when ESA agents are not contraindicated.

Dataset Information

Safety of Dynamic Intravenous Iron Administration Strategies in Hemodialysis Patients.

Publications

Safety of Dynamic Intravenous Iron Administration Strategies in Hemodialysis Patients.

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