Higher doses of intravenous (IV) iron do not appear to be associated with a greater risk for mortality and other adverse outcomes in dialysis patients, according to a new review and meta-analysis published online ahead of print in the Clinical Journal of American Society of Nephrology.
Navdeep Tangri, MD, PhD, of the University of Manitoba in Winnipeg, Canada, and collaborators analyzed data from 7 randomized controlled trials (RCTs) and 15 observational studies including more than 140,000 participants published on or before January 2017. The higher-dose IV iron group exceeded 200 and 400 mg per month in most of the observational studies and RCTS, respectively, and the lower-dose IV iron group fell below 200 mg per month.
The investigators observed no greater risks for mortality, infections, cardiovascular events, or hospitalizations in higher-dose IV iron recipients compared with the lower-dose group in either the RCTs or observational studies.
“From a clinical perspective, our findings on the basis of the currently available literature suggest that use of higher doses of intravenous iron in patients treated with dialysis may not increase risk of infections, hospitalizations, cardiovascular events, or mortality, although further study is warranted,” Dr Tangri and his colleagues stated.
In a discussion of study limitations, they noted that only 3 studies included patients on peritoneal dialysis, a population in which IV iron is used less frequently. In addition, most studies were conducted in the United States, so applicability to other settings may be limited given differences in patient mix across countries. The investigators pointed out that they did not specifically evaluate IV iron dosing in the context of IV iron strategies (bolus vs maintenance), “but there is presumably an overlap that could not be addressed due to a lack of individual patient data.”
In an accompanying editorial, Xiaojuan Li, PhD, MSPH, of Harvard Medical School in Boston, and Abhijit V. Kshirsagar, MD, MPH, of the University of North Carolina in Chapel Hill, pointed out that although the RCTs did not show significant statistical heterogeneity, “there seems to be important clinical differences among the studies.” They noted, for example, that the studies span 20 years of clinical practice and are potentially subject to the changing consensus on erythropoiesis-stimulating agents (ESAs) and target hemoglobin levels. The editorialists pointed out that the ESA strategies for individual studies listed in a table in the new paper vary widely, “with some being highly prescriptive and others having great latitude.”
In addition, Drs Li and Kshirsagar noted that the known benefits of any IV iron relate to their effects on erythropoiesis, ESA dosing, and possibly the need for blood transfusions, but little is known, about the benefit of high-dose vs low-dose IV iron on these outcomes.
Hougen I, Collister D, Bourrier M, et al. Safety of Intravenous Iron in Dialysis: A Systematic Review and Meta-Analysis. Clin J Am Soc Nephrol 2018;13. doi:10.2215/CJN.05390517
Li X and Kshirsagar AV. Rest Easy with Intravenous Iron for Dialysis Patients? High Dose IV Iron Safety. Clin J Am Soc Nephrol 2018;13. doi:10.2215/CJN.00930118