Improving the safety of intravenous iron treatments for patients with chronic kidney disease

ABSTRACT

Introduction: Iron-deficiency anemia in chronic kidney disease (CKD) is common and has prognostic, financial, and quality of life implications. Intravenous (IV) iron is a key intervention for optimal management, however, ongoing safety concerns exist.

Area covered: The potential side effects associated with IV iron use are addressed as we review the most recent studies. Hypersensitivity reactions and true anaphylaxis are indeed rare with a greater understanding of the nature of labile iron and ‘Fishbane’ reactions. Hypophosphatemia appears commoner with certain IV iron preparations, however its significance in CKD requires exploration. The long-standing questions regarding oxidative stress and the potential susceptibility to infections and worsening cardiovascular morbidity are discussed. Iron overload secondary to repeat IV iron infusions is plausible, however, a number of guidelines limit and strictly guide prescription.

Expert opinion: The past decade has improved our understanding of IV iron administration safety in patients with CKD. Third generation IV iron compounds have minimized hypersensitivity reactions while allowing high doses to be administered safely and rapidly in non-dialysis-dependent CKD patients. However, differences in safety profiles such as hypophosphatemia require further study and therapy should be tailored to the individual. Clinicians should feel confident in using IV iron therapy.

KEYWORDS:

• Chronic kidney disease
• hypersensitivity reactions
• hypophosphatemia
• intravenous iron
• iron-deficiency anemia
• iron overload
• labile iron
• oxidative stress
• safety

Article highlights

• Intravenous iron is a commonly used therapy in patients with iron deficiency anemia in chronic kidney disease (CKD).

• National and international guidelines govern and suggest the use of IV iron in patients with CKD and iron deficiency anemia however concerns on potential side-effects such as anaphylaxis, hypersensitivity, oxidative stress and susceptibility to infections and cardiovascular events, hypophosphatemia and iron overload exist.

• Greater understanding of hypersensitivity reactions and the development of third generation IV iron compounds appear to have minimized reactions and the potential oxidative stress.

• Conflicting studies exist as to whether IV iron and the dose administered may be associated with infections and cardiovascular events. The large-scale randomized controlled trial PIVOTAL confirms that a proactive IV iron stance benefits the patient with reduced cardiovascular morbidity and mortality in dialysis patients without an increasing infection risk . It is less clear on any association of IV iron and infection or cardiovascular events in the non-dialysis community given the conflicting data from REVOKE and FIND-CKD.

• Third generation IV iron compounds are safe and efficacious and based on recent evidence clinicians should feel empowered to use them in a high dose low frequency regime in non-dialysis CKD and consider a proactive approach with any iron in dialysis-dependent CKD.

Declaration of interest

S Bhandari has received honorarium, consultancy fees, membership advisory board and travel funding from Pharmacosmos A/S, Vifor Pharma and Astella. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are a partner in Matrix45 which has received research contracts for CKD-related, anemia-related, and iron chelation therapy work from Amgen, Roche, and Novartis. Prior to 2003, the reviewer was partner in The Epsilon Group, which received research contracts from Johnson & Johnson and its companies for anemia-related work in CKD, cancer, surgery, and intensive care. Per policies in both companies, employees and partners could not provide services independently nor be compensated independently by sponsor organizations, and neither could they hold equity in sponsor organizations. Both companies provide(d) services on a non-exclusivity basis. A further reviewer on this manuscript has disclosed that they have served on advisory boards for Vifor, a maker of IV iron compounds. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work has not received any external funding.