Intravenous iron therapy and the cardiovascular system: risks and benefits

Abstract

Anaemia is a common complication of chronic kidney disease (CKD). In this setting, iron deficiency is frequent because of the combination of increased iron needs to sustain erythropoiesis with increased iron losses. Over the years, evidence has accumulated on the involvement of iron in influencing pulmonary vascular resistance, endothelial function, atherosclerosis progression and infection risk. For decades, iron therapy has been the mainstay of therapy for renal anaemia together with erythropoiesis-stimulating agents (ESAs). Despite its long-standing use, grey areas still surround the use of iron therapy in CKD. In particular, the right balance between either iron repletion with adequate therapy and the avoidance of iron overload and its possible negative effects is still a matter of debate. This is particularly true in patients having functional iron deficiency. The recent Proactive IV Iron Therapy in Haemodialysis Patients trial supports the use of intravenous (IV) iron therapy until a ferritin upper limit of 700 ng/mL is reached in haemodialysis patients on ESA therapy, with short dialysis vintage and minimal signs of inflammation. IV iron therapy has also been proven to be effective in the setting of heart failure (HF), where it improves exercise capacity and quality of life and possibly reduces the risk of HF hospitalizations and cardiovascular deaths. In this review we discuss the risks of functional iron deficiency and the possible benefits and risks of iron therapy for the cardiovascular system in the light of old and new evidence.

Analysis of oxidative stress, inflammation and endothelial function following intravenous iron in chronic kidney disease in the Iron and Heart Trial

“…The optimal management of iron deficiency in patients with CKD is unclear with some evidence suggesting benefit with intravenous iron while others raising concerns about adverse effects 10 , 23 . These concerns surround issues such as oxidative stress leading to endothelial and cardiac dysfunction via lipid peroxidation, cytotoxicity and activation of monocytes 24 , 25 .…”

The Role of Iron in Calciphylaxis—A Current Review

“…In addition to the findings of iron deposition within CUA specimens, there have been several proposed theories as to why iron might be associated with CUA pathogenesis, such as its known toxic effect in overload, including iron-induced oxidative stress, and its role in conditions such as atherosclerosis and vascular calcification. Research into atherosclerosis has revealed elevated levels of vascular cell adhesion molecules (VCAMs) and an increase in intima-media thickness with iron excess or supplementation [ 24 ]. Iron accumulation is also found within atherosclerotic plaques, particularly those which are symptomatic [ 24 ].…”

“…Research into atherosclerosis has revealed elevated levels of vascular cell adhesion molecules (VCAMs) and an increase in intima-media thickness with iron excess or supplementation [ 24 ]. Iron accumulation is also found within atherosclerotic plaques, particularly those which are symptomatic [ 24 ]. Increased quantities of soluble adhesion molecules were found in CKD patients who received iron sucrose, with cumulative iron dose correlating with increased intima-media thickness [ 24 ].…”

Current Status of Renal Anemia Pharmacotherapy—What Can We Offer Today

“…Results from a prospective, multicentric, randomized controlled study of more than 2000 patients undergoing hemodialysis (HD) support the efficacy and safety of relatively high-dose iv iron therapy among hemodialysis-dependent patients treated with ESA [ 20 , 121 ]. Monthly administration of 400 mg iv iron in patients with serum ferritin < 700 µg/L and TSAT ≤ 40% decreases ESA use and lowers the risk of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure compared with iv iron administered in a reactive fashion for ferritin < 200 µg/L or TSAT < 20% [ 20 , 121 ]. FIND-CKD study in ND-CKD patients demonstrated that iv iron dosed to target ferritin of 400–600 µg/L compared with oral iron quickly reached and maintained Hb.…”