Iron deficiency is a major cause of hyporesponsiveness to
erythropoiesis-stimulating agents (ESAs) and is often observed in
chronic kidney disease (CKD) patients with
anemia. With
iron supplementation, ESA doses can be decreased, resulting in lower treatment costs and possibly lower cardiovascular risks that are associated with high-dose ESA
therapy. The 2012
Kidney Disease: Improving Global Outcomes Guideline specified
ferritin ≤ 500 ng/ml and
transferrin saturation (TSAT) ≤ 30% as thresholds of
iron parameters for CKD patients. However, long-term safety (in terms of mortality,
cardiovascular/infection risk and tissue deposition) of high-dose intravenous
iron supplementation with such high target levels of
ferritin/TSAT has not been confirmed. Recently, there has been increase in the use of intravenous
iron and average
ferritin levels in dialysis patients in the United States. Clinical trials conducted so far have been underpowered to conclusively establish the long-term safety of intravenous
iron supplementation. Results from observational studies are conflicting, and many experimental studies have even shown negative effects of intravenous
iron. Clearly, randomized clinical trials are urgently needed, studying various doses of intravenous
iron, with sufficient patient numbers and longer observation periods, to investigate mortality, cardiovascular effects and
infection risks of this treatment. Until the long-term safety of
iron supplementation at high doses is established, a more prudent decision on
iron supplementation with lower target levels of
ferritin/TSAT seems reasonable, in light of the decades of experience with ESA that has shown that definitive clinical outcomes have been dissociated from surrogate outcomes (especially
hemoglobin concentration).