Although patients with chronic kidney disease (CKD) are commonly affected by iron-deficiency anaemia, a randomized clinical trial (REVOKE) shows evidence that intravenous iron therapy may cause serious adverse events. In the trial, patients treated with intravenous iron had more adverse events than patients treated with oral iron and showed no statistical signs of improved benefit, leading to early termination of the trial.

“For now, oral iron seems to be a safer approach when confronted with iron-deficiency anaemia in patients with CKD,” said Dr. Rajiv Agarwal, lead researcher on the trial, in a research highlight from Nature Reviews Nephrology. “A larger randomized trial to establish the safety of intravenous iron should now be mandated by the FDA.”

These results may not be surprising. “Animal studies have consistently shown that iron administration worsens kidney disease,” stated Dr. Agarwal. The research team was interested in determining if the same was true in humans and if intravenous iron accelerates kidney function loss when compared to oral iron.

To answer this question, the team recruited 136 nondialysis CKD patients and randomized them to receive oral iron sulfate or intravenous iron sucrose for two years. During this time, patients were monitored for measured glomerular filtration rate (mGFR) and adverse effects. According to the results published in Kidney International, entitled “A Randomized Trial of Intravenous and Oral Iron in Chronic Kidney Disease,” both groups experienced similar changes in mGFR. However, the intravenous iron group experienced 2.51 times as many serious cardiovascular events. The intravenous group also experienced twice as many hospitalizations due to infection.

“These findings are consistent with the biology of the drug, and show that long-term safety should be established before using intravenous iron liberally in patients with nondialysis CKD,” said Dr. Agarwal. To avoid serious adverse events such as cardiovascular and infectious diseases, patients with iron deficiency and chronic kidney disease may want to use oral iron as a supplement rather than intravenous iron.