Intravenous iron therapy in peritoneal dialysis patients: short-term efficacy and long-term issues.

A nemia management in patients with renal disease remains a critical clinical issue. In particular, the best methods to assess iron (Fe) needs and optimal Fe replacement strategies have received ongoing attention. In this issue of CJASN, Singh et al. (1) make an important contribution by demonstrating that intravenous Fe replacement therapy (with Fe sucrose), when combined with erythropoietin (EPO), is efficacious in supporting hemoglobin (Hb) levels in chronic peritoneal dialysis (PD) patients. PD patients were entered into a multicenter, prospective, randomized trial and assigned to one of two groups. Group A received intravenous Fe sucrose EPO, whereas group B received EPO without Fe (either intravenously or oral) supplementation. A total of 126 patients at 27 sites were randomly assigned: 80 and 46 patients into group A and group B, respectively (a 2:1 group ratio was the study objective). The Fe sucrose treatment goal was to administer 1 g of intravenous Fe, given in three divided doses over 1 mo. The primary end point was an improvement in Hb concentration. This and secondary end points (decreased need for transfusion or EPO increases; improvements in Fe stores) were monitored for 70 d after initiation of treatment. The study met its primary objective as evidenced by a greater rise in Hb concentrations in group A versus group B patients (1.3 1.1 versus 0.7 1.1 g/dl; P 0.003; means 1 SD). In addition, secondary end points indicated the efficacy of intravenous Fe therapy. These included less need for acute anemia intervention (1.6 versus 16.7% for groups A and B, respectively; P 0.015) and greater improvements in Fe stores. For example, serum ferritin levels significantly increased only in Fe-supplemented patients. Fe therapy also was judged to be safe and well tolerated. For example, 78% of group A patients completed the study, versus just 56% for group B. Minimal or no serious adverse reactions to intravenous Fe were believed to occur. Furthermore, the incidence of infection was not increased with Fe therapy (a theoretical concern given that Fe is an obligate growth factor for selected fungi and bacteria). Specifically, the incidences of peritonitis and catheter-site infections were, if anything, slightly (albeit not statistically) lower in the intravenous Fe treatment group. On the basis of these results, the authors conclude that intravenous Fe, when combined with EPO, is both a safe and an effective means for combating anemia in PD patients. Therefore, this study makes an important contribution to and is supportive of the existing literature. As with any study, questions emerge from the data, some of which may be worthy of future consideration. First, it is notable that group A patients had statistically higher baseline transferrin saturations than did the non-Fe treatment group (P 0.005). In addition, group A patients seemed to be receiving higher EPO doses before the onset of intravenous Fe therapy (11,681 versus 7932 IU/wk for groups A and B, respectively), a difference that was close to statistical significance (P 0.1). One wonders whether less Fe deficiency/more EPO therapy in group A patients at baseline may have had a direct impact on subsequent end points or indicated other unexplained differences between the patient groups. Second, the study was designed to select patients with relatively modest anemia (lower limit Hb “cutoff” of 9.5 g/dl; except for patients from Mexico, where entry was permitted with Hb value of 8.5 g/dl). One wonders whether even greater benefits might have accrued had more severely anemic/Fe-deficient patients been studied. Alternatively, it remains possible that more severely anemic patients would have been less responsive to Fe therapy if the worse anemia were a reflection of more severe/frequent chronic underlying illnesses. Third, it is notable that many exclusion criteria were applied. For example, “chronic” or “serious” infections, malignancy, recent major surgery, severe concomitant liver or cardiovascular disease, or asthma were some of the exclusion criteria that were used. Given that many patients with ESRD face these types of complications, it seems important to learn in the future whether any of these diseases would have a negative impact on responses to intravenous Fe therapy. Fourth, although the data certainly seem to support the safety of intravenous Fe sucrose, it is notable that patients with a history of adverse Fe sucrose reactions were excluded appropriately from the study. However, by so doing, it may be that the overall safety of Fe sucrose therapy could have been overestimated. Fifth, although Fe sucrose did improve Hb levels, the absolute increases were relatively small ( 0.6 g/dl after 70 d of treatment). Given that the group B patients had statistically lower transferrin saturations at baseline and received no Fe therapy, the improvement with intravenous Fe therapy in Published online ahead of print. Publication date available at www.cjasn.org.