Original Investigation
Pathogenesis and Treatment of Kidney Disease
Intravenous Versus Oral Iron Supplementation for the Treatment of Anemia in CKD: An Updated Systematic Review and Meta-analysis

https://doi.org/10.1053/j.ajkd.2016.04.018Get rights and content

Background

Iron supplementation is crucial for the treatment of anemia of chronic kidney disease (CKD). Although intravenous (IV) iron is preferred for patients with CKD receiving dialysis (CKD stage 5D), the method of iron replacement for patients with CKD stages 3 to 5 is controversial.

Study Design

Systematic review and meta-analysis. A search was performed until October 2015 of MEDLINE, Cochrane Library, conference proceedings in nephrology, and reference lists of included trials.

Setting & Population

Patients with CKD stages 3 to 5 or 5D.

Selection Criteria for Studies

All randomized controlled trials, regardless of publication status or language.

Intervention

IV versus oral iron supplementation.

Outcomes

The primary outcome was defined as percentage of patients reaching an elevation in hemoglobin (Hb) concentration > 1 g/dL. Secondary end points included percentage of patients who reached Hb levels > 11 g/dL, absolute Hb concentration, change in Hb concentration, transferrin saturation, ferritin levels, erythropoiesis-stimulating agents and blood transfusion requirement, and quality of life. Safety analysis included all-cause mortality and serious and all adverse events.

Results

24 trials were identified, 13 including 2,369 patients with CKD stages 3 to 5 and 11 including 818 patients with CKD stage 5D. Patients treated with IV iron were more likely to reach an Hb response > 1 g/dL (risk ratios [RRs] of 1.61 [95% CI, 1.39-1.87] for CKD stages 3-5 and 2.14 [95% CI, 1.68-2.72] for CKD stage 5D). Safety analysis showed similar rates of mortality and serious and any adverse effects. IV iron replacement was associated with higher risk for hypotension (RR, 3.71; 95% CI, 1.74-7.94) and fewer gastrointestinal adverse events (RR, 0.43; 95% CI, 0.28-0.67).

Limitations

Significant heterogeneity between trials; follow-up was usually limited to 3 months.

Conclusions

Our results agree with current recommendations for IV iron replacement for patients with CKD stage 5D and support increased use of IV iron for patients with CKD stages 3 to 5.

Section snippets

Data Sources

The study protocol was written by D.S., B.R.-Z., and A.G.-G. We searched PubMed (January 1966 to October 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library up to October 2015), and conference proceedings of the American Society of Nephrology and the European Renal Association−European Dialysis and Transplant Association for 2001 to 2015. PubMed was searched using the terms “chronic kidney disease,” “chronic renal failure,” “dialysis,” “hemodialysis,”

Description of Included Studies

The literature search identified 513 publications; 66 of them were potentially eligible publications. Reasons for exclusion are shown in Fig 1. Twenty-four trials performed January 1990 to October 2015 fulfilled inclusion criteria. Thirteen trials included 2,369 patients with CKD stages 3 to 5,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28 1,325 of whom were treated with IV iron, and 1,044, treated with oral iron. Eleven trials included 818 patients with CKD stage 5D,29, 30, 31, 32, 33, 34,

Discussion

In this systematic review and meta-analysis, we gathered all trials that compared IV iron to oral iron therapy in patients with glomerular filtration rates < 60 mL/min/1.73 m2. In patients with CKD stage 5D, IV iron therapy was superior to oral iron: significantly more patients reached an increase in Hb level > 1 g/dL (RR, 2.14 [95% CI, 1.68-2.72]; number needed to treat, 3 [95% CI, 2-4]). Absolute Hb levels at the end of the study were increased by almost 1 g/dL (mean difference, 0.98 [95% CI,

Acknowledgements

Support: None.

Financial Disclosure: The authors declare that they have no relevant financial interests.

Contributions: Conception: AG-G, BR-Z, DS, UG; research design: all authors; search and data extraction: DS, AG-G, BR-Z. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and

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    Corrected online August 2, 2016 so that the legend to Figure 4 refers to the appropriate CKD stage. The error has been corrected in the print, PDF, and HTML versions of this article.

    ∗

    D.S. and B.R.-Z. contributed equally to this work.

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    © 2016 by the National Kidney Foundation, Inc.