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

Am J Kidney Dis. 2016 Nov;68(5):677-690. doi: 10.1053/j.ajkd.2016.04.018. Epub 2016 Jun 16.


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 > 1g/dL. Secondary end points included percentage of patients who reached Hb levels > 11g/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 > 1g/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.

Keywords: Hb response; IV iron; Iron; anemia; blood transfusion; chronic kidney disease (CKD); cideferron; dialysis; end-stage renal disease (ESRD); erythropoiesis-stimulating agent (ESA); ferric carboxymaltose; ferric gluconate; ferritin; ferumoxytol; haemoglobin; iron dextran; iron sucrose; iron supplementation; isomaltoside; oral iron; quality of life; safety; systematic review; transferrin saturation (TSAT).

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Anemia / drug therapy*
  • Anemia / etiology
  • Humans
  • Iron / administration & dosage*
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency, Chronic / complications


  • Iron