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


METHODS
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.


METHODS
Patients with CKD stages 3 to 5 or 5D.


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


METHODS
IV versus oral iron supplementation.


RESULTS
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).


CONCLUSIONS
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.
Department of Medicine A, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: shepshelovich@yahoo.com.
Daniel
D
Shepshelovich
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Department of Nephrology and Hypertension, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.
Benaya
B
Rozen-Zvi
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Department of Medicine E, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.
Tomer
T
Avni
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Department of Nephrology and Hypertension, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.
Uzi
U
Gafter
Department of Medicine A, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.
Anat
A
Gafter-Gvili
D061605:Administration, Intravenous; D000284:Administration, Oral; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007501:Iron / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000150:complications
D007501:Iron
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)