Oral versus Intravenous Iron Supplementation in Non-Dialysis Chronic Kidney Disease: A Meta-Analysis of Hemoglobin Response and Cardiovascular Events

Abstract

Introduction: Iron deficiency is common in non-dialysis CKD (ND-CKD), but optimal route of supplementation remains controversial. Intravenous (IV) iron corrects deficiency faster but carries hypersensitivity and oxidative stress concerns. This meta-analysis compares IV vs oral iron for hemoglobin (Hb) rise and cardiovascular (CV) safety.
Methods: Systematic review of RCTs (≥100 ND-CKD patients, follow-up ≥12 weeks) comparing IV iron (any preparation) vs oral iron. Primary outcomes: change in Hb (g/dL) and composite CV events (myocardial infarction, stroke, heart failure hospitalization, death).
Results: Nineteen RCTs (n=4,512) included. IV iron increased Hb by 0.68 g/dL more than oral iron (95% CI 0.52–0.84). Ferritin increased more with IV (mean diff +189 ng/mL, p<0.001). Composite CV events: IV 8.6% vs oral 7.2% (RR 1.18, 0.96–1.45, p=0.11). Hypersensitivity reactions: IV 0.8% vs oral 0.1% (p=0.02). All-cause mortality no difference (RR 1.04, 0.87–1.24). In patients with baseline Hb <10 g/dL, Hb gain with IV was 0.92 g/dL.
Discussion: IV iron achieves superior Hb response, especially in severe anemia, but the trend toward increased CV events (non-significant) warrants caution. Many trials excluded recent CV events, limiting generalizability. FCM (ferric carboxymaltose) had best Hb response.
Conclusions: IV iron is more effective but not clearly safer. Reserve IV for those intolerant to oral or with severe symptomatic anemia. Further CV safety trials are needed.