A systematic review investigating the safety and efficacy of intravenous iron in people with ND-CKD who are iron deficient but not anaemic

Background The role of intravenous (IV) iron in non-dialysis-dependent chronic kidney disease (ND-CKD) without anaemia remains uncertain. Iron deficiency (ID) in CKD is common and associated with impaired mitochondrial function, fatigue, cognitive decline, and restless legs syndrome (RLS), even when haemoglobin (Hb) levels are normalised. ID is linked to cardiovascular (CV) outcomes and increased hospitalisation risk. Guidelines are inconsistent, and the evidence base is limited. Methods Databases were searched for RCTs and cohort studies involving adults with ND-CKD (eGFR < 60) receiving IV iron compared with oral iron, placebo or no treatment. Primary outcome was change in iron indices. Secondary outcomes: CV events, infections, physical function, symptoms, cognition and quality of life (QoL). Results Six studies met the inclusion criteria. In pooled analyses restricted to randomised controlled trials, IV iron significantly improved TSAT (MD + 7.48%, 95% CI 5.64 to 9.32; P < 0.001; I² = 0.0%) and ferritin (MD + 208.83 ng/mL, 95% CI 128.39 to 289.26; P = 0.004; I² = 75.9%). IV iron was associated with a numerically greater increase in haemoglobin, although this did not reach statistical significance (MD + 5.33 g/L, 95% CI − 1.18 to 11.84; P = 0.080; I² = 57.4%). No significant effect was observed on 6-minute walk test distance (MD + 23.99 m, 95% CI − 77.44 to 125.41; P = 0.506; I² = 83.0%). Quality-of-life outcomes showed no significant difference in the primary SMD meta-analysis (SMD − 0.23, 95% CI − 1.44 to 0.98; P = 0.587; I² = 83.2%). Adverse events, cardiovascular outcomes and infections were sparsely reported, with no consistent safety signal identified. Conclusions IV iron improves biochemical markers of iron deficiency in ND-CKD without anaemia, with no clear signal of harm. However, evidence does not demonstrate measurable improvements in physical function or QoL.