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, even when haemoglobin (Hb) levels are normalized. ID is linked to cardiovascular (CV) outcomes and increased hospitalization risk. Guidelines are inconsistent, and the evidence base is limited.

METHODS

Databases were searched for randomized controlled trials (RCTs) and cohort studies involving adults with ND-CKD (estimated glomerular filtration rate [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 RCTs, IV iron significantly improved TSAT [mean difference (MD) +7.48%, 95% CI 5.64-9.32; P < .001; I² = 0.0%] and ferritin (MD +208.83 ng/ml, 95% CI 128.39-289.26; P = .004; I² = 75.9%). IV iron was associated with a numerically greater increase in Hb, although this did not reach statistical significance (MD +5.33 g/l, 95% CI -1.18 to 11.84; P = .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 = .506; I² = 83.0%). QoL outcomes showed no significant difference in the primary standardized mean difference (SMD) meta-analysis (SMD -0.23, 95% CI -1.44 to 0.98; P = .587; I² = 83.2%). Adverse events, CV outcomes and infections were sparsely reported, with no consistent safety signal identified.

CONCLUSIONS

IV iron improves biochemical markers of ID in ND-CKD without anaemia, with no clear signal of harm. However, evidence does not demonstrate measurable improvements in physical function or QoL.