Neither Sisters nor Cousins: Iron Levels in Brain and Serum Are Not Related

Background: Current guidelines recommend initiating intravenous iron therapy in patients on maintenance hemodialysis if ferritin levels are ≤ 500ng/mL.Patients with restless leg syndrome (RLS) may also benefit from intravenous iron, regardless of ferritin levels.Iron is an essential element but toxic at excess.Ferritin plays a role in transporting iron across epithelial cells of the blood-brain barrier;however, it remains unclear whether serum ferritin levels accurately reflect brain iron content in patients receiving maintenance hemodialysis. Methods: This ongoing cross-sectional study used ultrahigh-field 7T MRI(Siemens Magnetom, 32-channel head coil).The imaging protocol includes T2 fast spin echo and gradient-echo sequences with five echo times.Post-processing is performed using MATLAB, FSL, and ITK-SNAP to generate T2, T2*, R2, R2*, and R2′ maps (R2′ = R2*–R2/2), allowing indirect quantification of brain iron.Regions of interest (ROI) were manually delineated (Fig1).We included patients on hemodialysis (HD) and those with CKD on conservative management (CKD).A subgroup analysis was conducted for RLS. Iron storage was compared between the groups (Fig2). Results: Findings from 35 patients (HD, n=27; CKD, n=8) were analyzed.Age (p=0.602) and sex (p=0.869) distributions were similar between the groups.Median serum ferritin levels were 316 ng/dL (87–567) in the HD group and 154 ng/dL(34–652) in the CKD group (p=0.384).Brain iron-sensitive MRI parameters showed no correlation with serum ferritin in any ROI, including in the subgroup of patients with RLS.After 1:1 age-matching (p=0.915) across the 3 groups –CKD, HD with RLS, and HD without RLS-MRI revealed similar R2* values across all ROIs, including the substantia nigra. Conclusion: This is the first study to utilize 7T MRI to investigate brain iron content in patients undergoing hemodialysis. Our findings support the hypothesis that serum iron markers do not accurately reflect brain iron levels.