Prognostic Implications of Serum Ferritin Levels in Non-Anemic Women with Stage 3 Chronic Kidney Disease

Min-Tser Liao^1*Chien-Lin Lu²Yi-Chou Hou²Joshua Wang³Kuo-Wang Tsai³Li-Jane Shih¹Chia-Chao Wu⁴Yi-Chun Wang³Kuo-Cheng Lu³

• ¹Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan
• ²Fu Jen Catholic University Hospital, New Taipei, Taiwan
• ³Taipei Tzu Chi Hospital, Taipei City, Taiwan
• ⁴National Defense Medical Center, Taipei City, Taiwan

Abstract Introduction: Chronic kidney disease (CKD) is often accompanied by iron deficiency and persistent inflammation, both of which complicate the evaluation of iron metabolism and its clinical relevance. Although serum ferritin is commonly used to assess iron status in anemic CKD patients, data on its prognostic value in non-anemic, iron-deficient individuals remain limited and inconclusive. Methods: This retrospective cohort study utilized the TriNetX database to evaluate 5-year clinical outcomes in adult women with stage 3 chronic kidney disease (CKD), normal he-moglobin levels (≥12 g/dL), normal mean corpuscular volume (MCV, 80–100 fL), and varying serum ferritin concentrations. Patients were stratified into two groups based on ferritin levels: <100 ng/mL (low ferritin) and 100–700 ng/mL (adequate ferritin). Primary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), pneumonia, fractures, and progression to advanced CKD (estimated glomerular filtration rate < 30 mL/min/1.73 m²). Results: A total of 66,768 eligible non-anemic women with stage 3 CKD, low serum ferritin levels, and normal MCV were identified. Propensity score matching (1:1) based on demographic variables was performed prior to comparing outcomes between low ferritin (n = 52,295) and adequate ferritin (n = 52,295) cohorts. No significant differences were observed in all-cause mortality or MACE. Subgroup analysis revealed that low ferritin levels were especially protective against AKI and pneumonia in patients with elevated CRP (>10 mg/L), postmenopausal women, and those aged 18–64. The association of low ferritin levels with enhanced renal function preservation was more pronounced in postmenopausal women, individuals with vitamin D ≥30 ng/mL, and patients with diabetes. Conversely, adequate ferritin was associated with a lower fracture risk in older adults (>65 years) and those with vitamin D <20 ng/mL. Conclusion: This study of non-anemic female patients with stage 3 CKD found that adequate ferritin levels correlated with a heightened risk of AKI, renal disease progression, and pneumonia. In contrast, low ferritin levels were associated with a higher fracture risk but a lower likelihood of renal function deterioration.