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

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 hemoglobin 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. Over the 5-year follow-up, adequate ferritin levels were significantly associated with increased risks of AKI, CKD progression, and pneumonia (log-rank p < 0.05, < 0.01, and < 0.005, respectively). In contrast, fracture risk was significantly higher in the low ferritin group (log-rank p < 0.05). No significant differences were observed in all-cause mortality or MACE. Notably, low ferritin was associated with a significantly reduced risk of all-cause mortality during the 1–2 year follow-up period (p < 0.05) and a lower cumulative incidence of CKD progression during the 2–5 year period (p < 0.05). 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 linked to a lower fracture risk in older adults (>65 years) and those with vitamin D < 20 ng/mL. Conclusion: This study demonstrates that serum ferritin levels are linked to several adverse outcomes in non-anemic female patients with stage 3 CKD, including AKI, decline in renal function, pneumonia, and fractures.