Can chronic kidney disease (CKD) cause elevated ferritin levels?

Elevated Ferritin in Chronic Kidney Disease

Yes, chronic kidney disease (CKD) can cause elevated ferritin levels due to inflammation, altered iron metabolism, and reduced renal clearance. 1, 2

Mechanisms of Elevated Ferritin in CKD

• Inflammation: CKD is associated with chronic inflammation, which increases ferritin as an acute phase reactant independent of actual iron status 2
• Altered hepcidin metabolism: Reduced renal clearance of hepcidin in CKD leads to higher hepcidin levels, which blocks iron absorption and mobilization, contributing to functional iron deficiency despite high ferritin 2
• Impaired iron utilization: Despite adequate iron stores, CKD patients often have functional iron deficiency due to inflammatory blockade of iron release from storage sites 1

Interpreting Ferritin Levels in CKD Patients

Normal vs. Elevated Values

• In non-CKD patients:

  • Iron deficiency: <30 μg/L in the absence of inflammation 3
  • Normal range: 30-300 μg/L in men, 30-200 μg/L in women 3

• In CKD patients:

  • Absolute iron deficiency: ≤100 ng/mL in non-dialysis and peritoneal dialysis patients, or ≤200 ng/mL in hemodialysis patients (with TSAT ≤20%) 4
  • Functional iron deficiency: TSAT ≤20% with elevated ferritin 4

Impact of Inflammation

• Ferritin levels in CKD patients should be interpreted with caution as they may not accurately reflect iron stores due to inflammation 1, 2
• Consider measuring inflammatory markers (C-reactive protein) to assess the contribution of inflammation to elevated ferritin 1
• Transferrin saturation may be a more reliable marker of iron sufficiency in CKD patients as it is less affected by inflammation 1

Clinical Implications

Association with Outcomes

• High ferritin levels are associated with increased risk for renal replacement therapy and rapid renal progression in advanced CKD patients 5
• In Korean men, high ferritin levels (>200 ng/mL) were associated with a 1.57-fold higher risk of CKD after adjusting for covariates 6

Management Considerations

• Iron supplementation strategies should differ between CKD patients with and without inflammation 2
• For patients with elevated ferritin due to inflammation rather than iron overload, iron therapy may still be appropriate if functional iron deficiency is present 1, 4
• The upper limit of ferritin to predict iron overload is higher in CKD patients with inflammation than in those without 2

Monitoring Recommendations

• Regular monitoring of iron studies (ferritin and transferrin saturation) is recommended for CKD patients 1
• In hemodialysis patients, measure ferritin levels before the midweek dialysis session for consistency 1
• Consider that ferritin levels will decline in hemodialysis patients when IV iron is withheld due to repetitive dialyzer blood losses 1

Common Pitfalls

• Misinterpreting high ferritin as adequate iron stores: Despite high ferritin, functional iron deficiency may still be present in CKD patients 2, 7
• Overlooking other causes of elevated ferritin: In CKD patients with unexplained hyperferritinemia, consider other conditions such as liver disease, malignancy, or hemochromatosis 3, 7
• Assuming all elevated ferritin requires iron restriction: Moderate hyperferritinemia (500-2000 ng/mL) in CKD is often due to non-iron-related conditions and may not indicate iron overload 7

Remember that ferritin interpretation in CKD requires consideration of multiple factors including inflammation status, transferrin saturation, and clinical context.