What is the significance of monitoring ferritin (iron storage protein) levels?

From the Guidelines

Ferritin levels should be monitored every 3-6 months in patients with conditions affecting iron storage or metabolism, taking into account the patient's specific conditions, such as chronic kidney disease and underlying inflammatory states, as highlighted in the 2020 study 1. When monitoring ferritin levels, it is essential to consider the context of patient-specific conditions, as ferritin is an acute phase reactant that can be elevated during inflammation, infection, liver disease, or malignancy, potentially masking true iron status. For patients on iron supplementation therapy, checking levels after 4-8 weeks of treatment to assess response, then every 3 months until levels normalize, and every 6-12 months thereafter for maintenance is a reasonable approach, as suggested by the 2008 study 1. In patients with iron overload conditions like hemochromatosis, monitoring ferritin every 3 months during initial phlebotomy treatment, then every 6-12 months once levels stabilize, is recommended. Target ferritin levels are generally 50-100 ng/mL for iron deficiency treatment and below 50-100 ng/mL for iron overload conditions, as indicated in the 2001 study 1. Interpretation of ferritin levels should consider the patient's clinical symptoms, complete blood count, and transferrin saturation for a comprehensive iron status evaluation, as emphasized in the 2008 study 1. Regular monitoring helps prevent complications of both iron deficiency, such as fatigue, poor concentration, and reduced exercise capacity, and iron overload, including organ damage, particularly to the liver, heart, and pancreas. Key points to consider when monitoring ferritin levels include:

• Patient-specific conditions, such as chronic kidney disease and underlying inflammatory states
• Frequency of monitoring, which may vary depending on the patient's condition and response to treatment
• Interpretation of ferritin levels in the context of clinical symptoms, complete blood count, and transferrin saturation
• Target ferritin levels for iron deficiency treatment and iron overload conditions.

From the FDA Drug Label

Although serum ferritin is usually a good guide to body iron stores, the correlation of body iron stores and serum ferritin may not be valid in patients on chronic renal dialysis who are also receiving iron dextran complex Periodic monitoring of serum ferritin levels may be helpful in recognizing a deleterious progressive accumulation of iron resulting from impaired uptake of iron from the reticuloendothelial system in concurrent medical conditions such as chronic renal failure, Hodgkin’s disease, and rheumatoid arthritis.

Monitoring ferritin is recommended, especially in patients with certain medical conditions, as it can help recognize a progressive accumulation of iron.

• Serum ferritin levels should be periodically monitored in these patients.
• This is particularly important in patients with conditions such as chronic renal failure, Hodgkin’s disease, and rheumatoid arthritis 2, 2.

From the Research

Monitoring Ferritin

• Ferritin levels are a sensitive marker for iron status, but can be elevated in response to inflammation, complicating the diagnosis of iron deficiency in patients with inflammatory conditions such as inflammatory bowel disease (IBD), chronic heart failure (CHF), and chronic kidney disease (CKD) 3.
• In patients with CKD, iron deficiency anemia is a common complication, and the standard threshold for iron deficiency (<30 μg/L) does not apply due to increased hepcidin expression, which restricts uptake of dietary iron and promotes sequestration of iron by ferritin within storage sites 3, 4.
• A serum ferritin threshold of <100 μg/L or transferrin saturation (TSAT) < 20% can be considered diagnostic for iron deficiency in CHF, CKD, and IBD, and routine surveillance of serum ferritin and TSAT in these at-risk groups is advisable to detect and manage iron deficiency 3.
• In CKD patients, absolute iron deficiency is defined when the TSAT is ≤20% and the serum ferritin concentration is ≤100 ng/mL among predialysis and peritoneal dialysis patients or ≤200 ng/mL among hemodialysis patients, while functional iron deficiency is characterized by TSAT ≤20% and elevated ferritin levels 4.
• The use of ferritin as a diagnostic test of iron deficiency and overload is a common clinical practice, but its levels are elevated in inflammation and infection, and the diagnostic accuracy of ferritin concentrations for detecting iron deficiency and risk of iron overload is limited by potential bias, indirectness, and sparse and heterogenous evidence 5.
• At a threshold of 30 micrograms/L, there is low-certainty evidence that blood ferritin concentration is reasonably sensitive and a very specific test for iron deficiency in people presenting for medical care, but there is very low certainty that high concentrations of ferritin provide a sensitive test for iron overload in people where this condition is suspected 5.

Diagnosis and Treatment

• The diagnosis of iron deficiency anemia in CKD requires the assessment of serum ferritin and TSAT levels, and the treatment of iron deficiency anemia in CKD involves iron supplementation, which can be administered orally or intravenously 4, 6.
• The choice of iron supplementation route depends on the patient's clinical status and the severity of their iron deficiency, and intravenous iron supplementation is generally recommended for CKD patients on dialysis, while oral iron supplementation may be sufficient for patients with milder iron deficiency 4, 7.
• The potential risks and benefits of intravenous iron supplementation, including the risk of anaphylaxis and delayed complications such as infections and cardiovascular disease, must be carefully considered and weighed against the benefits of treatment 7.