What is the best approach to manage iron deficiency anemia in a patient with Chronic Kidney Disease (CKD) and laboratory results showing low ferritin, serum iron, and saturation percentage, along with an elevated Total Iron-Binding Capacity (TIBC)?

Evaluation of Laboratory Results: Iron Deficiency in CKD

Your laboratory results demonstrate absolute iron deficiency requiring immediate intravenous iron supplementation. The ferritin has dropped precipitously from 119.7 to 27 ng/mL, transferrin saturation is critically low at 24%, and serum iron is 65 μg/dL—all meeting diagnostic criteria for absolute iron deficiency in the context of chronic kidney disease. 1, 2

Laboratory Analysis

Iron Parameters Indicate Absolute Iron Deficiency

• Ferritin 27 ng/mL is severely depleted and falls well below the CKD threshold of <100 ng/mL for absolute iron deficiency in predialysis/peritoneal dialysis patients. 1, 2

• The dramatic ferritin decline from 119.7 to 27 ng/mL over time signals ongoing iron loss that must be investigated and corrected urgently. 1

• Transferrin saturation of 24% is below the critical 20% threshold traditionally used to define iron deficiency in CKD, though this is borderline and some patients with TSAT >20% may still be functionally iron deficient. 1

• Serum iron of 65 μg/dL with TIBC of 270 μg/dL confirms inadequate iron availability for erythropoiesis, as reflected in the low-normal TSAT. 1

Hemoglobin Status

• Hemoglobin 14.0 g/dL is currently normal (above the anemia threshold of <13 g/dL for males or <12 g/dL for females), but this will inevitably decline without iron repletion given the severely depleted iron stores. 1, 3

• The absence of anemia now does not negate the need for aggressive iron replacement, as iron deficiency precedes anemia and causes significant symptoms including fatigue and reduced exercise tolerance even with normal hemoglobin. 3

Other Hematologic Parameters

• MCV 90.5 fL, MCH 31 pg, and MCHC 34.2 g/dL are all normal, indicating normocytic, normochromic red cells consistent with early iron deficiency before microcytosis develops. 1

• RDW 13.8% is normal, though this may increase as iron deficiency progresses and a mixed population of normal and microcytic cells emerges. 1

Diagnostic Classification

This represents absolute iron deficiency in CKD, defined by ferritin <100 ng/mL and TSAT <20% (yours is borderline at 24%). 1, 2 This is distinct from functional iron deficiency, which would show ferritin 100-700 ng/mL with TSAT <20%, indicating adequate stores but insufficient iron release. 1

Immediate Management Algorithm

Step 1: Initiate Intravenous Iron Immediately

• For CKD patients (predialysis or peritoneal dialysis), intravenous iron is strongly preferred over oral iron due to superior efficacy, particularly when erythropoiesis-stimulating agents (ESAs) may be needed. 1, 2, 4

• Administer 100-125 mg IV iron at every hemodialysis session for 8-10 doses (or equivalent dosing schedule for non-hemodialysis patients: 100-125 mg weekly for 8-10 weeks). 1

• Available IV iron preparations include iron sucrose, ferric gluconate, ferumoxytol, ferric carboxymaltose, or low molecular weight iron dextran (avoid high molecular weight iron dextran due to anaphylaxis risk). 1, 5

Step 2: Investigate the Source of Iron Loss

• The precipitous ferritin drop from 119.7 to 27 ng/mL indicates ongoing blood loss that must be identified. 1

• Perform fecal occult blood testing immediately to screen for gastrointestinal bleeding, the most common source of iron loss in CKD. 1

• If stool guaiac is positive or patient has GI symptoms, proceed with bidirectional endoscopy (upper endoscopy and colonoscopy) to identify bleeding sources including malignancy, angiodysplasia, or peptic ulcer disease. 1, 3

• Screen for celiac disease with tissue transglutaminase antibodies (tTG), as celiac disease is present in 3-5% of iron deficiency cases and causes malabsorption. 3

• Test for H. pylori non-invasively (stool antigen or urea breath test), as H. pylori infection can cause iron deficiency through chronic gastritis and occult bleeding. 3

Step 3: Reassess Iron Parameters After Initial Repletion

• Recheck ferritin, TSAT, serum iron, and hemoglobin after completing the initial 8-10 dose course of IV iron (approximately 3 months). 1

• Target ferritin >100 ng/mL and TSAT >20% to ensure adequate iron stores and availability for erythropoiesis. 1, 2

• If ferritin remains <100 ng/mL or TSAT <20%, administer another course of IV iron (100-125 mg weekly for 8-10 weeks). 1

Step 4: Establish Maintenance IV Iron Regimen

• Once target iron parameters are achieved, most CKD patients require ongoing maintenance IV iron (25-125 mg weekly) to prevent recurrent deficiency due to chronic blood losses from uremia-related platelet dysfunction and frequent phlebotomy. 1, 4

• Monitor TSAT and ferritin every 3 months during maintenance therapy to ensure iron parameters remain in target range. 1

• Withhold IV iron if ferritin exceeds 800 ng/mL or TSAT exceeds 50% to avoid iron overload, and recheck parameters in 3 months before resuming. 1

Critical Pitfalls to Avoid

• Do not use oral iron in CKD patients, as it is inferior to IV iron due to impaired intestinal absorption from elevated hepcidin levels and uremia-related gastrointestinal dysfunction. 1, 4

• Do not delay iron repletion waiting for investigation results, as iron deficiency will worsen and anemia will develop, potentially necessitating ESA therapy that could have been avoided. 2, 5

• Do not assume normal hemoglobin excludes the need for iron replacement, as depleted iron stores (ferritin 27 ng/mL) will inevitably lead to anemia and cause symptoms even before hemoglobin falls. 3

• Do not confuse this with functional iron deficiency or inflammatory iron block, which would show ferritin >100 ng/mL with low TSAT and elevated inflammatory markers (CRP/ESR). 1, 3

• Do not overlook the dramatic ferritin decline as a red flag for ongoing blood loss, which requires urgent investigation to prevent recurrent iron deficiency despite supplementation. 1

Expected Outcomes

• With appropriate IV iron repletion, expect hemoglobin to increase by 1-2 g/dL and ferritin to rise above 100 ng/mL within 3 months, potentially avoiding the need for ESA therapy entirely. 5

• Approximately 55% of CKD patients with iron deficiency achieve target hemoglobin ≥12 g/dL with IV iron alone, without requiring erythropoietin. 5

• Failure to respond to adequate IV iron after 8-10 weeks suggests either ongoing uncontrolled blood loss, inflammatory iron block, or erythropoietin deficiency requiring ESA therapy. 1