Iron Correction Guidelines for CKD Patients
Diagnostic Thresholds for Iron Deficiency
Initiate iron supplementation when transferrin saturation (TSAT) is ≤20% and/or serum ferritin is <100 ng/mL in CKD patients, regardless of dialysis status or ESA use. 1, 2
Absolute vs. Functional Iron Deficiency
Absolute iron deficiency is defined as TSAT <20% AND ferritin <100 ng/mL in CKD patients (compared to ferritin <12 ng/mL and TSAT <16% in healthy individuals). 1
Functional iron deficiency occurs when TSAT <20% despite ferritin 100-700 ng/mL, indicating inadequate iron mobilization from stores to support erythropoiesis, particularly in ESA-treated patients. 1, 3
Ferritin is an acute-phase reactant and can be falsely elevated during inflammation or infection; always interpret ferritin alongside TSAT to avoid missing functional iron deficiency. 1, 2
Distinguishing Functional Iron Deficiency from Inflammatory Block
In functional iron deficiency, serial ferritin levels gradually decrease during ESA therapy but remain >100 ng/mL, while TSAT stays <20%. 1
In inflammatory iron block, there is an abrupt increase in ferritin with a sudden drop in TSAT. 1
If uncertain, administer weekly IV iron 50-125 mg for 8-10 doses; if no erythropoietic response occurs, an inflammatory block is likely and IV iron should be withheld until inflammation resolves. 1
Route of Iron Administration
Oral iron is NOT indicated for hemodialysis patients and should not be used as primary therapy in this population. 1, 2, 3
Hemodialysis patients cannot maintain adequate iron stores with oral iron due to substantial ongoing blood losses (dialyzer retention, tubing, frequent phlebotomy, GI bleeding) and poor intestinal absorption that cannot compensate for these losses. 1, 3
For non-dialysis dependent CKD (stages 3-5) and peritoneal dialysis patients, either IV or oral iron may be used, though IV iron demonstrates superior efficacy. 4, 5
Intravenous Iron Dosing Regimens
Initial Repletion Phase (Hemodialysis Patients)
Administer 100-125 mg IV iron at every hemodialysis session for 8-10 consecutive doses when TSAT ≤20% and/or ferritin <100 ng/mL. 1, 2, 3
This provides approximately 1,000 mg total iron, which is typically needed during initial ESA therapy to raise hematocrit from 25% to 35%. 1, 3
If TSAT remains ≤20% and/or ferritin remains <100 ng/mL after completing the initial course, repeat another course of 100-125 mg per week for 8-10 weeks. 1, 2
Alternative Dosing Schedules
Schedules ranging from three times per week to once every 2 weeks are acceptable, provided they deliver 250-1,000 mg iron within 12 weeks. 1
For patients weighing ≥50 kg, ferric carboxymaltose 750 mg IV in two doses separated by at least 7 days (total 1,500 mg per course) is FDA-approved. 6
Iron sucrose can be administered as 200 mg over 2-5 minutes five times within 14 days, or two 500 mg infusions on Day 1 and Day 14 (over 3.5-4 hours) for non-dialysis dependent CKD. 7
Maintenance Phase
Once target iron parameters are achieved (TSAT ≥20% and ferritin ≥100 ng/mL), administer 25-125 mg IV iron weekly to maintain hemoglobin 11-12 g/dL and prevent iron depletion. 1, 2, 3
The required maintenance dose varies widely among patients (25-125 mg/week) and should be individualized based on ongoing iron losses and ESA requirements. 1, 3
Monitor TSAT and ferritin at least every 3 months during maintenance therapy to guide dosing adjustments. 1, 2, 3
Target Iron Parameters
Maintain minimum thresholds of TSAT ≥20% and ferritin ≥100 ng/mL in all CKD patients. 1, 2, 3
Higher targets of TSAT 30-50% and ferritin >200 ng/mL optimize ESA response and can reduce ESA requirements by up to 40%. 3
Most patients achieve hemoglobin 11-12 g/dL with TSAT >20% and ferritin >800 ng/mL, though these upper levels approach safety thresholds. 1
Upper Safety Limits: When to Withhold IV Iron
Withhold IV iron when TSAT >50% and/or ferritin >800 ng/mL, and hold for up to 3 months before rechecking iron parameters. 1, 2, 3
When resuming iron after a 3-month hold, reduce the weekly dose by one-third to one-half. 1
Some guidelines suggest stopping when ferritin exceeds 500 ng/mL, as evidence of benefit beyond this threshold is insufficient and risks may increase. 2
Ferritin levels of 300-800 ng/mL are common in dialysis patients without clear evidence of adverse iron-mediated effects, though the exact threshold for iron overload remains unknown. 3
Special Populations
Patients with Functional Iron Deficiency on ESAs
When TSAT <25% and ferritin 800-1,200 ng/mL in patients with suboptimal hemoglobin or high ESA doses, IV iron should be administered to raise TSAT above 25% and improve erythropoiesis. 3
Continuation of IV iron is justified when ferritin is slightly above 800 ng/mL (e.g., ≈890 ng/mL) if TSAT remains <25%, as this indicates functional iron deficiency requiring treatment. 3
Peritoneal Dialysis Patients
- Iron sucrose 300 mg in 250 mL 0.9% NaCl over 1.5 hours on Days 1 and 15, plus 400 mg over 2.5 hours on Day 29, has demonstrated efficacy in peritoneal dialysis patients. 7
Pediatric Patients (≥2 Years Old)
- For maintenance therapy in pediatric CKD patients on stable ESA therapy, iron sucrose 0.5-2 mg/kg can be administered once every other week for hemodialysis patients or once every 4 weeks for peritoneal dialysis/non-dialysis patients. 7
Pregnant CKD Patients
- The provided evidence does not contain specific dosing recommendations for pregnant CKD patients; general CKD thresholds (TSAT ≤20%, ferritin <100 ng/mL) should guide initiation, with careful monitoring.
Administration Safety and Monitoring
Hypersensitivity Precautions
Monitor patients for signs of hypersensitivity during and for at least 30 minutes after IV iron administration until clinically stable. 6
Only administer IV iron when personnel and therapies are immediately available to treat anaphylaxis. 6
A 25 mg test dose is required before initiating iron dextran or iron gluconate therapy to monitor for immediate allergic reactions. 3
Extravasation Prevention
- Avoid extravasation, as brown discoloration at the site may be long-lasting; if extravasation occurs, discontinue administration at that site immediately. 6
Repeat Course Considerations
- Check serum phosphate levels in patients at risk for hypophosphatemia who require a repeat course of treatment or any patient receiving a repeat course within 3 months, as IV iron can cause hypophosphatemia. 6
Common Pitfalls to Avoid
Do not withhold iron based on elevated ferritin alone when TSAT is low; the combination signals functional iron deficiency requiring treatment, not iron overload. 1, 3
Do not rely on oral iron for hemodialysis patients; it is insufficient and should not be used as primary therapy in this population. 1, 2, 3
Do not administer IV iron during active infection, as iron is essential for microbial growth and may worsen outcomes. 2
Do not assume normal ferritin excludes iron deficiency in ESA-treated patients; functional iron deficiency is common and requires assessment of both TSAT and ferritin together. 1