When should iron polymaltose injection be reduced or discontinued in patients with renal disease?

When to Reduce or Discontinue Iron Polymaltose Injection in Renal Patients

Iron polymaltose injection should be immediately discontinued when serum ferritin exceeds 500–800 ng/mL or transferrin saturation (TSAT) exceeds 50%, as further administration provides no additional benefit and raises safety concerns. 1, 2, 3

Specific Thresholds for Discontinuation

Upper Safety Limits

• Stop all intravenous iron when ferritin rises above 500–800 ng/mL, as patients are unlikely to respond with further hemoglobin increases at these levels 1, 2, 3
• Discontinue immediately if TSAT exceeds 50%, regardless of ferritin level 1, 2, 3
• Withhold iron therapy when ferritin exceeds 1000 ng/mL, as the long-term safety of maintaining such levels remains untested in large randomized trials and is clinically unjustified 3

Product-Specific Considerations

• For iron polymaltose specifically, one study in peritoneal dialysis patients recommended stopping when ferritin exceeded 650 µg/L (650 ng/mL), though this threshold is lower than current guideline recommendations 4
• Iron polymaltose has a longer plasma elimination time (up to 1 month) compared to iron sucrose, requiring careful timing of laboratory monitoring 1

Monitoring Schedule During Treatment

Frequency of Assessment

• Check TSAT and ferritin every 3 months once maintenance therapy is established 1, 2, 5
• Measure hemoglobin at least monthly in hemodialysis patients and every 3 months in non-dialysis CKD patients 1, 5
• Wait at least 7 days (preferably 4 weeks) after any IV iron dose before rechecking ferritin and TSAT, as earlier measurements yield falsely elevated values 2, 3, 5

Target Maintenance Parameters

• Maintain minimum targets of TSAT ≥20% and ferritin ≥100 ng/mL during ongoing therapy 1, 2
• Optimal response is associated with TSAT ≥30% and ferritin 200–500 ng/mL 2

Algorithm for Dose Reduction vs. Complete Discontinuation

When Ferritin Reaches 500–800 ng/mL

1. Immediately withhold all IV iron administration 1, 2, 3
2. Continue monitoring ferritin and TSAT every 3 months during the withholding period 3, 5
3. Wait 2–3 months to allow ferritin levels to decline naturally; in hemodialysis patients, ferritin typically decreases from 754–836 ng/mL to 183–477 ng/mL within 3–4 months of withholding 3
4. Resume iron only when ferritin falls below 800 ng/mL AND TSAT falls below 50%, using a reduced dose (one-third to one-half of the previous weekly dose) 3

When Ferritin Exceeds 1000 ng/mL

• Complete discontinuation is mandatory, not just dose reduction 3
• Do not resume therapy until ferritin falls well below 800 ng/mL, even if hemoglobin remains suboptimal 3
• The patient is unlikely to respond with further hemoglobin increases and may have ESA hyporesponsiveness from other causes 3

Special Clinical Scenarios Requiring Discontinuation

Active Infection

• Withhold IV iron during acute infection, as iron can theoretically exacerbate infection risk 2, 6
• Iron therapy may be continued during chronic inflammation (elevated CRP without active infection), but not during acute infectious episodes 6

Lack of Hemoglobin Response

• Discontinue iron if no hemoglobin increase occurs after 8–9 weeks of therapy despite adequate iron stores (ferritin >100 ng/mL, TSAT >20%) 1
• Consider alternative causes of anemia rather than continuing to escalate iron doses 1

Peritoneal Dialysis Patients

• In peritoneal dialysis specifically, one study using iron polymaltose found that monthly doses of 100–200 mg were effective, with side effects occurring in only 0.9% after 100 mg but 5.9% after 200 mg doses 4
• This suggests lower, less frequent dosing may be preferable in PD patients compared to hemodialysis 4, 7

Critical Pitfalls to Avoid

Timing of Laboratory Assessment

• Never check ferritin within 4 weeks of IV iron administration, as circulating iron interferes with the assay and yields falsely elevated readings that do not reflect true iron stores 2, 3, 5
• For iron polymaltose specifically, wait at least 1 month before MRI imaging due to magnetic interference 1

Misinterpreting Ferritin in Inflammation

• Do not assume elevated ferritin always indicates adequate iron stores, as ferritin is an acute-phase reactant and may be falsely elevated during inflammation or infection 2, 3, 5
• However, this does not justify continuing IV iron at ferritin >800–1000 ng/mL given the lack of safety data at these levels 3

Continuing Iron Despite High Stores

• Do not continue IV iron simply because hemoglobin remains below target when ferritin exceeds 800 ng/mL, as the patient is unlikely to respond and may be experiencing ESA hyporesponsiveness from other causes 3
• Even with functional iron deficiency (TSAT <25% despite ferritin >1000 ng/mL), the safety of continuing IV iron remains unproven 3

Inadequate Monitoring After Discontinuation

• Do not assume iron stores remain adequate indefinitely after stopping therapy; hemodialysis patients experience ongoing blood losses and may require resumption of maintenance therapy once ferritin normalizes 3

Evidence Quality Considerations

The most recent high-quality guideline evidence comes from KDIGO 2012, which established the 500 ng/mL upper threshold 1. More recent evidence from 2016 highlights concerns about iron overload in dialysis patients, with MRI studies showing hepatic iron accumulation even at guideline-recommended doses 1. The 2026 Praxis Medical Insights summaries (based on American Journal of Kidney Diseases and Kidney International guidelines) provide the most current practical algorithms, recommending discontinuation at 500–800 ng/mL and mandatory withholding above 1000 ng/mL 2, 3, 5. While older studies suggested continuous low-dose maintenance therapy, more recent evidence demonstrates that even 31.25 mg weekly can lead to progressive iron accumulation and decreased transferrin levels 8.