When to initiate IV (intravenous) iron therapy in a patient with ESRD (end-stage renal disease) and anemia?

When to Initiate IV Iron Therapy in ESRD Patients with Anemia

Initiate IV iron therapy in ESRD patients when transferrin saturation (TSAT) is ≤20% and/or serum ferritin is <100 ng/mL, regardless of whether they are receiving erythropoiesis-stimulating agents (ESAs). 1

Iron Status Thresholds for Initiating IV Iron

For hemodialysis patients (the majority of ESRD patients):

• Start IV iron when TSAT is ≤20% and/or ferritin is <100 ng/mL 1
• Most hemodialysis patients will require IV iron on a regular basis to achieve and maintain target hemoglobin levels of 11-12 g/dL 1
• Oral iron is not indicated for hemodialysis patients, as it fails to maintain adequate iron stores in most cases 1, 2

For peritoneal dialysis patients:

• Apply the same thresholds: TSAT ≤20% and/or ferritin <100 ng/mL 1
• IV iron is preferred, though some peritoneal dialysis patients may maintain adequate stores with oral iron 1

Initial Dosing Regimens

For hemodialysis patients:

• Administer 100-125 mg IV iron at every hemodialysis session for 8-10 doses 1
• Alternative: 500-1,000 mg iron dextran as a single infusion after a 25 mg test dose 1
• Deliver the dose early during dialysis (generally within the first hour) 3

For peritoneal dialysis patients:

• Give 3 divided doses within 28 days: two 300 mg infusions over 1.5 hours (14 days apart), followed by one 400 mg infusion over 2.5 hours (14 days later) 3

For non-dialysis ESRD patients:

• Administer 200 mg IV iron as a slow injection over 2-5 minutes or as an infusion, given on 5 different occasions over 14 days 3
• Alternative: 500 mg infusions on Day 1 and Day 14 3

When to Continue or Repeat IV Iron

Maintenance therapy:

• After initial repletion, most hemodialysis patients require 25-125 mg/week of IV iron to maintain target hemoglobin and iron parameters 1
• Recheck TSAT and ferritin after completing the initial course 1
• If TSAT remains ≤20% and/or ferritin remains <100 ng/mL, administer another course of 100-125 mg per week for 8-10 weeks 1

Upper Safety Limits: When to Withhold IV Iron

Stop IV iron when:

• TSAT exceeds 50% and/or ferritin exceeds 800 ng/mL 1
• Withhold for up to 3 months, then remeasure iron parameters before resuming 1
• When resuming, reduce the weekly dose by one-third to one-half 1

More conservative thresholds from recent guidelines:

• Consider stopping when ferritin exceeds 500 ng/mL, as evidence of benefit beyond this threshold is insufficient and risks may increase 1, 4, 5

Monitoring Strategy

Frequency of monitoring:

• Measure TSAT and ferritin at least every 3 months during maintenance therapy 1
• For patients not on ESA therapy with TSAT <20% and ferritin <100 ng/mL, monitor every 3-6 months 1

Timing considerations after IV iron administration:

• Small doses (≤125 mg/week) do not require interruption for accurate iron parameter measurement 1
• After doses of 200-500 mg, wait at least 7 days before checking iron parameters 1
• After doses ≥1,000 mg, wait 2 weeks before accurate assessment 1

Special Considerations and Pitfalls

Functional iron deficiency:

• Normal or elevated ferritin does not exclude iron deficiency in ESRD patients 5, 6
• Ferritin acts as an acute-phase reactant and can be falsely elevated by inflammation 5
• Always check TSAT alongside ferritin—TSAT reflects iron availability to bone marrow, while ferritin only reflects storage 5
• Functional iron deficiency (TSAT ≤20-30% despite ferritin >100 ng/mL) is extremely common in CKD and requires IV iron 5, 6

When to withhold IV iron:

• Withhold during active infection, as iron is essential for microbial growth 2, 4, 7
• Do not withhold during inflammation alone (without active infection) 7

Why oral iron fails in ESRD:

• Elevated hepcidin levels in CKD block intestinal iron absorption, making oral supplementation largely ineffective 4, 6
• IV iron bypasses the hepcidin-ferroportin block, allowing more effective iron delivery 5
• Oral iron achieves hemoglobin increases of only 4-7 g/L compared to 7-10 g/L with IV iron 5

Risk of iron overload:

• Chronic indiscriminate use of IV iron can lead to iatrogenic hemosiderosis 8
• Adhere strictly to ferritin and TSAT upper limits to avoid excessive iron administration 1, 4, 8
• Monitor for signs of iron overload, particularly with cumulative high-dose therapy 8