Iron Supplementation in Chronic Kidney Disease

Introduction to Iron Supplementation

The National Kidney Foundation recommends that for oral iron supplementation in chronic kidney disease patients, iron sulfate, fumarate, or gluconate are equally acceptable choices, with iron sulfate being the most cost-effective option providing 65 mg elemental iron per 325 mg tablet 1, 2, 3

The American Journal of Kidney Diseases suggests that intravenous iron is superior to oral iron for most chronic kidney disease patients, particularly those on hemodialysis 4, 5
For hemodialysis patients, intravenous iron is the preferred route and should be used routinely 4

The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative guidelines state that oral iron should be in the form of ionic iron salts (sulfate, fumarate, or gluconate) because they provide known amounts of elemental iron at the lowest cost 1, 2, 3
Ferrous sulfate (325 mg) contains 65 mg elemental iron and is the most cost-effective option at $2.29/month 2, 6
Ferrous fumarate (325 mg) contains 108 mg elemental iron and costs $1.63/month 2, 6
Ferrous gluconate (325 mg) contains 35 mg elemental iron and costs $5.08/month 2, 6

Oral iron absorption is maximized when taken without food or other medications 1, 2, 3, 6
Food consumed within 2 hours before or 1 hour after iron reduces absorption by up to 50% 1, 2, 6
Aluminum-based phosphate binders reduce iron absorption 1, 2, 6

Oral iron usually cannot maintain adequate iron stores in hemodialysis patients treated with erythropoietin-stimulating agents (ESAs) 4, 5
Elevated hepcidin levels in chronic kidney disease patients impair intestinal iron absorption
ESA therapy increases iron demand beyond what oral supplementation can provide 4, 5
Among early non-responders to oral iron, only 21% respond to additional oral therapy versus 65% who respond to IV iron 7

If oral iron fails to maintain transferrin saturation ≥20% and ferritin ≥100 ng/mL (≥200 ng/mL for hemodialysis patients), transition to IV iron is indicated 4, 5

Iron gluconate (IV) is available in 125 mg doses, with no test dose required 4, 5
Iron dextran is available in larger doses (up to 1000 mg) but requires a test dose due to anaphylaxis risk 4, 8
Iron sucrose is available in 100 mg doses, with no test dose required 4, 5
Newer agents (ferumoxytol, ferric carboxymaltose) are available in higher single doses, with no test dose required 7

Do not use iron polysaccharide complex, as it is more expensive, no better tolerated, and was associated with the smallest Hct rise in comparative studies 1, 3
Do not continue oral iron indefinitely in hemodialysis patients, as they require IV iron for adequate erythropoiesis 4, 5
Do not assume test doses prevent anaphylaxis, as severe reactions can occur even after successful test doses and multiple prior administrations 2, 3