What is the recommended approach for using intravenous (IV) iron injections in patients with Chronic Kidney Disease (CKD) and anemia who also have heart failure?

IV Iron Therapy for CKD Anemia with Heart Failure

Intravenous iron therapy, particularly ferric carboxymaltose, is strongly recommended for patients with CKD and anemia who also have heart failure, as it improves exercise capacity, quality of life, and reduces hospitalizations without requiring a test dose. 1

Assessment of Iron Status

• Iron deficiency in CKD with heart failure should be evaluated by measuring ferritin and transferrin saturation, with absolute iron deficiency defined as transferrin saturation ≤20% with serum ferritin ≤100 μg/L in predialysis/peritoneal dialysis patients or ≤200 μg/L in hemodialysis patients 2
• Iron deficiency in heart failure is defined as ferritin <100 μg/L or ferritin 100-300 μg/L with transferrin saturation <20% 2
• Patients should be screened for gastrointestinal causes of iron deficiency when absolute iron deficiency is present, with decisions about endoscopic evaluation made in conjunction with nephrology and cardiology teams 2

IV Iron Formulation Selection

• Several IV iron formulations are available for CKD patients with anemia, including:
  • Ferric carboxymaltose (Injectafer): FDA-approved for both non-dialysis dependent CKD and heart failure patients, with demonstrated benefits in multiple trials 1
  • Iron sucrose: Approved for CKD patients, administered as slow IV infusion at maximum 200 mg per dose, no test dose required 2
  • Ferric gluconate: Indicated for CKD patients, given as slow IV infusion at maximum 125 mg per dose, no test dose required 2
  • Ferumoxytol: Approved for CKD patients, given as 510 mg initial dose followed by second 510 mg dose, no test dose required 2
  • Low molecular weight iron dextran: Requires test dose due to risk of anaphylaxis 2

Dosing Recommendations

• For ferric carboxymaltose in patients with iron deficiency and heart failure (FDA approved):

  • For patients weighing <70 kg with Hb <10 g/dL: 1,000 mg on day 1,500 mg at week 6 1
  • For patients weighing <70 kg with Hb 10-14 g/dL: 1,000 mg on day 1, no dose at week 6 1
  • For patients weighing ≥70 kg with Hb <10 g/dL: 1,000 mg on day 1,000 mg at week 6 1
  • For patients weighing ≥70 kg with Hb 10-14 g/dL: 1,000 mg on day 1,500 mg at week 6 1
  • Maintenance dose of 500 mg at 12,24, and 36 weeks if serum ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20% 1

• For CKD patients on hemodialysis, proactive monthly administration of 400 mg IV iron in patients with serum ferritin <700 μg/L and TSAT ≤40% is recommended based on the PIVOTAL trial 2

Evidence Supporting IV Iron in CKD with Heart Failure

• Multiple clinical trials have demonstrated that IV iron therapy in heart failure patients with iron deficiency:

  • Improves exercise capacity (6-minute walk test distance) 2
  • Improves NYHA functional class and quality of life 2
  • Reduces heart failure hospitalizations 2
  • Benefits are seen regardless of anemia status 2

• The CONFIRM-HF trial showed that ferric carboxymaltose significantly improved 6-minute walk test distance at 24 weeks, with benefits sustained to 52 weeks 2

• The FAIR-HF trial demonstrated improvements in Patient Global Assessment, NYHA class, and quality of life with ferric carboxymaltose 2

Oral vs. IV Iron

• IV iron is preferred over oral iron in CKD patients with heart failure because: 2
  • Oral iron may be poorly absorbed due to gut edema in heart failure 2
  • Oral iron frequently causes side effects (gastrointestinal irritation, constipation) 2
  • IV iron has demonstrated superior efficacy in improving heart failure symptoms 2
  • No prognostic benefit has been demonstrated for oral iron in heart failure 2

Safety Considerations

• Monitor patients for signs of hypersensitivity during and after IV iron administration for at least 30 minutes 1
• Withhold IV iron during active infections as these patients were excluded from clinical trials 2
• Check serum phosphate levels in patients at risk for hypophosphatemia who require repeat treatment 1
• While there are theoretical concerns about iron promoting oxidative stress or increasing infection risk, data from the PIVOTAL trial are reassuring regarding the safety of IV iron at doses used in clinical practice 2

Monitoring

• Evaluate iron status (TSAT and ferritin) at least every 3 months during therapy 2
• Test iron status more frequently when initiating or increasing ESA dose, when there is blood loss, or when monitoring response after IV iron administration 2
• For maintenance therapy in heart failure patients, monitor serum ferritin and transferrin saturation to determine need for additional doses 1