We recommend regular monitoring of iron status (every 1-3 months) in people receiving intravenous iron to avoid toxicity. (defined as a serum ferritin >800 mcg/L or TSAT >40%) (1B)
Guideline 2.7.1
We recommend that a serum ferritin consistently >800 mcg/L with no evidence of inflammation (normal CRP) is suggestive of iron overload or potential iron toxicity. (1B)
Rationale
Intravenous iron therapy has potential risks as well as benefits. Toxicity associated with high ferritin outcomes was originally reported in the context of multiple transfusions in the pre-ESA era. The risk persists that intravenous iron may reproduce similar toxicity and thus regular monitoring during therapy is required. Similarly, with ongoing iron losses on HD, regular monitoring to avoid worsening iron deficiency is required (1, 3). The safety of persistently very high ferritin levels remains unknown. In a cohort of 58058 prevalent people receiving haemodialysis in the USA, both all-cause and cardiovascular mortality had increasing rates across increasing ferritin levels, whereas the opposite (inverse) association was observed for TSAT increments. Serum ferritin levels between 200 and 1200 microgram/L and iron saturation ratio between 30 and 50% were associated with the lowest all-cause and cardiovascular death risks. However, association studies are biased by the fact that serum ferritin is also a marker of inflammation. In unadjusted, time-varying model, serum ferritin >800 microgram/L during each quarter was associated with increased death rate (4). Significant iron overload in the liver and spleen (assessed through T 2 magnetic resonance) has been described in 19 of 21 people receiving HD with serum ferritin >1000 microgram/L and severe comorbidities who were treated with IV iron (5). Similarly, Rostoker et al (6). prospectively studied a cohort of 119 fit people receiving HD who were receiving iron and ESA therapy and measured their liver iron content by means of T 1 and T 2 magnetic resonance. Mild to severe hepatic iron overload was observed in 84% of the people, 36% of whom had severe iron overload approaching that found in haemocromatosis (7).
Clinical settings in which more frequent iron testing may be necessary include the following:
- Initiation of ESA therapy
- Achieving less-than-target Hb level during ongoing ESA therapy
- Recent bleeding
- After surgery
- After hospitalisation
- Monitoring response after a course of IV iron
- Evaluation for ESA hypo-responsiveness
References
- National Collaborating Centre for Chronic Conditions, Royal College of Physicians. Guideline on anaemia management in chronic kidney disease. 2015. National Institute for Clinical Excellence. http://www.nice.org.uk/guidance/NG8/evidence. (accessed 15/06/2017)
- Locatelli F, Aljama P, Barany P et al. Revised European Best Practice Guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004; 19 Suppl 2:1-47.
- NKF-K/DOQI Clinical Practice Guidelines for Anaemia of Chronic Kidney Disease: update 2000. Am J Kidney Dis 2001; 37: S182-S238.4. Kalantar-Zadeh K, Regidor DL, McAllister CJ et al. Time-dependent associations between iron and mortality in haemodialysis patients. J Am Soc Nephrol 2005; 16: 3070–3080
- Rambod M, Kovesdy CP, Kalantar-Zadeh K. Combined high serum ferritin and low iron saturation in haemodialysis patients: the role of inflammation. Clin J Am Soc Nephrol 2008; 3: 1691–1701
- Ghoti H, Rachmilewitz EA, Simon-Lopez R et al. Evidence for tissue iron overload in long-term haemodialysis patients and the impact of withdrawing parenteral iron. Eur J Haematol 2012; 89: 87–93
- Rostoker G, Griuncelli M, Loridon C et al. Haemodialysis-associated hemosiderosis in the Era of erythropoiesis-stimulating Agents: A MRI Study. Am J Med 2012; 125: 991–999
- Ferrari P, Kulkarni H, Dheda S et al. Serum iron markers are inadequate for guiding iron repletion in chronic kidney disease. Clin J Am Soc Nephrol 2011; 6: 77–83