The safety of available treatment options for iron-deficiency anemia

Expert Opinion on Drug Safety

Volumn 17, Issue 2, 2018, Pages 149-159

  Muñoz, Manuel ^a   Gómez Ramírez, Susana ^b   Bhandari, Sunil ^c  

^a UNIVERSITY OF MÁLAGA   (Spain)

^b HOSPITAL UNIVERSITARIO VIRGEN DE LA VICTORIA   (Spain)

^c HULL AND EAST YORKSHIRE HOSPITALS NHS TRUST   (United Kingdom)

Author keywords

anaemia; intravenous iron; Iron deficiency; oral iron; safety

Indexed keywords

FERRITIN; IRON; IRON DERIVATIVE;

ALLERGIC REACTION; ANAPHYLAXIS; COMPARATIVE EFFECTIVENESS; DIAGNOSTIC ACCURACY; FERRITIN BLOOD LEVEL; GASTROINTESTINAL SYMPTOM; HUMAN; HYPOPHOSPHATEMIA; HYPOTENSION; INFECTION RISK; IRON DEFICIENCY ANEMIA; MAINTENANCE THERAPY; MINERAL SUPPLEMENTATION; MORTALITY; OXIDATIVE STRESS; PATIENT SAFETY; REVIEW; VITAMIN SUPPLEMENTATION; ANIMAL; COMPARATIVE STUDY; DOSE RESPONSE; INFLAMMATION; INTRAVENOUS DRUG ADMINISTRATION; ORAL DRUG ADMINISTRATION; PATHOLOGY;

ADMINISTRATION, INTRAVENOUS; ADMINISTRATION, ORAL; ANEMIA, IRON-DEFICIENCY; ANIMALS; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; INFLAMMATION; IRON COMPOUNDS;

EID: 85041104035     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1080/14740338.2018.1400009     Document Type: Review

References (119)

1. Kassebaum NJ, Jasrasaria R, Naghavi M, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014;123:615–624.
2. Camaschella C., Iron-deficiency anemia. N Engl J Med. 2015;372:1832–1843.
3. WHO. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Geneva, Switzerland: Vitamin and Mineral Nutrition Information System, World Health Organization; 2011.
4. Muñoz M, Gómez-Ramírez S, Campos A, et al. Pre-operative anaemia: prevalence, consequences and approaches to management. Blood Transfus. 2015;13:370–379.
5. Muñoz M, Acheson AG, Auerbach M, et al. International consensus statement on the peri-operative management of anaemia and iron deficiency. Anaesthesia. 2017;72:233–247.
6. Mast AE, Blinder MA, Gronowski AM, et al. Clinical utility of the soluble transferrin receptor and comparison with serum ferritin in several populations. Clin Chem. 1998;44:45–51.
7. Muñoz M, García-Erce JA, Remacha AF., Disorders of iron metabolism. Part II: iron deficiency and iron overload. J Clin Pathol. 2011;64:287–296.
8. Thomas DW, Hinchliffe RF, Briggs C, et al. British committee for standards in haematology. Guideline for the laboratory diagnosis of functional iron deficiency. Br J Haematol. 2013;161:639–648.
9. Auerbach M, Adamson JW. How we diagnose and treat iron deficiency anemia. Am J Hematol. 2016;91:31–38.
10. Martin-Cabrera P, Hung M, Ortmann E, et al. Clinical use of low haemoglobin density, transferrin saturation, bone marrow morphology, Perl’s stain and other plasma markers in the identification of treatable anaemia presenting for cardiac surgery in a prospective cohort study. J Clin Pathol. 2015;68:923–930.
11. Schrier SL, Auerbach M, Treatment of iron deficiency anemia in adults. UpToDate. 2017. cited 2017 Apr. Available from: https://www.uptodate.com/contents/treatment-of-iron-deficiency-anemia-in-adults
12. Parker MJ. Iron supplementation for anemia after hip fracture surgery: a randomized trial of 300 patients. J Bone Joint Surg Am. 2010 Feb;92(2):265–269.
13. Prasad N, Rajamani V, Hullin D, et al. Post-operative anaemia in femoral neck fracture patients: does it need treatment? A single blinded prospective randomised controlled trial. Injury. 2009 Oct;40(10):1073–1076.
14. Mundy GM, Birtwistle SJ, Power RA. The effect of iron supplementation on the level of haemoglobin after lower limb arthroplasty. J Bone Joint Surg Br. 2005 Feb;87(2):213–217.
15. Weatherall M, Maling TJ. Oral iron therapy for anaemia after orthopaedic surgery: randomized clinical trial. ANZ J Surg. 2004 Dec;74(12):1049–1051.
16. Sutton PM, Cresswell T, Livesey JP, et al. Treatment of anaemia after joint replacement. A double-blind, randomised, controlled trial of ferrous sulphate versus placebo. J Bone Joint Surg Br. 2004 Jan;86(1):31–33.
17. Crosby L, Palarski VA, Cottington E, et al. Iron supplementation for acute blood loss anemia after coronary artery bypass surgery: a randomized, placebo-controlled study. Heart Lung. 1994 Nov-Dec;23(6):493–499.
18. Goodnough LT, Comin-Colet J, Leal-Noval S, et al. Management of anemia in patients with congestive heart failure. Am J Hematol. 2017;92:88–93.
19. Lewis GD, Malhotra R, Hernandez AF, et al. Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: the IRONOUT HF randomized clinical trial. JAMA. 2017 May 16;317(19):1958–1966.
20. Shepshelovich D, Rozen-Zvi B, Avni T, et al. Intravenous versus oral iron supplementation for the treatment of anemia in CKD: an updated systematic review and meta-analysis. Am J Kidney Dis. 2016;68:677–690.
21. Muñoz M, García-Erce JA, Remacha AF. Disorders of iron metabolism. Part I: molecular basis of iron homeostasis. J Clin Pathol. 2011;64:281–286.
22. Santiago P. Ferrous versus ferric oral iron formulations for the treatment of iron deficiency: a clinical overview. Sci World J. 2012;2012:846824.
23. Kaltwasser JP, Hansen C, Oebike Y, et al. Assessment of iron availability using stable 54Fe. Eur J Clin Invest. 1991;21:436–441.
24. Moretti D, Goede JS, Zeder C, et al. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015;126:1981–1989.
25. Rimon E, Kagansky N, Kagansky M, et al. Are we giving too much iron? Low-dose iron therapy is effective in octogenarians. Am J Med. 2005;118:1142–1147.
26. WHO model formulary 2008 (based on WHO model list of essential medicines). [cited 2016 June 17]. Available from: http://www.who.int/selection_medicines/list/en/index.html
27. Gasche C, Ahmad T, Tulassay Z, et al. Ferric maltol is effective in correcting iron deficiency anemia in patients with inflammatory bowel disease: results from a phase-3 clinical trial program. Inflamm Bowel Dis. 2015;21:579–588.
28. Schmidt C, Ahmad T, Tulassay Z, et al., AEGIS Study Group. Ferric maltol therapy for iron deficiency anaemia in patients with inflammatory bowel disease: long-term extension data from a Phase 3 study. Aliment Pharmacol Ther. 2016 Aug; 44(3):259–270.
29. Mafodda A, Giuffrida D, Prestifilippo A, et al. Oral sucrosomial iron versus intravenous iron in anemic cancer patients without iron deficiency receiving darbepoietin alpha: a phase II prospective multicenter study. Support Care Cancer. 2017;25:2779–2786. Epub ahead of print. DOI:10.1007/s00520-017-3690-z
30. Pisani A, Riccio E, Sabbatini M, et al. Effect of oral liposomal iron versus intravenous iron for treatment of iron deficiency anaemia in CKD patients: a randomized trial. Nephrol Dial Transplant. 2015;30:645–652.
31. European Medicines Agency. New recommendations to manage risk of allergic reactions with intravenous iron containing medicines. EMA/579491/2013. cited 2017 Jan18. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/IV_iron_31/WC500151308.pdf
32. Muñoz M, Breymann C, García-Erce JA, et al. Efficacy and safety of intravenous iron therapy as an alternative/adjunct to allogeneic blood transfusion. Vox Sang. 2008;94:172–183.
33. Auerbach M, Muñoz M. Intravenous iron for treating cancer-induced anemia: meeting an unmet need? Chin Clin Oncol. 2012;1:21–23.
34. Auerbach M, Adamson J, Bircher A, et al. On the safety of intravenous iron, evidence trumps conjecture. Haematologica. 2015;100:e214–5.
35. Muñoz M, Gómez-Ramírez S, Besser M, et al. Current misconceptions in diagnosis and management of iron deficiency. Blood Transfus. 2017;15:422–437.
36. Chertow GM, Mason PD, Vaage-Nilsen O, et al. Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant. 2006;21(2):378–382.
37. Bolton-Maggs PH, Cohen H. Serious Hazards of Transfusion (SHOT) haemovigilance and progress is improving transfusion safety. Br J Haematol. 2013;163(3):303–314.
38. Auerbach M, Macdougall I. The available intravenous iron formulations: History, efficacy, and toxicology. Hemodial Int. 2017;21(Suppl 1):S83–S89.
39. Bhandari S. Update of a comparative analysis of cost minimization following the introduction of newly available intravenous iron therapies in hospital practice. Ther Clin Risk Manag. 2011;7:501–509.
40. Wilson PD, Hutchings A, Jeans A, et al. An analysis of the health service efficiency and patient experience with two different intravenous iron preparations in a UK anaemia clinic. J Med Econ. 2013;16:108–114.
41. Calvet X, Ruíz MÀ, Dosal A, et al. Cost-minimization analysis favours intravenous ferric carboxymaltose over ferric sucrose for the ambulatory treatment of severe iron deficiency. PLoS One. 2012;7:e45604.
42. Calvet X, Gene E, Ruiz MA, et al. Cost-minimization analysis favours intravenous ferric carboxymaltose over ferric sucrose or oral iron as preoperative treatment in patients with colon cancer and iron deficiency anaemia. Technol Health Care. 2016;24:111–120.
43. Fishbane SN, Singh AK, Cournoyer SH, et al. Ferric pyrophosphate citrate (Triferic™) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients. Nephrol Dial Transplant. 2015;30:2019–2026.
44. Gupta A, Lin V, Guss C, et al. Ferric pyrophosphate citrate administered via dialysate reduces erythropoiesis-stimulating agent use and maintains hemoglobin in hemodialysis patients. Kidney Int. 2015;88:1187–1194.
45. Cancelo-Hidalgo MJ, Castelo-Branco C, Palacios S, et al. Tolerability of different oral iron supplements: a systematic review. Curr Med Res Opin. 2013;29:291–303.
46. Tolkien Z, Stecher L, Mander AP, et al. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One. 2015;10:e0117383.
47. Avni T, Bieber A, Grossman A, et al. The safety of intravenous iron preparations: systematic review and meta-analysis. Mayo Clinic Proc. 2015;90:12–23.
48. Dull RB, Davis E. Heme iron polypeptide for the management of anaemia of chronic kidney disease. J Clin Pharm Ther. 2015 Aug;40(4):386–390.
49. Muñoz M, Martín-Montañez E. Ferric carboxymaltose for the treatment of iron-deficiency anemia. Expert Opin Pharmacother. 2012 Apr;13(6):907–921.
50. Kalra PA, Bhandari S. Efficacy and safety of iron isomaltoside (Monofer®) in the management of patients with iron deficiency anemia. Int J Nephrol Renovasc Dis. 2016 Mar;10(9):53–64.
51. Derman R, Roman E, Modiano MR, et al. A randomized trial of iron isomaltoside versus iron sucrose in patients with iron deficiency anemia. Am J Hematol. 2017 Mar;92(3):286–291.
52. Kalra PA, Bhandari S, Saxena S, et al. A randomized trial of ironisomaltoside 1000 versus oral iron in non-dialysis-dependentchronic kidney disease patients with anaemia. Nephrol Dial Transplant. 2016 Apr;31(4):646–655.
53. Rosner MH, Auerbach M. Ferumoxytol for the treatment of iron deficiency. Expert Rev Hematol. 2011 Aug;4(4):399–406.
54. Jahn MR, Andreasen HB, Fütterer S, et al. A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications. Eur J Pharm Biopharm. 2011 Aug;78(3):480–491.
55. European Medicines Agency. New recommendations to manage risk of allergic reactions with intravenous iron containing medicines. EMA/579491/2013. [cited 2017 Jan18]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/IV_iron_31/WC500151308.pdf
56. Auerbach M, Macdougall IC. Safety of intravenous iron formulations: facts and folklore. Blood Transfus. 2014 Jul;12(3):296–300.
57. Szebeni J, Fishbane S, Hedenus M, et al. Hypersensitivity to intravenous iron: classification, terminology, mechanisms and management. Br J Pharmacol. 2015 Nov;172(21):5025–5036.
58. Hempel JC, Poppelaars F, Gaya da Costa M, et al. Distinct in vitro complement activation by various intravenous iron preparations. Am J Nephrol. 2017;45(1):49–59.
59. Wang C, Graham DJ, Kane RC, et al. Comparative risk of anaphylactic reactions associated with intravenous iron products. Jama. 2015;314:2062–2068.
60. Kalra PA, Bhandari S. Safety of intravenous iron use in chronic kidney disease. Curr Opin Nephrol Hypertens. 2016;25:529–535.
61. DeLoughery TG, Auerbach M. Is low-molecular weight iron dextran really the most risky iron? Unconvincing data from an unconvincing study. Am J Hematol. 2016;91:451–452.
62. Wysowski DK, Swartz L, Borders-Hemphill BV, et al. Use of parenteral iron products and serious anaphylactic-type reactions. Am J Hematol. 2010;85:650–654.
63. Auerbach M, Ballard H, Glaspy J. Clinical update: intravenous iron for anaemia. Lancet. 2007;369:1502–1504.
64. Macdougall IC, Bircher AJ, Eckardt KU, et al. Conference Participants. Iron management in chronic kidney disease: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int. 2016;89:28–39.
65. Rampton D, Folkersen J, Fishbane S, et al. Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management. Haematologica. 2014;99(11):1671–1676.
66. Drakesmith H, Prentice AM. Hepcidin and the iron-infection axis. Science. 2012;338:768–772.
67. Pasricha S-R, Drakesmith H. Iron deficiency anemia. Hematol Oncol Clin America. 2016;30:309–325.
68. Agarwal R, Kusek JW, Pappas MK. A randomized trial of intravenous and oral iron in chronic kidney disease. Kidney Int. 2015;88:905–914.
69. Bhandari S, Kalra PA, Coyne DW. Data confusion. Kidney Int. 2015 Dec;88(6):1445. DOI:10.1038/ki.2015.303.
70. Litton E, Xiao J, Ho KM. Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials. Br Med J. 2013;347:f4822.
71. Muñoz M, Gómez-Ramírez S, Cuenca J, et al. Very-short-term perioperative intravenous iron administration and postoperative outcome in major orthopedic surgery: a pooled analysis of observational data from 2547 patients. Transfusion. 2014;54:289–299.
72. Torres S, Kuo YH, Morris K, et al. Intravenous iron following cardiac surgery does not increase the infection rate. Surg Infect (Larchmt). 2006 Aug;7(4):361–366.
73. Froessler B, Palm P, Weber I, et al. The important role for intravenous iron in perioperative patient blood management in major abdominal surgery: a randomized controlled trial. Ann Surg. 2016;264:41–46.
74. Keeler BD, Simpson JA, Ng O, et al. Randomized clinical trial of preoperative oral versus intravenous iron in anaemic patients with colorectal cancer. Br J Surg. 2017;104:214–221. Epub ahead of print. DOI:10.1002/bjs.10328
75. Bisbe E, Molto L, Arroyo R, et al. Randomised trial comparing ferric carboxymaltose vs oral ferrous glycine sulphate for postoperative anaemia after total knee arthroplasty. Br J Anaesth. 2014;113:402–409.
76. Litton E, Baker S, Erber WN, et al.; The IRONMAN Investigators. Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial. A randomized trial of IV iron in critical illness. Intensive Care Med. 2016;42:1715–1722.
77. Khalafallah AA, Yan C, Al-Badri R, et al. Intravenous ferric carboxymaltose versus standard care in the management of postoperative anaemia: a prospective, open-label, randomized controlled trial. Lancet Haematol. 2016;3:e415–25.
78. Beris P, Muñoz M, García-Erce JA, et al. Perioperative anaemia management: consensus statement on the role of intravenous iron. Br J Anaesth. 2008;100:599–604.
79. Zoller H, Schaefer B, Glodny B. Iron-induced hypophosphatemia: an emerging complication. Curr Opin Nephrol Hypertens. 2017 Jul;26(4):266–275.
80. Rosner MH, Auerbach M. Ferumoxytol for the treatment of iron deficiency. Expert Rev Hematol. 2011;4:399–406.
81. Schaefer B, Würtinger P, Finkenstedt A, et al. Choice of high-dose intravenous iron preparation determines hypophosphatemia risk. PLoS ONE. 2016;11:e0167146.
82. Food and drug administration center for drug evaluation and research. Summary minutes of the drug safety and risk management advisory committee, February 1, 2008. [cited 2010 Jan 25]. Available from: http://www.fda.gov/ohrms/dockets/AC/08/minutes/2008-4337m1-Final.pdf.
83. Wolf M, Koch TA, Bregman DB. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Mineral Res. 2013;28:1793–1803.
84. Wolf M, White KE. Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease. Curr Opin Nephrol Hypertens. 2014;23:411–419. Epub 2014/05/29. PubMed Central.
85. Bager P, Hvas CL, Dahlerup JF. Drug-specific hypophosphatemia and hypersensitivity reactions following different intravenous iron infusions. Br J Clin Pharmacol. 2016 Nov 17. Epub ahead of print. DOI:10.1111/bcp.13189
86. Prats M, Font R, García C, et al. Effect of ferric carboxymaltose on serum phosphate and C-terminal FGF23 levels in non-dialysis chronic kidney disease patients: post-hoc analysis of a prospective study. BMC Nephrol. 2013;14:167.
87. Hardy S, Vandemergel X. Intravenous iron administration and hypophosphatemia in clinical practice. Int J Rheumatol. 2015;2015:468675.
88. Bhandari S. Risk factors and metabolic mechanisms in the pathogenesis of uraemic cardiac disease. Front Biosci (Landmark Ed). 2011;16:1364–1387.
89. Halliwell B, Gutteridge J. Role of free radicals and catalytic metal ions in human disease: an overview. Meth Enzymol. 1990;186:1–85.
90. Knovich MA, Storey JA, Coffman LG, et al. Ferritin for the clinician. Blood Rev. 2009;23(3):95–104.
91. Aljwaid H, White DL, Collard KJ, et al. Non-transferrin-bound iron is associated with biomarkers of oxidative stress, inflammation and endothelial dysfunction in type 2 diabetes. J Diabetes Complicat. 2015;29(7):943–949.
92. Fell LH, Zawada AM, Rogacev KS, et al. Distinct immunologic effects of different intravenous iron preparations on monocytes. Nephrol Dial Transplant. 2014;29:809–822.
93. Kamanna VS, Ganji SH, Shelkovnikov S, et al. Iron sucrose promotes endothelial injury and dysfunction and monocyte adhesion/infiltration. Am J Nephrol. 2012;35:114–119.
94. Kuo KL, Hung SC, Wei YH, et al. Intravenous iron exacerbates oxidative DNA damage in peripheral blood lymphocytes in chronic hemodialysis patients. J Am Soc Nephrol. 2008;19(9):1817–1826.
95. Kuo KL, Hung SC, Lee TS, et al. Iron sucrose accelerates early atherogenesis by increasing superoxide production and up-regulating adhesion molecules in CKD. J Am Soc Nephrol. 2014;25(11):2596–2606.
96. Kuo K-L, Hung S-C, Lin Y-P, et al. Intravenous ferric chloride hexahydrate supplementation induced endothelial dysfunction and increased cardiovascular risk among hemodialysis patients. PLoS ONE. 2012;7(12):e50295.
97. Mimic-Oka J, Savić-Radojević A, Pljesa-Ercegovac M, et al. Evaluation of oxidative stress after repeated intravenous iron supplementation. Renal Failure. 2005;27(3):345–351.
98. Scheiber- Monjdehkar B, Lutzky B, Schaufler R, et al. Non–transferrin-bound iron in the serum of hemodialysis patients who receive ferric saccharate: no correlation to peroxide generation. J Am Soc Nephrol. 2004;15:1648–1655.
99. Feldman HI, Joffe M, Robinson B, et al. Administration of parenteral iron and mortality among hemodialysis patients. J Am Soc Nephrol. 2004;15(6):1623–1632.
100. Zager RA, Johnson AC, Hanson SY, et al. Parenteral iron formulations: a comparative toxicologic analysis and mechanisms of cell injury. Am J Kidney Dis. 2002;40(1):90–103.
101. Zager RA, Johnson AC, Hanson SY, et al. Parenteral iron nephrotoxicity: potential mechanisms and consequences. Kidney Int. 2004;66(1):144–156.
102. Shah S, Baliga R, Rajapurkar M, et al. Oxidants in chronic kidney disease. J Am Soc Nephro. 2007;18(1):16–28.
103. Agarwal R, Rizkala AR, Kaskas MO, et al. Iron sucrose causes greater proteinuria than ferric gluconate in non-dialysis chronic kidney disease. Kidney Int. 2007;72(5):638–642.
104. Agarwal R, Leehey DJ, Olsen SM, et al. Proteinuria induced by parenteral iron in chronic kidney disease–a comparative randomized controlled trial. Clin J Am Soc Nephrol. 2011;6(1):114–121.
105. Agarwal R, Kusek JW, Pappas MK. A randomized trial of intravenous and oral iron in chronic kidney disease. Kidney Int. 2015;88:905–914.
106. Connor JR, Zhang X, Nixon AM, et al. Comparative evaluation of nephrotoxicity and management by macrophages of intravenous pharmaceutical iron formulations. PLoS ONE. 2015;10(5):e0125272.
107. Martin-Malo A, Merino A, Carracedo A, et al. Effects of intravenous iron on mononuclear cells during the haemodialysis session. Nephrol Dial Transplant. 2012;27:2465–2471.
108. Bhandari S. Iron therapy in patients with chronic kidney disease. Transfus Alternatives Transfus Med. 2012;1–7. DOI:10.1111/j.1778-428X.2012.01156.x
109. Ponikowski P, Filippatos G, Colet JC, et al. The impact of intravenous ferric carboxymaltose on renal function: an analysis of the FAIR-HF study. Eur J Heart Fail. 2014;17(3):329–339.
110. Drüeke T, Witko-Sarsat V, Massy Z, et al. Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease. Circulation. 2002;106:2212–2217.
111. Ponikowski P, Van Veldhuisen DJ, Comin-Colet J, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J. 2014;36(11):657–668.
112. Taylor D, Bhandari S, Seymour A, M. Mitochondrial dysfunction in uremic cardiomyopathy. Am J Physiol Renal Physiol. 2015;308(6):F579–587.
113. Nuhu F, Seymour AM, Sturmey R, et al. Iron therapy modifies oxidative stress in uraemic cardiomyopathy [TH-PO486]. J Am Soc Nephrol 2017;28 (Abstract edition):225.
114. Bailie GR. Comparison of rates of reported adverse events associated with i.v. iron products in the United States. Am J Health Syst Pharm. 2012;69:310–320.
115. Bailie GR, Larkina M, Goodkin DA, et al. Data from the dialysis outcomes and practice patterns study validate an association between high intravenous iron doses and mortality. Kidney Int. 2015 Jan;87(1):162–168.
116. Carson JL, Stanworth SJ, Roubinian N, et al. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev. 2016;10:CD002042.
117. Weiss G. Anemia of chronic disorders: new diagnostic tools and new treatment strategies. Semin Hematol. 2015;52:313–320.
118. Besarab A, Chernyavskaya E, Motylev I, et al. Roxadustat (FG-4592): correction of anemia in incident dialysis patients. J Am Soc Nephrol. 2016;27:1225–1233.
119. Grabner A, Amaral AP, Schramm K, et al. Activation of cardiac fibroblast growth factor receptor 4 causes left ventricular hypertrophy. Cell Metab. 2015 Dec 1;22(6):1020–1023.