UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Treatment of iron deficiency in nondialysis chronic kidney disease (CKD) patients

Author
Jeffrey S Berns, MD
Section Editor
Thomas A Golper, MD
Deputy Editor
Alice M Sheridan, MD

INTRODUCTION

Anemia is common among patients with chronic kidney disease (CKD). Anemia underlies many of the symptoms associated with reduced kidney function and is associated with increased mortality and hospitalizations [1-4].

Among CKD patients, iron deficiency is a common, reversible cause of anemia and resistance to erythropoiesis-stimulating agents (ESAs). The administration of iron is necessary for treatment of iron deficiency and, in selected patients, may allow a higher hemoglobin (Hb) in the absence of ESAs.

This topic reviews screening for iron deficiency, the indications for iron therapy, and options for treatment of iron deficiency among nondialysis CKD patients. The treatment of iron deficiency in dialysis patients is discussed elsewhere. (See "Treatment of iron deficiency in hemodialysis patients" and "Treatment of iron deficiency in peritoneal dialysis patients".)

Indications for treatment with ESAs are discussed separately. (See "Treatment of anemia in hemodialysis patients" and "Treatment of anemia in peritoneal dialysis patients" and "Treatment of anemia in nondialysis chronic kidney disease".)

DIAGNOSIS OF IRON DEFICIENCY

We use the serum iron, total iron-binding capacity (TIBC), and ferritin and calculation of the percent transferrin saturation (TSAT) to estimate iron stores. Other methods including the percentage of hypochromic red blood cells (RBCs) or reticulocyte hemoglobin (Hb) content are not widely available in the United States but may be more widely used in Europe. Bone marrow biopsies are considered the gold standard for diagnosis but are not commonly used among CKD patients. (See "Diagnosis of iron deficiency in chronic kidney disease".)

            

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Thu Nov 17 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Ma JZ, Ebben J, Xia H, Collins AJ. Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol 1999; 10:610.
  2. Xia H, Ebben J, Ma JZ, Collins AJ. Hematocrit levels and hospitalization risks in hemodialysis patients. J Am Soc Nephrol 1999; 10:1309.
  3. Collins AJ, Li S, St Peter W, et al. Death, hospitalization, and economic associations among incident hemodialysis patients with hematocrit values of 36 to 39%. J Am Soc Nephrol 2001; 12:2465.
  4. Collins AJ, Ma JZ, Ebben J. Impact of hematocrit on morbidity and mortality. Semin Nephrol 2000; 20:345.
  5. World Health Organization. Nutritional Anaemias: Report of a WHO Scientific Group. Geneva, Switzerland: World Health Organization, 1968.
  6. Macdougall IC, Tucker B, Thompson J, et al. A randomized controlled study of iron supplementation in patients treated with erythropoietin. Kidney Int 1996; 50:1694.
  7. Tessitore N, Solero GP, Lippi G, et al. The role of iron status markers in predicting response to intravenous iron in haemodialysis patients on maintenance erythropoietin. Nephrol Dial Transplant 2001; 16:1416.
  8. Fishbane S, Kowalski EA, Imbriano LJ, Maesaka JK. The evaluation of iron status in hemodialysis patients. J Am Soc Nephrol 1996; 7:2654.
  9. Kalantar-Zadeh K, Höffken B, Wünsch H, et al. Diagnosis of iron deficiency anemia in renal failure patients during the post-erythropoietin era. Am J Kidney Dis 1995; 26:292.
  10. Fishbane S, Shapiro W, Dutka P, et al. A randomized trial of iron deficiency testing strategies in hemodialysis patients. Kidney Int 2001; 60:2406.
  11. Stancu S, Bârsan L, Stanciu A, Mircescu G. Can the response to iron therapy be predicted in anemic nondialysis patients with chronic kidney disease? Clin J Am Soc Nephrol 2010; 5:409.
  12. Van Wyck DB, Roppolo M, Martinez CO, et al. A randomized, controlled trial comparing IV iron sucrose to oral iron in anemic patients with nondialysis-dependent CKD. Kidney Int 2005; 68:2846.
  13. Stoves J, Inglis H, Newstead CG. A randomized study of oral vs intravenous iron supplementation in patients with progressive renal insufficiency treated with erythropoietin. Nephrol Dial Transplant 2001; 16:967.
  14. Charytan C, Qunibi W, Bailie GR, Venofer Clinical Studies Group. Comparison of intravenous iron sucrose to oral iron in the treatment of anemic patients with chronic kidney disease not on dialysis. Nephron Clin Pract 2005; 100:c55.
  15. Agarwal R, Rizkala AR, Bastani B, et al. A randomized controlled trial of oral versus intravenous iron in chronic kidney disease. Am J Nephrol 2006; 26:445.
  16. Albaramki J, Hodson EM, Craig JC, Webster AC. Parenteral versus oral iron therapy for adults and children with chronic kidney disease. Cochrane Database Syst Rev 2012; 1:CD007857.
  17. Agarwal R, Kusek JW, Pappas MK. A randomized trial of intravenous and oral iron in chronic kidney disease. Kidney Int 2015; 88:905.
  18. Macdougall IC, Roger SD. New data on the safety of IV iron-but why the discrepancy with FIND-CKD? Kidney Int 2015; 88:1445.
  19. Macdougall IC, Bock AH, Carrera F, et al. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant 2014; 29:2075.
  20. Auerbach M, Adamson J, Bircher A, et al. On the safety of intravenous iron, evidence trumps conjecture. Haematologica 2015; 100:e214.
  21. Chapter 1: Diagnosis and evaluation of anemia in CKD. Kidney Int Suppl (2011) 2012; 2:288.
  22. https://www.nice.org.uk/guidance/ng8/resources/chronic-kidney-disease-managing-anaemia-51046844101.
  23. Lewis JB, Sika M, Koury MJ, et al. Ferric citrate controls phosphorus and delivers iron in patients on dialysis. J Am Soc Nephrol 2015; 26:493.
  24. Block GA, Fishbane S, Rodriguez M, et al. A 12-week, double-blind, placebo-controlled trial of ferric citrate for the treatment of iron deficiency anemia and reduction of serum phosphate in patients with CKD Stages 3-5. Am J Kidney Dis 2015; 65:728.
  25. Nissenson AR, Berns JS, Sakiewicz P, et al. Clinical evaluation of heme iron polypeptide: sustaining a response to rHuEPO in hemodialysis patients. Am J Kidney Dis 2003; 42:325.
  26. Nagaraju SP, Cohn A, Akbari A, et al. Heme iron polypeptide for the treatment of iron deficiency anemia in non-dialysis chronic kidney disease patients: a randomized controlled trial. BMC Nephrol 2013; 14:64.
  27. Dull RB, Davis E. Heme iron polypeptide for the management of anaemia of chronic kidney disease. J Clin Pharm Ther 2015; 40:386.
  28. 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.
  29. Rodgers GM, Auerbach M, Cella D, et al. High-molecular weight iron dextran: a wolf in sheep's clothing? J Am Soc Nephrol 2008; 19:833.
  30. Auerbach M, Ballard H. Clinical use of intravenous iron: administration, efficacy, and safety. Hematology Am Soc Hematol Educ Program 2010; 2010:338.
  31. Auerbach M, Adamson JW. How we diagnose and treat iron deficiency anemia. Am J Hematol 2016; 91:31.
  32. Landry R, Jacobs PM, Davis R, et al. Pharmacokinetic study of ferumoxytol: a new iron replacement therapy in normal subjects and hemodialysis patients. Am J Nephrol 2005; 25:400.
  33. Spinowitz BS, Schwenk MH, Jacobs PM, et al. The safety and efficacy of ferumoxytol therapy in anemic chronic kidney disease patients. Kidney Int 2005; 68:1801.
  34. Spinowitz BS, Kausz AT, Baptista J, et al. Ferumoxytol for treating iron deficiency anemia in CKD. J Am Soc Nephrol 2008; 19:1599.
  35. Provenzano R, Schiller B, Rao M, et al. Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients. Clin J Am Soc Nephrol 2009; 4:386.
  36. Macdougall IC, Roche A. Administration of intravenous iron sucrose as a 2-minute push to CKD patients: a prospective evaluation of 2,297 injections. Am J Kidney Dis 2005; 46:283.
  37. Chandler G, Harchowal J, Macdougall IC. Intravenous iron sucrose: establishing a safe dose. Am J Kidney Dis 2001; 38:988.
  38. Grimmelt AC, Cohen CD, Fehr T, et al. Safety and tolerability of ferric carboxymaltose (FCM) for treatment of iron deficiency in patients with chronic kidney disease and in kidney transplant recipients. Clin Nephrol 2009; 71:125.
  39. Onken JE, Bregman DB, Harrington RA, et al. Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial. Nephrol Dial Transplant 2014; 29:833.
  40. Kalra PA, Bhandari S, Saxena S, et al. A randomized trial of iron isomaltoside 1000 versus oral iron in non-dialysis-dependent chronic kidney disease patients with anaemia. Nephrol Dial Transplant 2016; 31:646.
  41. Jain AK, Bastani B. Safety profile of a high dose ferric gluconate in patients with severe chronic renal insufficiency. J Nephrol 2002; 15:681.
  42. Sloand JA, Shelly MA, Erenstone AL, et al. Safety and efficacy of total dose iron dextran administration in patients on home renal replacement therapies. Perit Dial Int 1998; 18:522.
  43. Prakash S, Walele A, Dimkovic N, et al. Experience with a large dose (500 mg) of intravenous iron dextran and iron saccharate in peritoneal dialysis patients. Perit Dial Int 2001; 21:290.
  44. Blaustein DA, Schwenk MH, Chattopadhyay J, et al. The safety and efficacy of an accelerated iron sucrose dosing regimen in patients with chronic kidney disease. Kidney Int Suppl 2003; :S72.
  45. Bastani B, Jain A, Pandurangan G. Incidence of side-effects associated with high-dose ferric gluconate in patients with severe chronic renal failure. Nephrology (Carlton) 2003; 8:8.
  46. Danda RS, Kirk LJ, Pergola PE. High-dose iron gluconate in chronic kidney disease patients. Nephrology (Carlton) 2004; 9:47.
  47. Folkert VW, Michael B, Agarwal R, et al. Chronic use of sodium ferric gluconate complex in hemodialysis patients: safety of higher-dose (> or =250 mg) administration. Am J Kidney Dis 2003; 41:651.
  48. Kosch M, Bahner U, Bettger H, et al. A randomized, controlled parallel-group trial on efficacy and safety of iron sucrose (Venofer) vs iron gluconate (Ferrlecit) in haemodialysis patients treated with rHuEpo. Nephrol Dial Transplant 2001; 16:1239.
  49. Agarwal R, Vasavada N, Sachs NG, Chase S. Oxidative stress and renal injury with intravenous iron in patients with chronic kidney disease. Kidney Int 2004; 65:2279.