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554 Part VI: The Erythrocyte Chapter 37: Anemia of Chronic Disease 555

beyond 6 to 8 weeks in the absence of response (e.g., <1 to 2 g/dL rise 4. Carpenter WB: Principles of Human Physiology, edited by FG Smith. Blanchard and
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discontinued. The most recent specific guidelines for dose reduction 5. Wintrobe MM: Clinical Hematology, 5th ed. Lea & Febiger, Philadelphia, 1961.
6. Dallman PR, Yip R, Johnson C: Prevalence and causes of anemia in the United States,
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odic monitoring of iron, total iron-binding capacity, transferrin satu- 7. Ramakrishnan U, Yip R: Experiences and challenges in industrialized countries: Con-
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ration, or ferritin levels and instituting iron repletion when indicated 8. Hsu CY, McCulloch CE, Curhan GC: Epidemiology of anemia associated with chronic
may be valuable in limiting the need for EPO, maximizing symptom- renal insufficiency among adults in the United States: Results from the Third National
atic improvement for patients, and determining the reason for failure to Health and Nutrition Examination Survey. J Am Soc Nephrol 13:504, 2002.
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10. McClellan W, Aronoff SL, Bolton WK, et al: The prevalence of anemia in patients with
THERAPY FOR ANEMIA OF CHRONIC KIDNEY chronic kidney disease. Curr Med Res Opin 20:1501, 2004.
DISEASE 11. U.S. Renal Data System: USRDS 2013 Annual Data Report: Atlas of Chronic Kidney Dis-
ease and End-Stage Renal Disease in the United States. National Institutes of Health,
The most current recommendations are The Kidney Disease Improv- National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2013.
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ducted in October 2010 and supplemented with additional evidence 13. Libregts SF, Gutierrez L, de Bruin AM, et al: Chronic IFN-gamma production in
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that a newly anemic patient with CKD should have laboratory studies 14. Baer AN, Dessypris EN, Goldwasser E, et al: Blunted erythropoietin response to
to rule out vitamin B and folate deficiencies (Chap. 41), and a thera- anaemia in rheumatoid arthritis. Br J Haematol 66:559, 1987.
12
peutic trial of IV iron if their transferrin saturation is equal to or less 15. Hochberg MC, Arnold CM, Hogans BB, et al: Serum immunoreactive erythropoietin in
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than 30 percent and ferritin is equal to or less than 500 ng/mL. After 16. Vreugdenhil G, Wognum AW, van Eijk HG, et al: Anaemia in rheumatoid arthritis: The
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iron therapy delays or reduces the need for other anemia management 17. Kendall R, Wasti A, Harvey A, et al: The relationship of haemoglobin to serum ery-
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98
restrictive than those in the guidelines. The guidelines go on to recom- 18. Noe G, Augustin J, Hausdorf S, et al: Serum erythropoietin and transferrin receptor
levels in patients with rheumatoid arthritis. Clin Exp Rheumatol 13:445, 1995.
mend that individualized therapy with ESAs may be started when Hgb 19. Remacha AF, Rodriguez-de la Serna A, Garcia-Die F, et al: Erythroid abnormalities in
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exceeding 11.5 g/dL unless the patient perceives an increased quality of 20. Miller CB, Jones RJ, Piantadosi S, et al: Decreased erythropoietin response in patients
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ADJUNCTIVE USE OF INTRAVENOUS IRON 22. Safran M, Kaelin WG Jr: HIF hydroxylation and the mammalian oxygen-sensing path-
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WITH ERYTHROPOIETIN 23. Imagawa S, Nakano Y, Obara N, et al: A GATA-specific inhibitor (K-7174) rescues ane-
mia induced by IL-1beta, TNF-alpha, or L-NMMA. FASEB J 17:1742, 2003.
This use of IV iron is an empiric therapeutic strategy based on the idea 24. Frede S, Fandrey J, Pagel H, et al: Erythropoietin gene expression is suppressed after
that iron becomes limiting when marrow production of erythrocytes lipopolysaccharide or interleukin-1 beta injections in rats. Am J Physiol 273:R1067,
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is pharmacologically stimulated. In some cases occult iron deficiency 25. Adamson JW, Eschbach J, Finch CA: The kidney and erythropoiesis. Am J Med 44:725,
coexists with AI. 66,93 In other situations, limited iron stores may become 1968.
depleted when EPO is initiated. In hemodialysis patients with high 26. Sato Y, Yanagita M: Renal anemia: From incurable to curable. Am J Physiol Renal Phys-
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ferritin, low transferrin saturation (less than 25 percent), and above iol 305:F1239, 2013.
average EPO requirements, iron supplementation of EPO treatment 27. Asada N, Takase M, Nakamura J, et al: Dysfunction of fibroblasts of extrarenal origin
underlies renal fibrosis and renal anemia in mice. J Clin Invest 121:3981, 2011.
with a 1-g loading course of intravenous ferric gluconate was shown to 28. Bernhardt WM, Wiesener MS, Scigalla P, et al: Inhibition of prolyl hydroxylases
lead to a small increase in Hgb and decreased dosage of EPO. 99,100 It is increases erythropoietin production in ESRD. J Am Soc Nephrol 21:2151, 2010.
not yet certain whether this strategy is applicable to other AI settings. 29. Barany P: Inflammation, serum C-reactive protein, and erythropoietin resistance.
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Pending additional studies, the coadministration of iron with EPO in 30. Macdougall IC, Cooper AC: Erythropoietin resistance: The role of inflammation and
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51
inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113:1271,
IV iron is now common practice in CKD patients on hemodialysis, 2004.
without a clear consensus about the indications and potential risks of 32. Ganz T: Hepcidin, a key regulator of iron metabolism and mediator of anemia of
this strategy. Concerns exist that iron supplementation in AI or CKD inflammation. Blood 102:783, 2003.
83
may increase susceptibility to infections, 101,102 but epidemiologic studies 33. Nicolas G, Chauvet C, Viatte L, et al: The gene encoding the iron regulatory peptide
hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 110:1037,
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high bolus doses of iron in patients with intravenous catheters may be 34. Nemeth E, Rivera S, Gabayan V, et al: IL-6 mediates hypoferremia of inflammation by
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35. Nemeth E, Rivera S, Gabayan V, et al: IL-6 mediates hypoferremia of inflammation by
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