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Anemia of Chronic Disease

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Management of Anemia

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Abstract

Anemia is a common condition observed in chronic disease states and in these chronically ill patients has a negative impact on their quality of life and survival. Various cytokines and acute phase proteins play important roles in the pathogenesis of the anemia of chronic disease (ACD) and alterations in the metabolism of iron via the molecules, hepcidin, and ferritin are largely responsible for the consequent anemia. Because it is a non-specific anemia, it is often difficult to diagnose properly. To diagnose this disorder, the physician must correlate the possible clinical pathways of the underlying disease with changes in altered iron metabolism and response to erythropoietin (EPO). It is important to rule out concomitant iron deficiency and other causes of anemia since failure to do so will in most cases lead to failure of standard therapy. Treatment options involve the use of erythropoiesis-stimulating agents, blood transfusion, and iron supplementation, in addition to treating the underlying disease. This discourse will review the pathogenesis of ACD, suggest current therapeutic options, and suggest future targets for therapeutic intervention such as chelating agents, hepcidin antagonists, and other agents affecting erythropoiesis.

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Abbreviations

ACD:

Anemia of chronic disease

AMPK:

Adenosine monophosphate-activated kinase

BFU-E:

Burst-forming unit erythroid

BMP:

Bone morphogenetic protein

CFU-E:

Colony-forming unit erythroid

CFU-GEMM:

Colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte

CKD:

Chronic kidney disease

COX 2:

Cyclo-oxygenase 2

CRP:

C-reactive protein

DMT-1:

Divalent metal transporter 1

EPO:

Erythropoietin

EPOR:

Erythropoietin receptor

ERFE:

Erythroferrone

ESA:

Erythropoiesis-stimulating agents

ESRD:

End stage renal disease

FP:

Ferroportin

GDF:

Growth differentiation factor

GM-CSF:

Granulocyte-monocyte colony stimulating factor

Hb:

Hemoglobin

HLA:

Human leucocyte antigen

HMBGB1:

High mobility group box 1

HMGB:

High mobility group box

hsCRP:

High-sensitivity CRP

ID:

Iron deficiency

IDA:

Iron-deficiency anemia

IFN:

IFN

IgG:

Immunoglobulin G

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

IRE:

Iron-responsive element

IRE/IRP:

Iron-responsive element/iron regulatory protein

JAK/STAT:

JANUS-associated kinase/signal transducer and activator of transcription

LPI:

Labile plasma iron

LPS:

Lipopolysaccharides

MAPK:

Mitogen-activated protein kinases

Mb:

Myoglobin

mRNA:

Messenger RNA

NFκB:

Nuclear factor kappa B

NO:

Nitrous oxide

NTBI:

Non-transferrin bound iron

PAF:

Platelet activating factor

PDGF:

Platelet-derived growth factor

RA:

Rheumatoid arthritis

RES:

Reticuloendothelial system

ROS:

Reactive oxygen species

s-EPO:

Serum EPO levels

SLC4A1:

Soluble carrier family 4 (anion exchanger) member 1 (Diego blood group)

Smad:

Small body size/mothers against decapentaplegic

SOCS:

Suppressor of cytokine signaling

STAT:

Signal transducer and activator of transcription

TfR:

Transferrin receptor

TGF-β:

Transforming growth factor beta

TNF-α:

Tumor necrosis factor alpha

VEGF:

Vascular endothelial growth factor

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  1. Department of Nephrology, Stanford University, Stanford, CA, 94305, USA

    Anatole Besarab B.S.Ch.E., M.D.

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  1. Anatole Besarab B.S.Ch.E., M.D.
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  2. Stefan Hemmerich Ph.D.
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  1. Department of Nephrology, St. John Hospital & Medical Center/DaVita Healthcare Partners, Detroit, Michigan, USA

    Robert Provenzano

  2. University of Illinois at Chicago College of Medicine/Advocate Christ Medical Center, Oak Lawn, Illinois, USA

    Edgar V. Lerma

  3. Durham Nephrology Associates, Durham, North Carolina, USA

    Lynda Szczech

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Besarab, A., Hemmerich, S. (2018). Anemia of Chronic Disease. In: Provenzano, R., Lerma, E., Szczech, L. (eds) Management of Anemia. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7360-6_4

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