Anemia of Inflammation with An Emphasis on Chronic Kidney Disease
Abstract
:1. Introduction
2. Causes of Iron-Deficiency Anemia
3. Anemia of Inflammation or Anemia of Chronic Disease
4. Anemia of Cancer
5. Anemia of Heart Failure
6. Anemia of Surgery
7. Anemia of Inflammatory Bowel Disease (IBD)
8. Anemia of Rheumatoid Arthritis (RA)
9. Anemia of Chronic Kidney Disease
Hepcidin Expression and Function in CKD Patients
10. Treatment of Anemia in CKD
11. Iron Supplementation for the Treatment of Anemia of CKD
12. Novel Therapies for the Treatment of Anemia of CKD
12.1. Targeting Hepcidin
12.2. Hepcidin-Ferroportin Axis
12.3. Targeting Hif1α Inhibitors
12.4. Other Compounds
Potential New Therapy for Anemia of Chronic Disease in the Future
13. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ID | iron deficiency | IDA | Iron-deficiency anaemia |
GBD | Global Burden of Disease | CKD | chronic kidney disease |
ACD | Anemia of Chronic Disease | IBD | inflammatory bowel disease |
IV | intravenous | EPO | erythropoietin |
ESA | erythropoietin stimulating agent | rHuEPO | recombinant human erythropoietin |
FPN | ferroportin | DMT1 | divalent metal transporter |
Dcytb | duodenal cytochrome b | MCV | mean corpuscular volume |
Hb | haemoglobin | BMP | bone morphogenic protein |
HJV | hemojuvelin | SMAD | Mothers Against Decapentaplegic |
JAK2 | Janus kinase 2 | STAT 3 | Signal transducer and activator of transcription 3 |
GDF 15 | growth differentiation factor 15 | PDGF-BB | platelet-derived growth factor-BB |
HIF | hypoxia-inducible factor | VEGF | vascular endothelial growth factor |
IL | Interleukin | FCF23 | fibroblast growth factor |
KDIGO | Kidney Disease: Improving Global Outcomes | CHOIR | Correction of Haemoglobin and Outcomes in Renal Insufficiency |
CREATE | Cardiovascular Risk Reduction by Early Anemia Treatment | TREAT | Trial to Reduce Cardiovascular Events with Aranesp |
HIF-PHDI | Hypoxia-Inducible factor Prolyl Hydroxylase Inhibitor |
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Cells/Tissue | Cytokine | Effector Function |
---|---|---|
Hepatocytes | IL6 and lipopolysaccharide (LPS) | Induction of hepcidin expression in the liver. Hepcidin inhibits iron efflux from the macrophages and the duodenum by blocking or degrading ferroportin. |
Macrophage | ||
Lipopolysaccharide (LPS) and TNFα | Increase DMT1 expression and uptake of ferrous iron(Fe2+). | |
TNFα | Promotes damage of erythrocyte membranes and the stimulation of phagocytosis. | |
IFNɣ and LPS | Decrease expression of ferroportin to inhibit iron efflux and accentuated by hepcidin. | |
TNFα-IL1, IL6 and IL10 | Induction of ferritin expression, storage and retention of iron within macrophages. | |
Monocytes | IL10 | Enhances TfR1 expression to promote uptake of transferrin-bound iron. |
Kidney | TNFα, IFNɣ and IL1 | Dysregulated erythropoietin receptor EPOR expression and signalling via blunted expression of Scribble (Scb) and inhibition of erythropoietin (EPO) and erythroferrone (ERFE) which production. The cytokines also directly inhibit the differentiation and proliferation of erythroid progenitor cells. |
Name | Mode of Action | Adverse Effects | References |
---|---|---|---|
Hepcidin antagonist, e.g., hepcidin antibodies RNA Interference Atorvastatin, Sotatercept Luspatercept | Inhibit hepcidin action Inhibit hepcidin expression and promote FPN function | Viral delivery system—risk of random genome integration. Unfavorable immunological responses | [121,122,132,133,144,158] |
Hepcidin binding proteins Lipocalin, e.g., Anticalin (PRS-080) | Inhibit hepcidin function | Non-specificity | [159] |
Hepcidin production inhibitors BMP inhibitors, e.g., soluble HJV, Dorsomorphin, Anti-BMP6 monoclonal antibody | Inhibit hepcidin expression and the BMP6-HJV-SMAD pathway | Unknown | [134,160] |
Anti- IL6 monoclonal antibody, e.g., Siltuximab | Inhibits IL-6 STAT3 signaling cascade | Unknown | [158] |
Heparin | Decreases hepcidin levels Increases mobilisation of iron stores | Bleeding Thrombocytopenia Hyperkalaemia Alopecia Osteoporosis | [161] |
Vitamin D | Decreases hepcidin gene transcription | In excess causes nausea, vomiting, depression, weakness, and confusion. | [148,149,150] |
FPN stabilizers, e.g., anti-ferroportin monoclonal antibody | Increase ferroportin action | Unknown | [130,134] |
HIF-PHDI, e.g., Roxadustat Daprodustat, Vadadustatt, Molidustat, | Increase endogenous EPO expression | Pulmonary hypertension Increase in VEGF Tumour progression | [97,98,134,136,141] |
Anticalin PRS-080#22 | Decreases hepcidin levels Increases mobilisation of iron stores | Unknown | [144] |
FGF23 inhibitor | Stimulates and promotes erythropoeisis | Unknown | [153,157] |
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Begum, S.; Latunde-Dada, G.O. Anemia of Inflammation with An Emphasis on Chronic Kidney Disease. Nutrients 2019, 11, 2424. https://doi.org/10.3390/nu11102424
Begum S, Latunde-Dada GO. Anemia of Inflammation with An Emphasis on Chronic Kidney Disease. Nutrients. 2019; 11(10):2424. https://doi.org/10.3390/nu11102424
Chicago/Turabian StyleBegum, Sajidah, and Gladys O. Latunde-Dada. 2019. "Anemia of Inflammation with An Emphasis on Chronic Kidney Disease" Nutrients 11, no. 10: 2424. https://doi.org/10.3390/nu11102424