Mechanisms of Disease: erythropoietin resistance in patients with both heart and kidney failure
Anemia is associated with exacerbation of both renal and cardiac disease. A considerable proportion of patients whose anemia is treated with erythropoietin do not respond, and the safety and efficacy of this therapy in people that have both chronic heart and kidney disease has not been proven. Overc...
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| Veröffentlicht in: | Nature clinical practice. Nephrology 2008-01, Vol.4 (1), p.47-57 |
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| description | Anemia is associated with exacerbation of both renal and cardiac disease. A considerable proportion of patients whose anemia is treated with erythropoietin do not respond, and the safety and efficacy of this therapy in people that have both chronic heart and kidney disease has not been proven. Overcoming erythropoietin resistance in this population must be predicated on understanding the processes that contribute to this state. These are reviewed here.
Anemia is common in patients who have both heart failure and chronic kidney disease, and there is an association between anemia and progression of both diseases. The main causes of anemia are deficient production of erythropoietin (EPO), iron deficiency, and chronic disease with endogenous EPO resistance. EPO has been successfully used for over a decade to treat anemia in patients with chronic kidney disease. Less obvious are the safety and efficacy of EPO treatment in patients with both heart failure and renal disease. Up to 10% of patients receiving EPO are hyporesponsive to therapy and require large doses of the agent. Several mechanisms could explain resistance to endogenous and exogenous EPO. Proinflammatory cytokines antagonize the action of EPO by exerting an inhibitory effect on erythroid progenitor cells and by disrupting iron metabolism (a process in which hepcidin has a central role). EPO resistance might also be caused by inflammation, which has a negative effect on EPO receptors. Furthermore, neocytolysis could have a role. As resistance to exogenous EPO is associated with an increased risk of death, it is important to understand how cardiorenal failure affects EPO production and function.
Key Points
Anemia is common in patients with chronic kidney disease and chronic heart failure, and is associated with a negative outcome
Resistance to erythropoietin is a major cause of the anemia that affects patients with both chronic heart failure and chronic kidney disease
Inflammation has a key role in resistance to erythropoietin
Resistance to exogenous erythropoietin is associated with an increased risk of death in patients with chronic kidney disease |
| doi_str_mv | 10.1038/ncpneph0655 |
| format | Article |
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Anemia is common in patients who have both heart failure and chronic kidney disease, and there is an association between anemia and progression of both diseases. The main causes of anemia are deficient production of erythropoietin (EPO), iron deficiency, and chronic disease with endogenous EPO resistance. EPO has been successfully used for over a decade to treat anemia in patients with chronic kidney disease. Less obvious are the safety and efficacy of EPO treatment in patients with both heart failure and renal disease. Up to 10% of patients receiving EPO are hyporesponsive to therapy and require large doses of the agent. Several mechanisms could explain resistance to endogenous and exogenous EPO. Proinflammatory cytokines antagonize the action of EPO by exerting an inhibitory effect on erythroid progenitor cells and by disrupting iron metabolism (a process in which hepcidin has a central role). EPO resistance might also be caused by inflammation, which has a negative effect on EPO receptors. Furthermore, neocytolysis could have a role. As resistance to exogenous EPO is associated with an increased risk of death, it is important to understand how cardiorenal failure affects EPO production and function.
Key Points
Anemia is common in patients with chronic kidney disease and chronic heart failure, and is associated with a negative outcome
Resistance to erythropoietin is a major cause of the anemia that affects patients with both chronic heart failure and chronic kidney disease
Inflammation has a key role in resistance to erythropoietin
Resistance to exogenous erythropoietin is associated with an increased risk of death in patients with chronic kidney disease</description><identifier>ISSN: 1745-8323</identifier><identifier>ISSN: 1759-5061</identifier><identifier>EISSN: 1745-8331</identifier><identifier>EISSN: 1759-507X</identifier><identifier>DOI: 10.1038/ncpneph0655</identifier><identifier>PMID: 18094727</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Anemia ; Anemia - drug therapy ; Anemia - etiology ; Anemia - physiopathology ; Care and treatment ; Chronic illnesses ; College professors ; Complications and side effects ; Drug Resistance ; Erythropoietin ; Erythropoietin - therapeutic use ; Health aspects ; Heart failure ; Heart Failure - complications ; Humans ; Inflammation ; Internal medicine ; Iron ; Kidney diseases ; Medicine ; Medicine & Public Health ; Nephrology ; Nervous system ; Nitric oxide ; Pathogenesis ; Pathophysiology ; Physiology ; Prevention ; Renal Insufficiency - complications ; review-article ; Risk factors ; Signal transduction ; Vitamin deficiency</subject><ispartof>Nature clinical practice. Nephrology, 2008-01, Vol.4 (1), p.47-57</ispartof><rights>Springer Nature Limited 2008</rights><rights>COPYRIGHT 2008 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c445t-8db1d4bde781854f9692d745d58606d0001503c20ae98eb68b9ae2a49b8af46b3</citedby><cites>FETCH-LOGICAL-c445t-8db1d4bde781854f9692d745d58606d0001503c20ae98eb68b9ae2a49b8af46b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2727,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18094727$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gaillard, Carlo AJM</creatorcontrib><creatorcontrib>van der Putten, Karien</creatorcontrib><creatorcontrib>Braam, Branko</creatorcontrib><creatorcontrib>Jie, Kim E</creatorcontrib><title>Mechanisms of Disease: erythropoietin resistance in patients with both heart and kidney failure</title><title>Nature clinical practice. Nephrology</title><addtitle>Nat Rev Nephrol</addtitle><addtitle>Nat Clin Pract Nephrol</addtitle><description>Anemia is associated with exacerbation of both renal and cardiac disease. A considerable proportion of patients whose anemia is treated with erythropoietin do not respond, and the safety and efficacy of this therapy in people that have both chronic heart and kidney disease has not been proven. Overcoming erythropoietin resistance in this population must be predicated on understanding the processes that contribute to this state. These are reviewed here.
Anemia is common in patients who have both heart failure and chronic kidney disease, and there is an association between anemia and progression of both diseases. The main causes of anemia are deficient production of erythropoietin (EPO), iron deficiency, and chronic disease with endogenous EPO resistance. EPO has been successfully used for over a decade to treat anemia in patients with chronic kidney disease. Less obvious are the safety and efficacy of EPO treatment in patients with both heart failure and renal disease. Up to 10% of patients receiving EPO are hyporesponsive to therapy and require large doses of the agent. Several mechanisms could explain resistance to endogenous and exogenous EPO. Proinflammatory cytokines antagonize the action of EPO by exerting an inhibitory effect on erythroid progenitor cells and by disrupting iron metabolism (a process in which hepcidin has a central role). EPO resistance might also be caused by inflammation, which has a negative effect on EPO receptors. Furthermore, neocytolysis could have a role. As resistance to exogenous EPO is associated with an increased risk of death, it is important to understand how cardiorenal failure affects EPO production and function.
Key Points
Anemia is common in patients with chronic kidney disease and chronic heart failure, and is associated with a negative outcome
Resistance to erythropoietin is a major cause of the anemia that affects patients with both chronic heart failure and chronic kidney disease
Inflammation has a key role in resistance to erythropoietin
Resistance to exogenous erythropoietin is associated with an increased risk of death in patients with chronic kidney disease</description><subject>Anemia</subject><subject>Anemia - drug therapy</subject><subject>Anemia - etiology</subject><subject>Anemia - physiopathology</subject><subject>Care and treatment</subject><subject>Chronic illnesses</subject><subject>College professors</subject><subject>Complications and side effects</subject><subject>Drug Resistance</subject><subject>Erythropoietin</subject><subject>Erythropoietin - therapeutic use</subject><subject>Health aspects</subject><subject>Heart failure</subject><subject>Heart Failure - complications</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Internal medicine</subject><subject>Iron</subject><subject>Kidney diseases</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Nephrology</subject><subject>Nervous system</subject><subject>Nitric oxide</subject><subject>Pathogenesis</subject><subject>Pathophysiology</subject><subject>Physiology</subject><subject>Prevention</subject><subject>Renal Insufficiency - complications</subject><subject>review-article</subject><subject>Risk factors</subject><subject>Signal transduction</subject><subject>Vitamin deficiency</subject><issn>1745-8323</issn><issn>1759-5061</issn><issn>1745-8331</issn><issn>1759-507X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkctrFTEUxoMo9qEr9xIR3OitSSaZSdyV1hdU3Og6ZJIzndSZZEwyyP3vTbmX9iolcPL6nY_v8CH0gpIzShr5PtglwDKSVohH6Jh2XGxk09DHd2fWHKGTnG8I4ZJR9hQdUUkU71h3jPQ3sKMJPs8ZxwFf-gwmwwcMaVvGFJfoofiAE2SfiwkWcL0tpngIJeM_voy4j7WMYFLBJjj8y7sAWzwYP60JnqEng5kyPN_vp-jnp48_Lr5srr5__npxfrWxnIuyka6njvcOOkml4INqFXPVvROyJa0jhFBBGsuIASWhb2WvDDDDVS_NwNu-OUVvdrpLir9XyEXPPluYJhMgrll3hLYto00FX_8H3sQ1hepN004qwUTTynvq2kygfRhiScbeSupzqkjHlZSqUmcPUHU5mL2NAQZf3_9peLtrsCnmnGDQS_KzSVtNib4NUx-EWemXe6trP4O7Z_fpVeDdDsj1K1xDOpjlQb1XOzyYUqO50ztk_gJwAbWp</recordid><startdate>200801</startdate><enddate>200801</enddate><creator>Gaillard, Carlo AJM</creator><creator>van der Putten, Karien</creator><creator>Braam, Branko</creator><creator>Jie, Kim E</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>200801</creationdate><title>Mechanisms of Disease: erythropoietin resistance in patients with both heart and kidney failure</title><author>Gaillard, Carlo AJM ; van der Putten, Karien ; Braam, Branko ; Jie, Kim E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c445t-8db1d4bde781854f9692d745d58606d0001503c20ae98eb68b9ae2a49b8af46b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Anemia</topic><topic>Anemia - drug therapy</topic><topic>Anemia - etiology</topic><topic>Anemia - physiopathology</topic><topic>Care and treatment</topic><topic>Chronic illnesses</topic><topic>College professors</topic><topic>Complications and side effects</topic><topic>Drug Resistance</topic><topic>Erythropoietin</topic><topic>Erythropoietin - therapeutic use</topic><topic>Health aspects</topic><topic>Heart failure</topic><topic>Heart Failure - complications</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Internal medicine</topic><topic>Iron</topic><topic>Kidney diseases</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Nephrology</topic><topic>Nervous system</topic><topic>Nitric oxide</topic><topic>Pathogenesis</topic><topic>Pathophysiology</topic><topic>Physiology</topic><topic>Prevention</topic><topic>Renal Insufficiency - complications</topic><topic>review-article</topic><topic>Risk factors</topic><topic>Signal transduction</topic><topic>Vitamin deficiency</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gaillard, Carlo AJM</creatorcontrib><creatorcontrib>van der Putten, Karien</creatorcontrib><creatorcontrib>Braam, Branko</creatorcontrib><creatorcontrib>Jie, Kim E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Nature clinical practice. Nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gaillard, Carlo AJM</au><au>van der Putten, Karien</au><au>Braam, Branko</au><au>Jie, Kim E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanisms of Disease: erythropoietin resistance in patients with both heart and kidney failure</atitle><jtitle>Nature clinical practice. Nephrology</jtitle><stitle>Nat Rev Nephrol</stitle><addtitle>Nat Clin Pract Nephrol</addtitle><date>2008-01</date><risdate>2008</risdate><volume>4</volume><issue>1</issue><spage>47</spage><epage>57</epage><pages>47-57</pages><issn>1745-8323</issn><issn>1759-5061</issn><eissn>1745-8331</eissn><eissn>1759-507X</eissn><abstract>Anemia is associated with exacerbation of both renal and cardiac disease. A considerable proportion of patients whose anemia is treated with erythropoietin do not respond, and the safety and efficacy of this therapy in people that have both chronic heart and kidney disease has not been proven. Overcoming erythropoietin resistance in this population must be predicated on understanding the processes that contribute to this state. These are reviewed here.
Anemia is common in patients who have both heart failure and chronic kidney disease, and there is an association between anemia and progression of both diseases. The main causes of anemia are deficient production of erythropoietin (EPO), iron deficiency, and chronic disease with endogenous EPO resistance. EPO has been successfully used for over a decade to treat anemia in patients with chronic kidney disease. Less obvious are the safety and efficacy of EPO treatment in patients with both heart failure and renal disease. Up to 10% of patients receiving EPO are hyporesponsive to therapy and require large doses of the agent. Several mechanisms could explain resistance to endogenous and exogenous EPO. Proinflammatory cytokines antagonize the action of EPO by exerting an inhibitory effect on erythroid progenitor cells and by disrupting iron metabolism (a process in which hepcidin has a central role). EPO resistance might also be caused by inflammation, which has a negative effect on EPO receptors. Furthermore, neocytolysis could have a role. As resistance to exogenous EPO is associated with an increased risk of death, it is important to understand how cardiorenal failure affects EPO production and function.
Key Points
Anemia is common in patients with chronic kidney disease and chronic heart failure, and is associated with a negative outcome
Resistance to erythropoietin is a major cause of the anemia that affects patients with both chronic heart failure and chronic kidney disease
Inflammation has a key role in resistance to erythropoietin
Resistance to exogenous erythropoietin is associated with an increased risk of death in patients with chronic kidney disease</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>18094727</pmid><doi>10.1038/ncpneph0655</doi><tpages>11</tpages></addata></record> |
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| subjects | Anemia Anemia - drug therapy Anemia - etiology Anemia - physiopathology Care and treatment Chronic illnesses College professors Complications and side effects Drug Resistance Erythropoietin Erythropoietin - therapeutic use Health aspects Heart failure Heart Failure - complications Humans Inflammation Internal medicine Iron Kidney diseases Medicine Medicine & Public Health Nephrology Nervous system Nitric oxide Pathogenesis Pathophysiology Physiology Prevention Renal Insufficiency - complications review-article Risk factors Signal transduction Vitamin deficiency |
| title | Mechanisms of Disease: erythropoietin resistance in patients with both heart and kidney failure |
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