Soluble neprilysin, NT-proBNP, and growth differentiation factor-15 as biomarkers for heart failure in dialysis patients (SONGBIRD)
Background Dialysis patients are at increased risk of HF. However, diagnostic utility of NT-proBNP as a biomarker is decreased in patients on dialysis. GDF-15 and cNEP are biomarkers of distinct mechanisms that may contribute to HF pathophysiology in such cohorts. The aim of this study was to determ...
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| Veröffentlicht in: | Clinical research in cardiology 2020-08, Vol.109 (8), p.1035-1047 |
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| creator | Claus, Robert Berliner, Dominik Bavendiek, Udo Vodovar, Nicolas Lichtinghagen, Ralf David, Sascha Patecki, Margret Launay, Jean-Marie Bauersachs, Johann Haller, Hermann Hiss, Marcus Balzer, Michael S. |
| description | Background
Dialysis patients are at increased risk of HF. However, diagnostic utility of NT-proBNP as a biomarker is decreased in patients on dialysis. GDF-15 and cNEP are biomarkers of distinct mechanisms that may contribute to HF pathophysiology in such cohorts. The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) and circulating neprilysin (cNEP) improve the diagnosis of congestive heart failure (HF) in patients on dialysis.
Methods and results
We compared circulating concentrations of NT-proBNP, GDF-15, and cNEP along with cNEP activity in patients on chronic dialysis without (
n
= 80) and with HF (
n
= 73), as diagnosed by clinical parameters and post-dialysis echocardiography. We used correlation, linear and logistic regression as well as receiver operating characteristic (ROC) analyses. Compared to controls, patients with HF had higher median values of NT-proBNP (16,216 [interquartile range, IQR = 27739] vs. 2883 [5866] pg/mL,
p
|
| doi_str_mv | 10.1007/s00392-020-01597-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7376515</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2425989825</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-1c6b5c9e1ff964f98d393c2c0173ec64483705a46b137635ef151f9313c06003</originalsourceid><addsrcrecordid>eNp9kV9PFDEUxRujEUS_gA-miS-YMHL7b2b6YgIoSEIWI_vedLrtbnG2XdsZhGe_OF0XV-XBpza55_x6bg9Crwm8JwDNYQZgklZAoQIiZFPdPkG7pK1JBbWkT7f3lu-gFzlfAwgCjD9HO4wC0JrRXfTzKvZj11sc7Cr5_i77cIAn02qV4vHkywHWYYbnKf4YFnjmnbPJhsHrwceAnTZDTBURWGfc-bjU6ZtNGbuY8MLqNBSF78dksQ_FrNfwjFfFXBgZ719dTs6Oz79-fPcSPXO6z_bVw7mHpqefpiefq4vLs_OTo4vK8IYPFTF1J4y0xDlZcyfbGZPMUAOkYdbUnLesAaF53RHW1ExYRwRxkhFmoC5ftYc-bLCrsVvamSkpku5VWbskv1NRe_XvJPiFmscb1RScIKIA9h8AKX4fbR7U0mdj-14HG8esKBMAklJBivTtI-l1HFMo2ynKqZCtbOkaSDcqk2LOybptGAJqXbHaVKxKxepXxeq2mN78vcbW8rvTImAbQS6jMLfpz9v_wd4DpumyCw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2425989825</pqid></control><display><type>article</type><title>Soluble neprilysin, NT-proBNP, and growth differentiation factor-15 as biomarkers for heart failure in dialysis patients (SONGBIRD)</title><source>Springer Nature - Complete Springer Journals</source><creator>Claus, Robert ; Berliner, Dominik ; Bavendiek, Udo ; Vodovar, Nicolas ; Lichtinghagen, Ralf ; David, Sascha ; Patecki, Margret ; Launay, Jean-Marie ; Bauersachs, Johann ; Haller, Hermann ; Hiss, Marcus ; Balzer, Michael S.</creator><creatorcontrib>Claus, Robert ; Berliner, Dominik ; Bavendiek, Udo ; Vodovar, Nicolas ; Lichtinghagen, Ralf ; David, Sascha ; Patecki, Margret ; Launay, Jean-Marie ; Bauersachs, Johann ; Haller, Hermann ; Hiss, Marcus ; Balzer, Michael S.</creatorcontrib><description>Background
Dialysis patients are at increased risk of HF. However, diagnostic utility of NT-proBNP as a biomarker is decreased in patients on dialysis. GDF-15 and cNEP are biomarkers of distinct mechanisms that may contribute to HF pathophysiology in such cohorts. The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) and circulating neprilysin (cNEP) improve the diagnosis of congestive heart failure (HF) in patients on dialysis.
Methods and results
We compared circulating concentrations of NT-proBNP, GDF-15, and cNEP along with cNEP activity in patients on chronic dialysis without (
n
= 80) and with HF (
n
= 73), as diagnosed by clinical parameters and post-dialysis echocardiography. We used correlation, linear and logistic regression as well as receiver operating characteristic (ROC) analyses. Compared to controls, patients with HF had higher median values of NT-proBNP (16,216 [interquartile range, IQR = 27739] vs. 2883 [5866] pg/mL,
p
< 0.001), GDF-15 (7512 [7084] vs. 6005 [4892] pg/mL,
p
= 0.014), but not cNEP (315 [107] vs. 318 [124] pg/mL,
p
= 0.818). Median cNEP activity was significantly lower in HF vs. controls (0.189 [0.223] vs. 0.257 [0.166] nmol/mL/min,
p
< 0.001). In ROC analyses, a multi-marker model combining clinical covariates, NT-proBNP, GDF-15, and cNEP activity demonstrated best discrimination of HF from controls (AUC = 0.902, 95% CI 0.857–0.947,
p
< 0.001 vs. base model AUC = 0.785).
Conclusion
We present novel comparative data on physiologically distinct circulating biomarkers for HF in patients on dialysis. cNEP activity but not concentration and GDF-15 provided incremental diagnostic information over clinical covariates and NT-proBNP and may aid in diagnosing HF in dialysis patients.
Graphic abstract</description><identifier>ISSN: 1861-0684</identifier><identifier>EISSN: 1861-0692</identifier><identifier>DOI: 10.1007/s00392-020-01597-x</identifier><identifier>PMID: 32002632</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Biomarkers ; Cardiology ; Congestive heart failure ; Diagnostic systems ; Dialysis ; Differentiation ; Echocardiography ; Heart failure ; Hemodialysis ; Medicine ; Medicine & Public Health ; Neprilysin ; Original Paper ; Regression analysis ; Songbirds</subject><ispartof>Clinical research in cardiology, 2020-08, Vol.109 (8), p.1035-1047</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-1c6b5c9e1ff964f98d393c2c0173ec64483705a46b137635ef151f9313c06003</citedby><cites>FETCH-LOGICAL-c474t-1c6b5c9e1ff964f98d393c2c0173ec64483705a46b137635ef151f9313c06003</cites><orcidid>0000-0001-7578-3853 ; 0000-0003-0508-1260</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00392-020-01597-x$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00392-020-01597-x$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32002632$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Claus, Robert</creatorcontrib><creatorcontrib>Berliner, Dominik</creatorcontrib><creatorcontrib>Bavendiek, Udo</creatorcontrib><creatorcontrib>Vodovar, Nicolas</creatorcontrib><creatorcontrib>Lichtinghagen, Ralf</creatorcontrib><creatorcontrib>David, Sascha</creatorcontrib><creatorcontrib>Patecki, Margret</creatorcontrib><creatorcontrib>Launay, Jean-Marie</creatorcontrib><creatorcontrib>Bauersachs, Johann</creatorcontrib><creatorcontrib>Haller, Hermann</creatorcontrib><creatorcontrib>Hiss, Marcus</creatorcontrib><creatorcontrib>Balzer, Michael S.</creatorcontrib><title>Soluble neprilysin, NT-proBNP, and growth differentiation factor-15 as biomarkers for heart failure in dialysis patients (SONGBIRD)</title><title>Clinical research in cardiology</title><addtitle>Clin Res Cardiol</addtitle><addtitle>Clin Res Cardiol</addtitle><description>Background
Dialysis patients are at increased risk of HF. However, diagnostic utility of NT-proBNP as a biomarker is decreased in patients on dialysis. GDF-15 and cNEP are biomarkers of distinct mechanisms that may contribute to HF pathophysiology in such cohorts. The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) and circulating neprilysin (cNEP) improve the diagnosis of congestive heart failure (HF) in patients on dialysis.
Methods and results
We compared circulating concentrations of NT-proBNP, GDF-15, and cNEP along with cNEP activity in patients on chronic dialysis without (
n
= 80) and with HF (
n
= 73), as diagnosed by clinical parameters and post-dialysis echocardiography. We used correlation, linear and logistic regression as well as receiver operating characteristic (ROC) analyses. Compared to controls, patients with HF had higher median values of NT-proBNP (16,216 [interquartile range, IQR = 27739] vs. 2883 [5866] pg/mL,
p
< 0.001), GDF-15 (7512 [7084] vs. 6005 [4892] pg/mL,
p
= 0.014), but not cNEP (315 [107] vs. 318 [124] pg/mL,
p
= 0.818). Median cNEP activity was significantly lower in HF vs. controls (0.189 [0.223] vs. 0.257 [0.166] nmol/mL/min,
p
< 0.001). In ROC analyses, a multi-marker model combining clinical covariates, NT-proBNP, GDF-15, and cNEP activity demonstrated best discrimination of HF from controls (AUC = 0.902, 95% CI 0.857–0.947,
p
< 0.001 vs. base model AUC = 0.785).
Conclusion
We present novel comparative data on physiologically distinct circulating biomarkers for HF in patients on dialysis. cNEP activity but not concentration and GDF-15 provided incremental diagnostic information over clinical covariates and NT-proBNP and may aid in diagnosing HF in dialysis patients.
Graphic abstract</description><subject>Biomarkers</subject><subject>Cardiology</subject><subject>Congestive heart failure</subject><subject>Diagnostic systems</subject><subject>Dialysis</subject><subject>Differentiation</subject><subject>Echocardiography</subject><subject>Heart failure</subject><subject>Hemodialysis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neprilysin</subject><subject>Original Paper</subject><subject>Regression analysis</subject><subject>Songbirds</subject><issn>1861-0684</issn><issn>1861-0692</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kV9PFDEUxRujEUS_gA-miS-YMHL7b2b6YgIoSEIWI_vedLrtbnG2XdsZhGe_OF0XV-XBpza55_x6bg9Crwm8JwDNYQZgklZAoQIiZFPdPkG7pK1JBbWkT7f3lu-gFzlfAwgCjD9HO4wC0JrRXfTzKvZj11sc7Cr5_i77cIAn02qV4vHkywHWYYbnKf4YFnjmnbPJhsHrwceAnTZDTBURWGfc-bjU6ZtNGbuY8MLqNBSF78dksQ_FrNfwjFfFXBgZ719dTs6Oz79-fPcSPXO6z_bVw7mHpqefpiefq4vLs_OTo4vK8IYPFTF1J4y0xDlZcyfbGZPMUAOkYdbUnLesAaF53RHW1ExYRwRxkhFmoC5ftYc-bLCrsVvamSkpku5VWbskv1NRe_XvJPiFmscb1RScIKIA9h8AKX4fbR7U0mdj-14HG8esKBMAklJBivTtI-l1HFMo2ynKqZCtbOkaSDcqk2LOybptGAJqXbHaVKxKxepXxeq2mN78vcbW8rvTImAbQS6jMLfpz9v_wd4DpumyCw</recordid><startdate>20200801</startdate><enddate>20200801</enddate><creator>Claus, Robert</creator><creator>Berliner, Dominik</creator><creator>Bavendiek, Udo</creator><creator>Vodovar, Nicolas</creator><creator>Lichtinghagen, Ralf</creator><creator>David, Sascha</creator><creator>Patecki, Margret</creator><creator>Launay, Jean-Marie</creator><creator>Bauersachs, Johann</creator><creator>Haller, Hermann</creator><creator>Hiss, Marcus</creator><creator>Balzer, Michael S.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7Z</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7578-3853</orcidid><orcidid>https://orcid.org/0000-0003-0508-1260</orcidid></search><sort><creationdate>20200801</creationdate><title>Soluble neprilysin, NT-proBNP, and growth differentiation factor-15 as biomarkers for heart failure in dialysis patients (SONGBIRD)</title><author>Claus, Robert ; Berliner, Dominik ; Bavendiek, Udo ; Vodovar, Nicolas ; Lichtinghagen, Ralf ; David, Sascha ; Patecki, Margret ; Launay, Jean-Marie ; Bauersachs, Johann ; Haller, Hermann ; Hiss, Marcus ; Balzer, Michael S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-1c6b5c9e1ff964f98d393c2c0173ec64483705a46b137635ef151f9313c06003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biomarkers</topic><topic>Cardiology</topic><topic>Congestive heart failure</topic><topic>Diagnostic systems</topic><topic>Dialysis</topic><topic>Differentiation</topic><topic>Echocardiography</topic><topic>Heart failure</topic><topic>Hemodialysis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neprilysin</topic><topic>Original Paper</topic><topic>Regression analysis</topic><topic>Songbirds</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Claus, Robert</creatorcontrib><creatorcontrib>Berliner, Dominik</creatorcontrib><creatorcontrib>Bavendiek, Udo</creatorcontrib><creatorcontrib>Vodovar, Nicolas</creatorcontrib><creatorcontrib>Lichtinghagen, Ralf</creatorcontrib><creatorcontrib>David, Sascha</creatorcontrib><creatorcontrib>Patecki, Margret</creatorcontrib><creatorcontrib>Launay, Jean-Marie</creatorcontrib><creatorcontrib>Bauersachs, Johann</creatorcontrib><creatorcontrib>Haller, Hermann</creatorcontrib><creatorcontrib>Hiss, Marcus</creatorcontrib><creatorcontrib>Balzer, Michael S.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</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>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical research in cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Claus, Robert</au><au>Berliner, Dominik</au><au>Bavendiek, Udo</au><au>Vodovar, Nicolas</au><au>Lichtinghagen, Ralf</au><au>David, Sascha</au><au>Patecki, Margret</au><au>Launay, Jean-Marie</au><au>Bauersachs, Johann</au><au>Haller, Hermann</au><au>Hiss, Marcus</au><au>Balzer, Michael S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Soluble neprilysin, NT-proBNP, and growth differentiation factor-15 as biomarkers for heart failure in dialysis patients (SONGBIRD)</atitle><jtitle>Clinical research in cardiology</jtitle><stitle>Clin Res Cardiol</stitle><addtitle>Clin Res Cardiol</addtitle><date>2020-08-01</date><risdate>2020</risdate><volume>109</volume><issue>8</issue><spage>1035</spage><epage>1047</epage><pages>1035-1047</pages><issn>1861-0684</issn><eissn>1861-0692</eissn><abstract>Background
Dialysis patients are at increased risk of HF. However, diagnostic utility of NT-proBNP as a biomarker is decreased in patients on dialysis. GDF-15 and cNEP are biomarkers of distinct mechanisms that may contribute to HF pathophysiology in such cohorts. The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) and circulating neprilysin (cNEP) improve the diagnosis of congestive heart failure (HF) in patients on dialysis.
Methods and results
We compared circulating concentrations of NT-proBNP, GDF-15, and cNEP along with cNEP activity in patients on chronic dialysis without (
n
= 80) and with HF (
n
= 73), as diagnosed by clinical parameters and post-dialysis echocardiography. We used correlation, linear and logistic regression as well as receiver operating characteristic (ROC) analyses. Compared to controls, patients with HF had higher median values of NT-proBNP (16,216 [interquartile range, IQR = 27739] vs. 2883 [5866] pg/mL,
p
< 0.001), GDF-15 (7512 [7084] vs. 6005 [4892] pg/mL,
p
= 0.014), but not cNEP (315 [107] vs. 318 [124] pg/mL,
p
= 0.818). Median cNEP activity was significantly lower in HF vs. controls (0.189 [0.223] vs. 0.257 [0.166] nmol/mL/min,
p
< 0.001). In ROC analyses, a multi-marker model combining clinical covariates, NT-proBNP, GDF-15, and cNEP activity demonstrated best discrimination of HF from controls (AUC = 0.902, 95% CI 0.857–0.947,
p
< 0.001 vs. base model AUC = 0.785).
Conclusion
We present novel comparative data on physiologically distinct circulating biomarkers for HF in patients on dialysis. cNEP activity but not concentration and GDF-15 provided incremental diagnostic information over clinical covariates and NT-proBNP and may aid in diagnosing HF in dialysis patients.
Graphic abstract</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32002632</pmid><doi>10.1007/s00392-020-01597-x</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-7578-3853</orcidid><orcidid>https://orcid.org/0000-0003-0508-1260</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1861-0684 |
| ispartof | Clinical research in cardiology, 2020-08, Vol.109 (8), p.1035-1047 |
| issn | 1861-0684 1861-0692 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7376515 |
| source | Springer Nature - Complete Springer Journals |
| subjects | Biomarkers Cardiology Congestive heart failure Diagnostic systems Dialysis Differentiation Echocardiography Heart failure Hemodialysis Medicine Medicine & Public Health Neprilysin Original Paper Regression analysis Songbirds |
| title | Soluble neprilysin, NT-proBNP, and growth differentiation factor-15 as biomarkers for heart failure in dialysis patients (SONGBIRD) |
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