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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.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods and results<\/jats:title>\n<jats:p>We compared circulating concentrations of NT-proBNP, GDF-15, and cNEP along with cNEP activity in patients on chronic dialysis without (<jats:italic>n<\/jats:italic>\u2009=\u200980) and with HF (<jats:italic>n<\/jats:italic>\u2009=\u200973), 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\u2009=\u200927739] vs. 2883 [5866] pg\/mL, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), GDF-15 (7512 [7084] vs. 6005 [4892] pg\/mL, <jats:italic>p<\/jats:italic>\u2009=\u20090.014), but not cNEP (315 [107] vs. 318 [124] pg\/mL, <jats:italic>p<\/jats:italic>\u2009=\u20090.818). Median cNEP activity was significantly lower in HF vs. controls (0.189 [0.223] vs. 0.257 [0.166] nmol\/mL\/min, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). 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\u2009=\u20090.902, 95% CI 0.857\u20130.947, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001 vs. base model AUC\u2009=\u20090.785).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Graphic abstract<\/jats:title>\n\n<\/jats:sec>","DOI":"10.1007\/s00392-020-01597-x","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T18:02:36Z","timestamp":1580407356000},"page":"1035-1047","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Soluble neprilysin, NT-proBNP, and growth differentiation factor-15 as biomarkers for heart failure in dialysis patients (SONGBIRD)"],"prefix":"10.1007","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7578-3853","authenticated-orcid":false,"given":"Robert","family":"Claus","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Berliner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Udo","family":"Bavendiek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas","family":"Vodovar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Lichtinghagen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha","family":"David","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margret","family":"Patecki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Marie","family":"Launay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann","family":"Bauersachs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermann","family":"Haller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Hiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0508-1260","authenticated-orcid":false,"given":"Michael S.","family":"Balzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,1,30]]},"reference":[{"issue":"13","key":"1597_CR1","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1056\/NEJMoa041031","volume":"351","author":"AS Go","year":"2004","unstructured":"Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. 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