Soluble neprilysin, NT-proBNP, and growth differentiation factor-15 as biomarkers for heart failure in dialysis patients (SONGBIRD)

• Published in: Clinical research in cardiology Vol. 109; no. 8; pp. 1035 - 1047
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-08-2020; Springer Nature B.V
• Subjects: Biomarkers; Cardiology; Congestive heart failure; Diagnostic systems; Dialysis; Differentiation; Echocardiography; Heart failure; Hemodialysis; Medicine; Medicine & Public Health; Neprilysin; Original Paper; Regression analysis; Songbirds; Congestive heart failure (HF); Growth differentiation factor-15 (GDF-15); Biomarker; Peritoneal dialysis (PD); Hemodialysis (HD); Chronic kidney disease (CKD); Neprilysin (NEP)
• ISSN: 1861-0684; 1861-0692
• DOI: 10.1007/s00392-020-01597-x

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