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

Clin Res Cardiol. 2020 Aug;109(8):1035-1047. doi: 10.1007/s00392-020-01597-x. Epub 2020 Jan 30.

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.

Keywords: Biomarker; Chronic kidney disease (CKD); Congestive heart failure (HF); Growth differentiation factor-15 (GDF-15); Hemodialysis (HD); Neprilysin (NEP); Peritoneal dialysis (PD).

Publication types

  • Multicenter Study

MeSH terms

  • Biomarkers / blood
  • Female
  • Follow-Up Studies
  • Growth Differentiation Factor 15 / blood*
  • Heart Failure / blood*
  • Heart Failure / etiology
  • Heart Failure / physiopathology
  • Heart Failure / therapy
  • Humans
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Neprilysin / blood*
  • Peptide Fragments / blood*
  • Predictive Value of Tests
  • Prognosis
  • Protein Precursors
  • ROC Curve
  • Renal Dialysis / adverse effects*
  • Retrospective Studies
  • Stroke Volume / physiology

Substances

  • Biomarkers
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Peptide Fragments
  • Protein Precursors
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Neprilysin