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Abstract: TH-PO707

Soluble Neprilysin, NT-ProBNP, and Growth Differentiation Factor 15 as Biomarkers for Heart Failure in Dialysis Patients (SONGBIRD)

Session Information

Category: Hypertension and CVD

  • 1402 Hypertension and CVD: Clinical, Outcomes, and Trials

Authors

  • Claus, Robert, Hannover Medical School, Hannover, Germany
  • Berliner, Dominik, Hannover Medical School, Hannover, Germany
  • Bavendiek, Udo, Hannover Medical School, Hannover, Germany
  • Vodovar, Nicolas, Inserm UMR-S 942, Paris, France
  • David, Sascha, Hannover Medical School, Hannover, Germany
  • Patecki, Margret, Hannover Medical School, Hannover, Germany
  • Launay, Jean-Marie, Inserm UMR-S 942, Paris, France
  • Haller, Hermann G., Hannover Medical School, Hannover, Germany
  • Hiss, Marcus, Hannover Medical School, Hannover, Germany
  • Balzer, Michael S., Hannover Medical School, Hannover, Germany

Group or Team Name

  • SONGBIRD investigators
Background

Dialysis patients are at increased risk of congestive heart failure (HF). However, diagnostic utility of NT-proBNP as a biomarker is decreased in patients on hemodialysis or peritoneal dialysis. Growth differentiation factor-15 (GDF15) and neprilysin (NEP) are biomarkers of distinct mechanisms that may contribute to HF pathophysiology in such cohorts.

Methods

We compared circulating concentrations of NT-proBNP, GDF15, and NEP along with NEP activity, individually or in combination, in patients on chronic dialysis without (n=80) and with HF (n=73; composite of HF with reduced [n=40] and preserved ejection fraction [n=33]), as diagnosed by clinical parameters and post-dialysis echocardiography. We used correlation, linear and logistic regression as well as receiver operating characteristic (ROC) analyses.

Results

Compared to controls, patients with HF had higher medians of NT-proBNP (16216 [interquartile range, IQR=27739] vs. 2883 [5866] pg/mL, p<0.001), GDF15 (7512 [7084] vs. 6005 [4892] pg/mL, p=0.014), but not NEP (315 [107] vs. 318 [124] pg/mL, p=0.818). Median NEP 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 base model combining clinical covariates (age, dyspnea score, systolic blood pressure, Charlson comorbidity index, history of HF or severe valve disease, extracellular to total body water ratio) and NT-proBNP distinguished HF from controls with an area under the curve (AUC) of 0.785 (95% confidence interval [CI] 0.714-0.856). NEP activity and GDF15 provided incremental utility over the base model. A multi-marker model combining clinical covariates, NT-proBNP, GDF15 and NEP activity demonstrated best discrimination of HF from controls (AUC=0.902, 95% CI 0.857-0.947, p<0.001 vs. base model).

Conclusion

We present novel comparative data on physiologically distinct circulating biomarkers for HF in patients on dialysis. NEP activity but not concentration and GDF15 provided incremental predictive information over clinical covariates and NT-proBNP and may aid in diagnosing HF in dialysis patients.

Funding

  • Private Foundation Support