Urine N-terminal pro-B-type natriuretic peptide and plasma proenkephalin are promising biomarkers for early diagnosis of cardiorenal syndrome type 1 in acute decompensated heart failure: a prospective, double-center, observational study in real-world

Abstract

Background: Patients with acute decompensated heart failure (ADHF) show cardiorenal syndrome type 1 (CRS-1) are more likely to have a poor outcome. However, the current criteria often lead to delayed CRS-1 diagnosis. Therefore, we evaluated the predictive value of plasma proenkephalin (pPENK) and urine NT-proBNP (uNT-proBNP) for early diagnosis of CRS-1 and vulnerable-phase prognosis in ADHF patients.

Methods: The plasma NT-proBNP (pNT-proBNP), pPENK, and uNT-proBNP were measured in 121 ADHF patients on admission. The plasma neutrophil gelatinase-associated lipocalin (pNGAL) was chosen as the reference. Logistic regression was used to determine the predictors of CRS-1. The area under the receiver operating curves (ROCs) was calculated to assess the early diagnostic value of pNGAL, pPENK, and uNT-proBNP/uCr for CRS-1. To evaluate the prognostic risk of factors for the 90-d outcomes of all ADHF patients, the Cox regression was performed and the cumulative risk curve was plotted.

Results: We found that pPENK [OR 1.093 (95% CI 1.022-1.169), p = 0.010; AUROC = 0.899 (95% CI 0.831-0.946)] and uNT-proBNP/uCr ratio [OR 1.015 (95% CI 1.003-1.028), p = 0.012; AUROC = 0.934 (95% CI 0.874-0.971)] could independently predict the occurrence of CRS-1 in hospitalized patients with ADHF. The pPENK [HR 1.014 (95% CI 1.000-1.042), p = 0.044] and uNT-proBNP/uCr ration [HR 0.998 (95% CI 0.997-1.000), p = 0.045] were also independent predictors of the risk of HF readmission or all-cause death 90 d after discharge in ADHF patients.

Conclusions: The newly found pPENK and noninvasive test of uNT-proBNP/uCr ratio (pg/nmol) on admission may be two promising novel predictive biomarkers for early diagnosis of CRS-1 occurrence and vulnerable-phase outcomes in ADHF patients.

Keywords: Cardiorenal syndrome type 1; acute decompensated heart failure; prediction; proenkephalin; urine N-terminal pro-B-type natriuretic peptide.

Figure 1.

Recruiting, grouping, and follow-up of study population. CRS-1: cardiorenal syndrome type 1.

Figure 2.

Association between the pNGAL and the uNT-proBNP/uCr ratio or pPENK in ADHF patients. After undergoing logarithmic transformation, there was a positive linear correlation between pNGAL and nT-probNP /uCr ratio (A) or pPENK (B). pNGAL: plasma neutrophil gelatinase-associated lipocalin; uNT-proBNP: urine N-terminal pro-B-type natriuretic peptide; uCr: urine creatinine; pPENK: plasma proenkephalin; CRS-1: cardiorenal syndrome type 1.

Figure 3.

The receiver operating curves (ROC) of plasma NGAL, plasma PENK, uNT-proBNP/uCr ratio, and plasma PENK combined with uNT-proBNP/uCr ratio for predicting CRS-1 in ADHF patients. NGAL: neutrophil gelatinase-associated lipocalin; PENK: plasma proenkephalin; uNT-proBNP: urine N-terminal pro-B-type natriuretic peptide; uCr: urine creatinine.

Figure 4.

Association between incidence of CRS-1 and quartiles of the pPENK (A) and uNT-proBNP/uCr ratio (B) in ADHF patients. pPENK: plasma proenkephalin; uNT-proBNP: urine N-terminal pro-B-type natriuretic peptide; uCr: urine creatinine; CRS-1: cardiorenal syndrome type 1.

Figure 5.

The cumulative risk curve of the pPENK (A) and uNT-proBNP/uCr ratio (B) for the composite-outcome of all-cause death or HF readmission 90 d after discharge in ADHF patients. uNT-proBNP: urine N-terminal pro-B-type natriuretic peptide; uCr: urine creatinine; pPENK: plasma proenkephalin.