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. 2017 Jul 8;18(7):1470.
doi: 10.3390/ijms18071470.

Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure

Kevin Damman  1 , Mattia A E Valente  2 , Dirk J van Veldhuisen  3 , John G F Cleland  4 , Christopher M O'Connor  5 , Marco Metra  6 , Piotr Ponikowski  7 , Gad Cotter  8 , Beth Davison  9 , Michael M Givertz  10 , Daniel M Bloomfield  11 , Hans L Hillege  12   13 , Adriaan A Voors  14
Affiliations

Plasma Neutrophil Gelatinase-Associated Lipocalin and Predicting Clinically Relevant Worsening Renal Function in Acute Heart Failure

Kevin Damman et al. Int J Mol Sci. .

Abstract

The aim of this study was to evaluate the ability of Neutrophil Gelatinase-Associated Lipocalin (NGAL) to predict clinically relevant worsening renal function (WRF) in acute heart failure (AHF). Plasma NGAL and serum creatinine changes during the first 4 days of admission were investigated in 1447 patients hospitalized for AHF and enrolled in the Placebo-Controlled Randomized Study of the Selective A₁Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) study. WRF was defined as serum creatinine rise ≥ 0.3 mg/dL through day 4. Biomarker patterns were described using linear mixed models. WRF developed in 325 patients (22%). Plasma NGAL did not rise earlier than creatinine in patients with WRF. After multivariable adjustment, baseline plasma NGAL, but not creatinine, predicted WRF. AUCs for WRF prediction were modest (<0.60) for all models. NGAL did not independently predict death or rehospitalization (p = n.s.). Patients with WRF and high baseline plasma NGAL had a greater risk of death, and renal or cardiovascular rehospitalization by 60 days than patients with WRF and a low baseline plasma NGAL (p for interaction = 0.024). A rise in plasma NGAL after baseline was associated with a worse outcome in patients with WRF, but not in patients without WRF (p = 0.007). On the basis of these results, plasma NGAL does not provide additional, clinically relevant information about the occurrence of WRF in patients with AHF.

Keywords: NGAL; Neutrophil Gelatinase-Associated Lipocalin; acute heart failure; creatinine; heart failure; worsening renal function.

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Conflict of interest statement

Mattia A.E. Valente, Kevin Damman, Dirk J. van Veldhuisen and Hans L. Hillege have nothing to disclose. Adriaan A. Voors has received speakers and consultancy fees from Merck and NovaCardia. Christopher M. O’Connor is a consultant to Merck. Michael M. Givertz has received honoraria and reimbursements from Bayer, Novartis, and Sevier, and NovaCardia, sponsors of the study, and from Merck, that purchased the rights to rolofylline after completion of the PROTECT pilot study. Piotr Ponikowski has received honoraria from Merck. Gad Cotter and Beth Davison are employees of Momentum Research Inc., which was contracted to perform work on the project by Merck & Co, Inc. John G.F. Cleland was on the Steering Committee for the study, served on the Advisory Board for MSD, and received payments for both. Michael M. Givertz has received institutional research support and served on a scientific Advisory Board for Merck. Daniel M. Bloomfield is an employee of Merck.

Figures

Figure 1
Figure 1
(a) Change in serum creatinine in patients with and without WRF; (b) Change in plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL) in patients with and without WRF. Least square means, with 95% confidence intervals, WRF: worsening renal function, defined as a creatinine increase of ≥0.3 mg/dL by day 4.
Figure 2
Figure 2
Relative changes in serum creatinine and NGAL. Least square means with 95% confidence intervals. WRF: worsening renal function, defined as creatinine increase of ≥0.3 mg/dL by day 4.
Figure 3
Figure 3
(a) Changes in serum Creatinine; and (b) NGAL in patients with and without worsening renal function, by vital status, at 180 days. Least square means with 95% confidence intervals. WRF: worsening renal function, defined as a creatinine increase of ≥0.3 mg/dL by day 4.
Figure 4
Figure 4
180-day survival in patients with vs. without WRF, high vs. low NGAL change. Creat: creatinine. NGAL: Neutrophil Gelatinase-Associated Lipocalin. High vs. low, defined as an NGAL increase of ≥1 standard deviation (≥88 ng/mL increase).
See this image and copyright information in PMC

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