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Multicenter Study
. 2018 Apr 26;22(1):108.
doi: 10.1186/s13054-018-2035-8.

Urinary biomarkers predict advanced acute kidney injury after cardiovascular surgery

Jian-Jhong Wang  1   2 , Nai-Hsin Chi  3 , Tao-Min Huang  2   4 , Rory Connolly  5 , Liang Wen Chen  3 , Shih-Chieh Jeff Chueh  6 , Wei-Chih Kan  7 , Chih-Cheng Lai  8 , Vin-Cent Wu  9   10 , Ji-Tseng Fang  11   12 , Tzong-Shinn Chu  2   4 , Kwan-Dun Wu  2   4
Affiliations
Multicenter Study

Urinary biomarkers predict advanced acute kidney injury after cardiovascular surgery

Jian-Jhong Wang et al. Crit Care. .

Abstract

Background: Acute kidney injury (AKI) after cardiovascular surgery is a serious complication. Little is known about the ability of novel biomarkers in combination with clinical risk scores for prediction of advanced AKI.

Methods: In this prospectively conducted multicenter study, urine samples were collected from 149 adults at 0, 3, 6, 12 and 24 h after cardiovascular surgery. We measured urinary hemojuvelin (uHJV), kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), α-glutathione S-transferase (uα-GST) and π-glutathione S-transferase (uπ-GST). The primary outcome was advanced AKI, under the definition of Kidney Disease: Improving Global Outcomes (KDIGO) stage 2, 3 and composite outcomes were KDIGO stage 2, 3 or 90-day mortality after hospital discharge.

Results: Patients with advanced AKI had significantly higher levels of uHJV and uKIM-1 at 3, 6 and 12 h after surgery. When normalized by urinary creatinine level, uKIM-1 in combination with uHJV at 3 h post-surgery had a high predictive ability for advanced AKI and composite outcome (AUC = 0.898 and 0.905, respectively). The combination of this biomarker panel (normalized uKIM-1, uHJV at 3 h post-operation) and Liano's score was superior in predicting advanced AKI (AUC = 0.931, category-free net reclassification improvement of 1.149, and p < 0.001).

Conclusions: When added to Liano's score, normalized uHJV and uKIM-1 levels at 3 h after cardiovascular surgery enhanced the identification of patients at higher risk of progression to advanced AKI and composite outcomes.

Keywords: Acute kidney injury; Biomarkers; Hemojuvelin; Kidney injury molecule-1; Liano’s score; Neutrophil gelatinase-associated lipocalin; α-Glutathione S-transferase; π-Glutathione S-transferase.

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Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the research ethics review board of National Taiwan University Hospital (201105040RC) along with established written informed consent. This research was carried out in accordance with the approved guidelines. Written informed consent was obtained from all participants before inclusion.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Urinary levels of five biomarkers after cardiovascular surgery. The vertical box represents the 25th percentile (bottom line), median (middle line) and 75th percentile (top line) values, whereas the vertical bars represent the intervals between maximum and minimum values. a Creatinine-normalized urinary hemojuvelin (uHJV). b Creatinine-normalized urinary kidney injury molecule-1 (uKIM-1). c Creatinine-normalized urinary neutrophil gelatinase-associated lipocalin (uNGAL). d Creatinine-normalized urinary α-glutathione S-transferase (uα-GST). e Creatinine-normalized urinary π-glutathione S-transferase (uπ-GST). *p < 0.05. AKI, acute kidney injury
Fig. 2
Fig. 2
Receiver-operating characteristic (ROC) curves for the best prediction model for advanced acute kidney injury. The best biomarker panel combination alone (thick dashed line), clinical risk prediction model alone (thin dashed line) and combination of the clinical risk prediction model and combined biomarker panel (solid line) are shown at hour 3 (a), hour 6 (b), hour 12 (c) and hour 24 (d). The clinical risk prediction model is calculated from Liano’s score. The area under the ROC curve (AUC) values and 95% confidence intervals (CIs) are also shown
Fig. 3
Fig. 3
Urinary biomarker concentrations related to advanced acute kidney injury (AKI). The creatinine-normalized biomarker concentrations were analyzed by unsupervised clustering to determine their relationship to advanced AKI. Full-length view of the cluster diagram has cases orientated along the vertical axis and biomarkers orientated along the horizontal axis. α-GST, α-glutathione S-transferase; π-GST, π-glutathione S-transferase; HJV, hemojuvelin; KIM-1, kidney injury molecule-1; NGAL, neutrophil gelatinase associated lipocalin; UCr, urinary creatinine
See this image and copyright information in PMC

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