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. 2016 Aug 16:6:26335.
doi: 10.1038/srep26335.

Urinary π-glutathione S-transferase Predicts Advanced Acute Kidney Injury Following Cardiovascular Surgery

Kai-Hsiang Shu  1   2   3 , Chih-Hsien Wang  2   4 , Che-Hsiung Wu  2   5 , Tao-Min Huang  2   6 , Pei-Chen Wu  2   7 , Chien-Heng Lai  2   4 , Li-Jung Tseng  2   4 , Pi-Ru Tsai  2   4 , Rory Connolly  8 , Vin-Cent Wu  1   2
Affiliations

Urinary π-glutathione S-transferase Predicts Advanced Acute Kidney Injury Following Cardiovascular Surgery

Kai-Hsiang Shu et al. Sci Rep. .

Abstract

Urinary biomarkers augment the diagnosis of acute kidney injury (AKI), with AKI after cardiovascular surgeries being a prototype of prognosis scenario. Glutathione S-transferases (GST) were evaluated as biomarkers of AKI. Urine samples were collected in 141 cardiovascular surgical patients and analyzed for urinary alpha-(α-) and pi-(π-) GSTs. The outcomes of advanced AKI (KDIGO stage 2, 3) and all-cause in-patient mortality, as composite outcome, were recorded. Areas under the receiver operator characteristic (ROC) curves and multivariate generalized additive model (GAM) were applied to predict outcomes. Thirty-eight (26.9%) patients had AKI, while 12 (8.5%) were with advanced AKI. Urinary π-GST differentiated patients with/without advanced AKI or composite outcome after surgery (p < 0.05 by generalized estimating equation). Urinary π-GST predicted advanced AKI at 3 hrs post-surgery (p = 0.033) and composite outcome (p = 0.009), while the corresponding ROC curve had AUC of 0.784 and 0.783. Using GAM, the cutoff value of 14.7 μg/L for π-GST showed the best performance to predict composite outcome. The addition of π-GST to the SOFA score improved risk stratification (total net reclassification index = 0.47). Thus, urinary π-GST levels predict advanced AKI or hospital mortality after cardiovascular surgery and improve in SOFA outcome assessment specific to AKI.

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Conflict of interest statement

The human alpha GST and piGST assays were performed by Rory Connolly, R&D Scientist at EKF Diagnostics. No other potential conflicts of interest relevant to this article were reported.

Figures

Figure 1
Figure 1
(A) Urinary π-GST levels for patients with/without advanced AKI (KDIGO stage 2 or 3) (over time, p < 0.001). (B) Adjusted urinary π-GST levels for patients with/without advanced AKI (over time, p = 0.005). All expressed as mean ± standard error of mean.
Figure 2
Figure 2. ROC curves for urinary π-GST levels predicting advanced AKI.
Curves for different time points labeled as 3 hours [T3], 6 hours [T6], 9 hours [T9], 12 hours [T12], and 24 hours post-surgery [T24].
Figure 3
Figure 3. GAM plot for the probability of advanced AKI for urinary π-GST levels at T3 (3 hours post surgery).
The model incorporates the subject-specific (longitudinal) random effects, expressed as the logarithm of the odd (logit). The probability of outcome events was constructed with π-GST level and was centered to have an average of zero over the range of the data as constructed with the GAM. Log [π-GST (μg/L)] = 2.8 was an independent factor predicting postoperative stage 2 or 3 AKI.
Figure 4
Figure 4
(A) Urinary π-GST for patients with/without the composite outcome of advanced AKI or in-hospital mortality (over time, p < 0.001). (B) Adjusted urinary π-GST levels for patients with/without the composite outcome (over time, p = 0.017). All expressed as mean ± standard error of mean.
Figure 5
Figure 5. ROC curves for urinary π-GST levels predicting the composite outcome of advanced AKI or in-hospital mortality.
Curves for various time points labeled as 3 hours [T3], 6 hours [T6], 9 hours [T9], 12 hours [T12], and 24 hours post-surgery [T24].
Figure 6
Figure 6. GAM plot for the probability of composite outcome (advanced AKI or in-hospital mortality) for urinary π-GST levels at T3 (3 hours post surgery).
The model incorporates the subject-specific (longitudinal) random effects, expressed as the logarithm of the odd (logit). The probability of outcome events was constructed with π-GST level and was centered to have an average of zero over the range of the data as constructed with the GAM. Log [π-GST (μg/L)] = 2.7 was an independent factor predicting postoperative stage 2 or 3 AKI or in hospital mortality.
See this image and copyright information in PMC

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