Urinary biomarkers TIMP-2 and IGFBP7 early predict acute kidney injury after major surgery.

Ivan Gocze,Florian Zeman,Michael Nerlich,Bernhard M Graf,Marc H Dahlke,Matthias Koch,Hans J Schlitt,John A Kellum,Philipp Renner,Thomas Bein

doi:10.1371/journal.pone.0120863

Abstract

ObjectiveTo assess the ability of the urinary biomarkers IGFBP7 (insulin-like growth factor-binding protein 7) and TIMP-2 (tissue inhibitor of metalloproteinase 2) to early predict acute kidney injury (AKI) in high-risk surgical patients.IntroductionPostoperative AKI is associated with an increase in short and long-term mortality. Using IGFBP7 and TIMP-2 for early detection of cellular kidney injury, thus allowing the early initiation of renal protection measures, may represent a new concept of evaluating renal function.MethodsIn this prospective study, urinary [TIMP-2]×[IGFBP7] was measured in surgical patients at high risk for AKI. A predefined cut-off value of [TIMP-2]×[IGFBP7] >0.3 was used for assessing diagnostic accuracy. Perioperative characteristics were evaluated, and ROC analyses as well as logistic regression models of risk assessment were calculated with and without a [TIMP-2]×[IGFBP7] test.Results107 patients were included in the study, of whom 45 (42%) developed AKI. The highest median values of biomarker were detected in septic, transplant and patients after hepatic surgery (1.24 vs 0.45 vs 0.47 ng/l2/1000). The area under receiving operating characteristic curve (AUC) for the risk of any AKI was 0.85, for early use of RRT 0.83 and for 28-day mortality 0.77. In a multivariable model with established perioperative risk factors, the [TIMP-2]×[IGFBP7] test was the strongest predictor of AKI and significantly improved the risk assessment (p<0.001).ConclusionsUrinary [TIMP-2]×[IGFBP7] test sufficiently detect patients with risk of AKI after major non-cardiac surgery. Due to its rapid responsiveness it extends the time frame for intervention to prevent development of AKI.

Highlights

Postoperative acute kidney injury (AKI) is associated with an increase in short and long-term mortality
In a multivariable model with established perioperative risk factors, the [TIMP2]×[IGFBP7] test was the strongest predictor of AKI and significantly improved the risk assessment (p
The prognosis of patients with AKI is still poor, intervention for prevention and therapy of AKI are currently only initiated in the late phase of already established injury; benefits remain limited [6]

Summary

Methods

Urinary [TIMP-2]×[IGFBP7] was measured in surgical patients at high risk for AKI. Perioperative characteristics were evaluated, and ROC analyses as well as logistic regression models of risk assessment were calculated with and without a [TIMP-2]×[IGFBP7] test. Continuous variables were compared by the Student's t test or the Mann-Whitney U test, depending on the distribution of the observed data. Receiver-operating characteristic (ROC) analyses were conducted to differentiate between patient groups ((all stages of AKI [yes/no], moderate or severe AKI [yes/no], RRT [yes/no], and ICU mortality [yes/no]), and the optimal cutoff was estimated according to the Youden Index. Multivariable logistic regression models were calculated by means of odds ratios (OR’s) and corresponding 95% CI’s to assess the predictive ability of [TIMP-2]×[IGFBP7] for AKI development, for use of RRT and for 28-day mortality. To compare the fit of two nested models, we calculated AUCs of the predicted probabilities and conducted a likelihood-ratio test. All analyses were done with IBM SPSS Statistics 21.0.0.1 and R (version 3.0.2)

Results

Discussion

Conclusion