Urinary biomarkers in the clinical prognosis and early detection of acute kidney injury

Jay L Koyner, Vishal S Vaidya, Michael R Bennett, Qing Ma, Elaine Worcester, Shahab A Akhter, Jai Raman, Valluvan Jeevanandam, Micheal F O'Connor, Prasad Devarajan, Joseph V Bonventre, Patrick T Murray, Jay L Koyner, Vishal S Vaidya, Michael R Bennett, Qing Ma, Elaine Worcester, Shahab A Akhter, Jai Raman, Valluvan Jeevanandam, Micheal F O'Connor, Prasad Devarajan, Joseph V Bonventre, Patrick T Murray

Abstract

Background and objectives: Several novel urinary biomarkers have shown promise in the early detection and diagnostic evaluation of acute kidney injury (AKI). Clinicians have limited tools to determine which patients will progress to more severe forms of AKI at the time of serum creatinine increase. The diagnostic and prognostic utility of novel and traditional AKI biomarkers was evaluated during a prospective study of 123 adults undergoing cardiac surgery.

Design, setting, participants, & measurements: Urinary neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CyC), kidney injury molecule-1 (KIM-1), hepatocyte growth factor (HGF), π-glutathione-S-transferase (π-GST), α-GST, and fractional excretions of sodium and urea were all measured at preoperative baseline, postoperatively, and at the time of the initial clinical diagnosis of AKI. Receiver operator characteristic curves were generated and the areas under the curve (AUCs) were compared.

Results: Forty-six (37.4%) subjects developed AKI Network stage 1 AKI; 9 (7.3%) of whom progressed to stage 3. Preoperative KIM-1 and α-GST were able to predict the future development of stage 1 and stage 3 AKI. Urine CyC at intensive care unit (ICU) arrival best detected early stage 1 AKI (AUC = 0.70, P < 0.001); the 6-hour ICU NGAL (AUC = 0.88; P < 0.001) best detected early stage 3 AKI. π-GST best predicted the progression to stage 3 AKI at the time of creatinine increase (AUC = 0.86; P = 0.002).

Conclusion: Urinary biomarkers may improve the ability to detect early AKI and determine the clinical prognosis of AKI at the time of diagnosis.

Figures

Figure 1.
Figure 1.
Urinary biomarkers during the perioperative period for those subjects without AKI, those with stage 1 and stage 2 AKI, and those with stage 3 AKI. Stage 1 AKI was defined as a ≥50% relative increase or 0.3-mg/dl absolute increase in plasma creatinine from preoperative baseline or within the first 72 postoperative hours. (A) NGAL (ng/mg creatinine; mean ± SEM), (B) CyC (mg/g creatinine; mean ± SEM), (C) HGF (ng/mg creatinine; mean ± SEM), (D) KIM-1 (ng/mg creatinine; mean ± SEM), (E) α-GST (ng/mg creatinine; median [IQR 25% to 75%]) (F) π-GST (ng/mg creatinine; median [IQR 25% to 75%]). Note that the No AKI plot (red) is obscured from view by the plot for those with stage 1 and 2 AKI (blue). *P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001.

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