Abstract: TH-OR104

Cell-Cycle Arrest Biomarkers TIMP2*IGFBP7 Predict Worse Outcomes in Septic Patients without Clinical Evidence of AKI

Session Information

  • Predicting AKI
    November 02, 2017 | Location: Room 282, Morial Convention Center
    Abstract Time: 05:42 PM - 05:54 PM

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational


  • Fiorentino, Marco, University of Pittsburgh, Pittsburgh, United States
  • Keener, Christopher M., University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Smith, Ali, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Kellum, John A., University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Acute kidney injury (AKI) is associated with both short and long-term adverse outcomes in patients with sepsis. Standard criteria for AKI, like serum creatinine (sCr) and urine output (UO), are poor, late and non-specific diagnostic tools. The aim of this study is to analyze the performance of several biomarkers in addition to standard criteria for early prediction of sepsis-associated AKI.


We analyzed data from 1243 patients with septic shock enrolled in the ProCESS trial of early goal-directed therapy, for which biomarkers at admission were available. TIMP2*IGFBP7, uNGAL and uKIM1 at the time of admission were independently combined with clinical parameters for AKI (sCr and UO). Our primary endpoint was the development of severe AKI (KDIGO stage 3), renal replacement therapy (RRT) or death in the first 7 days of enrollment. We analyzed the frequency of the outcome and the odds ratios (ORs) for each combination, compared to a reference (normal sCr, UO and negative biomarkers). We also examined the effect of different resuscitation strategies on the endpoint.


Excluding patients with stage 3 AKI at admission and those with missing data, we analyzed 493 patients with availability of biomarkers at time 0. No significant differences in the outcome were found when uNGAL and uKIM1 were added to sCr and UO. By contrast, in patients with normal sCr and UO, the proportion of patients who developed the endpoint was significantly higher in those with positive (>0.3 ng/ml2/1000) urine TIMP2*IGFBP-7 (16.2% vs 5.7%, p=0.02) and the odds ratio for developing the endpoint was 3 times greater (OR 3.03, 95%CI 1.27-7.22). Similar results were found in sensitivity analyses using the highest cut-off for TIMP2*IGFBP7 (>2 ng/ml2/1000; OR 2.8, 95%CI 1.14-6.84) and using different outcomes (death/dialysis at 30 days OR 3, 95%CI 1.26-7.15, p=0.005; death/dialysis at 1 year OR 3.32, 95%CI 1.41-7.85, p=0.002). Moreover, the effect of the protocolized resuscitation vs usual care on the endpoint was negative and not different across TIMP2*IGFBP7 strata.


Early assessment of TIMP2*IGFBP7 at the time of admission in ICUs may significantly improve the ability to predict hard outcomes (severe AKI, RRT and death within 7 days) in apparently “asymptomatic” septic patients (normal sCr and UO).


  • Other NIH Support