Abstract: TH-OR101

Urine Insulin like Growth Factor Binding Protein1 (IGFBP1): Novel Prognostic Biomarker in AKI

Session Information

  • Predicting AKI
    November 02, 2017 | Location: Room 282, Morial Convention Center
    Abstract Time: 05:06 PM - 05:18 PM

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Karakala, Nithin, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Edmondson, Ricky, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Herzog, Christian, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
  • Arthur, John M., University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States
Background

Serum creatinine (Cr) is a poor prognostic marker in early AKI. Prognostic urine biomarkers could be valuable tools to detect high risk patients in early AKI. We identified urine IGFBP1 as a potential biomarker using discovery proteomics and validated it in a larger cohort.

Methods

We performed liquid chromatography/ tandem mass spectrometry on urine from patients who developed stage 1 AKI within 48 hours after cardiac surgery. 10 patients that required renal replacement therapy within 7 days after surgery were matched to 20 patients with similar comorbities, baseline Cr, surgical type, bypass status and change in Cr at urine collection. The biomarker concentration was subsequently measured in 213 patients by ELISA to validate the prognostic ability. The primary outcome in the validation set was the composite of death, renal replacement therapy (RRT) and KDIGO stage 3.

Results

In the discovery phase we identified 2065 high confidence proteins of which 126 had p values of less than 0.01 between groups. IGFBP1 had the largest fold increase in RRT (14.8-fold). Median amino acid coverage of IGFBP1 in controls was 0% (range 0-15%) and 26% (0-38%) in RRT. Based on these data, we performed validation with ELISA in a larger cohort. Of the 213 patients included in the validation set, 27 met the primary outcome. The median time to urine collection from cardiac surgery was 22 hours (range:19-43) . There were no significant differences between the outcome groups with respect to demographics, underlying medical conditions, type of surgery or pre-op Cr. The median concentration of IGFBP1 was significantly higher in the primary outcome group at 40 (95%CI:10-244) vs 3 (1-11) ng/ml; p<0.05. Median concentration of IGFBP1 was significantly higher in those that met secondary outcomes of mortality (40, 95%CI: 10-333 vs 3: 1-16 ng/ml; p<0.05) and RRT (81: 13-353 vs 4: 1-17 ng/ml; p<0.05 ) compared those who did not meet these outcomes. Urine IGFBP1 levels were highly discriminative for identifying the primary outcome (ROC AUC: 0.85) and the secondary outcomes death (0.82) and dialysis (0.85). The results did not significantly change when urine IGFBP1 concentrations were normalized to urine Cr.

Conclusion

Urinary IGFBP1 is a prognostic biomarker of AKI after cardiac surgery and can predict adverse outcomes early in the course of disease.

Funding

  • NIDDK Support