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Published on: November 10, 2021
CLEAVAGE OF IGFBP-1 BY AN ENZYME IN URINE PREDICTS THE FUTURE NEED FOR KIDNEY REPLACEMENT THERAPY IN ACUTE KIDNEY
John M Arthur1, Joseph H Holthoff1
1Little Rock, AR.
Insights
A new biomarker, cleaved insulin-like growth factor-binding protein 1 (IGFBP-1), shows promise for predicting severe acute kidney injury (AKI) progression to dialysis with 100% sensitivity and a low false positive rate.
Area of Science:
- Biochemistry
- Nephrology
- Biomarker Discovery
Background:
- Current Food and Drug Administration (FDA)-approved biomarkers for acute kidney injury (AKI) exhibit a 50% false positive rate (FPR).
- Insulin-like growth factor-binding protein 1 (IGFBP-1) has been identified as a potential predictor of severe AKI.
Purpose of the Study:
- To evaluate the efficacy of IGFBP-1 cleavage in urine as a biomarker for predicting the progression of AKI to the point of requiring dialysis.
- To assess the sensitivity and FPR of IGFBP-1 cleavage in various stages of AKI.
Main Methods:
- Urine samples were analyzed for the cleavage of IGFBP-1, an enzyme-mediated process.
- The study included patients with stage 1 AKI who progressed to dialysis, healthy controls, and patients with varying stages of AKI who did not require dialysis.
Main Results:
- Urine IGFBP-1 cleavage demonstrated 100% sensitivity in predicting progression to dialysis among patients with stage 1 AKI.
- The FPR was 0% in healthy controls.
- FPRs varied among patients with stage 1 AKI: 11% (no progression), 15% (stage 2), and 50% (stage 3 without dialysis).
Conclusions:
- Cleaved IGFBP-1 shows high potential as a sensitive biomarker for predicting AKI progression to dialysis.
- In a typical intensive care unit (ICU) setting, a test based on IGFBP-1 cleavage could achieve 100% sensitivity and a 6% FPR.
Abstract:
The only Food and Drug Administration (FDA)-approved biomarker for prediction of acute kidney injury (AKI) in adults has a false positive rate (FPR) of 50%. We identified insulin-like growth factor-binding protein 1 (IGFBP-1) as a good but not great predictor of severe AKI. IGFBP-1 was cleaved by an enzyme in the urine. We tested the ability of IGFBP-1 cleavage to predict progression to dialysis. Urine from all 12 patients with stage 1 AKI that progressed to require dialysis cleaved the protein (100% sensitivity). FPR was 0% among healthy controls. FPRs among patients with stage 1 AKI at the time of collection were 11% for patients who did not progress beyond stage 1, 15% for patients who progressed to stage 2, and 50% for patients who progressed to stage 3 but did not require dialysis. The sensitivity of a test with these characteristics would be 100% in a typical intensive care unit (ICU) population, and the FPR would be 6%.
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