Abstract: FR-PO095

AKI Detection Using a Novel 5-Plex Panel

Session Information

  • AKI Clinical: Predictors
    November 03, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Patient Safety

  • 1501 Patient Safety

Authors

  • Adamo, Candace M., Pacific Biomarkers, Seattle, Washington, United States
  • Carlson, Timothy H., Pacific Biomarkers, Seattle, Washington, United States
  • Mccole, Eibhlin M., Randox Teoranta, Dungloe, Ireland
  • Mcgarvey, Marie, Randox Teoranta, Dungloe, Ireland
  • Richardson, Ciaran, Randox Teoranta, Dungloe, Ireland
  • Fitzgerald, Peter, Randox Laboratories Limited, Crumlin, United Kingdom
  • Lamont, John, Randox Laboratories Limited, Crumlin, United Kingdom
  • Sethi, Amar, Pacific Biomarkers, Seattle, Washington, United States
Background

Acute kidney injury (AKI) is classified using serum creatinine and urine output. However, since creatinine is a lagging index of impending AKI, studies are now underway to qualify a set of biomarkers for detecting drug-induced kidney injury (DIKI) in clinical trials. Since assessment of renal injury using multiple biomarkers is more clinically discriminating than single biomarker analysis, we report here the development and optimization of the first human multiplex for determining early and robust diagnosis of AKI.

Methods

Randox Biochip Array technology was used to develop a multiplex immunoassay panel for the below biomarkers. Performance goals for the multiplex were established by testing >1000 subjects using the predicate ELISA methods for KIM-1, NGAL, cystatin C, clusterin, and osteopontin (OPN). Functional sensitivity, cross reactivity, and interference were assessed, along with a sample correlation in 30 subjects.

Results

The 1000 patient samples provided dynamic ranges of 31.3-4000pg/mL; 1-100ng/mL; 1.5-150ng/mL; 10-1000ng/mL; 80-8000ng/mL for KIM-1, NGAL, cystatin C, clusterin, and OPN, respectively.
The functional sensitivity was confirmed for all analytes at the low end of the dynamic range as the precision of the lowest non-zero standard was <20%CV for all five biomarkers (n=6). The effective upper limits of measurement, determined by calculating precision of the highest standard were <10%CV.
There was no significant cross reactivity (<1% cross reactivity or <10% interference) for any of the analytes when spiked with x10 concentration of the highest standard of the other panel antigens. Cross reactivity from non-panel proteins were tested for cystatin C, clusterin and KIM-1 showing no significant cross-reactivity.
Method comparison between the two methods provided correlations (r2) of 0.927; 0.962; 0.872; 0.812; 0.899 for KIM-1, NGAL, cystatin C, clusterin and OPN, respectively. Slopes were 0.994, 0.544, 0.636, 1.67, and 0.685, respectively.

Conclusion

The AKI multiplex panel simultaneously detects KIM-1, NGAL, cystatin C, clusterin, and OPN with a solid performance and improved dynamic ranges compared to the predicate ELISA methods. This multiplex panel provides a robust and cost-effective solution for detecting DIKI in, not only, clinical trials, but potentially also in kidney patients for future diagnostic use.

Funding

  • Commercial Support