Kidney Week

Abstract: FR-PO020

Optimization of a Novel 5-Plex Panel for AKI

Session Information

• AKI: Clinical, Outcomes, Trials - I
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Adamo, Candace M., Pacific Biomarkers, Seattle, Washington, United States

Candace M. Adamo,

• McCole, Eibhlin M., Randox Teoranta, Dungloe, Ireland

Eibhlin M. McCole,

• Richardson, Ciaran, Randox Teoranta, Dungloe, Ireland

Ciaran Richardson,

• Carlson, Timothy H., Pacific Biomarkers, Seattle, Washington, United States

Timothy H. Carlson,

• Donnellan, Grainne, Randox Teoranta, Dungloe, Ireland

Grainne Donnellan,

• Sethi, Amar, Pacific Biomarkers, Seattle, Washington, United States

Amar Sethi,

Background

Since creatinine is a lagging index of AKI progression, studies are now underway to qualify a new set of biomarkers for detecting drug-induced kidney injury (DIKI). Here, following optimization, we present performance data for a novel multiplex composed of urine AKI biomarkers.

Methods

The AKI multiplex panel quantifies KIM-1, cystatin C, clusterin, OPN and NGAL levels in urine. Multiplex results were compared to those from ELISA using urine from one cohort (n=60) treated with a preservative prior to freezing, and urine from a second cohort (n=122) left untreated. Cross reactivity for each analyte with non-panel related proteins was tested. Interfering substances were tittered to determine non-interfering concentrations (within ± 10%). Potential interferents assessed included human albumin (HA), hemoglobin, bilirubin, pH, glucose, sodium chloride and creatinine.

Results

Comparison of preserved urine biomarkers obtained using the two analytical methods provided correlations (r²) of 0.816, 0.970, 0.842, 0.718, and 0.741 for KIM-1, NGAL, cystatin C, clusterin and OPN, respectively. Slopes were 0.32, 0.87, 1.33, 0.53, and 1.06, respectively. The methods were poorly correlated for unpreserved urine with r² ranging from 0.203 to 0.705. Cross reactivity was <1% for all tested non-panel, related proteins. Interfering concentration for HA was <0.5 mg/mL for clusterin and was insignificant for remaining biomarkers. Hemoglobin interference was <62.5 µg/mL for clusterin and insignificant for all other biomarkers. Bilirubin, glucose, sodium chloride and creatinine interferences were insignificant for all biomarkers.

Conclusion

All five biomarkers tested with the novel panel and predicate ELISA methods correlated well when preserved urine was used. Recovery of some urinary AKI biomarkers is susceptible to variability, which can be controlled with preservative. No clinical significant interference was observed for several substances known to be present in urine and cross-reactivity for non-panel proteins was not significant. Previously reported performance of this multiplex combined with the present data demonstrate good multiplex selectivity, and document an in vitro diagnostic that fills the need for a robust and cost-effective approach to diagnosis and monitoring of DIKI.