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Kidney Week

Abstract: SA-PO0116

Onconephrology Clinical Decision-Making: Qualified Urine Biomarkers Sensitivities and Specificities May Vary When Using Different Laboratory Assays and Platforms

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Bonventre, Joseph V., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Dieterle, Frank, Novartis AG, Basel, BS, Switzerland
  • Friedman, Gary Steven, Critical Path Institute, Tucson, Arizona, United States
  • Murray, Patrick T., University College Dublin, Dublin, Leinster, Ireland
  • Richfield, Owen, Yale University, New Haven, Connecticut, United States
  • Roberts, Glenda V., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Strader, Michael, University College Dublin, Dublin, Leinster, Ireland
  • Sultana, Stefan, AstraZeneca R&D Cambridge, Cambridge, England, United Kingdom
  • Hoffmann, Steven C., Foundation for the National Institutes of Health, North Bethesda, Maryland, United States
  • Camerlingo, Nunzio, Pfizer Inc, New York, New York, United States
  • Peron, Katrina Jolene, Critical Path Institute, Tucson, Arizona, United States
  • King, Nicholas M., Critical Path Institute, Tucson, Arizona, United States

Group or Team Name

  • PSTC Biomarker Data Repository (BmDR).
Background

US FDA (2018) qualified PSTC’s non-standard of care urine biomarkers (NBM) panel-of-6 (urine clusterin, cystatin C, KIM-1, NAG, NGAL, osteopontin/creatinine) alongside standard-of-care kidney injury biomarkers (SBM) (serum creatinine, cystatin C, urine albumin- and protein-to-creatinine ratios) to better detect nephrotoxicant exposure and drug-induced kidney injury (DIKI) in Phase 1 healthy volunteer cohorts.

Methods

Two exploratory cisplatin studies were conducted by PSTC and SAFE-T. PSTC (n=60 + 81 healthy volunteers) defined a composite geometric mean threshold for the panel-of-6 NBMs to assess exposure and AKI across the cohort. SAFE-T (n=75) assessed individual urine biomarkers’ sensitivity/specificity using median change (95% CI) from baseline for NBMs (urine α-GST, clusterin, cystatin C, KIM-1, NGAL, and osteopontin corrected to urine creatinine) and SBMs.

Results

See individual biomarker sensitivity and specificity thresholds in Figure 1

Conclusion

SAFE-T and PSTC NBM sensitivities and specificities are based upon use of median value and upper limit of normal, respectively. Furthermore, NBMs were quantified by different vendors using different assay platforms. Going forward, use of validated/cleared assays and devices should further clarify NBM performance characteristics.

SAFE-T and PSTC NBM Sensitivities and Specificities

Funding

  • Other U.S. Government Support

Digital Object Identifier (DOI)