Abstract: FR-PO107
Renal Tubular Injury Biomarkers (BMs) in the Identification of Subclinical AKI and Drug-Induced Kidney Injury: IMI/SAFE-T/TransBioLine
Session Information
- AKI: Diagnosis and Outcomes
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Strader, Michael, University College Dublin, Dublin, Ireland
- Benain, Xavier, Sanofi SA, Paris, Île-de-France, France
- Camerlingo, Nunzio, Pfizer Inc, New York, New York, United States
- Friedman, Gary Steven, Pfizer Inc, New York, New York, United States
- Sultana, Stefan, AstraZeneca PLC, Cambridge, Cambridgeshire, United Kingdom
- Murray, Patrick T., University College Dublin, Dublin, Ireland
Background
Drug-induced kidney injury (DIKI), a subphenotype of AKI, is a side effect of cisplatin chemotherapy. Current AKI functional BMs are limited and therefore at the 23rd ADQI consensus conference proposed using novel BMs to enhance AKI criteria.
Methods
In this prospective study, 105 cisplatin-treated patients (Treated), 20 non-cisplatin-treated cancer controls (Non-Treated), and 34 Healthy controls were enrolled. Blood and urine samples from the Treated group were collected at specified timepoints. Standard BMs and novel BMs (eight urinary, one serum) were assessed. Three blinded nephrologists determined the presence or absence of DIKI in cisplatin-treated patients. BM accuracy was defined by sensitivity, specificity, AUROC, and changes (absolute and percentage) from baseline were compared between groups, with median time to peaks calculated.
Results
All biomarkers showed significant changes from baseline in the Treated group versus Non-Treated group. Most urinary BMs effectively detected cisplatin exposure (AUROC > 0.8). Novel BMs peaked earlier, with α-GST peaking first (Day 1), followed by serum CYSC and KIM-1 (Day 2). Treated group were adjudicated into DIKI (N = 24) and No-DIKI (N = 71) groups. Significant differences were observed in all BMs between both DIKI and No-DIKI groups compared to controls. No significant differences were found in urinary BMs, except for neutrophil gelatinase-associated lipocalin and cystatin-C, between DIKI and No-DIKI groups.
Conclusion
Novel BMs detected DIKI more sensitively and timely than standard BMs. A panel of BMs is likely superior for comprehensive nephrotoxicity assessment, which aligns with FDA's 2018 qualification letter supporting novel BMs with standard BMs in phase 1 drug development.
Funding
- Commercial Support – EFPIA