Abstract: FR-PO254
Urine EGF and TNFR2: A Pilot Study of Novel Biomarkers to Predict Long-Term Renal Outcomes in Pre-Clinical Model of Cisplatin-Induced Chronic Kidney Injury
Session Information
- Onconephrology: From AKI to CKD and Everything in Between
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Mosquera Vasquez, Claudia Alejandra, Nationwide Children's Hospital, Columbus, Ohio, United States
- Vasquez Martinez, Gabriela, Nationwide Children's Hospital, Columbus, Ohio, United States
- Mayoral Andrade, Gabriel, Nationwide Children's Hospital, Columbus, Ohio, United States
- Zeid, Ahmed S., Nationwide Children's Hospital, Columbus, Ohio, United States
- Zepeda-Orozco, Diana, Nationwide Children's Hospital, Columbus, Ohio, United States
Background
Cisplatin is associated with development of chronic kidney disease (CKD) and hypertension affecting around 45% of pediatric oncology patients. Novel urine biomarkers may allow early identification of patients at risk of CKD progression. Urine EGF (uEGF) has been shown to be an independent predictor of CKD progression in humans with an inverse correlation between uEGF and estimated glomerular filtration rate (GFR) decline. Tumor Necrosis Factors Receptor 2 (TNFR2) is a promising biomarker of inflammation with higher levels associated with increased risk of CKD progression. Murine cisplatin pre-clinical models result in long-term renal function decline and could facilitate identification of biomarkers to predict CKD progression.
Methods
Ten-week-old C57Bl6J male mice received 3 weekly intraperitoneal (IP) injections of cisplatin 8 mg/kg/dose vs 0.9% NaCl control (n = 18/group). Urine was collected at 14 days and 3 months after initial cisplatin dose, and transdermal GFR (tGFR) measurements were performed at 3 and 6 months after initial cisplatin dose. uEGF (ELISA, MEG00, R&D Systems) and uTNFR2 (R-PLEX assay, MESO QuickPlex SQ instrument) were measured according to manufacturer’s instructions. tGFR analysis was performed calculating FITC-sinistrin clearance after retroorbital injection. Veterinarian Pathologist quantified tubular injury, inflammation and fibrosis in kidney sections (score 0-4).
Results
Survival was 89% (control 94% vs 83% cisplatin). At 6 months, cisplatin treated mice had lower tGFR, and higher tubular injury, interstitial fibrosis, and inflammation on histological analysis. Cisplatin treated mice had significant reduction in uEGF at 14 days, and 3 months and a significant increase in uTNFR2 at 14 days compared to control group (p<0.05 2way ANOVA). There is a significant negative correlation between uEGF at 3 months and tubular injury, inflammation, and fibrosis at 6 months and a positive correlation with tGFR at 6 months. There is a significant positive correlation between uTNFR2 at 14 days and tubular injury, glomerular changes, and fibrosis at 6 months (Pearson, p<0.05).
Conclusion
uEGF and uTNFR2 could be promising early biomarkers to predict CKD in pre-clinical models of cisplatin-induced CKD.