48 - Urine Epidermal Growth Factor (EGF) correlates with long term renal outcomes in pre-clinical models of Cisplatin-Chronic Kidney Injury

Sunday, April 30, 2023

3:30 PM – 6:00 PM ET

Poster Number: 48
Publication Number: 48.35

Claudia A. Mosquera Vasquez, Nationwide Children's Hospital, Dublin, OH, United States; Gabriel Mayoral Andrade, Nationwide Children's Hospital, Columbus, OH, United States; Gabriela Vasquez Martinez, Nationwide Children's Hospital, Columbus, OH, United States; Ahmed Zeid, Nationwide Children's Hospital, Columbus, OH, United States; Sarah C. Linn-Peirano, Nationwide Children's Hospital, Columbus, OH, United States; DIANA ZEPEDA-OROZCO, Nationwide Children's Hospital, Columbus, OH, United States

Presenting Author(s)

Claudia A. Mosquera Vasquez, MD (she/her/hers)

Nephrology Fellow
Nationwide Children's Hospital
Dublin, Ohio, United States

Background: Cisplatin associated chronic kidney disease (CKD) is present in up to 45% of the pediatric patients. Epidermal growth factor (EGF) is a tubule specific protein critical in cell growth, migration, proliferation, and differentiation. The amount of 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. The concentration of uEGF may allow early identification of CKD progression risk in cisplatin pre-clinical models that could facilitate evaluating its pathophysiology and testing novel targeted therapeutic approaches.

Objective:

To determine the correlation between uEGF and risk of CKD progression in pre-clinical model of cisplatin-induced CKD.

Design/Methods: Ten-week-old C57Bl6J male mice received 3 doses of 8 mg/k/dose of cisplatin vs. 0.9% NaCl control weekly (n = 6 vehicles, n= 6 cisplatin). Urine was collected 3 months and 6 months post last dose administration. uEGF concentration was measured via ELISA (MEG00, R&D Systems) and GFR was measured using transdermal glomerular filtration rate (tGFR) monitors that calculate FITC-sinistrin clearance after retroorbital injection.

Results: Survival was 66.7% in cisplatin treated mice vs. 100% in vehicle control. uEGF concentration was significantly lower in cisplatin treated mice compared to vehicle control at 3 months (mean 271 vs. 1651 ng/ml, p< 0.05 by t-test) and at 6 months (mean 279 vs 1472 ng/mL, p< 0.05 by t-test). tGFR did not differ significantly between cisplatin and vehicle treated mice at 3 months (0.59 vs 0.84 mL/min/100g b.w. respectively), however, it was significantly lower 6 months (mean 1.053 vs. 0.6 mL/min/100g b.w. respectively, p< 0.05 by t-test). There was a significant correlation between uEGF at 3 months and tGFR at 6 months (R 0.7, p< 0.05, Pearson correlation)

Conclusion(s):

uEGF could be a promising biomarker to predict GFR decline in pre-clinical models of cisplatin-induced CKD.