245 - Modulation of Radiation Induced AKI by Photobiomodulation and Sodium Iodide Treatment in a Pediatric Animal Model

Saturday, April 29, 2023

3:30 PM – 6:00 PM ET

Poster Number: 245
Publication Number: 245.25

Angela M. Groves, University of Rochester School of Medicine and Dentistry, ROCHESTER, NY, United States; Carl Johnston, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States; Nicole Paris, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States; Brian Marples, University of Rochester, Rochester, NY, United States; Alison Kent, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States

Presenting Author(s)

Angela M. Groves, PhD

Research Assistant Professor
University of Rochester School of Medicine and Dentistry
ROCHESTER, New York, United States

Background: Kidneys are susceptible to nephropathy following oncologic radiotherapy. In pediatric oncology patients, the addition of radiotherapy to surgical treatments reduces glomerular filtration rate and increases risk for developing acute and chronic kidney injury.

Objective:

To examine effects of photobiomodulation (PBM) and sodium iodide (NaI) on radiation-induced acute kidney injury (AKI) in a pediatric model.

Design/Methods: Day 21 Sprague Dawley pups received bilateral kidney irradiation using single doses (SD) of either 5.3Gy or 10Gy, or fractionated doses of 2.6Gyx3 or 8.1Gyx3, sufficient to produce AKI. Control pups received sham irradiation with identical handling. Pups were treated with PBM (670nm red light, providing 30 Jcm² over 10 minutes) immediately following each dose of radiation then once daily for 5 additional days, or NaI (6 mg/kg/day) immediately after their final fraction and maintained for the study duration. Kidneys were collected at 4hr, 24hr, 1wk or 4wk post irradiation for RT-PCR analysis of pro-inflammatory markers. Urine was obtained at sacrifice for AKI biomarkers (NGAL, KIM-1, albumin).

Results: Both 5.3Gy and 10Gy SD significantly increased (p< 0.05) hemeoxygenase-1 (Hmox1) expression in the kidney and the inflammasome component Nlrp3 4hr post exposure; these markers remained elevated at the 4wk time point at 10Gy. Significantly elevated urinary levels of NGAL and albumin was evident after 10Gy but not 5.3Gy. Elevated Hmox1 expression was seen after both fractionated doses at 1wk but was only increased at 4wk after 8.1Gyx3. Increased Nlrp3 was seen at 1wk and 4wks, and significantly elevated urinary albumin and KIM-1 at 4wk after 8.1Gyx3, but not 2.6Gyx3. PBM did not alter urinary biomarker concentration but significantly reduced Hmox1 expression at all radiation doses. However, PBM significantly reduced elevated Hmox1 and Nlrp3 at 4wk post 8.1Gyx3. Whereas, NaI reduced the AKI urinary biomarker albumin but did not alter inflammatory gene expression.

Conclusion(s): Kidney-targeted radiation elevated inflammatory genes in the kidney at all doses, but AKI was only detected after 10Gy and 8.1Gyx3. PBM and NaI treatment ameliorated local and systemic elevation of markers of kidney injury, respectively. These early-stage data demonstrate the promise of PBM and NAI at reducing AKI although additional studies are needed.