A novel mouse model of image-guided radiation-induced acute kidney injury using SARRP

Abstract

Radiation therapy is crucial for cancer treatment, but it often causes tissue damage. The kidney, which is sensitive to radiation, is under-researched in this context. This study aimed to develop a mouse model for radiation- induced acute kidney injury (AKI) using a small animal radiation research platform (SARRP) to mimic clinical radiation conditions. To establish the optimal AKI model, six-week-old male BALB/c mice were irradiated at doses of 5, 10, 20, and 30 Gy. Based on serum creatinine and blood urea nitrogen (BUN) levels, as well as immunohistochemical staining for neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), a 30 Gy dose was selected. This dose was applied in three ways: (1) single arc after a CT scan (K1, one kidney), (2) two arcs and two static beams after a CT scan (K2, both kidneys), and (3) abdominal irradiation after a single X-ray image (AI, including the kidneys). AKI was assessed 5 days post-irradiation. All irradiated groups exhibited more weight loss compared to the sham group, with the K2 group showing the most significant loss (p < 0.001 vs. K1,p < 0.05 vs. AI). The K2 group also demonstrated a significant reduction in kidney weight (p <0.05 vs. K1) and higher serum BUN levels (p <0.05 vs. sham,p < 0.01 vs. K1). Histopathological analysis revealed severe damage in the K2 group, including granular casts and tubular necrosis. The K2 group had elevated NGAL, KIM-1, gamma-H2AX, malondialdehyde, and caspase-3 levels, indicating increased AKI severity and DNA damage. The SARRP-created AKI model effectively targeted renal tissue while sparing extra- renal tissues, offering a more clinically relevant model compared to traditional methods. This model bridges the gap between clinical and preclinical studies, enhancing the accuracy and relevance of research on radiation- induced kidney injury.