The chicken embryo model as a tool for investigating drug-induced acute kidney injury

Nephrotoxicity remains a critical concern in drug development, with limited preclinical models that balance physiological relevance, ethical considerations, and scalability. Here, we evaluate the chicken embryo (CE) as an in vivo platform for nephrotoxicity assessment, using gentamicin-induced acute kidney injury as a proof-of-principle. Using an ex ovo culture system, we assessed renal responses in the developing CE kidney. By embryonic day 12, the CE exhibited advanced organogenesis, including a functional metanephric kidney. Immunohistochemical analyses demonstrated conservation of key structural and vascular markers between chicken and human kidneys, including α-smooth muscle actin, von Willebrand factor, and integrins. Gentamicin exposure induced dose- and time-dependent tubular injury, with significant dilation and vacuolization observed at 48 h following exposure to 0.4 mg/mL, which subsided by 96 h. As a proof-of-principle study, these findings demonstrate that the CE can detect acute tubular injury in a developing kidney. The model's primary relevance lies in developmental nephrotoxicity research, where accessible and physiologically integrated experimental systems remain limited.