Kidney-based in vivo model for drug-induced nephrotoxicity testing

Area of Science:

• Biomedical Sciences
• Toxicology
• Genetics

Background:

• Acute kidney injury (AKI) diagnosis requires urgent, sensitive, and specific biomarkers.
• Current diagnostic methods often lag behind the onset of kidney damage.
• Drug-induced nephrotoxicity is a significant clinical concern.

Purpose of the Study:

• To develop a Miox-NanoLuc transgenic mouse model for early detection of drug-induced nephrotoxicity.
• To establish a sensitive and specific biomarker for real-time AKI monitoring.
• To investigate the utility of this model in quantifying kidney injury.

Main Methods:

• Generation of Miox-NanoLuc transgenic mice with kidney-specific NanoLuc overexpression.
• Assessment of luminescence stability under various conditions (temperature, freeze-thaw).
• Monitoring of serum and urine luminescence, BUN, creatinine, and renal pathology in response to nephrotoxic agents (cisplatin, aristolochic acid).

Main Results:

• Miox-NanoLuc luminescence was kidney-specific and stable.
• Luminescence levels increased significantly earlier (day 1 for cisplatin, day 3 for AAI) than BUN/creatinine increases (day 2-3 for cisplatin, day 5 for AAI).
• Renal pathological changes were observed later than luminescence increases.

Conclusions:

• The Miox-NanoLuc mouse model enables early quantification of drug-induced nephrotoxicity.
• This platform detects kidney injury before significant changes in traditional biomarkers or observable pathology.
• The model shows promise for early detection of drug- and food-induced nephrotoxicity and for studying tubular injury.