Early and Stable Mouse Model of Amphotericin B‐Induced Acute Kidney Injury: Application of Continuous Non‐Invasive GFR Monitoring

ABSTRACT Background Amphotericin B (AmB) remains a cornerstone in antifungal therapy, but its clinical use is limited by dose‐dependent nephrotoxicity. Lipid‐based formulations such as amphotericin B cholesterol sulfate complex dispersion (ABCD) were developed to mitigate renal injury, though their comparative renal safety profiles remain incompletely defined. Objective This study aimed to establish a pharmacologically relevant mouse model to characterise the nephrotoxicity of conventional AmB (AmB‐D) and ABCD formulations, using continuous non‐invasive glomerular filtration rate (GFR) monitoring and renal injury biomarkers. Methods Male C57BL/6 mice received a single intravenous dose of AmB‐D or ABCD at low or high doses. Renal function was assessed via real‐time GFR monitoring, serum creatinine (SCr), blood urea nitrogen (BUN) and mRNA expression of kidney injury molecule‐1 (KIM‐1) and neutrophil gelatinase‐associated lipocalin (NGAL). Histopathological injury was evaluated at defined time points. Results High‐dose AmB‐D (2 mg/kg) and ABCD (20 mg/kg) induced rapid GFR decline within 2 h, preceding significant increases in SCr, BUN, and injury biomarkers. ABCD demonstrated 6–10‐fold lower nephrotoxic potency compared to AmB‐D. Low‐dose groups exhibited mild, reversible changes in GFR and minimal tubular injury. Conclusion Continuous GFR monitoring enables sensitive detection of early renal dysfunction and reveals distinct nephrotoxic profiles between AmB‐D and ABCD. This pharmacologically relevant model provides a powerful tool for preclinical nephrotoxicity assessment and for quantitatively comparing the renal safety of different drug formulations.