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

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.