Amphotericin B-Induced Acute Kidney Injury

Mechanism of Nephrotoxicity

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest that amphotericin B causes AKI through direct tubular damage and renal vasoconstriction, leading to cellular dysfunction and death, affecting renal tubular cells, particularly those with high cholesterol content in mammalian cell membranes 1, 2

The KDIGO guidelines provide a Grade 1A recommendation to use azole antifungals and/or echinocandins rather than conventional amphotericin B when equal therapeutic efficacy can be assumed, as conventional formulations cause nephrotoxicity in the majority of patients 1, 2
The lipid formulation of amphotericin B reduces direct exposure of renal tubular cells to free amphotericin B, explaining the improved safety profile, with 19-50% of patients still developing some degree of renal injury with liposomal preparations 3

Before each amphotericin B dose, discontinue diuretics, and implement sodium loading and volume repletion by administering 0.9% saline intravenously 30 minutes before infusion, and provide potassium and magnesium supplementation, particularly with non-liposomal preparations, to reduce the risk of nephrotoxicity 3, 4
Administer lipid formulations over at least 2 hours to prevent hypotension and arrhythmias, and avoid concomitant nephrotoxic medications, such as aminoglycosides, vancomycin, cyclosporine, pentamidine, and NSAIDs, which enhance nephrotoxicity risk 5, 6

Monitor serum creatinine and electrolytes at minimum once or twice weekly, and check magnesium and potassium levels regularly, as amphotericin B-induced hypokalemia can potentiate cardiac dysfunction and digitalis toxicity 3

Concomitant administration of catecholamines or immunosuppressants increases AKI likelihood, and prior treatment with ACE inhibitors/ARBs or carbapenems is associated with higher AKI rates, according to the American Journal of Transplantation 6

Dialysis does not remove amphotericin B, and neither hemodialysis nor hemofiltration significantly reduces serum concentrations, so dose adjustment for renal replacement therapy is not required, as stated by the Praxis Medical Insights 3
The decreased incidence of AKI and associated reduction in hospitalization costs makes lipid formulations cost-effective compared to conventional amphotericin B despite higher acquisition costs, according to the American Journal of Kidney Diseases 4, 7