Amphotericin B causes nephrotoxicity primarily through which mechanism?
- A Competitive inhibition of renal tubular transporters for organic anions, causing drug accumulation
- B Immune-complex deposition in glomerular basement membrane causing membranous nephropathy
- C Precipitation in renal tubules due to low solubility at physiological pH
- D Binding to ergosterol in fungal membranes cross-reacts with cholesterol in renal tubular cell membranes, causing increased membrane permeability, electrolyte leakage, and direct tubular cell injury ✓
Explanation
Amphotericin B's antifungal mechanism is binding to ergosterol in fungal cell membranes and forming pores that allow leakage of intracellular contents. Nephrotoxicity results from the same mechanism applied to human renal tubular cells, which contain cholesterol (a sterol related to ergosterol). Binding to membrane cholesterol in renal tubular cells increases their permeability, causing potassium and magnesium wasting (tubular dysfunction), reduced GFR via tubuloglomerular feedback (afferent arteriolar vasoconstriction), and direct tubular cell necrosis. Liposomal amphotericin B (L-AmB) significantly reduces nephrotoxicity by preferentially delivering the drug to fungal membranes (which have higher ergosterol content) and reducing free drug concentration at renal tubular cells.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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