Amphotericin B causes nephrotoxicity despite the fact that ergosterol (not cholesterol) is its primary membrane target. The mechanism of nephrotoxicity is:
- A Amphotericin B is renally excreted as a nephrotoxic metabolite after hepatic oxidation
- B Amphotericin B activates complement in the renal vasculature, causing immune-mediated glomerulonephritis
- C Amphotericin B inhibits renal prostaglandin synthesis, causing afferent arteriolar vasoconstriction without direct tubular toxicity
- D Amphotericin B binds cholesterol in renal tubular cell membranes with lower but significant affinity, creating pores causing potassium/magnesium wasting and tubular damage, plus renal vasoconstriction ✓
Explanation
Amphotericin B inserts into ergosterol-containing fungal membranes as its primary action, but it also interacts with cholesterol in mammalian cell membranes (lower affinity but not negligible at therapeutic concentrations); in renal tubular cells and glomerular endothelium, pore formation causes K+ and Mg2+ wasting (hypokalemia, hypomagnesemia) and tubular apoptosis. Additionally, amphotericin B causes renal afferent arteriolar vasoconstriction (possibly via thromboxane A2 and decreased prostaglandin E2), reducing GFR. Lipid formulations reduce nephrotoxicity by preferentially interacting with fungal ergosterol.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.