Amphotericin B causes nephrotoxicity by a specific mechanism distinct from its antifungal action. The nephrotoxic mechanism is:
- A Insertion into renal tubular cell membranes (which also contain ergosterol) and disrupting intracellular ion homeostasis
- B Competitive inhibition of proximal tubular sodium-potassium ATPase causing tubular dysfunction
- C Vasoconstriction of afferent renal arterioles causing ischemia-mediated tubular damage, compounded by direct tubular membrane disruption ✓
- D Immune-mediated interstitial nephritis from amphotericin-albumin conjugate antigen presentation
Explanation
Amphotericin B nephrotoxicity occurs via two mechanisms: (1) direct tubular toxicity — amphotericin B binds to cholesterol (in addition to ergosterol) in mammalian tubular cell membranes, forming pores that cause potassium and magnesium wasting and tubular acidification (renal tubular acidosis type 1 pattern); (2) vasoconstriction of renal afferent arterioles reduces GFR, causing ischemic tubular injury. Liposomal formulations (AmBisome) reduce nephrotoxicity by limiting free drug exposure to renal vessels while maintaining concentrations in macrophage-rich tissues where fungi reside.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.