A 65-year-old man with congestive heart failure is started on an aminoglycoside antibiotic for pneumonia. Three days later his creatinine rises sharply. Renal biopsy shows necrosis restricted to the proximal tubular epithelium with preserved tubular basement membrane. What is the predominant mechanism of injury?

• A Immune-complex deposition in the glomerulus
• B Obstruction of collecting ducts by casts
• C Interstitial granuloma formation
• D Direct tubular epithelial cell toxicity via mitochondrial dysfunction ✓

Explanation

Aminoglycosides cause acute tubular necrosis (ATN) primarily by accumulating in proximal tubular epithelial cells and generating reactive oxygen species that impair mitochondrial function, leading to ATP depletion and cell death. The proximal tubule is most vulnerable due to its high metabolic demands and active transport uptake of these drugs. The intact basement membrane allows tubular regeneration if the offending agent is removed promptly.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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