Tenofovir disoproxil fumarate (TDF), a key component of HIV HAART regimens, can cause proximal renal tubular dysfunction (Fanconi syndrome). The mechanism is:

• A TDF precipitates in tubular lumen causing crystalline nephropathy
• B TDF is nephrotoxic via direct glomerular podocyte injury
• C TDF causes immune-complex deposition in tubules via anti-TDF antibodies
• D TDF inhibits mitochondrial DNA polymerase gamma in renal proximal tubular cells, causing mitochondrial dysfunction and tubular toxicity ✓

Explanation

Tenofovir (as its active metabolite tenofovir diphosphate) is preferentially taken up by renal proximal tubular cells and accumulates there. At the mitochondrial level, it inhibits mitochondrial DNA polymerase gamma—the enzyme responsible for replicating mitochondrial DNA—causing mitochondrial dysfunction, ATP depletion, and impaired tubular transport functions. The result is proximal tubular dysfunction (Fanconi syndrome): phosphaturia, glycosuria, aminoaciduria, and reduced vitamin D activation. Tenofovir alafenamide (TAF) has lower renal and bone toxicity due to more targeted intracellular activation.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.