Tenofovir disoproxil fumarate (TDF) causes renal toxicity in some HIV patients. The specific renal syndrome associated with TDF toxicity is:

• A Fanconi syndrome (proximal renal tubular dysfunction) due to mitochondrial toxicity in proximal tubular cells ✓
• B Glomerulonephritis with proteinuria and hematuria
• C Nephrogenic diabetes insipidus from aquaporin-2 downregulation
• D Obstructive nephropathy from crystal deposition in collecting ducts

Explanation

TDF (a nucleotide reverse transcriptase inhibitor) is concentrated in proximal renal tubular cells and is poorly excluded from mitochondria. It inhibits mitochondrial DNA polymerase gamma, causing mitochondrial dysfunction and depletion of mitochondrial DNA in proximal tubular cells. This impairs the energy-dependent transporters in the proximal tubule, resulting in Fanconi syndrome: glycosuria (with normal blood glucose), phosphaturia, aminoaciduria, bicarbonaturia, and uricosuria. Hypophosphatemia from phosphaturia can cause osteomalacia and fractures. Tenofovir alafenamide (TAF), a newer prodrug of tenofovir, achieves lower plasma tenofovir concentrations and has significantly less renal and bone toxicity than TDF.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.