A 45-year-old HIV-positive patient on tenofovir disoproxil fumarate (TDF)-based ART develops proximal tubular dysfunction: hypophosphatemia, glycosuria with normal blood glucose, hypokalemia, low urine uric acid reabsorption, and low serum uric acid. Serum creatinine is 1.6 mg/dL (rising from baseline 1.0). What is the likely diagnosis and best management?
- A TDF-induced Fanconi syndrome — switch TDF to TAF (tenofovir alafenamide) ✓
- B HIVAN (HIV-associated nephropathy) — optimize ART
- C Acute tubular necrosis from TDF — aggressive IV hydration
- D TMP-SMX induced tubular acidosis — discontinue co-trimoxazole
Explanation
Tenofovir disoproxil fumarate (TDF) causes mitochondrial toxicity in proximal tubular cells, leading to Fanconi syndrome: urinary wasting of phosphate, glucose (normoglycemic glycosuria), uric acid, potassium, amino acids, and bicarbonate. This is a known class effect of TDF (and didanosine). Management is switching to TAF (tenofovir alafenamide), a prodrug that delivers higher intracellular drug concentrations with lower plasma exposure and reduced renal toxicity, without losing antiviral efficacy. HIVAN presents as nephrotic syndrome with collapsing FSGS. TMP-SMX causes hyperkalemia and tubular acidosis, not full Fanconi.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.