A 42-year-old woman with HIV on tenofovir, emtricitabine, and efavirenz for 4 years develops proximal muscle weakness, polyuria, and bone pain. Labs: serum phosphate 0.45 mmol/L (low), K+ 2.9 mmol/L, bicarb 18 mmol/L, urine glucose ++ (serum glucose normal), mild proteinuria. X-ray shows pseudofractures. This syndrome is BEST explained by:
- A Efavirenz-induced mitochondrial toxicity in the CNS causing electrolyte wasting
- B HIV nephropathy causing collapsing FSGS with electrolyte wasting
- C Tenofovir disoproxil fumarate (TDF)-induced Fanconi syndrome (proximal tubular dysfunction) ✓
- D Primary hyperparathyroidism developing in an HIV-infected patient on HAART
Explanation
Tenofovir disoproxil fumarate (TDF) — the older form of tenofovir — causes mitochondrial dysfunction in proximal tubular cells due to inhibition of mitochondrial polymerase gamma. This leads to Fanconi syndrome: generalised proximal tubular dysfunction with glycosuria (normoglycaemic), phosphaturia (hypophosphataemia), aminoaciduria, bicarbonaturia (RTA type 2), kaliuresis, and proteinuria. Hypophosphataemia causes osteomalacia (pseudofractures on X-ray). This is a well-recognised nephrotoxic complication of TDF. The newer formulation, tenofovir alafenamide (TAF), has significantly lower nephrotoxic potential. Efavirenz does not cause Fanconi syndrome. HIVAN causes nephrotic syndrome/FSGS, not Fanconi.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.