TDF Fanconi Syndrome HIV Proximal Tubulopathy — ESENeph MCQ

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ModerateTubular DisordersTDF Fanconi Syndrome HIV Proximal TubulopathyESENeph

A 35-year-old woman presents with proximal muscle weakness, bone pain, and hypophosphataemia (phosphate 0.4 mmol/L). She has glycosuria (normoglycaemic), aminoaciduria, and a non-anion gap metabolic acidosis. Her medication list includes tenofovir disoproxil fumarate, efavirenz, and emtricitabine for HIV. What is the unifying diagnosis?

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Correct answer: D — Drug-induced Fanconi syndrome from tenofovir

TDF-induced Fanconi syndrome is a well-characterised proximal tubulopathy. TDF (tenofovir disoproxil fumarate) concentrates in proximal tubular cells via organic anion transporters and causes mitochondrial toxicity, impairing ATP-dependent tubular reabsorption. The result is a generalised proximal tubular dysfunction: phosphaturia (causing hypophosphataemia and osteomalacia), glycosuria (normoglycaemic), aminoaciduria, tubular proteinuria, and bicarbonate wasting (causing type 2 RTA with non-anion gap acidosis). The bone pain and proximal weakness reflect phosphate-depletion osteomalacia. Management: switch TDF to TAF (tenofovir alafenamide), which achieves equivalent intracellular levels with ~90% less plasma tenofovir, and supplement phosphate and vitamin D. Recovery may be slow or incomplete.

Reference: Hall et al 2011 – TDF Fanconi Syndrome; BHIVA 2024 – Antiretroviral Renal Toxicity