Case Presentation: A 69-year-old male with history of HIV and disseminated tuberculosis presented to the Emergency department. He was found to be septic and ultimately diagnosed with VRE faecium bacteremia. During his hospitalization, he was noted to have decreased phosphate levels throughout the admission which required repletion nearly every day. His phosphate decreased to as low as 0.8 mg/dL even while being repleted with IV Phosphate. He was also noted to have mild bicarbonate loss, as low as 14 mEq/L. Initial considerations included malnutrition and poor GI absorption given he had a PEG tube. However, after multiple days of the non-resolving hypophosphatemia, we theorized that the tenofovir he was on for his HIV could possibly be causing Fanconi syndrome and thus leading to hypophosphatemia and mild bicarbonate losses. His HIV regimen was then switched to abacavir and lamivudine. About two days after his regimen was switched, his phosphate levels and bicarbonate levels stabilized, and have since never dipped down below 2.8 mg/dL and 20 mEq/L.
Discussion: Tenofovir is widely used to manage HIV and Hepatitis B. However, its potential nephrotoxicity is well documented. One of the rare but serious side effects include Fanconi syndrome, which is a disorder of the proximal tubular dysfunction that is characterized by hypophosphatemia, glycosuria, proteinuria, and metabolic acidosis. In our patient, his persistent hypophosphatemia despite continued supplementation of IV phosphate caused us to consider Tenofovir induced Fanconi syndrome. This was confirmed by stabilization of his phosphate and bicarbonate levels upon discontinuing the drug.Tenofovir is taken up into proximal tubular cells via organic anion transporters on the basolateral membrane. Once inside, it is secreted into the tubular lumen by multidrug resistance proteins. However, if efflux is inefficient or uptake is excessive, tenofovir accumulates intracellularly which can cause mitochondrial damage and impairs cellular energy metabolism. This mitochondrial toxicity disrupts the function of transporters responsible for reabsorbing phosphate and bicarbonate, notably the sodium-phosphate cotransporter and sodium-bicarbonate cotransporter, which results in hypophosphatemia and bicarbonate losses.While this is a rare adverse effect, there is still clinical significance. Medland et al., (2018) reported an incidence of Fanconi syndrome in 1.09 per 1,000 person years for Tenofovir monotherapy compared to 5.5 per 1,000 person years when co-administered with ritonavir. This study found that onset can be delayed, with a mean duration of exposure around 55 months, however cases have also been reported earlier, particularly in older patients or those with comorbidities. Another study, Li et al., (2023) found a patient with HBV on long term Tenofovir who developed severe hypophosphatemia and osteomalacia, which improved after discontinuing it. This mirrored a rapid clinical response seen in our patient.
Conclusions: Tenofovir induced Fanconi syndrome, while uncommon, should be considered in patients who develop persistent hypophosphatemia despite repletion. Early recognition and discontinuation of the offending drug is essential, as this can lead to rapid normalization of phosphate levels and can help prevent long term renal complications. This case highlights the importance of maintaining high index of suspicion for Tenofovir induced Fanconi syndrome, especially in patients with complex medical histories.