Fanconi Syndrome Leading to Hypophosphatemic Osteomalacia Related to Tenofovir Use

Abstract

Tenofovir disoproxil fumarate (TDF) is used worldwide to treat and prevent Human Immunodeficiency Virus (HIV) infection. Fanconi syndrome is a complication of TDF use and is characterized by inadequate reabsorption of glucose, phosphate and protein in the proximal tubule of the kidney which may eventually lead to osteomalacia manifested by symptoms of pain, muscular weakness and difficulty ambulating. We present a patient with severe osteomalacia due to progressive and unrecognized Fanconi’s syndrome, who responded rapidly to TDF withdrawal, oral phosphate repletion and calcitriol. With the widespread use of TDF-containing antiviral regimens, it is critically important that physicians adhere to screening recommendations to detect early Fanconi syndrome, and recognize symptoms of osteomalacia as a serious complication.

Fanconi Syndrome and Osteomalacia Induced by Tenofovir

“…Tenofovir Disoproxil Fumarate (TDF) 300 mg daily has been used as a preferential treatment for HIV and HBV. 5 However, chronic TDF usage has serious side effects, especially bone and kidney toxicity. 5 Tenofovir is eliminated by active tubular secretion and also by passive glomerular filtration; circulating plasma tenofovir may damage the proximal tubule which could lead to renal impairment and Fanconi Syndrome.…”

“…5 However, chronic TDF usage has serious side effects, especially bone and kidney toxicity. 5 Tenofovir is eliminated by active tubular secretion and also by passive glomerular filtration; circulating plasma tenofovir may damage the proximal tubule which could lead to renal impairment and Fanconi Syndrome. 8 In Fanconi Syndrome, the defect only occurs in tubular proximal which can be classified as renal tubular acidosis.…”

“…4 Even though the correlation between TDF and the mechanism of bone density loss remains unclear, it has been suggested that TDF phosphonate molecules could impact osteoclast and osteoblast function by altering their gene expression. 5 And Fanconi syndrome with hypocalcemia and hypophosphatemia, may worsen the osteomalacia state. 5 Grant, et al, found that patients treated with TDF showed greater BMD loss and increased…”

“…5 And Fanconi syndrome with hypocalcemia and hypophosphatemia, may worsen the osteomalacia state. 5 Grant, et al, found that patients treated with TDF showed greater BMD loss and increased…”

Two-Drug Regimens for HIV—Current Evidence, Research Gaps and Future Challenges

“…On the other hand, TDF is related to chronic kidney disease and bone demineralization [9]. Although rare, TDF can produce proximal tubulopathy, and some cases of Fanconi syndrome have been reported [10,11]. The novel tenofovir formulation, TAF, has lower renal and bone toxicity compared to TDF [12,13].…”