Fanconi's Syndrome in HIV+ Adults: Report of Three Cases and Literature Review

Abstract

We diagnosed Fanconi's syndrome (phosphate depletion and dysfunction of the renal tubules) in three HIV؉ patients. This was temporally related to their HIV treatment. Physicians caring for patients with HIV should recognize the association of this rare syndrome with antiretroviral medications and monitor their patients carefully.Introduction: Fanconi's syndrome is caused by increased excretion of phosphate, glucose, amino acids, and other intermediary metabolites, and can result in osteomalacia. Materials and Methods:We diagnosed this syndrome in three HIV ϩ patients. Results: The first was a 43-year-old woman referred for multiple painful stress fractures. She demonstrated hypophosphatemia, metabolic acidosis, phosphaturia, glucosuria, and generalized aminoaciduria. These abnormalities resolved with oral phosphate replacement and discontinuation of the antiretroviral medication tenofovir. The second patient was a 39-year-old man with hypophosphatemia and bone pain. His symptoms improved with discontinuation of adefovir and supplementation of phosphate, potassium, and calcitriol. The third patient was a 48-year-old man who presented with symptomatic tetany caused by hypocalcemia (total serum calcium of 6.5 mg/dl [8.5-10.5 mg/dl]). Nine months before presentation, he had been treated with cidofovir for retinitis caused by cytomegalovirus. With calcium, phosphate, potassium, and calcitriol therapy, his laboratory abnormalities improved substantially, although he continues to require daily electrolyte replacement. Conclusions: Each patient demonstrated generalized renal tubular dysfunction temporally related to treatment with antiretroviral drugs. The mechanism responsible for these abnormalities is not known; however, physicians caring for patients with HIV disease should recognize the association of Fanconi's syndrome with antiretroviral medications and monitor susceptible patients to prevent potential skeletal and neuromuscular complications.

Tenofovir-associated bone density loss

“…42,61,[64][65][66][67][68][69][70][71][72] The failure of renal proximal tubular cells to reabsorb filtered bicarbonate from the urine would result in urinary bicarbonate wasting and subsequent acidemia and a more general dysfunction of the proximal tubular cells -called Fanconi's syndrome. Commonly observed conditions in Fanconi syndrome include aminoaciduria, glycosuria, tubular proteinuria, and uricosuria.…”

The development of hypophosphataemic osteomalacia with myopathy in two patients with HIV infection receiving tenofovir therapy

“…Tenofovir causes recognized Fanconi syndrome and hypophosphataemia [5,6], although osteomalacia has rarely been linked to such treatment [7]. Osteomalacia has also occasionally been linked to cidofovir and adefovir, other nucleotide analogues [7]. In animal studies using high-dose tenofovir, osteomalacia was a frequent adverse event [8].…”

Misdiagnosis of Bone Metastasis Cancer After Using Adefovir Dipivoxi in a Hepatitis B Patient with Fanconi Syndrome

“…The resulting electrolyte imbalance and osteomalacia cause symptoms of muscle weakness, fatigue, bone pain, and fractures. Acquired forms of Fanconi syndrome are caused by paraproteinemia, Sjögren syndrome, primary biliary cirrhosis (PBC) and drugs such as cisplatin [4][5][6]. Osteomalacia is a metabolic bone disease that leads to softening of the bones and can be caused by hypophosphatemia [7].…”