Hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose adefovir dipivoxil: a case report and literature review suggesting ethnic predisposition

Abstract

Hypophosphatemic osteomalacia and renal Fanconi syndrome can be associated with low-dose ADV. Clinicians treating CHB patients with ADV 10 mg daily over long periods of time should be aware of this infrequent but serious complication.

Adefovir-induced Fanconi syndrome: diagnostic pearls and perils of late or missed diagnosis

“…Nephrotoxicity associated with high-dose ADV typically has a late onset ([6 months) [15]. The time to onset of low-dose ADV-induced FS, based on case reports, ranges from a few months to [5 years [4][5][6][7][8][9][10][11][12]. In our patient, it took more than 2 years before the tubulopathy became apparent.…”

“…The first report of ADV-associated hypophosphatemic osteomalacia was published in 2008 [4], with a number of reported cases of ADV-induced FS [5][6][7][8][9][10][11][12] since then. Most of the cases published were in East Asian subjects, which may either suggest a racial predilection, or an indication of the increased prevalence of hepatitis B infection requiring ADV treatment in East Asia.…”

“…From the series of case reports so far, the time to resolution after cessation of ADV ranged from a few weeks to months [4][5][6][7][8][9][10][11][12]. A previous trial with high-dose ADV treatment showed a median time to resolution of renal dysfunction of 15 weeks, with the nephrotoxicity failing to resolve completely at 41 weeks after onset in 16 % of the patients [15].…”

Osteomalacia and Fanconi's syndrome caused by long-term low-dose adefovir dipivoxil

“…Although the mechanisms of ADV nephrotoxicity are not fully understood, suggestions include impaired renal tubular transport, apoptosis and mitochondrial toxicity in the renal tubular epithelium …”

Urinary β-2 Microglobulin Levels Sensitively Altered in an Osteomalacia Patient Receiving Add-on Adefovir Dipivoxil Therapy for Hepatitis B Virus Infection

“…A daily administration of ADV at 10 mg is referred to as ADV therapy for hepatitis B virus (HBV) infection and was considered to be non-nephrotoxic in randomized control trials and cohort studies in Western countries (4)(5)(6). However, reports from East Asia clearly indicate that prolonged ADV therapy induces renal injury (7)(8)(9). Therefore, a sensitive and simple marker is required for long-term ADV administration to predict the early stage of renal injury and prevent serious complications, such as osteomalacia and bone fractures.…”