Fanconi's Syndrome Associated with Prolonged Adefovir Dipivoxil Therapy in a Hepatitis B Virus Patient.

Department of Internal Medicine, Gachon University of Medicine and Science Gil Medical Center, Incheon, Korea.
Gut and liver (Impact Factor: 1.49). 09/2010; 4(3):389-93. DOI: 10.5009/gnl.2010.4.3.389
Source: PubMed

ABSTRACT Adefovir dipivoxil (ADV) is commonly used as an antiviral agent in the treatment of chronic hepatitis B or human immunodeficiency virus infection. Nephrotoxicity has been shown to occur at daily dosages of 60-120 mg. Fanconi's syndrome is a generalized dysfunction of the renal proximal tubular cells, which is usually accompanied by complications. Here we report a case of Fanconi's syndrome in a chronic hepatitis B patient who had been treated with a prolonged regimen of ADV at 10 mg/day. A 47-year-old man complained of severe back and chest-wall pain. He had chronic hepatitis B and had been treated with ADV at a daily dose of 10 mg for 38 months. He was hospitalized because of severe bone pain, and laboratory and radiologic findings suggested a diagnosis of Fanconi's syndrome with osteomalacia. After discontinuation of the ADV, he recovered and was discharged from hospital. His laboratory findings had normalized within 2 weeks. This case indicates that Fanconi's syndrome can be acquired by a chronic hepatitis B patient taking ADV at a conventional dosage of 10 mg/day. Therefore, patients treated with long-term ADV should be checked regularly for the occurrence of ADV-induced Fanconi's syndrome.

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    ABSTRACT: Background: generalised proximal, type 2, Renal Tubular Acidosis, also known as Fanconi syndrome, is a generalised dysfunction of the proximal renal tubule characterized by impaired reabsorption and increased urinary loss of phosphate and other solutes such as uric acid, glucose, amino acids and bicarbonate. Chronic hypophosphatemia is the second most common cause of osteomalacia after vitamin D deficiency in adult patients. It can have a heterogeneous presentation ranging from mild symptoms such as muscle weakness and skeletal pain to more severe presentation such as disabling myopathy, severe bone and joint pain, difficult walking, and even bone fractures.Objective: this report describes a case of severe hypophosphatemic osteomalacia with multiple fragility fractures induced by adefovir, which was worsened and confounded by a previous treatment with zoledronic acid and required prolonged i.v. potassium phosphate administration. Results and conclusions: we highlight the limited diagnostic value of DXA and bone scintigraphy in this challenging diagnosis. Bone metabolism should be always assessed in patients treated with adefovir for early detection of osteomalacia due to Fanconi Syndrome. Although rare, this condition may be life-threatening and mimic other bone metabolic disorders that are treated with drugs which may further impair phosphate balance.
    Endocrine Practice 08/2014; 1(-1):1-15. DOI:10.4158/EP14251.CR · 2.59 Impact Factor
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    ABSTRACT: Adefovir dipivoxil (ADV) is a nucleotide used as long-term therapy of chronic hepatitis B. Many published reports have shown that long-term high-dose therapy with adefovir can be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemia, renal insufficiency and osteomalacia. We have encountered two patients who developed evidence of hypophosphatemic osteomalacia while on long-term low-dose adefovir therapy for chronic hepatitis B. We report on its clinical features and its potential resolution with cessation of the drug and supplementation with phosphate. We also reviewed the other published cases associated with hypophosphatemic osteomalacia after low-dose adefovir therapy. The symptoms and the hypophosphatemia improved after cessation of the drug and supplementation with phosphate in most cases. Patients taking adefovir long-term should receive regular investigation of the phosphate level and renal function.
    02/2014; 21(1):76-83. DOI:10.11005/jbm.2014.21.1.76
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    ABSTRACT: To investigate the predictors of proximal kidney tubular dysfunction (PKTD) induced by adefovir dipivoxil (ADV) treatment for chronic hepatitis B. Seventy-nine patients (age at the evaluation of PKTD: 56.9 ± 10.7 years) with chronic hepatitis B undergoing long-term oral antiviral nucleos(t)ide analogue treatment were consecutively recruited. PKTD was defined by the presence of at least two of the following five abnormalities: phosphate diabetes, nondiabetic glucosuria, metabolic acidosis, β2-microglobulinuria, or renal hypouricemia. The single-nucleotide polymorphisms (SNPs) in the SLC22A6 gene encoding human organic anion transporter 1 (hOAT1) and ABCC2 encoding multidrug resistance protein 2 (MRP2) were analyzed using the TaqMan Allelic Discrimination Demonstration Kit. Nine (30.0%) of the 30 ADV-treated patients were diagnosed with PKTD, while no patients without ADV developed PKTD (P < 0.001). Three patients with ADV were diagnosed with symptomatic osteomalacia. Among the patients who took ADV, those with PKTD were of higher age at initiation, had significantly longer treatment duration, and had a significantly lower body mass index than those without PKTD. The incidence of PKTD dramatically increased after 96 mo from the start of ADV administration. In contrast, the SNPs were not correlated with PKTD. Logistic regression analysis extracted older age at initiation (OR = 5.0, 95%CI: 1.1-23.4; P = 0.040) and longer treatment duration (OR = 3.2, 95%CI: 1.2-8.6; P = 0.020) as significant factors associated with PKTD. Our results suggest that the tubular function of the kidney of older patients undergoing long-term ADV treatment should be carefully evaluated.

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