Acquired Fanconi syndrome due to long-term adefovir administration in a patient with IgG-kappa monoclonal gammopathy and kappa Bence-Jones protein

A 77-year-old man was admitted to our hospital for a right femoral neck fracture. He had been prescribed lamivudine for chronic hepatitis B infection for 11 years, and adefovir was added 5 years ago. After hospitalization, a right femoral head prosthesis was performed successfully, but an unknown hypokalemia was revealed. Hypophosphatemia, hypouricemia, glucosuria, and panaminoaciduria were also revealed, and multiple microfractures were detected by bone scintigraphy. We diagnosed him as ‘osteomalacia associated with Fanconi syndrome,’ which was likely due to the adefovir. Moreover, a monoclonal IgG-kappa and a kappa Bence-Jones protein were detected in his serum and urine, respectively. We switched from adefovir plus lamivudine to entecavir and started calcitriol. His excessive urinary β2-microglobulin excretion and glucosuria had decreased dramatically at 10 weeks after the modification of drugs; those of the phosphate, uric acid and total protein, however, continued. Renal biopsy specimens obtained at 10 weeks after discontinuation of adefovir revealed focal tubular atrophic changes with/without inflammatory cells, which were predominantly observed next to glomeruli. Kappa-dominant staining was not observed in either glomeruli or tubules with immunostaining by the enzyme-labeled antibody method. Electron microscopy revealed neither crystalline structures in the cytoplasm of proximal tubules nor electron-dense deposits. Because of the remarkable proportional reduction of other urinary protein fractions, urinary M-peak appeared 26 weeks after discontinuation of adefovir, but the net amounts of the fraction decreased gradually.