Osteomalacia due to Fanconi’s syndrome and renal failure caused by long-term low-dose adefovir dipivoxil

Abstract

To the Editor Acquired Fanconi’s syndrome is a disorder of the proximal tubules and causes hypophosphatemic osteomalacia, glucosuria, aminoaciduria and metabolic acidosis. The several causes of adult Fanconi’s syndrome include dysproteinemias, glomerular disease, after acute tubular necrosis, tetracycline, cancer chemotherapy agents and toxins [1]. The acyclic nucleoside phosphonates also cause Fanconi’s syndrome as well as renal damage. Among them, adefovir dipivoxil is often used to treat lamivudine-resistant hepatitis B and its nephrotoxicity is dose dependent. Therefore, low-dose use of this drug is recommended to avoid renal tubular damage. Here, we report a case of osteomalacia due to Fanconi’s syndrome caused by low-dose adefovir. A 56-year-old male with chronic hepatitis B infection was referred to our hospital in July 2011 to investigate the cause of renal impairment. He also had a history of cirrhosis and hepatocellular carcinoma. Adefovir at 10 mg a day had been added to lamivudine 100 mg a day in 2007 because of lamivudine resistance. Laboratory data on his first visit to our hospital showed elevated serum creatinine (2.23 mg/dL; 0.6–1.1 mg/dL) and low serum uric acid level (2.7 mg/dL; 3.0–7.5 mg/dL). Hemoglobin, serum albumin and platelet count were 12.6, 4.6 g/dL and 10.9 9 10/lL, respectively. C-reactive protein, alanine, aspartate aminotransferase, blood glucose, and serum levels of immunoglobin G, A, M were all normal. Urinalysis showed proteinuria (726 mg/gCre) and glucosuria with phosphaturia and general aminoaciduria. Urinary N-acetylglucosaminidase and b-2 microglobulin were 19.2 U/L (\11.5 U/L), and 45942 lg/L (\200 lg/L), respectively. Blood gas analysis showed metabolic acidosis. Computed tomography scan of the abdomen showed normal kidney size with some small calcification. From these results, we diagnosed acquired Fanconi’s syndrome in this patient. The patient also had a history of bone pain and waddling gait due to osteomalacia and had been treated by administration of alfacalcidol 3 lg and dibasic calcium phosphate dehydrate. His serum alkaline phosphatase level was elevated to 674 U/L (104–338 U/L), but serum creatine phosphokinase level was normal. At the first visit to our hospital, the reason for his osteomalacia was not clear, but he was diagnosed with osteomalacia associated with Fanconi’s syndrome after renal examination. Concomitant with this diagnosis, we suspected that adefovir was the cause of the Fanconi’s syndrome, and this drug was reduced to three times a week. After reduction of adefovir, his bone pain and waddling gait was alleviated gradually during ambulatory care. Seven months after the reduction, his proteinuria, glucosuria, phosphaturia and general aminoaciduria had disappeared and renal function was improved (serum creatinine was1.5 mg/dL). From these results, we considered that adefovir might be a cause of renal impairment. Several hypophosphatemic osteomalacia cases induced by low-dose adefovir therapy (10 mg daily) have been reported [2, 3]. In previously reported cases, the symptoms H. Shimohata Y. Ogawa K. Hirayama M. Kobayashi (&) Department of Nephrology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami, Inashiki, Ibaraki 300-0395, Japan e-mail: masaki-k@tokyo-med.ac.jp