Journal of Peking University(Health Sciences) >
Low-dose adefovir-induced Fanconi syndrome and hypophosphatemic osteomalacia: A case report and literature review
Received date: 2018-06-14
Online published: 2020-10-15
A young male patient with a clear diagnosis of chronic hepatitis B, had taken long-term adefovir dipivoxil and lamivudine antiviral therapy. Osteomalacia related symptoms, such as bone pain and walking difficulties appeared 10 months ago. Renal damage related symptoms, such as urine volume change and increased urinary foam appeared 7 months ago. The examination showed signs of osteomalacia after admission, such as duck step, osteoarticular tenderness, thoracic and pelvic compression sign positive. Relevant examinations showed that hypophosphatemic osteomalacia related signs, such as hypophosphatemia, normal blood calcium, elevated blood alkaline phosphatase, no significant decline in active vitamin D3 and intact parathyroid hormone (iPTH). In bone mineral density test, bone fracture line could be noted. Bone scan suggested multiple metabolic lesions. At the same time, there were Fanconi syndrome related performances, such as elevated serum creatinine, decreased blood uric acid, urine glucose positive, elevated urinary and uric acid, urinary protein positive with mainly small molecule proteins, increased renal tubular damage indicators, and the clearance test suggested a decrease in renal tubular reabsorption of phosphorus. Kidney stones could be seen in urinary ultrasound. Therefore, combined with the patient’s clinical manifestations, past history and examinations, we definitely considered his diagnosis was adefovir dipivoxil related renal injury. Adefovir has been widely used for the treatment of chronic hepatitis B. Some studies confirmed that the nephrotoxicity of adefovir, including Fanconi syndrome and hypophosphatemic osteomalacia, was dose-dependent. A daily high-dose of 60-120 mg/d adefovir was concluded in the treatment of human immunodeficiency virus (HIV) infection, inducing nearly 1/2 patients of renal injury. A daily moderate-dose of 30 mg/d adefovir was used for patients in chronic hepatitis B, with nearly 1/3 patients of renal injury. Long-term low-dose adefovir (10 mg/d) used for chronic hepatitis B patients was found to be responsible for renal injury, but the incidence was significantly reduced. We studied this patient and related literature to analyze the pathogenesis, clinical characteristics and treatment outcomes in low-dose adefovir-induced Fanconi syndrome and hypophosphatemic osteomalacia.
Key words: Adefovir; Kidney injury; Fanconi syndrome; Osteomalacia
Wen SUN , Ang LI , Jun-qing ZHANG , Zhen-fang YUAN . Low-dose adefovir-induced Fanconi syndrome and hypophosphatemic osteomalacia: A case report and literature review[J]. Journal of Peking University(Health Sciences), 2020 , 52(5) : 975 -979 . DOI: 10.19723/j.issn.1671-167X.2020.05.031
| [1] | Izzedine H, Launay-Vacher V, Deray G. Antiviral drug-induced nephrotoxicity[J]. Am J Kidney Dis, 2005,45(5):804-817. |
| [2] | Miller DS. Nucleoside phosphonate interactions with multiple organic anion transporters in renal proximal tubule[J]. J Pharmacol Exp Ther, 2001,299(2):567-574. |
| [3] | Tanaka M, Suzuki F, Seko Y, et al. Renal dysfunction and hypophosphatemia during long-term lamivudine plus adefovir dipivoxil therapy in patients with chronic hepatitis B[J]. J Gastroenterol, 2014,49(3):470-480. |
| [4] | Cirillo M, Ciacci C, De Santo NG. Age, renal tubular phosphate reabsorption, and serum phosphate levels in adults[J]. N Engl J Med, 2008,359(8):864-866. |
| [5] | Kim YJ, Cho HC, Sinn DH, et al. Frequency and risk factors of renal impairment during long-term adefovir dipivocil treatment in chronic hepatitis B patients[J]. J Gastroenterol Hepatol, 2012,27(2):306-312. |
| [6] | Jeong HJ, Lee JM, Lee TH, et al. Two cases of hypophosphate-mic osteomalacia after long-term low dose adefovir therapy in chronic hepatitis B and literature review[J]. J Bone Metab, 2014,21(1):76-83. |
| [7] | 曲云东, 叶茜, 王磊, 等. 39例阿德福韦酯相关肾性低磷血症及骨软化症临床分析和初步转归[J]. 中华传染病杂志, 2015,33(11):678-681. |
| [8] | Shimizu M, Furusyo N, Ikezaki H, et al. Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B[J]. World J Gastroenterol, 2015,21(7):2116-2123. |
| [9] | Law ST, Li KK, Ho YY. Nephrotoxicity, including acquired Fanconi’s syndrome, caused by adefovir dipivoxil—is there a safe dose?[J]. J Clin Phann Ther, 2012,37(2):128-131. |
| [10] | 张楠, 邵明玮, 黄爱, 等. 阿德福韦酯致低磷性骨软化症六例分析[J]. 中华内分泌代谢杂志, 2013,29(5):414-416. |
| [11] | Wei Z, He JW, Fu WZ, et al. Osteomalacia induced by long-term low-dose adefovir dipivoxil: Clinical characteristics and genetic predictors[J]. Bone, 2016,93:97-103. |
| [12] | 孙晓方, 张化冰, 李新萍, 等. 阿德福韦酯导致低血磷性骨软化症一例并文献复习[J]. 中华内科杂志, 2011,50(9):754-757. |
| [13] | Laing CM, Toye AM, Capasso G, et al. Renal tubular acidosis: developments in our understanding of the molecular basis[J]. Int J Biochem Cell Biol, 2005,37(6):1151-1161. |
| [14] | Tanji N, Tanji K, Kambham N, et al. Adefovir nephrotoxicity: possible role of mitochondrial DNA depletion[J]. Hum Pathol, 2001,32(7):734-740. |
| [15] | Carney EF. Tubular disease: mistargeted protein disrupts mitochondrial metabolism in inherited Fanconi syndrome[J]. Nat Rev Nephrol, 2014,10(3):125. |
| [16] | Prie D, Huart V, Bakouh N, et al. Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter[J]. N Engl J Med, 2002,347(13):983-991. |
| [17] | Levi M, Breusegem S. Renal phosphate-transporter regulatory proteins and nephrolithiasis[J]. N Engl J Med, 2008,359(11):1171-1173. |
| [18] | Xu LJ, Jiang Y, Liao RX, et al. Low-dose adefovir dipivoxil may induce Fanconi syndrome: clinical characteristics and long-term follow-up for Chinese patients[J]. Antivir Ther, 2015,20(6):603-611. |
| [19] | 廖二元, 谭利华. 代谢性骨病学 [M]. 北京: 北京人民卫生出版社, 2003: 16-26. |
/
| 〈 |
|
〉 |