热带病与寄生虫学

热带病与寄生虫学 ›› 2016, Vol. 14 ›› Issue (2): 90-92.doi: 10.3969/j.issn.1672-2302.2016.02.009

• 论著 • 上一篇    下一篇

低剂量阿德福韦酯致范可尼综合征5例分析

孔令义，佟晖   

  1. 061001 河北沧州市，沧州市传染病医院
  • 出版日期:2016-06-10 发布日期:2016-07-11

Report and analysis of Fanconi syndrome caused by low dose of adefovir dipivoxil in 5 cases

Kong Lingyi, Tong Hui   

  1. Cangzhou. Infectious Disease Hospital, Cangzhou 061001, China
  • Online:2016-06-10 Published:2016-07-11

PDF (PC)

1513

摘要： 【摘要】 目的  对5例长期服用阿德福韦酯（ADV）引起的慢性肾脏病合并范可尼综合征进行分析，并对早期发现ADV的肾毒性和避免引发范可尼综合征提出监测和防治措施。 方法  研究对象为2008年1月~2013年1月我院确诊的5例阿德福韦酯致范可尼综合征患者，总结其临床特点及治疗方法。 结果  患者服药剂量均为10mg/d，平均服药时间42.6个月，平均服药至症状出现时间为35.4个月。临床表现为进行性全身多处骨及关节疼痛。2例有夜尿增多情况。所有患者血磷均有不同程度的下降；低尿酸血症3例；5例eGFR均降低；ALP增高4例；尿蛋白异常3例；尿糖异常3例。误诊情况：3例被误诊为原发性骨质疏松症。影像学检查：3例患者的双能骨密度及X线检查均显示骨质疏松。转归：停用阿德福韦酯，改为恩替卡韦0.5mg/d抗病毒；口服中性磷溶液、阿法迪三胶囊、钙尔奇D片。所有患者骨痛3~10个月缓解；5例低磷血症者于1~3个月血磷恢复正常；3例低尿酸血症者中有2例在1、11个月恢复正常；4例ALP增高者中有2例在1、12个月恢复正常；2例尿蛋白阳性分别在停药后5、12个月蛋白尿消失；2例尿糖异常者在4、8个月恢复正常。 结论  低剂量阿德福韦酯可导致范可尼综合征。对长期服用阿德福韦酯的老年人、饮酒、合并慢性病者，用药期间应定期监测，尤其是血磷、ALP水平及肾功能、尿常规，一旦出现肾损伤，要及时更换为其他抗病毒药物或者根据GFR水平延长用药间隔时间，并给予中性磷治疗。

关键词: 范可尼综合征, 阿德福韦酯, 慢性肾脏病

Abstract:

【Abstract】 Objective  To analyze the causes of acquired Fanconi syndrome(FS) and chronic renal damage due to prolonged use of adefovir dipivoxil(ADV) in low dose for hepatitis B, and suggest early diagnosis of ADV-induced FS and preventive measures for nephrotoxicity. Methods  The data were collected in 5 cases of FS confirmed in our hospital between January 2008 and 2013, and the clinical manifestations and therapy were analyzed. Results  Generally, the five patients received ADV in dose of 10 mg/d and average medication of 42.6 months. The FS symptoms averagely developed at 35.4 months. Clinical pictures were progressive systemic bone and joint pain, and 2 cases showed increased nocturnal urination frequencies. Serum phosphorus level was decreased to a certain extent in the 5 patients, in whom 3 had hypouricemia. Reduced estimated glomerular filtration rate(eGFR) was seen in the 5 cases, and increased alkaline phosphatase(ALP) in 4. Positive urine protein and abnormal glucose in urine were respectively found in 4 and 3 cases. Three patients were misdiagnosed as primary osteoporosis by dual-energy X-ray absorptiometry. After ADV withdrawal and replacement with entecavir in dose of 0.5 mg/d combined with oral neutral phosphate solution, alfacalcidol and calcium, bone pain was released in the 5 patients in 3 to 10 months, and blood phosphorus level restored to normal in 1 to 3 months. Hypouricemia was reversed in 2 of the 3 cases at the first and the eleventh month, and increased ALP was corrected in 2 of the 4 cases at the first and the twelfth month. Urine protein disappeared in 2 cases at the fifth and the twelfth month after ADV withdrawal, and another 2 cases with abnormal urine glucose were recovered in 4 and 8 months. Conclusion  Low-dose ADV can induce Fanconi syndrome. Patients, particularly those of the aged, with drinking habit or chronic diseases, needing prolonged use of ADV should be regularly monitored for the levels of serum phosphorus and ALP as well as renal function and routine urine test findings. Once renal damage occurs, ADV should be withdrawn in timely fashion and therapy regime may be replaced by other antiviral drugs with oral neutral phosphate solution, or prolonged ADV medication interval is decided by eGFR level.

Key words: Fanconi syndrome, Adefovir dipivoxil, Chronic Kidney Disease