Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
Aliment Pharmacol Ther. 2012 Jun;35(11):1317-25. doi: 10.1111/j.1365-2036.2012.05093.x. Epub 2012 Apr 16.
Adefovir and tenofovir are nucleotide analogues used as long-term therapy of chronic hepatitis B. Side effects are few, but prolonged and high-dose therapy has been associated with proximal renal tubular dysfunction (RTD).
To assess the incidence of RTD during long-term nucleotide therapy of chronic hepatitis B.
A total of 51 patients being treated at the Clinical Center, National Institutes of Health were studied. Diagnosis of RTD required de novo appearance of at least three of five features: hypophosphataemia, hypouricaemia, serum creatinine elevation, proteinuria or glucosuria.
Among 51 patients treated for 1-10 (mean 7.4) years with adefovir (n = 42), tenofovir (n = 4) or adefovir followed by tenofovir (n = 5), 7 (14%) developed RTD. Time to onset ranged from 22 to 94 (mean 49) months with an estimated 10-year cumulative rate of 15%. All seven had low urinary percent maximal tubular reabsorption of phosphate (<82%). Patients with RTD were older (58 vs. 44 years; P = 0.01) and had lower baseline glomerular filtration rates (82 vs. 97 cc/min; P = 0.08) compared to those without; but did not differ in other features. Six patients with RTD were switched to entecavir, all subsequently had improvements in serum phosphate (2.0-3.0 mg/dL), creatinine (1.6-1.1 mg/dL), uric acid (2.7-3.8 mg/dL) and proteinuria.
Renal tubular dysfunction develops in 15% of patients treated with adefovir or tenofovir for 2-9 years and is partially reversible with change to other antivirals. Monitoring for serum phosphate, creatinine and urinalysis is prudent during long-term adefovir and tenofovir therapy.
阿德福韦和替诺福韦是用于慢性乙型肝炎长期治疗的核苷酸类似物。副作用很少，但长期和高剂量治疗与近端肾小管功能障碍（RTD）有关。
评估慢性乙型肝炎长期核苷酸治疗期间 RTD 的发生率。
研究了在国立卫生研究院临床中心接受治疗的 51 名患者。RTD 的诊断需要至少出现五个特征中的三个新特征：低磷血症、低尿酸血症、血清肌酐升高、蛋白尿或糖尿。
51 名患者接受阿德福韦（n = 42）、替诺福韦（n = 4）或阿德福韦序贯替诺福韦（n = 5）治疗 1-10 年（平均 7.4 年），其中 7 名（14%）发生 RTD。发病时间从 22 到 94 个月不等（平均 49 个月），估计 10 年累积发生率为 15%。所有 7 名患者的尿最大肾小管磷重吸收率均<82%。发生 RTD 的患者年龄较大（58 岁 vs. 44 岁；P = 0.01），肾小球滤过率较低（82 比 97 cc/min；P = 0.08），但其他特征无差异。6 名 RTD 患者转为恩替卡韦，所有患者的血清磷（2.0-3.0mg/dL）、肌酐（1.6-1.1mg/dL）、尿酸（2.7-3.8mg/dL）和蛋白尿均有所改善。
阿德福韦或替诺福韦治疗 2-9 年后，15%的患者会发生肾小管功能障碍，改用其他抗病毒药物后部分可逆转。长期阿德福韦和替诺福韦治疗期间应监测血清磷、肌酐和尿液分析。
