阿德福韦酯相关肾脏损害

Biopsy-proven nephrotoxicity induced by adefovir

目的:探讨阿德福韦酯引起的肾脏损害临床病理特点。方法:回顾性分析4例因慢性乙型肝炎长期使用阿德福韦酯出现肾脏损害患者的临床病理资料。结果:4例均为男性患者,年龄34～44岁,3例慢性乙型肝炎病史10年,1例慢性乙型肝炎病史20年,使用阿德福韦酯治疗3～6年。肾脏疾病病程3～23月,患者血压均正常。4例血清肌酐(SCr)均轻度升高(116.7～158.3μmol/L),1例出现低磷血症,2例伴低尿酸血症,2例少量蛋白尿(0.54g/24h和0.57g/24h),1例蛋白尿0.79～1.72g/24h,1例尿蛋白阴性,1例尿糖阳性,4例患者均无镜下血尿,肝功能正常,无低白蛋白血症和高脂血症。肾活检病理示3例患者光镜下肾小球节段轻度系膜增生,1例合并IgA肾病。4例患者肾小管间质病变均较轻,见小灶性近端肾小管上皮细胞刷状缘脱落,其中3例伴慢性病变轻～中度,灶性肾小管萎缩、基膜增厚。电镜下均见肾小管上皮细胞胞质内线粒体外形不规则、变形、体积增大。药物停用后,随访3～25月,3例患者SCr恢复正常,1例SCr稳定,血磷恢复正常,所有患者尿蛋白阴性。结论:长期使用阿德福韦酯可导致肾脏损害,患者表现轻度肾功能下降,部分患者血清磷、尿酸减低,伴肾小管功能损伤。阿德福韦酯肾脏损害可单独出现,也可和原发性肾脏疾病同时出现。形态学主要表现肾小管损伤,肾小管上皮细胞刷状缘脱落,电镜下肾小管上皮细胞胞质内异常增大和变形的线粒体。

Objective： To explore the clinical and pathological characteristics of adefovir nephrotoxicity. Methodology： The clinical and pathological data of four patients with biopsy-proven adefovir nephrotoxicity due to hepatitis B were retrospectively analyzed. Results ： All of them were male with age from 34 - 44 years old. three patients had been history of hepatitis B for ten years and one had 20 years. They had received adefovir for 3 to 6 years. The duration of renal disease was 3 to 23 months. The levels of serum creatitine were slightly elevated （116.7 -158.3 μmol/L）, with hypophosphatemia in one and hypourecimia in two cases. Three of them had proteinuria from 0. 54 g/d to 1.72 g/d ,and one patient had positive urine glucose. They had no hypoabulminemia, hyperlepidemia and heamaturia. Renal biopsy showed mild segmental mesangial proliferation with acute tubular lesion including flatted and occasional detached tubular epithelial cells in three patients. One was diagnosed as IgA nephropathy with flatted and occasional detached tubular epithelial cells. Three had mild chronic tubular atrophy and interstitial fibrosis. Electron microscopy examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. The patient diagnosied as IgAN had mesangial dense deposits. After withdrawing Adefovir, the level of serum creatinine returned to normal and stable. Conclusion： Adefovir-induced nephrotoxicity manifested by slightly elevated serum creatine with abnormal tubular dysfunction which could accompanied with IgA nephropathy. Histologic characteristics included proximal tubular mitochondria extremely enlarged and dysmorphic with loss and disorientation of their cristae.