Medland Nicholas A, Chow Eric Pf, Walker Rowan G, Chen Marcus, Read Tim Rh, Fairley Christopher K
1 Monash University Central Clinical School, Carlton, Australia.
2 Alfred Hospital, Melbourne, Australia.
Int J STD AIDS. 2018 Mar;29(3):227-236. doi: 10.1177/0956462417722133. Epub 2017 Aug 1.
The objective of this study was to determine the incidence and predictors of Fanconi Syndrome (FS) in a cohort of patients taking tenofovir disoproxil fumarate (TDF). Clinical records and laboratory investigations from patients receiving TDF between 2002 and 2016 were extracted. FS was defined as normoglycaemic glycosuria and proteinuria and at least one other marker of renal dysfunction. Regression analysis was performed with time to development of FS and the following covariates: ritonavir co-administration, age, gender, co-morbidities (hypertension, hyperlipidaemia, diabetes, viral hepatitis), CD4 cell count nadir and baseline eGFR. One thousand and forty-four patients received TDF without ritonavir and 398 patients with ritonavir. Thirteen cases of FS were identified with a mean duration of exposure of 55 months. The incidence of FS was 1.09/1000PY (0.54-1.63) of TDF exposure (without ritonavir) and 5.50/1000PY (3.66-7.33) of TDF-ritonavir co-administration (p=0.0057). The adjusted hazards ratio for ritonavir co-administration was 4.71 (1.37-16.14, p=0.014). Known risk factors for chronic kidney disease were not associated with development of FS. Ritonavir co-administration, but not other factors, is associated with a greater risk of FS. FS developed late. Known risk factors for chronic kidney disease and length of treatment are not useful for identifying patients most at risk of developing FS in patients taking TDF.
本研究的目的是确定在服用替诺福韦酯(TDF)的患者队列中范科尼综合征(FS)的发病率及预测因素。提取了2002年至2016年间接受TDF治疗患者的临床记录和实验室检查结果。FS定义为血糖正常性糖尿、蛋白尿以及至少一项其他肾功能不全标志物。对FS发生时间与以下协变量进行回归分析:联合使用利托那韦、年龄、性别、合并症(高血压、高脂血症、糖尿病、病毒性肝炎)、CD4细胞计数最低点以及基线估算肾小球滤过率(eGFR)。1044例患者接受了未联合利托那韦的TDF治疗,398例患者接受了联合利托那韦的TDF治疗。确定了13例FS病例,平均暴露时间为55个月。FS的发病率在TDF暴露(未联合利托那韦)时为1.09/1000人年(0.54 - 1.63),在TDF与利托那韦联合使用时为5.50/1000人年(3.66 - 7.33)(p = 0.0057)。联合使用利托那韦的校正风险比为4.71(1.37 - 16.14,p = 0.014)。已知的慢性肾脏病风险因素与FS的发生无关。联合使用利托那韦而非其他因素与FS风险增加相关。FS发病较晚。已知的慢性肾脏病风险因素和治疗时长对于识别服用TDF患者中发生FS风险最高的患者并无帮助。