Suzuki Soichiro, Nishijima Takeshi, Kawasaki Yohei, Kurosawa Takuma, Mutoh Yoshikazu, Kikuchi Yoshimi, Gatanaga Hiroyuki, Oka Shinichi
1 AIDS Clinical Center, National Center for Global Health and Medicine , Tokyo, Japan .
2 Department of Drug Evaluation and Informatics, Graduate School of Pharmaceutical Sciences, University of Shizuoka , Shizuoka, Japan .
AIDS Patient Care STDS. 2017 Mar;31(3):105-112. doi: 10.1089/apc.2016.0286.
Little evidence is available for the incidence of chronic kidney disease (CKD) and rate of estimated glomerular filtration rate (eGFR) decrement among Asians with low body weight who are susceptible to tenofovir disoproxil fumarate (TDF) nephrotoxicity. In this 12-year observational cohort in Tokyo, we examined 1383 treatment-naïve HIV-1-infected Asians [720 started TDF-containing (TDF group) and 663 started non-TDF-containing (control) combination antiretroviral therapy (cART)]. The CKD incidence was calculated, and the effect of TDF use on CKD development was estimated using logistic regression. The eGFR slopes, before and after cART initiation, were estimated using mixed-effects linear spline models. Most patients were males (median weight, 62.6 kg; 83% started ritonavir-boosted protease inhibitors; median observation duration, 5.08 years). CKD developed in 150 patients (10.8%), with an incidence of 20.6 per 1000 person-years [confidence interval (95% CI), 17.6-24.2]. None developed end-stage renal disease. TDF use was associated with CKD [odds ratio (OR), 1.8; 95% CI, 1.00-3.13; p = 0.052]. The cumulative mean loss in the TDF group, relative to the control, increased over time after 1, 4, and 8 years of TDF exposure (-3.8, -5.5, and -9.0 mL/min/1.73 m, respectively; p < 0.0001). The eGFR rapidly declined during the first 3 months of cART, particularly in the TDF group (-26.4 vs. -7.4 mL/min/1.73 m/year in the control). In the TDF group, cART introduction was significantly associated with a faster rate of eGFR decline (from -0.44 to -2.11 mL/min/1.73 m/year; p = 0.010), whereas in the control, the difference was not significant. For HIV-1-infected Asian patients with low body weight, TDF-containing cART is associated with CKD and faster eGFR declines.
对于体重较低且易发生富马酸替诺福韦二吡呋酯(TDF)肾毒性的亚洲人,慢性肾脏病(CKD)的发病率以及估计肾小球滤过率(eGFR)下降速率方面的证据较少。在东京进行的这项为期12年的观察性队列研究中,我们检查了1383例初治的HIV-1感染亚洲人[720例开始含TDF的(TDF组)和663例开始不含TDF的(对照组)联合抗逆转录病毒治疗(cART)]。计算CKD发病率,并使用逻辑回归估计使用TDF对CKD发生的影响。使用混合效应线性样条模型估计cART开始前后的eGFR斜率。大多数患者为男性(中位体重62.6 kg;83%开始使用利托那韦增强的蛋白酶抑制剂;中位观察时间5.08年)。150例患者(10.8%)发生了CKD,发病率为每1000人年20.6例[置信区间(95%CI),17.6 - 24.2]。无人发展为终末期肾病。使用TDF与CKD相关[比值比(OR),1.8;95%CI,1.00 - 3.13;p = 0.052]。与对照组相比,TDF组在暴露1、4和8年后,累积平均损失随时间增加(分别为-3.8、-5.5和-9.0 mL/min/1.73 m²;p < 0.0001)。在cART开始的前3个月,eGFR迅速下降,尤其是在TDF组(对照组为-7.4 mL/min/1.73 m²/年,TDF组为-26.4 mL/min/1.73 m²/年)。在TDF组,开始cART与eGFR下降速度加快显著相关(从-0.44至-2.11 mL/min/1.73 m²/年;p = 0.010),而在对照组中,差异不显著。对于体重较低的HIV-1感染亚洲患者,含TDF的cART与CKD以及更快的eGFR下降相关。