Liu Fang, Xu Aifang, Zhao Huaqing, Yang Zongxing, Chen Chen, Ranieri Brona, Bao Jianfeng, Zheng Guoxiang, Wang Miaochan, Wang Ying, Xun Yunhao
Medical Laboratory, Xixi Hospital of Hangzhou, Hangzhou, People's Republic of China.
Temple University School of Medicine, Department of Clinical Sciences, Philadelphia, PA, USA.
Ther Clin Risk Manag. 2020 Apr 17;16:299-310. doi: 10.2147/TCRM.S243913. eCollection 2020.
Estimated glomerular filtration rate (eGFR) decline in HIV-1-infected patients exposure to tenofovir disoproxil fumarate (TDF) has been widely assessed using linear models, but nonlinear assumption is not well validated. We constructed a retrospective cohort study to assess whether eGFR decline follows nonlinearity during antiviral therapy.
We examined 823 (299 of TDF users and 524 of non-TDF users) treatment-naïve HIV-1-infected participants (age ≥ 17 years, initial eGFR ≥ 90 mL/min/1.73m). Estimated GFR trajectories were compared by one-linear and piecewise-linear mixed effects models, before and after propensity score matching, respectively. Whether the incidence of renal dysfunction (reduced renal function [RRF], eGFR < 90 mL/min/1.73 m and rapid kidney function decline [RKFD], eGFR > -3 mL/min/1.73 m/year) follows nonlinearity was assessed by logistic regression.
The median follow-up time of this study was 10 (interquartile range, 2-20) months, during which 178 (21.6%) experienced RRF, and 451 (54.8%) experienced RKFD. The slopes (mL/min/1.73 m/year) of eGFR were -5.31 (95% CI: -6.57, -4.06) before 1.40 years, 4.83 (95% CI: 1.38, 8.28) from years 1.40 to 2.30 and -3.71 (95% CI: -5.97, -1.45) after 2.30 years among TDF users. Within years 1.40-2.30, each year of TDF exposure was associated with a 78% decreased risk of RKFD (95% CI: -91%, -49%). In comparison, eGFR increased slightly at the initiation of antiviral therapy, declined after 2.15 years (-4.96; 95% CI: -5.76, -4.17) among non-TDF users. Such a progression nonlinear trajectory was missed on the assumption of one-linearity, whether in TDF or non-TDF users.
Over the piecewise mixed-effects analyses with the advantage of revealing the true nature of the exposure outcome relationships, an interesting reverse S-shaped relationship was observed. A routine screen based on nonlinearity could be more helpful for patient management.
使用线性模型广泛评估了接受富马酸替诺福韦二吡呋酯（TDF）治疗的HIV-1感染患者的估计肾小球滤过率（eGFR）下降情况，但非线性假设尚未得到充分验证。我们开展了一项回顾性队列研究，以评估抗病毒治疗期间eGFR下降是否呈非线性。
我们研究了823例初治的HIV-1感染参与者（年龄≥17岁，初始eGFR≥90 mL/min/1.73m²）（299例TDF使用者和524例非TDF使用者）。分别在倾向评分匹配前后，通过单一线性和分段线性混合效应模型比较估计的GFR轨迹。通过逻辑回归评估肾功能不全（肾功能降低[RRF]，eGFR<90 mL/min/1.73m²和肾功能快速下降[RKFD]，eGFR>-3 mL/min/1.73m²/年）的发生率是否呈非线性。
本研究的中位随访时间为10（四分位间距，2-20）个月，在此期间，178例（21.6%）出现RRF，451例（54.8%）出现RKFD。TDF使用者中，1.40年前eGFR的斜率（mL/min/1.73m²/年）为-5.31（95%CI：-6.57，-4.06），1.40至2.30年为4.83（95%CI：1.38，8.28），2.30年后为-3.71（95%CI：-5.97，-1.45）。在1.40-2.30年期间，每年使用TDF与RKFD风险降低78%相关（95%CI：-91%，-49%）。相比之下，抗病毒治疗开始时eGFR略有上升，非TDF使用者在2.15年后下降（-4.96；95%CI：-5.76，-4.17）。无论是TDF使用者还是非TDF使用者，在单一线性假设下都未发现这种进展性非线性轨迹。
通过分段混合效应分析，该分析有助于揭示暴露与结局关系的真实性质，观察到了一种有趣的倒S形关系。基于非线性的常规筛查可能对患者管理更有帮助。
