Gallant Joel E, Winston Jonathan A, DeJesus Edwin, Pozniak Anton L, Chen Shan-Shan, Cheng Andrew K, Enejosa Jeffrey V
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
AIDS. 2008 Oct 18;22(16):2155-63. doi: 10.1097/QAD.0b013e3283112b8e.
Cases of renal dysfunction in patients receiving tenofovir disoproxil fumarate (TDF) have been reported. We analyzed the renal safety of TDF compared with thymidine analogue-containing (control) regimens through 144 weeks from two clinical trials in antiretroviral-naive HIV-infected patients.
We evaluated the changes in renal parameters in 1111 patients (TDF, n = 556; control, n = 555) who were enrolled in two randomized, controlled trials (Studies 903 and 934) comparing TDF vs. either stavudine or zidovudine in combination with efavirenz and either lamivudine or emtricitabine. The studies included patients with serum creatinine less than 1.5 mg/dl, serum phosphorus at least 2.2 mg/dl and estimated glomerular filtration rate by Cockcroft-Gault at least 60 and at least 50 ml/min at screening.
Baseline characteristics were similar between groups. No patient discontinued due to renal abnormalities in the TDF arm. Through 144 weeks, the proportion of patients who experienced confirmed abnormalities in serum creatinine (>1.5 mg/dl) or serum phosphorus (<2.0 mg/dl) was less than 1% in both groups; a similar proportion of patients experienced urine proteinuria at least 100 mg/dl (TDF, 5%; control, 6%). The median change from baseline to week 144 in glomerular filtration rate was -2 and 3 ml/min by Cockcroft-Gault, and -2 and -1 ml/min per 1.73 m by modification of diet in renal disease in the TDF and control groups (P < 0.05), respectively.
In two randomized, controlled trials, small differences in glomerular filtration rate over time were noted but no clinically relevant renal disease or adverse events were demonstrated in antiretroviral-naive patients treated with TDF through 144 weeks. Additional studies on renal health and renal safety in HIV are important goals for future clinical trials.
已有接受替诺福韦酯（TDF）治疗的患者出现肾功能障碍的病例报告。我们通过两项针对未接受过抗逆转录病毒治疗的HIV感染患者的临床试验，分析了TDF与含胸苷类似物（对照）方案相比在144周内的肾脏安全性。
我们评估了1111例患者（TDF组，n = 556；对照组，n = 555）的肾脏参数变化，这些患者参加了两项随机对照试验（研究903和934），比较TDF与司他夫定或齐多夫定联合依非韦伦以及拉米夫定或恩曲他滨的疗效。研究纳入了筛查时血清肌酐低于1.5 mg/dl、血清磷至少2.2 mg/dl且根据Cockcroft - Gault公式估算的肾小球滤过率至少60且至少50 ml/min的患者。
两组的基线特征相似。TDF组没有患者因肾脏异常而停药。在144周内，两组中血清肌酐（>1.5 mg/dl）或血清磷（<2.0 mg/dl）出现确诊异常的患者比例均低于1%；出现尿蛋白至少100 mg/dl的患者比例相似（TDF组为5%；对照组为6%）。根据Cockcroft - Gault公式，TDF组和对照组从基线到第144周肾小球滤过率的中位数变化分别为 -2和3 ml/min，根据肾脏病饮食改良公式每1.73 m²分别为 -2和 -1 ml/min（P < 0.05）。
在两项随机对照试验中，随着时间推移肾小球滤过率存在微小差异，但在接受TDF治疗144周的未接受过抗逆转录病毒治疗的患者中，未发现具有临床意义的肾脏疾病或不良事件。关于HIV患者肾脏健康和肾脏安全性的更多研究是未来临床试验的重要目标。
