Department of Medicine, University of Alberta, Edmonton, Canada.
Clin Infect Dis. 2010 Sep 1;51(5):496-505. doi: 10.1086/655681.
The efficacy of tenofovir disoproxil fumarate (TDF) as part of combination antiretroviral treatment (ART) has been demonstrated in several randomized, controlled trials. However, an increasing number of case reports suggest that TDF use may be associated with significant nephrotoxicity. Our objective was to determine the renal safety of TDF-containing ART regimens for HIV-infected individuals.
MEDLINE, EMBASE, Global Health, Scopus, Biosis Previews, Cochrane Library, Web of Science, and existing systematic reviews were searched. Prospective studies comparing TDF-containing with non-TDF containing ART regimens were selected for inclusion. We extracted data on study characteristics, participant characteristics, therapeutic interventions, renal function, bone density, and fracture rates.
A total of 17 studies (including 9 randomized, controlled trials) met the selection criteria. Median sample size was 517 participants. Constituent ART regimens were diverse. There was a significantly greater loss of kidney function among the TDF recipients, compared with control subjects (mean difference in calculated creatinine clearance, 3.92 mL/min; 95% confidence interval [CI], 2.13-5.70 mL/min), as well as a greater risk of acute renal failure (risk difference, 0.7%; 95% CI, 0.2-1.2). There was no evidence that TDF use led to increased risk of severe proteinuria, hypophosphatemia, or fractures.
Although TDF use was associated with a statistically significant loss of renal function, the clinical magnitude of this effect was modest. Our findings do not support the need to restrict TDF use in jurisdictions where regular monitoring of renal function and serum phosphate levels is impractical.
富马酸替诺福韦二吡呋酯（TDF）作为联合抗逆转录病毒治疗（ART）的一部分，已在多项随机对照试验中得到证实。然而，越来越多的病例报告表明，TDF 的使用可能与显著的肾毒性有关。我们的目的是确定 TDF 包含的 ART 方案对 HIV 感染者的肾脏安全性。
我们检索了 MEDLINE、EMBASE、全球卫生、Scopus、Biosis Previews、Cochrane 图书馆、Web of Science 和现有的系统评价。选择比较 TDF 包含与非 TDF 包含的 ART 方案的前瞻性研究进行纳入。我们提取了关于研究特征、参与者特征、治疗干预、肾功能、骨密度和骨折率的数据。
共有 17 项研究（包括 9 项随机对照试验）符合入选标准。中位样本量为 517 名参与者。组成的 ART 方案多种多样。与对照组相比，TDF 接受者的肾功能丧失明显更大（估计肌酐清除率的平均差异为 3.92 毫升/分钟；95%置信区间 [CI]，2.13-5.70 毫升/分钟），并且急性肾衰竭的风险更高（风险差异，0.7%；95%CI，0.2-1.2）。没有证据表明 TDF 的使用会增加严重蛋白尿、低磷血症或骨折的风险。
尽管 TDF 的使用与肾功能的统计学显著丧失相关，但这种影响的临床幅度是适度的。我们的发现并不支持在常规监测肾功能和血清磷酸盐水平不可行的司法管辖区限制 TDF 使用的必要性。
