Urinary β2-microglobulin as a possible sensitive marker for renal injury caused by tenofovir disoproxil furnarate
Urinary β2-microglobulin as a possible sensitive marker for renal injury caused by tenofovir disoproxil furnarate
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DOI：
10.1089/aid.2006.22.744
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发表时间：
2006-08-01
影响因子：
1.5
通讯作者：
Oka, Shinichi
中科院分区：
文献类型：
--
作者：
Gatanaga, Hiroyuki;Tachikawa, Natsuo;Oka, Shinichi
富马酸替诺福韦酯（TDF）通过肾小球滤过和主动肾小管分泌的组合经肾排泄，并且已基于血清肌酐（sCr）水平的有限升高报告了其肾脏安全性特征。然而，肾小管功能以前没有得到很好的监测。我们对70例接受TDF治疗的患者[TDF（+）]和90例从未接触过TDF [TDF（-）]的接受其他抗逆转录病毒治疗的患者进行了sCr和尿β 2-微球蛋白（U-β 2-MG）水平的横断面测量。TDF（+）患者的平均U-β（2）MG显著高于TDF（-）患者（p < 0.0001），但使用Cockcroft-Gault方程估计的肌酐清除率无统计学差异。多变量分析显示，在TDF（+）患者中，联合使用加强的洛匹那韦（LPV）和患者体重与U-β（2）MG水平相关。接受加强LPV [TDF（+）LPV（+）]的患者U-β 2 MG水平显著升高（p = 0.0007），其中67.7%的患者U-β 2 MG水平异常升高。此外，在TDF（+）LPV（+）组中，U-β（2）MG水平与患者体重呈显著负相关（p = 0.0029），在所有6例体重低于55 kg的患者中均观察到U-β（2）MG异常。在4例患者中，停止TDF后U-β 2 MG迅速下降。相对于sCr，U-β（2）MG可能是TDF引起的肾小管损伤的更敏感的标志物。LPV联合给药和低体重可能是TDF诱导的肾小管功能障碍的危险因素，可能是因为这些因素与TDF浓度增加相关。
Tenofovir disoproxil fumarate (TDF) is renally excreted by a combination of glomerular filtration and active tubular secretion, and its renal safety profiles have been reported based on a limited increase of serum creatinine (sCr) levels. However, renal tubular function has not previously been well monitored. We measured sCr and urinary beta(2)-microglobulin (U-beta(2)MG) levels cross-sectionally in 70 patients treated with TDF [TDF(+)] and 90 patients on other antiretroviral therapy who had never been exposed to TDF [TDF(-)]. The mean U-beta(2)MG was significantly higher in TDF(+) patients than that in TDF(-) patients (p < 0.0001), though no statistical difference was detected in their creatinine clearance estimated by using the Cockcroft-Gault equation. Multivariate analysis showed that coadministration of boosted lopinavir (LPV) and patients' body weight were associated with U-beta(2)MG levels in TDF(+) patients. U-beta(2)MG levels were significantly higher in those who also received boosted LPV [TDF(+)LPV(+)] (p = 0.0007), and abnormally high levels were noted in 67.7% of them. Furthermore, in the TDF(+)LPV(+) group, U-beta(2)MG levels showed significant negative correlation with patients' body weight (p = 0.0029) and abnormal U-beta(2)MG was observed in all six patients with body weight less than 55 kg. In four patients, a rapid fall in U-beta(2)MG occurred after cessation of TDF. Relative to sCr, U-beta(2)MG could be a more sensitive marker of renal tubular injury caused by TDF. Boosted LPV co-administration and low body weight may be risk factors for TDF-induced renal tubular dysfunction, probably because these factors are associated with an increase in TDF concentration.