Urinaryβ2-Microglobulin as a Possible Sensitive Marker for Renal Injury Caused by Tenofovir Disoproxil Fumarate

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Abstract
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 β2-microglobulin (U-β2MG) 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-β2MG 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-β2MG levels in TDF(+) patients. U-β2MG 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-β2MG levels showed significant negative correlation with patients’ body weight (p = 0.0029) and abnormal U-β2MG was observed in all six patients with body weight less than 55 kg. In four patients, a rapid fall in U-β2MG occurred after cessation of TDF. Relative to sCr, U-β2MG 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.