Urinary β2-microglobulin as a possible sensitive marker for renal injury caused by tenofovir disoproxil furnarate

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.