title: Urinary beta2-microglobulin as a possible sensitive marker for renal injury caused by tenofovir disoproxil fumarate.
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 beta2-microglobulin (U-beta2MG) 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-beta2MG 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 2MG levels in TDF+ patients. U-beta2MG 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-beta2MG levels showed significant negative correlation with patients' body weight (p = 0.0029) and abnormal U-beta2MG was observed in all six patients with body weight less than 55 kg. In four patients, a rapid fall in U-beta2MG occurred after cessation of TDF. Relative to sCr, U-beta2MG 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.
authors.affiliation: AIDS Clinical Center, International Medical Center of Japan, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.forename: Natsuo
authors.initials: N
authors.lastname: Tachikawa
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Katsuji
authors.initials: K
authors.lastname: Teruya
authors.forename: Ikumi
authors.initials: I
authors.lastname: Genka
authors.forename: Miwako
authors.initials: M
authors.lastname: Honda
authors.forename: Junko
authors.initials: J
authors.lastname: Tanuma
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yazaki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ueda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000652:urine; D003404:Creatinine / Q000378:metabolism / Q000652:urine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects*; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects*; D011744:Pyrimidinones / Q000627:therapeutic use; D000068698:Tenofovir; D013851:Thinness / Q000150:complications / Q000652:urine; D001613:beta 2-Microglobulin / Q000652:urine*
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D063065:Organophosphonates; D011744:Pyrimidinones; D001613:beta 2-Microglobulin; D061466:Lopinavir; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine