title: Urinary beta-2 microglobulin and alpha-1 microglobulin are useful screening markers for tenofovir-induced kidney tubulopathy in patients with HIV-1 infection: a diagnostic accuracy study.
abstract: Kidney tubulopathy is a well-known adverse event of antiretroviral agent tenofovir. A cross-sectional study was conducted to compare the diagnostic accuracy of five tubular markers, with a collection of abnormalities in these markers as the reference standard. The study subjects were patients with HIV-1 infection on ritonavir-boosted darunavir plus tenofovir/emtricitabine with suppressed viral load. Kidney tubular dysfunction (KTD) was predefined as the presence of at least three abnormalities in the following five parameters: β2-microglobulinuria (β2M), α1-microglobulinuria (α1M), high urinary N-acetyl-β-D-glucosaminidase (NAG), fractional excretion of phosphate (FEIP), and fractional excretion of uric acid (FEUA). Receiver operating characteristic curves and areas under the curves (AUC) were estimated, and the differences between the largest AUC and each of the other AUCs were tested using a nonparametric method. The cutoff value of each tubular marker was determined using raw data of 100% sensitivity with maximal specificity. KTD was diagnosed in 19 of the 190 (10%) patients. The AUCs (95% CIs) of each tubular marker were β2M, 0.970 (0.947-0.992); α1M, 0.968 (0.944-0.992); NAG, 0.901 (0.828-0.974); FEIP, 0.757 (0.607-0.907), and FEUA, 0.762 (0.653-0.872). The AUCs of β2M and α1M were not significantly different, whereas those of the other three markers were smaller. The optimal cutoff values with 100% sensitivity were 1,123 μg/gCr (β2M, specificity 89%), 15.4 mg/gCr (α1M, specificity 87%), 3.58 U/gCr (NAG, specificity 46%), 1.02% (FEIP, specificity 0%), and 3.92% (FEUA, specificity 12%). Urinary β2M and α1M are potentially suitable screening tools for tenofovir-induced KTD. Monitoring either urinary β2M or α1M should be useful in early detection of tenofovir nephrotoxicity.
authors: AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku, Tokyo, 162-0052, Japan.
authors: Takeshi
authors: T
authors: Nishijima
authors: Takuro
authors: T
authors: Shimbo
authors: Hirokazu
authors: H
authors: Komatsu
authors: Misao
authors: M
authors: Takano
authors: Junko
authors: J
authors: Tanuma
authors: Kunihisa
authors: K
authors: Tsukada
authors: Katsuji
authors: K
authors: Teruya
authors: Hiroyuki
authors: H
authors: Gatanaga
authors: Yoshimi
authors: Y
authors: Kikuchi
authors: Shinichi
authors: S
authors: Oka
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000510:Alpha-Globulins / Q000652:urine*; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers / Q000652:urine; D016009:Chi-Square Distribution; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000652:urine*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000652:urine* / Q000821:virology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D000068698:Tenofovir; D001613:beta 2-Microglobulin / Q000652:urine*
chemical_list: D000510:Alpha-Globulins; D044966:Anti-Retroviral Agents; D015415:Biomarkers; D063065:Organophosphonates; C016001:alpha-1-microglobulin; D001613:beta 2-Microglobulin; D000068698:Tenofovir; D000225:Adenine