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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

  • Original Article
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Journal of Infection and Chemotherapy

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.

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Acknowledgments

The authors thank all the patients who participated in the study, and Fumihiko Hinoshita, Hirohisa Yazaki, Haruhito Honda, Ei Kinai, Koji Watanabe, Takahiro Aoki, Daisuke Mizushima, Yohei Hamada, Michiyo Ishisaka, Mikiko Ogata, Minami Takahashi, and Akiko Nakano, and all other clinical staff at the AIDS Clinical Center for their help in completion of this study. This work was supported by a Grant-in Aid for AIDS research from the Japanese Ministry of Health, Labour, and Welfare (H23-AIDS-001), and the Global Center of Excellence Program (Global Education and Research Center Aiming at the Control of AIDS) from the Japanese Ministry of Education, Science, Sports and Culture. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

Shinichi Oka has received a research grant from MSD K.K., Abbott Japan Co., Janssen Pharmaceutical K.K., Pfizer Co., and Roche Diagnostics K.K. The other authors declare no conflict of interest.

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Authors and Affiliations

  1. AIDS Clinical Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku, Tokyo, 162-0052, Japan

    Takeshi Nishijima, Misao Takano, Junko Tanuma, Kunihisa Tsukada, Katsuji Teruya, Hiroyuki Gatanaga, Yoshimi Kikuchi & Shinichi Oka

  2. Department of Clinical Research and Informatics, International Clinical Research Center, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku, Tokyo, Japan

    Takuro Shimbo

  3. Center for AIDS Research, Kumamoto University, Kumamoto, Japan

    Takeshi Nishijima, Hiroyuki Gatanaga & Shinichi Oka

  4. Department of Community Care, Saku Central Hospital, Nagano, Japan

    Hirokazu Komatsu

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  1. Takeshi Nishijima
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  2. Takuro Shimbo
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  3. Hirokazu Komatsu
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Correspondence to Hiroyuki Gatanaga.

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Nishijima, T., Shimbo, T., Komatsu, H. et al. 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. J Infect Chemother 19, 850–857 (2013). https://doi.org/10.1007/s10156-013-0576-y

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  • DOI: https://doi.org/10.1007/s10156-013-0576-y

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