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

作者：Nishijima Takeshi; Shimbo Takuro; Komatsu Hirokazu; Takano Misao; Tanuma Junko; Tsukada Kunihisa; Teruya Katsuji; Gatanaga Hiroyuki^*; Kikuchi Yoshimi; Oka Shinichi

来源：Journal of Infection and Chemotherapy, 2013, 19(5): 850-857.

DOI：10.1007/s10156-013-0576-y

• Tenofovir
• Kidney tubular dysfunction
• Screening
• Urinary beta-2 microglobulin
• Urinary alpha-1 microglobulin
• HIV-1 infection

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 dysKTD) was predefined as the presence of at least three abnormalities in the following five parameters: beta 2-microglobulinuria (beta 2M), alpha 1-microglobulinuria (alpha 1M), high urinary N-acetyl-beta-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 beta 2M, 0.970 (0.947-0.992); alpha 1M, 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 beta 2M and alpha 1M were not significantly different, whereas those of the other three markers were smaller. The optimal cutoff values with 100 % sensitivity were 1,123 mu g/gCr (beta 2M, specificity 89 %), 15.4 mg/gCr (alpha 1M, specificity 87 %), 3.58 U/gCr (NAG, specificity 46 %), 1.02 % (FEIP, specificity 0 %), and 3.92 % (FEUA, specificity 12 %). Urinary beta 2M and alpha 1M are potentially suitable screening tools for tenofovir-induced KTD. Monitoring either urinary beta 2M or alpha 1M should be useful in early detection of tenofovir nephrotoxicity.

• 出版日期2013-10