title: Urine alpha1-microglobulin is a better marker for early tubular dysfunction than beta2-microglobulin among tenofovir-exposed human immunodeficiency virus-infected men who have sex with men.
abstract: OBJECTIVE
  Men who have sex with men are at risk of tenofovir nephrotoxicity due to its wide use in both treatment and prophylaxis for human immunodeficiency virus infection, but little is known about the urinary biomarkers of early renal dysfunction in this population. This study aims to identify useful biomarkers of early renal dysfunction among human immunodeficiency virus-infected men who have sex with men exposed to tenofovir.
  
  
  METHODS
  In a cross-sectional study urinary alpha1-microglobulin, beta2-microglobulin, N-acetyl-β-d-glucosaminidase and albumin were measured and expressed as the ratio-to-creatinine in 239 human immunodeficiency virus-infected men who have sex with men who were treatment naïve or receiving antiretroviral therapy with tenofovir-containing or non-tenofovir-containing regimens. Additionally, 56 patients in the non-antiretroviral therapy group started a tenofovir-containing regimen and were assessed after 3 and 6 months on antiretroviral therapy.
  
  
  RESULTS
  Both the frequency of alpha1-microglobulin proteinuria (alpha1-microglobulin-creatinine ratio >25.8mg/g) and the median urinary alpha1-microglobulin-creatinine ratio were higher in the tenofovir disoproxil fumarate group than the other two groups (all p<0.05). A higher frequency of beta2-microglobulin proteinuria (beta2-microglobulin-creatinine ratio >0.68mg/g) was also observed in the tenofovir group (28.9%) compared to the non-tenofovir group (13.6%, p=0.024). There were no significant differences between groups for N-acetyl-β-d-glucosaminidase and albumin. In the longitudinal study, the median urinary alpha1-microglobulin-creatinine ratio after 3 and 6 months on tenofovir-containing therapy (16.8 and 17.3mg/g) was higher than baseline (12.3mg/g, p=0.023 and 0.011, respectively), while no statistically important changes were observed in urinary beta2-microglobulin-creatinine ratio or in the other biomarkers after 3 and 6 months on antiretroviral therapy (all p>0.05).
  
  
  CONCLUSIONS
  Urinary alpha1-microglobulin seems to be a more sensitive and stable indicator of tubular dysfunction than urinary beta2-microglobulin for assessing tenofovir-related nephrotoxicity and can be significantly altered after tenofovir exposure.
authors.affiliation: Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, PR China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Kang
authors.affiliation: Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, PR China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, PR China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Ding
authors.affiliation: Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, PR China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, PR China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, PR China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, PR China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Geng
authors.affiliation: Key Laboratory of AIDS Immunology of National Health and Family Planning Commission, Department of Laboratory Medicine, The First Affiliated Hospital, China Medical University, Shenyang 110001, PR China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, PR China. Electronic address: hongshang100@hotmail.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000139:chemically induced* / Q000175:diagnosis / Q000652:urine; D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D000419:Albuminuria / Q000139:chemically induced; D000510:Alpha-Globulins / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D003430:Cross-Sectional Studies; D018451:Homosexuality, Male; D006801:Humans; D007687:Kidney Tubules, Proximal; D008137:Longitudinal Studies; D008297:Male; D000068698:Tenofovir / Q000009:adverse effects* / Q000627:therapeutic use; D001613:beta 2-Microglobulin / Q000652:urine*
chemical_list: D000510:Alpha-Globulins; D015415:Biomarkers; C016001:alpha-1-microglobulin; D001613:beta 2-Microglobulin; D000068698:Tenofovir; D000118:Acetylglucosaminidase
keywords: Alpha1-microglobulin; Beta2-microglobulin; Human immunodeficiency virus; Tenofovir