HIV Infection, Tenofovir, and Urine α₁-Microglobulin: A Cross-sectional Analysis in the Multicenter AIDS Cohort Study

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• 作者：Vasantha Jotwani ; MD¹ ; ² ; ^{vasantha.jotwani@ucsf.edu" class="auth_mail" title="E-mail the corresponding author} ; Rebecca Scherzer ; PhD¹ ; ² ; Michelle M. Estrella ; MD ; MHS³ ; Lisa P. Jacobson ; ScD⁴ ; Mallory D. Witt ; MD⁵ ; Frank J. Palella Jr. ; MD⁶ ; Bernard Macatangay ; MD⁷ ; Michael Bennett ; PhD⁸ ; Chirag R. Parikh ; MD ; PhD⁹ ; ¹⁰ ; Joachim H. Ix ; MD ; MAS¹¹ ; ¹² ; Michael G. Shlipak ; MD ; MPH¹ ; ¹³
• 关键词：Tenofovir disoproxil fumarate (TDF) ; nephrotoxicity ; HIV infection ; proximal tubular dysfunction ; tubular toxicity ; biomarker ; urine α1-microglobulin (A1M) ; kidney damage ; antiretroviral (ARV) medication ; Multicenter AIDS Cohort Study (MACS)
• 刊名：American Journal of Kidney Diseases
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：68
• 期：4
• 页码：571-581
• 全文大小：416 K

文摘

Tenofovir disoproxil fumarate (TDF) can cause proximal tubular damage and chronic kidney disease in human immunodeficiency virus (HIV)-infected individuals. Urine α₁-microglobulin (A1M), a low-molecular-weight protein indicative of proximal tubular dysfunction, may enable earlier detection of TDF-associated tubular toxicity.

Study Design

Cross-sectional.

Setting & Participants

883 HIV-infected and 350 -uninfected men enrolled in the Multicenter AIDS Cohort Study.

Predictors

HIV infection and TDF exposure.

Outcome

Urine A1M level.

Results

Urine A1M was detectable in 737 (83%) HIV-infected and 202 (58%) -uninfected men (P < 0.001). Among HIV-infected participants, 573 (65%) were current TDF users and 112 (13%) were past TDF users. After multivariable adjustment including demographics, traditional kidney disease risk factors, and estimated glomerular filtration rate, HIV infection was associated with 136% (95% CI, 104%-173%) higher urine A1M levels and 1.5-fold (95% CI, 1.3- to 1.6-fold) prevalence of detectable A1M. When participants were stratified by TDF exposure, HIV infection was associated with higher adjusted A1M levels, by 164% (95% CI, 127%-208%) among current users, 124% (95% CI, 78%-183%) among past users, and 76% (95% CI, 45%-115%) among never users. Among HIV-infected participants, each year of cumulative TDF exposure was associated with 7.6% (95% CI, 5.4%-9.9%) higher A1M levels in fully adjusted models, a 4-fold effect size relative to advancing age (1.8% [95% CI, 0.9%-2.7%] per year). Each year since TDF treatment discontinuation was associated with 4.9% (95% CI, −9.4%-−0.2%) lower A1M levels among past users.

Limitations

Results may not be generalizable to women.

Conclusions

HIV-infected men had higher urine A1M levels compared with HIV-uninfected men. Among HIV-infected men, cumulative TDF exposure was associated with incrementally higher A1M levels, whereas time since TDF treatment discontinuation was associated with progressively lower A1M levels. Urine A1M appears to be a promising biomarker for detecting and monitoring TDF-associated tubular toxicity.