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

• DOI: 10.1053/j.ajkd.2016.03.430
• Publication Date: 2016-06-09T04:41:58Z
• Authors: Vasantha Jotwani; Rebecca Scherzer; Michelle M. Estrella; Lisa P. Jacobson; Mallory D. Witt; Frank J. Palella; Bernard Macatangay; Michael Bennett; Chirag R. Parikh; Joachim H. Ix; Michael G. Shlipak
• Keywords: Male; Kidney Disease; Multicenter AIDS Cohort Study; Anti-HIV Agents; Clinical Sciences; 610; Clinical sciences; HIV Infections; Cohort Studies; Kidney Tubules, Proximal; 03 medical and health sciences; 0302 clinical medicine; Clinical Research; Tenofovir disoproxil fumarate; 616; Alpha-Globulins; antiretroviral (ARV) medication; Humans; urine α(1)-microglobulin; Tenofovir; urine alpha(1)-microglobulin; Biomedical and Clinical Sciences; Prevention; nephrotoxicity; tubular toxicity; Proximal; Urology & Nephrology; Middle Aged; HIV infection; 16. Peace & justice; kidney damage; 6. Clean water; 3. Good health; Infectious Diseases; Good Health and Well Being; Kidney Tubules; Cross-Sectional Studies; Medical Microbiology; Public Health and Health Services; Sexually Transmitted Infections; HIV/AIDS; biomarker; Infection; proximal tubular dysfunction

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.Cross-sectional.883 HIV-infected and 350 -uninfected men enrolled in the Multicenter AIDS Cohort Study.HIV infection and TDF exposure.Urine A1M level.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.Results may not be generalizable to women.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.