Tenofovir Use and Urinary Biomarkers Among HIV-Infected Women in the Women's Interagency HIV Study (WIHS)

Background: Tenofovir (TDF) has been associated with renal tubular injury. Biomarkers that signal early tubular dysfunction are needed because creatinine rise lags behind TDF-associated kidney dysfunction. We examined several urinary biomarkers to determine if rises accompanying TDF initiation preceded creatinine changes. Methods: Three urinary biomarkers of tubular impairment-neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG), and beta-2-microglobulin (beta 2MG)-were measured across 3 time points (one pre-TDF visit and 2 post-TDF visits) in 132 HIV-positive women from the Women's Interagency HIV Study. Women initiating highly active antiretroviral therapy (HAART) containing TDF were propensity score matched to women initiating HAART without TDF and women not on HAART. Results: There were no differences between groups for NGAL or NAG, but beta 2MG was 19 times more likely to be elevated among TDF users at the second post-TDF visit compared with non-TDF users at the pre-TDF visit (P < 0.01). History of proteinuria was associated with elevated NGAL (P < 0.01). Factors associated with elevated NAG were glomerular filtration rate,60 mL/minute, history of proteinuria, hepatitis C (P < 0.01 for all), and diabetes mellitus (P = 0.05). Factors associated with increased odds of elevated beta 2MG were HIV RNA >100,000 copies/mL, hepatitis C, boosted protease inhibitor use, and glomerular filtration rate <60 mL/minute (P < 0.01 for all). Conclusions: beta 2MG levels are elevated in women on TDF, indicating probable early renal dysfunction. Biomarker elevation is additionally associated with baseline chronic kidney disease, uncontrolled viremia, and boosted protease inhibitor use. Future studies are needed to explore urinary biomarker thresholds in identifying treated HIV-infected individuals at risk for renal dysfunction.