Abstract
BackgroundNovel urine biomarkers have enabled the characterization of kidney tubular dysfunction and injury among persons living with HIV, a population at an increased risk of kidney disease. Even though several urine biomarkers predict progressive kidney function decline, antiretroviral toxicity, and mortality in the setting of HIV infection, the relationships among the risk factors for chronic kidney disease (CKD) and urine biomarkers are unclear.MethodsWe assessed traditional and infection-related CKD risk factors and measured 14 urine biomarkers at baseline and at follow-up among women living with HIV in the Women’s Interagency Health Study (WIHS). We then used simultaneously adjusted multivariable linear regression models to evaluate the associations of CKD risk factors with longitudinal changes in biomarker levels.ResultsOf the 647 women living with HIV in this analysis, the majority (67%) were Black, the median age was 45 years and median follow-up time was 2.5 years. Each traditional and infection-related CKD risk factor was associated with a unique set of changes in urine biomarkers. For example, baseline hemoglobin a1c was associated with worse tubular injury (higher interleukin [IL]-18), proximal tubular reabsorptive dysfunction (higher α1-microglobulin), tubular reserve (lower uromodulin) and immune response to injury (higher chitinase-3-like protein-1 [YKL-40]). Furthermore, increasing hemoglobin a1c at follow-up was associated with further worsening of tubular injury (higher kidney injury molecule-1 [KIM-1] and IL-18), as well as higher YKL-40. HCV co-infection was associated with worsening proximal tubular reabsorptive dysfunction (higher β2-microglobulin [β2m]), and higher YKL-40, whereas HIV viremia was associated with worsening markers of tubular and glomerular injury (higher KIM-1 and albuminuria, respectively).ConclusionsCKD risk factors are associated with unique patterns of biomarker changes among women living with HIV, suggesting that serial measurements of multiple biomarkers may help in detecting and monitoring kidney disease in this setting.
Highlights
Standard markers of kidney disease, including estimated glomerular filtration rate and albuminuria, predominantly reflect glomerular dysfunction and injury and do not adequately detect kidney tubular health [1,2,3]
chronic kidney disease (CKD) risk factors are associated with unique patterns of biomarker changes among women living with HIV, suggesting that serial measurements of multiple biomarkers may help in detecting and monitoring kidney disease in this setting
Beginning in 2009, urine samples were collected and stored annually. In this nested study within Women’s Interagency Health Study (WIHS), we included 647 women living with HIV who had two available serial urine and serum specimens and with preserved kidney function at the time of the first specimen collection
Summary
Standard markers of kidney disease, including estimated glomerular filtration rate (eGFR) and albuminuria, predominantly reflect glomerular dysfunction and injury and do not adequately detect kidney tubular health [1,2,3]. CKD risk factors in the setting of HIV infection often appear in combination and include traditional risk factors, such as diabetes and hypertension [22], as well as infection-related risk factors, such as uncontrolled viremia [23], hepatitis C virus (HCV) co-infection [24], and exposure to potentially nephrotoxic antiretroviral therapy (ART) [25]. These risk factors may simultaneously cause injury at diverse parts of the nephron. Even though several urine biomarkers predict progressive kidney function decline, antiretroviral toxicity, and mortality in the setting of HIV infection, the relationships among the risk factors for chronic kidney disease (CKD) and urine biomarkers are unclear
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