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Publication Date

10-2-2024

Abstract

Antiretroviral therapy (ART) has significantly improved the clinical outcomes of patients infected with human immunodeficiency virus (HIV). However, long-term use of certain antiretroviral drugs has been associated with renal mitochondrial toxicity (MtT), leading to potentially severe renal dysfunction. To date, there is no available test for renal MtT. Urine-derived stem cells (USCs) have emerged as a valuable non-invasive tool for studying renal pathology. In this study, we examine the effects of antiretroviral drugs on mitochondrial function in USCs from HIV patients as a first step towards establishing USCs as a tool for renal mitochondrial toxicity testing. USCs were isolated from urine samples of adult HIV patients taking ART drugs and compared to an age-matched (30 years old) healthy donor as a control. No changes in cell morphology and cell proliferation were found at passage 3; however, mitochondrial DNA levels were significantly decreased, while superoxide dismutase-2 (SOD2), cytochrome P450 2E1 (CYP2E1), caspase-3, and kidney injury molecule-1 (KIM-1) levels were significantly increased in HIV patient USCs compared to control. Thus, USCs from HIV patients exhibit decreased mitochondrial function, excessive oxidative stress conditions, increased apoptosis and acute kidney injury markers, all indicating renal mitochondrial dysfunction. These findings highlight the potential of urine-derived stem cells as a promising platform for non-invasive monitoring of renal mitochondrial toxicity in HIV patients undergoing antiretroviral therapy.

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