Urinary exosome-derived microRNAs as biomarkers of tenofovir disoproxil fumarate (TDF)-induced renal toxicity in people with HIV-1.

OBJECTIVES

Tenofovir disoproxil fumarate (TDF) has been associated with proximal tubular renal toxicity, though the timing, severity, and long-term outcomes remain controversial. This study aimed to assess urinary exosome-derived microRNAs (miRNAs) as potential early biomarkers of TDF-associated renal toxicity.

METHODS

In this cross-sectional study of virologically suppressed people with HIV (PWH) on TDF-based therapy (median exposure: 65 months), we isolated urinary exosomes and quantified eight pre-selected miRNAs using real-time qPCR, analysing their associations with tubular function parameters and urinary low-molecular-weight proteins.

RESULTS

The 60 selected participants had median TDF exposure of 65 months with mean eGFR-SCr of 90.9 mL/min/1.73m² (6% with chronic kidney disease). Three miRNAs showed significant upregulation with longer TDF exposure: miR-Let-7d (P = 0.049), miR-203 (P = 0.008), and miR-29a (P = 0.02), while miR-127 negatively correlated (P = 0.009). MiR-Let-7d demonstrated strongest associations with tubular dysfunction biomarkers and highest diagnostic value (AUC 0.782; CI, 0.612-0.952). MiR-23a best identified individuals at risk for subsequent eGFR-SCr decline (AUC 0.655; CI, 0.506-0.805) after median 9-month follow-up. Multivariate analysis revealed years living with HIV, miR-Let-7d, and miR-423 were independently associated with tubular dysfunction.

CONCLUSIONS

Urinary exosome-derived miRNAs demonstrate their potential as early, non-invasive biomarkers for detecting and predicting TDF-associated renal dysfunction in PWH, potentially enabling earlier clinical intervention before irreversible damage occurs.