Urinary Extracellular Vesicles as a Source of Biomarkers for Kidney Allograft Rejection: A Systematic Review.
Cahyani Gita Ambarsari, Nathanael Ibot David, Dong-Hyun Kim et al.
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In 30 seconds
This systematic review assessed urinary extracellular vesicle (uEV) biomarkers for detecting kidney allograft rejection. Sixteen studies were included, using varied vesicle-isolation methods and proteomic, transcriptomic, or genomic analyses; only one study involved pediatric recipients. Reported uEV signatures mainly reflected immune activation. Several studies achieved an area under the curve >0.75 in externally validated cohorts, with negative predictive values >90% and positive predictive values of 38%-63%. The review concludes that uEV molecular profiling may complement current diagnostic approaches, but protocols and clinical validation remain insufficiently standardized.
Key findings
- Sixteen studies met inclusion criteria; only 1 examined pediatric kidney transplant recipients.
- Several studies reported an area under the curve >0.75 in externally validated cohorts.
- Reported negative predictive values were >90%, while positive predictive values ranged from 38%-63%.
- Biomarkers predominantly reflected immune activation, including interferon/JAK-STAT, chemokine/CXCR3, antigen-presentation, TLR/inflammasome, and complement pathways.
Why it matters
Rejection diagnosis still depends largely on invasive biopsy, so molecular signals in urine-derived vesicles could offer complementary diagnostic information. The review suggests that some candidate biomarkers show useful discrimination and high negative predictive values, but the diversity of methods and study designs makes performance difficult to compare and limits confidence in routine clinical application.
What to keep in mind
The review identifies small samples, cross-sectional designs, nonstandardized protocols, and lack of normalization. Concerns about blinding and prespecified thresholds were noted in 13 studies.