Background: Kidney transplantation is the optimal treatment for end-stage kidney disease. The analytes currently used to assess allograft function lack sensitivity and specificity, while histopathologic analysis of biopsy tissue is invasive, costly, and associated with potential complications. We investigated the applicability of extracellular vesicle (uEV)-associated miRNAs in urine as potential non-invasive biomarkers for the detection of kidney allograft rejection.
Methods: Using quantitative PCR, we analyzed the expression profile of miRNA extracted from uEVs, which were isolated from second-morning urine by size exclusion chromatography, and associated their expression with kidney allograft injury. Based on histopathological characterization of surveillance or for-cause allograft biopsies, we divided patients into 3 groups: normal histology (NH, n = 16), non-rejection injury (NRI, n = 13), and rejection injury (RI, n = 19).
Results: Patient groups showed significant differences in type of biopsy (p < 0.001), time between transplantation and biopsy (p = 0.006), presence of donor-specific antibodies (DSA; p < 0.001), serum creatinine (p = 0.021), and estimated glomerular filtration rate (p = 0.019). The NRI or RI group had significantly higher normalized uEV concentrations compared to NH patients (p = 0.019). Higher expression of miR-223-3p was found in the RI group (p = 0.035). miR-155 (p = 0.012) and miR-181a (p = 0.004) expression were associated with the type of biopsy, while miR-223-3p correlated with the presence of DSA (p = 0.024).
Conclusion: Increased levels of uEVs are associated with kidney allograft injury. miR-223-3p, extracted from uEVs, may serve as a potential non-invasive biomarker for kidney allograft rejection.
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