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Kidney Week

Abstract: FR-PO1000

Urinary Extracellular Vesicles: Early Indicators of Kidney Allograft Injury after Transplantation

Session Information

  • Transplantation: Basic
    October 25, 2024 | Location: Exhibit Hall, Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 2101 Transplantation: Basic

Authors

  • Vodusek, Maja, Department of Nephrology, University Medical Centre Ljubljana, Ljubljana, Slovenia
  • Stalekar, Maja, Department of Biotechnology and Systems Biology, National Institute of Biology, Ljubljana, Slovenia
  • Goricar, Katja, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
  • Holcar, Marija, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
  • Kogovšek, Polona, Department of Biotechnology and Systems Biology, National Institute of Biology, Ljubljana, Slovenia
  • Lenassi, Metka, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
  • Arnol, Miha, Department of Nephrology, University Medical Centre Ljubljana, Ljubljana, Slovenia
Background

Allograft biopsy is the standard method for assessing the status of transplanted kidneys. Our aim was to determine whether urinary extracellular vesicles (uEVs) and their characteristics can predict kidney injury (KI) one year after transplantation (Tx).

Methods

In a prospective longitudinal study, 49 well-defined adult kidney transplant patients were followed up 1, 3, 6 and 12 months post-Tx. Blood and second morning urine samples were collected at each visit. At the time of surveillance biopsy (Bx) (382 (330-404) days post-Tx), patients were categorized into two groups based on histologic and molecular analysis (MMDx) of allograft tissue: normal histology (NH, n=33, 67%) or KI (rejection and non-rejection; n=16, 33%). uEVs were isolated by size exclusion chromatography and their characteristics were analyzed by nanoparticle tracking analysis, genotyping and digital droplet PCR.

Results

After 6 months, the KI group had higher uEV mode size (P=0.0229) and increased uEV DNA copy number normalized to urine creatinine (P=0.0055; Figure). Using a multivariable model at 6 months, we were able to predict the diagnosis of KI at the time of surveillance biopsy with an area under the curve of 0.88 (95% CI: 0.77 to 0.99), a sensitivity of 0.69 and a specificity of 0.89 (P=0.0001). The negative predictive value was 86% and the positive predictive value was 75%.

Conclusion

Our results emphasize the potential of uEV characteristics for monitoring and early diagnosis of kidney allograft injury, which could reduce the need for invasive biopsy procedures.

Funding

  • Government Support – Non-U.S.