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Kidney-derived Urinary Extracellular Vesicles are Increased During Acute Rejection after Kidney Transplantation: A
Liang Wu1,2, Carla C Baan1, Derek Reijerkerk1
1Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center Transplant Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
Transplantation Direct
|August 1, 2025
Summary
Kidney-derived urinary extracellular vesicles (kd-uEVs) show increased release starting day 7 post-kidney transplant. Elevated kd-uEVs can help differentiate acute rejection (AR) from acute tubular necrosis (ATN), indicating their potential as early, noninvasive biomarkers.
Area of Science:
- Nephrology
- Biomarker Discovery
- Transplantation Immunology
Background:
- Urinary extracellular vesicles (uEVs), particularly kidney-derived uEVs (kd-uEVs), are emerging as noninvasive biomarkers for kidney health.
- Assessing kidney allograft status and diagnosing post-transplant complications like acute rejection (AR) are critical.
- The release dynamics of kd-uEVs following kidney transplantation remain incompletely understood.
Purpose of the Study:
- To investigate the release dynamics of kd-uEVs after kidney transplantation.
- To evaluate the potential of kd-uEVs to differentiate acute rejection (AR) from acute tubular necrosis (ATN) and nonbiopsied controls.
- To establish kd-uEVs as early, noninvasive diagnostic markers for kidney transplant recipients.
Main Methods:
- Urine samples were collected from kidney transplant recipients and donors at various time points (pre-transplant, post-transplant days 3, 7, 180) and before biopsies.
- Kidney-specific markers (aquaporin 2 [AQP2] and podocalyxin [PODXL]) were used to identify kd-uEVs via imaging flow cytometry.
- The percentage of kd-uEVs among total CD63+ uEVs was calculated to normalize for urine dilution.
Main Results:
- Kidney-derived uEV (kd-uEV) levels were significantly higher in donors compared to pre-transplant recipients.
- kd-uEV levels remained stable on post-transplant day 3 but increased significantly by day 7 and persisted up to day 180.
- Elevated AQP2+ and PODXL+ kd-uEVs were observed in acute rejection (AR) cases within the first two weeks post-transplant, distinguishing them from acute tubular necrosis (ATN) and controls, a finding validated in a separate cohort.
Conclusions:
- Kidney-derived urinary extracellular vesicle (kd-uEV) release becomes prominent around day 7 post-kidney transplantation.
- Increased kd-uEV levels are significantly associated with acute rejection (AR).
- kd-uEVs show promise as noninvasive biomarkers for the early diagnosis of AR in kidney transplant recipients, differentiating it from ATN.
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