Renal Tubular-cell-specific Urinary Extracellular Vesicles: A Novel Biomarker for Diabetic Nephropathy After Kidney Transplantation

N. Eguchi¹, H. Lau¹, F. Zaldivar², U. G. Reddy³, E. Tantisattamo³, A. Ferrey³, D. Dafoe¹, H. Ichii¹

¹Surgery, University of California Irvine, Orange, CA, ²Pediatric Execise and Genomics Research Center, University of California Irvine, Irvine, CA, ³Medicine, University of California Irvine, Orange, CA

Meeting: 2021 American Transplant Congress

Abstract number: 637

Keywords: FACS analysis, Kidney, Post-transplant diabetes, Renal dysfunction

Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes

Session Information

Session Name: Biomarkers, Immune Assessment and Clinical Outcomes

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: Diabetes(DM) is a leading cause of ESRD among renal transplant recipients(RTRs). However, the kinetics of diabetic nephropathy recurrence after renal transplantation(RT) remains unclear. Currently, diabetic nephropathy, which involves damages to renal tubular cells, is diagnosed by allograft biopsy. Non-invasive methods that can detect renal tubular cell injury post RT may provide early diagnosis and guide prompt management to enhance graft survival. Urinary extracellular vesicles (UEVs) secreted by various types of renal cells contain cell-specific molecular cargos that may serve as an attractive source of diagnostic biomarkers for kidney diseases. This study aims to measure the level of renal tubular-cell-specific UEVs in RTRs with DM to determine whether renal tubular cell damage could be detected before clinical presentation.

*Methods: UEVs from urine samples of healthy control RTRs (CTL, n=4), RTRs with DM without insulin dependency (NI-DM, n=4), RTRs with DM with insulin dependency (I-DM, n=4) were isolated within 24 hours. All patient’s serum creatinine was in their baseline range. Insulin dependency was defined as the need for exogenous insulin therapy within 1 month of urine collection date. Isolated UEVs were stained with Annexin V, CD63, and Megalin antibody, and then analyzed by flow cytometry.

*Results: The number of Annexin V- and CD63- positive UEVs was higher for I-DM (1.4±0.43×10⁵UEVs) compared to CTL (1.0±0.62 x 10⁴UEVs, p<0.5) and NI-DM (2.2±0.61 x 10⁴UEVs, p<0.5). The number of renal-tubular-cell-specific UEVs were also significantly elevated in the I-DM group (2.6 ±1 x 10⁴UEVs) compared to the CTL (1.1±0.6 x 10³UEVs, p<0.5) and NI-DM (1.5±0.2 x 10³UEVs, p<0.5) groups.

*Conclusions: There is significantly higher numbers of renal-tubular-cell-specific UEVs present in I-DM group compared to CTL and NI-DM groups, suggesting that cell-specific UEVs may serve as a novel biomarker for renal tubular cell damage in RTRs with potential progression towards diabetic nephropathy.

To cite this abstract in AMA style:

Eguchi N, Lau H, Zaldivar F, Reddy UG, Tantisattamo E, Ferrey A, Dafoe D, Ichii H. Renal Tubular-cell-specific Urinary Extracellular Vesicles: A Novel Biomarker for Diabetic Nephropathy After Kidney Transplantation [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/renal-tubular-cell-specific-urinary-extracellular-vesicles-a-novel-biomarker-for-diabetic-nephropathy-after-kidney-transplantation/. Accessed November 21, 2024.

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