Development and validation of urinary exosomal microRNA biomarkers for the diagnosis of acute rejection in kidney transplant recipients

Jung Woo Seo, Yu Ho Lee, Dong Hyun Tae, Yang Gyun Kim, Ju Young Moon, Su Woong Jung, Jin Sug Kim, Hyeon Seok Hwang, Kyung Hwan Jeong, Hye Yun Jeong, So Young Lee, Byung Ha Chung, Chan Duck Kim, Jae Berm Park, Junhee Seok, Yeong Hoon Kim, Sang Ho Lee

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Introduction: Acute rejection (AR) continues to be a significant obstacle for short- and long-term graft survival in kidney transplant recipients. Herein, we aimed to examine urinary exosomal microRNAs with the objective of identifying novel biomarkers of AR. Materials and methods: Candidate microRNAs were selected using NanoString-based urinary exosomal microRNA profiling, meta-analysis of web-based, public microRNA database, and literature review. The expression levels of these selected microRNAs were measured in the urinary exosomes of 108 recipients of the discovery cohort using quantitative real-time polymerase chain reaction (qPCR). Based on the differential microRNA expressions, AR signatures were generated, and their diagnostic powers were determined by assessing the urinary exosomes of 260 recipients in an independent validation cohort. Results: We identified 29 urinary exosomal microRNAs as candidate biomarkers of AR, of which 7 microRNAs were differentially expressed in recipients with AR, as confirmed by qPCR analysis. A three-microRNA AR signature, composed of hsa-miR-21-5p, hsa-miR-31-5p, and hsa-miR-4532, could discriminate recipients with AR from those maintaining stable graft function (area under the curve [AUC] = 0.85). This signature exhibited a fair discriminative power in the identification of AR in the validation cohort (AUC = 0.77). Conclusion: We have successfully demonstrated that urinary exosomal microRNA signatures may form potential biomarkers for the diagnosis of AR in kidney transplantation recipients.

Original languageEnglish
Article number1190576
JournalFrontiers in immunology
Volume14
DOIs
Publication statusPublished - 2023

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea, funded by the Korean Government Ministry of Science and ICT (grant number 2018M3A9E8078807 and RS-2023-00213976), the Korean Health Technology R&D Project, Ministry of Health & Welfare (grant number HI13C1232), and a grant from Research year of Inje University in 2020.

Publisher Copyright:
Copyright © 2023 Seo, Lee, Tae, Kim, Moon, Jung, Kim, Hwang, Jeong, Jeong, Lee, Chung, Kim, Park, Seok, Kim and Lee.

Keywords

  • acute rejection
  • exosome
  • kidney transplantation
  • microRNA
  • urine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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