Non-Invasive Diagnosis for Acute Rejection Using Urinary mRNA Signature Reflecting Allograft Status in Kidney Transplantation

Jung Woo Seo, Yu Ho Lee, Dong Hyun Tae, Seon Hwa Park, Ju Young Moon, Kyung Hwan Jeong, Chan Duck Kim, Byung Ha Chung, Jae Berm Park, Yeong Hoon Kim, Junhee Seok, Sun Hyung Joo, Seung Hwan Lee, Jong Soo Lee, Sang Ho Lee

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Urine has been regarded as a good resource based on the assumption that urine can directly reflect the state of the allograft or ongoing injury in kidney transplantation. Previous studies, suggesting the usefulness of urinary mRNA as a biomarker of acute rejection, imply that urinary mRNA mirrors the transcriptional activity of the kidneys. We selected 14 data-driven candidate genes through a meta-analysis and measured the candidate genes using quantitative PCR without pre-amplification in the cross-sectional specimens from Korean kidney transplant patients. Expression of 9/14 genes (CXCL9, CD3ϵ, IP-10, LCK, C1QB, PSMB9, Tim-3, Foxp3, and FAM26F) was significantly different between acute rejection and stable graft function with normal pathology and long-term graft survival in 103 training samples. CXCL9 was also distinctly expressed in allografts with acute rejection in in situ hybridization analysis. This result, consistent with the qPCR result, implies that urinary mRNA could reflect the magnitude of allograft injury. We developed an AR prediction model with the urinary mRNAs by a binary logistic regression and the AUC of the model was 0.89 in the training set. The model was validated in 391 independent samples, and the AUC value yielded 0.84 with a fixed manner. In addition, the decision curve analysis indicated a range of reasonable threshold probabilities for biopsy. Therefore, we suggest the urine mRNA signature could be used as a non-invasive monitoring tool of acute rejection for clinical application and could help determine whether to perform a biopsy in a recipient with increased creatinine.

Original languageEnglish
Article number656632
JournalFrontiers in immunology
Volume12
DOIs
Publication statusPublished - 2021 Jun 10

Keywords

  • acute rejection
  • kidney
  • non-invasive diagnosis
  • transplantation
  • urinary mRNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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