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Intragraft MicroRNAs Foretell Fibrosis in Kidney Transplant Recipients

H. Yang,1 L. Amrouche,2 K. Akat,3 C. Li,1 Z. Khan,1 C. Tinel,2 T. Tuschl,3 D. Anglicheau,2 T. Muthukumar.1

1Weill Cornell Medicine, New York
2Hôpital Necker, Paris, France
3Rockefeller University, New York.

Meeting: 2018 American Transplant Congress

Abstract number: A6

Keywords: Fibrosis, Gene expression, Kidney transplantation

Session Information

Session Name: Poster Session A: Biomarkers, Immune Monitoring and Outcomes

Session Type: Poster Session

Date: Saturday, June 2, 2018

Session Time: 5:30pm-7:30pm

 Presentation Time: 5:30pm-7:30pm

Location: Hall 4EF

Background

Identifying biomarkers that anticipate tubulointerstitial fibrosis (IFTA) of the kidney allograft will be a transformative advance.

Aim/Hypothesis

Intragraft microRNA profile of 3-month surveillance biopsies reported as normal is associated with the presence of IFTA in 12-month surveillance biopsies.

Methods

Using RNA-sequencing, we studied the intragraft miRNA profile of 16 kidney allograft surveillance biopsies from 16 recipients at 3 months post–transplantation. None of the biopsies had IFTA (Banff ci/ct scores=0). Based on the presence of IFTA in the 12-month surveillance biopsy, 10 recipients were classified as 'Progressor' (ci/ct scores ≥2) and 6 as 'Non Progressor' (ci/ct scores=0). Two transplant pathologists reported the biopsies independently.

We compared the differential abundance of miRNA between Progressor and Non Progressor. We did qRT-PCR assay of the top differentially abundant miRNAs.

Results

Sixteen miRNAs were differentially abundant (fold change ≥2, P<0.05) between Progressor and Non Progressor. By qRT-PCR assay, the differential abundance of 3 miRNAs (miR-34a, miR-96 and miR-375) were statistically significant.

To assess the relevance of the 3 miRNAs in IFTA, we studied their intragraft abundance, by qRT-PCR assay, in 6 for-cause kidney allograft biopsies reported as IFTA and 6 surveillance biopsies reported as Normal. All 3 miRNAs were of higher abundance in IFTA (P<0.05) biopsies and had an AUC of >0.90 to distinguish IFTA from Normal.

Conclusion

Alterations in intragraft miRNA abundance in 3-month surveillance kidney allograft biopsies foretell the presence of IFTA in 12-month surveillance biopsies. The findings of our pilot study, if validated in a larger cohort, will be of considerable diagnostic and therapeutic significance.

CITATION INFORMATION: Yang H., Amrouche L., Akat K., Li C., Khan Z., Tinel C., Tuschl T., Anglicheau D., Muthukumar T. Intragraft MicroRNAs Foretell Fibrosis in Kidney Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Yang H, Amrouche L, Akat K, Li C, Khan Z, Tinel C, Tuschl T, Anglicheau D, Muthukumar T. Intragraft MicroRNAs Foretell Fibrosis in Kidney Transplant Recipients [abstract]. https://atcmeetingabstracts.com/abstract/intragraft-micrornas-foretell-fibrosis-in-kidney-transplant-recipients/. Accessed May 16, 2025.

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