In Pre-Implantation Biopsies Expression of Micro RNAs Is Not a Good Surrogate for Established mRNA Markers of Kidney Injury

K. Famulski,¹ S. Niederhaus,² J. Reeve,¹ J. Bromberg,² P. Halloran.¹

¹University of Alberta, Edmonton, Canada
²University of Marlyland, Baltimore.

Meeting: 2015 American Transplant Congress

Abstract number: B90

Keywords: Cadaveric organs, Graft acceptance, Renal ischemia

Session Information

Session Name: Poster Session B: Kidney and Donor Evaluation/Utilization

Session Type: Poster Session

Date: Sunday, May 3, 2015

Session Time: 5:30pm-6:30pm

Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Kidneys from brain dead donors>50 years old are often discarded based on conventional (clinical and histologic) criteria, despite their poor predictive value for subsequent performance of the transplants. We previously showed that elevated expression of mRNA features of kidney injury (AKI score and IFNG effects) in implantation biopsies (Bx) was a better predictors of future function than conventional assessments. Given current interest in micro RNAs (MIRs), we tested the hypothesis that the MIR expression in transplanted and discarded kidneys can substitute for the AKI score and give similar or superior support for the decision to transplant.

MIRs and mRNAs expression was measured by microarrays, in pre-implantation kidney Bx from brain dead donors >50 years. Decision to transplant was based on conventional criteria.

Principal Component Analysis (PCA) based on MIRs expression identified two sets of kidneys: Group 1 and Group 2. Group 2 kidneys contained 5 discarded kidneys and 4 transplanted kidneys, while Group 1 contained 4 discarded kidneys and one transplanted kidney. PCA based on AKI scores showed the same numerical distribution of Bx but some transplanted kidneys and discarded kidneys moved in opposite direction.

We then analyzed mRNA features of kidney injury in MIR PCA groups.

Expression of established mRNA markers of kidney in MIR PCA groups 1 and 2.
mRNA injury markers	mRNA-based Scores in MIR PCA Group 1	mRNA-based Scores in MIR PCA Group 2	p value
Acute kidney injury	7.8	7.5	0.43
IFNG effects	8.5	8.4	0.81

None of the mRNA feature scores was significant associated with the MIR PCA groups. Thus the use of MIRs did not provide the same information as mRNAs.

To find biological associations of MIRs, we compared MIR expression in Group 1vs. Group 2 kidneys. 95 MIRs had increased expression in Group 1 kidneys. Analysis of MIR targets revealed potential negative association with phosphoinositide biosynthesis (p<1E-67) and the regulator of lipid metabolism, PPRA (p<1E-26). Thus in pre-implantation biopsies MIRs are not associated with established mRNA markers of kidney injury.

To cite this abstract in AMA style:

Famulski K, Niederhaus S, Reeve J, Bromberg J, Halloran P. In Pre-Implantation Biopsies Expression of Micro RNAs Is Not a Good Surrogate for Established mRNA Markers of Kidney Injury [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/in-pre-implantation-biopsies-expression-of-micro-rnas-is-not-a-good-surrogate-for-established-mrna-markers-of-kidney-injury/. Accessed November 21, 2024.

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