Age-Related Differences in Gene Expression Among Kidney Allografts with Normal Histology and Calcineurin Inhibitor Nephrotoxicity.

E. Rhone,¹ S. Bontha,¹ P. Walker,² C. Dumur,³ D. Maluf,¹ J. Almenara,³ V. Mas.¹

¹University of Virginia, Charlottesville
²Arkana Laboratories, Little Rock
³Virginia Commonwealth University, Richmond

Meeting: 2017 American Transplant Congress

Abstract number: D171

Keywords: Age factors, Gene expression, Kidney transplantation, Nephrotoxicity

Session Information

Session Name: Poster Session D: Kidney: Pediatric

Session Type: Poster Session

Date: Tuesday, May 2, 2017

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Background Most biomarker research first occurs in adult populations, with consequent extrapolation to children. However, age-related differences may impact gene expression, such as variations in immune system response, drug-handling, primary kidney disease, and presence of co-morbidities.

Objective To evaluate gene expression changes with recipient age in renal allografts with 1)normal histology and 2)calcineurin inhibitor nephrotoxicity (CNIT).

Methods Gene expression profiling using microarrays (Affymetrix™ GeneChip® HG-U133 2.0) was conducted in 4 groups: pediatric normal allograft (pNA), pediatric CNIT (pCNIT), adult normal allograft (aNA), adult CNIT (aCNIT). First, normal allograft (NA) kidney biopsies were compared between pediatric and adult groups (pNA vs aNA). For a separate CNIT analysis, pCNIT vs pNA and aCNIT vs aNA were compared. Differentially expressed genes (p<0.05, FDR<10%, ≥2-fold change) were analyzed. Isolated total RNA was evaluated using SensationPlus™ (formalin-fixed paraffin-embedded pNA, pCNIT, aNA samples) or 3' IVT Express Kit® (fresh frozen aNA, aCNIT samples). Gene ontology and pathway analysis was used to evaluate biological significance.

Results NA: 1078 gene probe sets were differentially expressed between pNA and aNA. Top canonical pathways demonstrated activation of B-cell receptor (p=3E-12), LPS-stimulated MAPK (p=8.12E-9), and IL-6 (p=1.31E-8) signaling in pNA. Molecular and cellular functions associated with pNA included cell survival (p=6.69E-21), proliferation of lymphocytes (p=5.9E-13) and immune cells (p=6.52E-13). CNIT: 439 genes were differentially expressed between pCNIT vs pNA, with 405 genes between aCNIT vs aNA. 46 genes (6%) were common between pediatric and adult comparisons, including genes associated with renal necrosis/cell death (SOD2, MAPT, GSTA1). A comparison analysis of differentially expressed genes between pCNIT vs pNA and aCNIT vs aNA showed differences in toxicity functions (upregulation of glomerulosclerosis (p=2.178E-2) and fibrosis of kidney (p=2.17E-2) in the adult group).

Conclusions Age-related differences in immune system response and renal cell senescence may impact the interpretation of biomarkers. These data support the necessity of developing pediatric-specific molecular markers in kidney transplantation.

CITATION INFORMATION: Rhone E, Bontha S, Walker P, Dumur C, Maluf D, Almenara J, Mas V. Age-Related Differences in Gene Expression Among Kidney Allografts with Normal Histology and Calcineurin Inhibitor Nephrotoxicity. Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Rhone E, Bontha S, Walker P, Dumur C, Maluf D, Almenara J, Mas V. Age-Related Differences in Gene Expression Among Kidney Allografts with Normal Histology and Calcineurin Inhibitor Nephrotoxicity. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/age-related-differences-in-gene-expression-among-kidney-allografts-with-normal-histology-and-calcineurin-inhibitor-nephrotoxicity/. Accessed May 13, 2025.

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