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Abstract: TH-OR064

Can Nephrectomy Tissue Be Considered as Normal? A Comparison of the Molecular Expression between Nephrectomy and Donor Kidney Tissue

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Mohandes, Samer, Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Song, Huijuan, Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Shapiro, John P., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Fadda, Paolo, Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Zhang, Jianying, Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Yu, Lianbo, Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Satoskar, Anjali A., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Parikh, Samir V., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Background

The molecular interrogation of kidney tissue provides important information on disease pathogenesis. Uninvolved areas of tumor nephrectomies have been used as normal reference tissue. We postulated that nephrectomy tissue may be remotely affected by the tumor and tested this by comparing compared renal transcript expression of nephrectomy tissue to biopsies of living donor (LD) kidneys at the time of implantation.

Methods

Formalin-fixed paraffin-embedded nephrectomy (n=8) and LD (n=8) tissue was laser dissected and RNA from the glomerular and tubulointerstitial (TI) compartments was extracted. The expression of 564 immune transcripts was analyzed using Nanostring technology. Transcript expression between nephrectomy and LD samples was compared. Differences are reported by fold change (FC) and p-value.

Results

Overall, 116 glomerular transcripts and 67 TI transcripts were differentially expressed between nephrectomy and LD. The top overexpressed nephrectomy glomerular transcripts were FCER1G (FC: 8.5, P: 0.02), CD45RB (FC: 7, P: 0.02), and PDCD1LG2 (FC: 5, P: 0.014), and the top TI transcripts were TNFRSF1B (FC: 6.7, P=0.01), CD45RB (FC: 6, P: 0.02), and C1R (FC: 4.9, P: 0.02). The top under-expressed glomerular transcripts included AIRE (FC: 0.1, P: 0.0001), XCL1 (FC: 0.1, P: 0.02) and IL-20 (FC: 0.13, P: 0.001), and ATM (FC: 0.15, P: 0.03), VTN (FC: 0.16, P: 0.03) and CD160 (FC: 0.17, P: 0.008) in the TI. Panther Pathway analysis revealed upregulation of inflammation mediated by cytokine/chemokines, integrin and interleukin signaling pathways in nephrectomy compared to LD.

Conclusion

To our knowledge, this is the first study comparing the gene expression between nephrectomy and LD. Despite being ostensibly unafflicted by the tumor, the gene expression of nephrectomies was different than LD and reflected overexpression of inflammatory and immune pathways. This study highlights the potential pitfall in using nephrectomy samples as controls, especially when comparing to autoimmune and inflammatory kidney diseases.

Funding

  • NIDDK Support