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Kidney Week

Abstract: FR-PO875

Molecular Assessment of Pre-Implantation Transplant Kidney Biopsies

Session Information

Category: Transplantation

  • 1802 Transplantation: Clinical

Authors

  • Akalin, Enver, Montefiore Medical Center, Bronx, New York, United States
  • Barbachan e Silva, Mariel, National University of Ireland, Galway, Galway, Ireland
  • Ajaimy, Maria, Montefiore Medical Center, Bronx, New York, United States
  • Mas, Valeria, University of Virginia, Charlottesville, Virginia, United States
  • Ó Broin, Pilib, NUI Galway, Galway, Ireland
Background

Deceased-donor (DD) kidneys are at higher risk for ischemia/reperfusion injury leading to increased inflammatory mediators compared to living donors (LD). We investigated the association between intragraft molecular gene expression profiles and clinical outcomes including delayed graft function (DGF) and allograft function.

Methods

The study included 48 pre-implantation kidney biopsy samples (29 LD and 19 DD). Patients were grouped on the basis of cold ischemia time (CIT) < 16 or > 16 hrs and presence of poor clinical/histological markers (final donor serum creatinine > 1.9 mg/dl, donor age > 60 yo, glomerulosclerosis/interstitial fibrosis/vascular sclerosis > 10%). The gene expression profiles were assayed using Affymetrix HuGene 1.0 ST arrays.

Results

DD pre-implantation biopsies showed increased expression of injury and repair (IRIT), gamma interferon and rejection (GRIT), cytotoxic T cell (CAT) and constitutive macrophage (CMAT) associated pathogenesis based transcripts (PBTs) compared to LD biopsies. CIT did not affect intragraft gene expression profiles. Biopsies with poor clinical/histological markers had increased expression of NKAT and endothelial cell associated transcripts (ENDAT). DGF occurred in 47% of DD patients but intragraft gene expression profiles were similar to patients who did not develop DGF. Patients with lower eGFR (<50 ml/min) at 1 year had increased expression of CAT, NKAT, CMAT and B cell associated transcripts at their pre-implantation biopsies compared to patients with higher eGFR (> 50 ml/min).

Conclusion

Pre-implantation DD biopsies showed increased expression of transcripts associated with increased immune activity. This is exacerbated if the donor had any poor clinical/histological markers, but not with increased CIT. Molecular analysis of pre-implantation biopsies did not differentiate patients based on DGF status but did show association of specific PBTs with better allograft function at 1 year

Figure