Background: Delayed graft function (DGF) is mainly a consequence of ischemia and reperfusion injury (IRI) resulting in acute tubular necrosis. The degree of IRI is dependent on a complex interplay of pre-transplant injury and subsequent innate and adaptive immune responses after reperfusion known to affect long term graft survival post-kidney transplantation (KT). Here, we investigate the principal mechanisms of IRI in KT aiming to identify predictors of graft function and recovery.

Methods: Gene expression using Affymetrix human genome microarrays were evaluated in a training set of 73 KT recipients. Renal biopsy samples at pre implantation (K1) and 90 min post implantation (K2) were utilized (n=146). The samples were categorized based on presence or absence of DGF. K1 vs. K2 gene expression analysis was performed using RMA algorithm. IPA was used for gene ontology and molecular pathway analysis of differentially expressed genes (fold change ≥2, FDR ≤ 5% and p value ≤ 0.001). A similar analysis was done in DGF samples classified based on eGFR at 1 month post-KT (eGFR ≤40 ml/min/1.7m² and eGFR ≥40 ml/min/1.7m²) as measure for recovery.

Results: A distinct gene expression pattern was present in both DGF and non-DGF groups. Inflammation promoting genes like TNFSF6, TNFAIP, and SOCS1 were differentially expressed in DGF group and IRI ameliorating effects like SLC19A2, TGIF1, MT1M were differentially expressed in non-DGF group. Further analysis of K1 Vs K2 biopsies grouped based on recovery from DGF at 1 month post-transplantation showed unique differential gene expression in both groups. Disease and function analysis of the specific genes expressed in non-recovery group belong to development (zscore=3.18), proliferation (zscore=3.298) and growth (zscore=3.38) of connective tissue in addition to differentiation, proliferation and growth of different immune cells (zscore > 2). 8 genes were uniquely expressed in DGF recovery group.

Conclusion: The exacerbated molecular immune response distinguish non-recovery group within 90 min of transplantation. The mechanistic insights gained in this study can be used for developing early intervention protocols that might lower the incidence of DGF in renal transplant patients.

CITATION INFORMATION: Bontha S, Suh L, Dormish P, Gehrau R, Rhone E, Gallon L, King A, Dumur C, Maluf D, Mas V. The First Impressions: A Study in Pre and Post-Implantation Renal Grafts for Early Detection Markers of Delayed Graft Function and Recovery. Am J Transplant. 2016;16 (suppl 3).

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