Background: Use of extended criteria donor kidneys (ECD) carries the fear of to transplant of inferior quality and therefore of high discard rate. Clinical tools available to assess the allografts have conflicting results to predict outcomes of organs. Objectives: To evaluated the molecular profiling of ECD in biopsies (Bx) and sought possible changes induced by immunosuppressive regimens. Methodology: Standard (SCD) and ECD recipients were randomized to tacrolimus (Tac) or everolimus (Eve) and Bx were performed pre-implantation (T0; n=80), 15 (T15; n=64) and 90 days (T90; n=51) post-Tx. Subgroups SCD-Tac, ECD-Tac, SCD-Eve and ECD-Eve were analyzed for clinical outcomes and risk factors were associated with the gene expression of MCP-1, RANTES, TGF-β, FOXP3 and IL-10 Results: Overall, ECD-Eve had inferior 1 year patient and graft survivals than other groups while CMV and de novo diabetes pos-Tx were higher in patients with Tac. After 1 year ECD-Eve had higher serum creatinine than ECD-Tac (p=0.03) and acute rejection rates were higher in Eve group regardless donor type. T0 Bx of ECD showed similar FOXP3 but significantly higher expression of MCP-1, RANTES, TGF-β1 and IL-10 when compared with SCD and the only donor variable associated with this profile was the type of donor (ECD). At T15 Bx of patients from both groups taking Eve had increased FOXP3 transcripts while MCP-1 and RANTES were upregulated only in the SCD-Eve group. Use of Eve was the only variable associated with upregulation of FOXP3, MCP-1, RANTES and IL-10. In T90 Bx a similar molecular profiling was observed except by an increase in FOXP3 transcripts being restrict only to SCD-Eve group. Independent variables associated with FOXP3 were use of Eve and DGF was associated with both MCP-1 and IL-10. Conclusion: BxT0 of ECD have an inflammatory molecular profile clearly distinct from SCD. Post-Tx, the immunosuppressive regimen given modifies the initial cytokine expression pattern at different time points. Thus, identification of molecular profiles could provide insights for pre and post-Tx clinical approaches and would help to improve the fate of ECD allograft.

CITATION INFORMATION: Mazeti C, Caldas H, Fernandes-Charpiot I, Baptista M, Abbud-Filho M. Preimplantation and Post-Transplant Serial Biopsies of Standard and Extended Criteria Donor Kidneys: Intragraft Molecular Profiles and Effect of Different Immunosuppressive Protocols. Am J Transplant. 2016;16 (suppl 3).

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