Kidney Week

Abstract: PO2409

Monitoring of Gene Expression in Tacrolimus-Treated De Novo Renal Allograft Recipients Facilitates Individualized Immunosuppression: Results of the IMAGEN Study

Session Information

• Clinical and Immunologic Predictors of Post-Transplant Outcomes
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1902 Transplantation: Clinical

Authors

• Sommerer, Claudia, Nephrology, University Hospital Heidelberg, Heidelberg, Germany

Claudia Sommerer,

• Brunet, Merce, Pharmacology and Toxicology Laboratory, Barcelona, Spain

Merce Brunet,

• Budde, Klemens, Nephrology, University Hospital Charite, Berlin, Germany

Klemens Budde,

• Millan, Olga, Pharmacology and Toxicology Laboratory, Barcelona, Spain

Olga Millan,

• Guirado, Lluis, Renal Transplant Unit, Nephrology Department, Fundació Puigvert Barcelona, Barcelona, Spain

Lluis Guirado,

• Glander, Petra, Nephrology, University Hospital Charite, Berlin, Germany

Petra Glander,

• Meuer, Stefan, Immunology, University Hospital Heidelberg, Heidelberg, Germany

Stefan Meuer,

• Zeier, Martin G., Nephrology, University Hospital Heidelberg, Heidelberg, Germany

Martin G. Zeier,

• Giese, Thomas, Immunology, University Hospital Heidelberg, Heidelberg, Germany

Thomas Giese,

Background

The expression of nuclear factor of activated T-cells (NFAT)-regulated genes in the peripheral blood has been suggested as a potentially useful immune monitoring tool to individualize tacrolimus (Tac) therapy. The aim of the present study was to characterize the possibility and clinical utility of monitoring of residual NFAT-regulated gene expression in renal allograft recipients in a multicenter approach.

Methods

The IMAGEN study enrolled 64 de novo renal transplant recipients from three European centers. All patients were treated with Tac, mycophenolic acid, and corticosteroids. NFAT-regulated gene expression (NFAT-RGE; IL-2, IFN-g, GM-CSF) was evaluated by quantitative real-time PCR in whole blood samples at day 7, month 1, 2, 3, and 6 after transplantation.

Results

Altogether, 60 patients could be evaluated. Tac concentrations (C0 and C1.5) correlated inversely with gene expression (p<0.001). NFAT-RGE showed a high interindividual variability (1 to 61%). RGE increased in the first two months from 16±9% to 34±21%. Patients (n=20) with high residual gene expression (NFAT-RGE≥30%) were at the increased risk of acute rejection in the following months (35% vs 5%, p=0.002), whereas patients (n=40) with low residual gene expression (NFAT-RGE<30%) showed a higher incidence of viral complications, especially cytomegalovirus and BK virus replication (52.5% vs 10%, p=0.001).

Conclusion

NFAT-RGE was confirmed as a potential non-invasive early predictive pharmacodynamic marker in the immediate post-transplant period for the risk of acute rejection and infectious complications in Tac-treated renal allograft recipients. Monitoring of NFAT-RGE may provide additional useful information for physicians to achieve individualized treatment adjustments based on the immunomodulatory effect of Tac, thus preventing serious clinical events. The method of NFAT-RGE measurements can be applied in trials with multicenter approach.