ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

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

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Sommerer, Claudia, Nephrology, University Hospital Heidelberg, Heidelberg, Germany
  • Brunet, Merce, Pharmacology and Toxicology Laboratory, Barcelona, Spain
  • Budde, Klemens, Nephrology, University Hospital Charite, Berlin, Germany
  • Millan, Olga, Pharmacology and Toxicology Laboratory, Barcelona, Spain
  • Guirado, Lluis, Renal Transplant Unit, Nephrology Department, Fundació Puigvert Barcelona, Barcelona, Spain
  • Glander, Petra, Nephrology, University Hospital Charite, Berlin, Germany
  • Meuer, Stefan, Immunology, University Hospital Heidelberg, Heidelberg, Germany
  • Zeier, Martin G., Nephrology, University Hospital Heidelberg, Heidelberg, Germany
  • Giese, Thomas, Immunology, University Hospital Heidelberg, Heidelberg, Germany
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.