Abstracts (complete list) - Wissenschaft Online

Thomas Giese, Claudia Sommerer, Martin Zeier, Stefan Meuer
Pharmacodynamic controlled tapering of Cyclosporine A – a
new step towards individualized immunosuppressive therapy
in transplanted patients
Background. At present it is unclear which dose of Cyclosporine A (CsA) is optimal with
respect to immunosuppressive efficacy and drug specific side effects at the level of the
individual patient. Recently we proposed the quantitative assessment of NFAT regulated
gene expression in peripheral lymphocytes as a new tool to measure the individual
degree of immunosuppression by CsA and demonstrated that a significant correlation
exists between suppression of NFAT-regulated genes and clinical complications such as
infections and malignancies. The reduction of CsA dosage under close pharmacodynamic
monitoring may lead to reduced drug specific side effects while maintaining optimal
graft protection.
Methods. Eight stable renal transplant recipients were enrolled and longitudinally
followed for 27 (12-44) months. Median CsA dose was 1.83 mg/kg/day at the time of
enrolment and was tapered to 1.19 mg/kg/day. NFAT-regulated gene expression was
measured in peripheral blood lymphocytes stimulated with PMA and ionomycin ex vivo.
All patients had an ultrasound guided allograft biopsy.
Results. The stepwise reduction of CsA was inversely correlated to the residual NFATregulated
gene expression. In seven patients there were no signs of acute rejection in
the whole study period. One patient had a BANFF Ia rejection. In this patient the mean
residual NFAT-regulated gene expression had increased up to 47% in the 6 month prior
to rejection. All patients without rejection had a median NFAT-regulated gene
expression of 25%.
Conclusion. The measurement of residual NFAT-related gene expression is a helpful
and reliable tool in individualizing the immunosuppressive therapy in long-term allograft
recipients.