Abstract

Background: Strategies based on monitoring pharmacodynamic effects are increasingly evaluated to optimize immunosuppressive therapy. Pharmacodynamic monitoring is either specific for the particular drug or aimed at a general estimation of the immunosuppression. We have monitored both drug specific and general phramacodynamic parameters and looked on their association with clinical events early after KTx.
Material/Methods: 35 patients receiving basiliximab, EC-MPS (2-720 mg/day), steroids, and tacrolimus (target: 6-8 μg/L) were included. Blood was drawn on days 7(±1) and 21(±2) at C0 h and C2 h. Mononuclear leucocytes were isolated and the following parameters were investigated: IMPDH activity (HPLC-DAD), cell proliferation (BRdU test), CD25[sup]+/[/sup]CD3[sup]+[/sup]- CD71[sup]+[/sup]/CD3[sup]+[/sup]-, and CD26[sup]+[/sup] /CD3[sup]+[/sup] -expression by flow cytometry. Acute rejection, gastrointestinal side effects, leucopenia, and infections were monitored over three month. Results were statistically evaluated by the Mann-Whitney test and odds ratios.
Results: There was no association between events and IMPDH activity apart that patients with diarrhea showed a significantly higher IMPDH activity 2 h after drug intake (p<0.05). Cell proliferation (0h) was significantly reduced in patients with leucopenia (p<0.01). CD71[sup]+[/sup] /CD3[sup]+[/sup]-expression was less inducible in patients with infections  (p<0.05). CD26[sup]+[/sup] /CD3[sup]+[/sup]-expression was highly and significantly associated with rejection particularly on day 7 after KTx (p=0.01; odds-ratio: 16.3). No assotiations were found for the CD25[sup]+[/sup] /CD3[sup]+[/sup] -expression.
Conclusions: A potential of pharmacodynamic monitoring to optimize immunosuppressive combination therapy has been demonstrated. Particularly CD26[sup]+[/sup] /CD3[sup]+[/sup] expression seems to be a promising parameter to predict acute rejection. The lack of association between IMPDH activity and events should be proven in further trials with more
patients.

Keywords: catherer, Tacrolimus, leucopenia