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Pharmacodynamic Evaluation of the First Dose of Mycophenolate Mofetil Before Kidney Transplantation

Nassim Kamar^*,,, Petra Glander^*, Jochen Nolting^*, Torsten Böhler^*,, Pia Hambach^*, Lutz Liefeldt^*, Lionel Rostaing, Hans-Hellmut Neumayer^*, and Klemens Budde^*

^* Department of Nephrology, Charité-Universitaetsmedizin Berlin, Berlin, Germany; Department of Nephrology, Dialysis, and Multiorgan Transplantation, Toulouse University Hospital, Toulouse, France; INSERM U858, IFR 31, Toulouse, France

Correspondence: Nassim KAMAR MD, PhD, Department of Nephrology, Dialysis and Transplantation, CHU Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 France. Phone: + (33) 5 61 32 26 84; Fax: + (33) 5 61 32 28 64; E-mail: kamar.n{at}chu-toulouse.fr

Background and objectives: The effect of mycophenolate mofetil (MMF) on T cell function has not been evaluated in patients undergoing kidney transplantation. The aim of this study was to assess the effect of 1g of MMF on T cell function, that is, intralymphocyte cytokine expression, T cell activation (CD25 and CD71), and T cell proliferation, as well as inosine monophosphate dehydrogenase (IMPDH) activity, to better understand the relationship between pharmacokinetic and pharmacodynamic markers in patients receiving the first dose of MMF before kidney transplantation.

Patients: Twenty-four patients undergoing a kidney transplantation from a living donor were enrolled in this study.

Results: Compared with baseline (before MMF intake), T cell proliferation (93%), IMPDH activity (74%), CD25 (46%), and CD71 (50%) expression significantly decreased during the first hour after MMF intake, in parallel to the rise in MPA concentration. Thereafter, all pharmacodynamic markers, except IMPDH activity, returned back to baseline level. There was a complex inverse relationship between pharmacokinetic and pharmacodynamic markers. The inhibition of T cell proliferation was highly correlated to IMPDH activity, but also to T cell activation markers.

Conclusion: The administration of MMF to patients is associated not only with a dramatic decrease in both T cell proliferation and IMPDH activity, but also with in a decrease in CD25 and CD71 expression.