CLINICAL IMMUNOSUPPRESSION - KIDNEY LATE

S.M. Goh¹, A. Vathsala^2
1Renal Medicine, TAN TOCK SENG HOSPITAL, SINGAPORE/SINGAPORE, ², NATIONAL UNIVERSITY HOSPITAL, Singapore/SINGAPORE

Body: Introduction Therapeutic drug monitoring (TDM) for mycophenolic acid (MPA) levels in clinical kidney transplantation has been suggested to optimise outcomes by reducing rejection or drug related toxicities. While area under the curve is the ideal TDM tool for monitoring MPA, its use is difficult in clinical practice. This study explored the impact of trough MPA level (TrMPA) monitoring and dose adjustments for toxicity on clinical outcomes in a prevalent kidney transplant (KTX) population. Patients and Methods 56 KTX (62.5% Chinese, 33.9% female, 66.1% on Mycophenolate mofetil (MMF), and 44.6% on Cyclosporine) receiving MPA in combination with calcineurin inhibitors and corticosteroids and who had undergone TrMPA monitoring (enzyme multiplied immunoassay technique, Roche), between July 2008 and Sept 2009 constituted the study population. KTX underwent dose reductions for TrMPA >3.5 and 3.7 ng/mL in the presence or absence of infections respectively. Data on hematological indices, renal function, clinical events such as infections, rejections, malignancy and cardiovascular events was collected for the 6 month period before and after the MPA level was done. Patients were stratified into 3 groups based on TrMPA: >3.5 ng/mL (Group A, n=14); Group B (1-3.5 ng/mL, n=32) and Group C (<1 ng/mL, n=10). Results Mean TrMPA were 2.37 and 2.50 ng/mL on MPA doses of 15.4 and 10.1 mg/kg/day for KTX receiving MMF and mycophenolate sodium (MYF) respectively. KTX on cyclosporine had a statistically significantly lower mean TrMPA of 1.77 and 1.95 ng/mL in KTX on MMF and MYF respectively compared to 3.64 and 2.56 ng/mL on MMF and MYF respectively for KTX on tacrolimus. At baseline, viral infections were higher among Group A: 3 Group A KTX had CMV, BK virus or parvovirus infections in contrast to none in the other 2 groups. Although baseline hematological indices including hemoglobin, total white (TWC) and platelet counts were similar between the groups, there were 2 KTX in Group A and 1 in Group B with TWC<4.10⁹/L. 11 Group A KTX, including all 3 with infections, underwent MPA dose reductions from 16.0 mg/kg/day pre to 13.4 mg/kg/day post MMF reduction and from 10.8 mg/kg/day pre to 7.9 mg/kg/day post MYF reduction respectively. 2 other Group A KTX had repeat TrMPA which was in the normal range without any intervention. 1 Group B KTX underwent MPA dose reduction for leucopenia while none in Group C underwent dose adjustments. TrMPA after dose reduction was 2.31 and 2.20 ng/mL for KTX receiving MMF and MYF respectively (p<0.05) than at baseline. After dose reductions, all patients in Groups A and B with infections or leucopenia had resolution of these problems and did not experience any rejection episodes. There were no rejection episodes in Group C. Conclusions These results demonstrate that high TrMPA are associated with viral infections and that MPA dose reductions for high trough levels is associated with resolution of viral infections or leucopenia with no increased risk of rejection. Therapeutic drug monitoring of MPA is clinically relevant in kidney transplant patients to optimize immunosuppression and minimize its morbidity.

Disclosure: All authors have declared no conflicts of interest.