CLINICAL IMMUNOSUPPRESSION - KIDNEY LATE

M.C. Raggi¹, S.B. Siebert¹, D.K. Abendroth², M. Stangl¹, H. Friess¹, S. Thorban^1
1Department Of Surgery, Transplantation, Klinikum rechts der Isar, TU Muenchen, Muenchen/GERMANY, ²Zentrum Für Chirurgie, Universitätsklinik Ulm, Ulm/GERMANY

Body: Introduction:

In our study we investigated the impact of MPA itself on the gastrointestinal system by making a correlation between MPA values and the patients’ self reported gastrointestinal satisfactionwhich was evaluated by several standardized questionnaires and if MPA can be used as a marker to predict gastrointestinal disorders.


Patients and methods:

Altogether we enrolled 63 patients who underwent renal transplantation. Two patients discontinued the study, 16 patients dropped out because of inadequate completion of the questionnaires or missingblood values due to interruption of EC-MPA therapy, severe side effects or viral infections. In the end the data of 45 people could be statistically analysed.

To evaluate gastrointestinal side effect, we used the Gastrointestinal Symptom Rating Scale (GSRS) as a standardised and validated questionnaire. The questionnaire was filled at three different timepoints: T1 (3-5 days after transplantation), T2 (10-15 days) and T3 (3 months).
MPA was measured in plasma samples by mass spectroscopy.
The blood samples were taken at fixed points. In total, patients underwent 3 drug kinetics: at point 1, 2 and 3. The samples were taken at fixed points of time: before EC-MPA intake (7:00), half anhour (9:30), 1 hour (10:00), 2 hours (11:00) and 4 hours (13:00) after EC-MPA intake.


Results:

There was evidently no correlation between MPA levels and gastrointestinal side effects.
There is hardly any difference in MPA levels at point 1 between patients with and without side effects. At 7:00, 9:30 and 10:00 the MPA levels in both groups are similar, at 11:00 the MPA level risesin the side effect group.
At point 2, the difference in MPA levels is rising in favour of the group with side effects. The biggest difference can be noticed at the end of the observation (11:00 and 13:00). However thediscrepancy is not significant.
At point 3 the difference in MPA levels is even increased compared to point 2 and can be seen in all 5 measurement with more or less equal intervals.
To sum it up the overall correlation between MPA blood levels and patient reported gastrointestinal side effects is not significant.



Discussion:

In our study we investigated whether there is a correlation between the active drug (MPA) and gastrointestinal side effects. We considered that high blood levels of MPA correlates with stronggastrointestinal dissatisfaction and could be equivalent to an overdosage of EC-MPA. EC-MPA is administered as a fixed dose regiment with 720 mg twice a day, however there is evidence that the targetenzyme of MPA, inositol-monophosphate-dehydrogenasis (IMPDH), is not equally expressed in individuals. Accordingly, the dosage of MPA can cause different effects in patients with varying IMPDHexpression. This interindividual variety is also reflected in adverse effects as standard dosage in individuals with low IMPDH has much stronger impacts as in people with high IMPDH activity.
The data that we collected suggests that there is no overall correlation between MPA blood levels and gastrointestinal side effects and that there is no connection between MPA values and IMPDHactivity.

Disclosure: All authors have declared no conflicts of interest.