CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY

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 previous in vitro studies the metabolite Ac-MPAG was suspected to be responsible for the gastrointestinal side effects. In our study we examined the correlation between Ac-MPAG blood levels andthe patients gastrointestinal satisfaction which was evaluated by standardised and validated questionnaires. Furthermore, the question arises whether Ac-MPAG should be defined as a single value or inthe context of an area under curve (AUC).

Patients and methods:

63 patients who underwent renal transplantation were enrolled in this study. Two patients discontinued the study, 16 patients dropped out because of inadequate completion of the questionnaires ormissing blood values due to discontinuation of EC-MPA therapy, severe side effects or viral infections. 45 people underwent statistical analysis finally.
Gastrointestinal side effects were examined using the standardised and validated questionnaire GSRS, Gastrointestinal Symptom Rating Scale (at three different time points: T1 (3-5 days aftertransplantation), T2 (10-15 days) and T3 (3 months).
Ac-MPAG was measured with mass spectroscopy using a standardised protocol.
The blood samples were taken at fixed points leading to three pharmacokinetic profiles.

Results:

According to the GSRS results two groups were formed. The cut off value was set at a score of 4 points for each item; scores less than 4 were assumed as “no side effects”, ≥4 to“side effects”.
There was no relation between high Ac-MPAG blood values and gastrointestinal dissatisfaction. Surprisingly, significantly higher Ac-MPAG values were found in patients without gastrointestinal sideeffects in all 5 profiles at point 1. At point 2 and 3 the interindividual variability was high in the questionnaire and the Ac-MPAG values, leading to non significant results.
Ac-MPAG AUCs and Ac-MPAG peak values did not correltate with gastrointestinal satisfaction. In the AUC group the levels of significance were 0.654 at point 1, 0.163 at point 2 and 1,00 at point 3, inthe peak level group 0.426 at point 1, 0.501 at point 2 and 0.693 at point three.

Discussion:


In this study, patients self reported gastrointestinal satisfaction and plasma Ac-MPAG levels plasma levels were prospectively investigated. Surprisingly, there was no correlation at any point . Thefact that overall correlation between mean Ac-MPAG with GSRS scores did not show any significance was to be expected, but according to previous studies we expected results from Ac-MPAG maximum valuesor alternatively Ac-MPAG AUCs in relation to side effects. What we could see in the mean Ac-MPAG group at point one were much higher Ac-MPAG levels in patients without side effects, therefore Ac-MPAGis obviously not the metabolite causing side effects.

Analysing the relationship between Ac-MPAG AUCs and GI side effects the interpatient variability ishigh, the same effects could be observed comparing maximum Ac-MPAG levels with adverse events.

In summary, the results that we found in our study can not reproduce the effects that were shown under in vitro conditions. The Ac-MPAG levels in either way (mean Ac-MPAG, AUC and maximum level) didnot correlate with patients’ self-reported outcome concerning gastrointestinal quality of life.

Disclosure: All authors have declared no conflicts of interest.