SAFE CONVERSION TO MYCOPHENOLATE MOFETIL IN STABLE LIVER TRANSPLANTED PATIENTS WITH TOXICITY SECONDARY TO ANTICALCINEURINICS

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P513 Aims: The aim of this study is to analyze our results obtained with the clinical use of mycophenolate mofetil (MMF) in stable liver transplantation (LT) patients presenting adverse events (AE) related to prolonged use of anti-calcineurinics (ACN). Special attention has been paid to changes in renal function before and after conversion. Methods: From May-91 to July-02, 323 patients surviving more than 1 year have been transplanted in our center. Conversion to MMF was performed in 56 LT because AE related to ACN: 24 (43%) were converted to MMF in monotherapy and 32 (57%) were converted to MMF + low doses of ACN (around 5 ng/ml for FK 506 and between 25-75 ng/ml for Neoral-CyA). Patients converted to MMF, presented more severe preconversion chronic renal failure (CRF) compared to patients converted to ACN + MMF, and this severity was significantly maintained during the first 18 months postconversion. Follow-up post-transplant varied from 1 to 11 years. Indications for conversion were: CRF in 38 patients (68%), CRF plus refractory hypertension in 9 (16%), CRF plus other causes in 9 (16%). Preconversion therapy was: FK 506 in 23 patients and Neoral-CyA in 23. The mean time between LT and AE onset was 38.7 months (r:2-101 m). The mean MMF dose was 1 gr/day (0.5 - 2.0) with a follow-up post-conversion of 25 months (r: 3-96 m). Although MMF trough levels were obtained regularly, doses were adjusted according to tolerability and side effects. Results: Renal function improved significantly along the whole conversion period. (table-1). In patients converted to MMF, improvement was seen during the first 18 months for urea and during the first 6 months for creatinine, but not thereafter. However patients converted to MMF + ACN, for urea and creatinine was maintained throughout the conversion period. This could probably be related to the higher severity of preconversion CRF in MMF-converted group. Concerning liver function, 11 (19.6%) patients (6 in MMF and 5 in MMF+ACN, p=ns) presented acute rejection (2 severe, 9 mild) after conversion. The two severe rejections appeared in the group of MMF and boluses of steroids plus FK 506 was necesary to control rejection, although 1 finally died for reasons related to conversion and non compliance. In the rest of patients rejection was treated increasing levels of ACN in 4; and reintroducing ACN in 5. Hypertension was present in 41 patients (73%) but only 8 (14%) improved. Dislipemia was present in 15 (27%) and 4 (7%) improved. Diabetes Mellitus was present in 16 (28%) and 1 (2%) mproved. In those patients HCV positive the course of hepatitis was not affected by the conversion.FigureConclusions: MMF is useful as conversion therapy in stable LT patients with CRF due to ACN. Improvement in renal function depends on the severity of CRF preconversion. Patients with severe CRF are usually converted to MMF in monotherapy, which is penalised with higher severity in rejections, compared to patients with milder CRF and converted to low doses of ACN + MMF. So, when AE secondary to prolonged use of ACN appear, we propose an early conversion to MMF + low doses of ACN as first step. If patient remain stable and AE persist, conversion to MMF in monotherapy is advisable.

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