PERSISTENT HIGH C2 LEVEL AS A RISK FACTOR FOR DEVELOPING CSA RELATED ADVERSE EFFECT IN STABLE LIVER TRANSPLANT PATIENTS

Abstract

P509 Aims: A single blood concentration measurement 2 hours after cyclosporine administration (C2) has been shown to be a more sensitive indicator of drug exposure in de novo transplant recipients from the first week to 6 months after initiation of cyclosporine administration than trough concentrations (C0). To detect the risk factor according to C0 and C2 levels in stable liver transplantation, a prospective cohort study has been executed in our institute.. Methods: In 50 stable liver transplant recipients (0.5-13.5 years post-transplant), we determined C2 levels in addition to conventional C0 repeatedly up to 5 times and observed clinical outcome over a period of 10±5 months. The cyclosporine dosage was adjusted according to predetermined C0 target range (80-180 ng/ml) and clinical status. Besides regular physical examination and routine laboratory measurements, a separate questionnaire containing questions specifically on the adverse effects of cyclosporine was documented. Results: Totally 128 questionnaire and paired C0 and C2 values were obtained. Percutaneous liver needle biopsy has been performed in 13 patients during the study. No rejection episode has been observed. However, 94% patients (47/50) had at least one of CsA related adverse events, such as hypertension, elevation of serum creatinine or neurotoxic symptom. The C0 levels were 145±37 ng/ml whereas the corresponding C2 were 690±222 ng/ml. A C2 level above 750 ng/ml, determined at least twice in an interval of 3 months, was identified as a relevant risk factor for the presence of serious adverse effect, which was defined as the combination of hypertension, renal insufficiency and more than two neurological complaints (RR=4, p<0.01). Single elevated C2 value was not a statistically significant risk factor. Conclusions: In this study we prospectively analysed C2 values in stable liver recipients on maintenance immunosuppression based on C0 monitoring. C2 level exceeding 750 ng/ml over 6 months was found to be associated with sever adverse events from cyclosporine whereas C0 was failed to identified this population.