RESUMO
Liver transplantation means surgical replacement of a diseased liver with a healthy liver. The survival rate used to be 30 % after 1 year and LTx was considered to be the last procedure when all medical or surgical intervention failed. Advances in donor organ preservation, surgical techniques, patient selection, immunosuppressive regimens and treatments for opportunistic infections all have contributed to substantially improve the survival rates. Despite substantial technological, medical and surgical advances, liver transplantation remains a complex procedure that is accompanied by significant morbidity and mortality. The post-operative outcome of each patient varies greatly depending on the patient's pre- operative state, quality of the donated organ and the complexity of the surgery. Complications occur both immediately post transplant and in the long term. Most of the problems can be satisfactorily assessed with a panel of routine LFTs results of which are generated quickly, cheaply on the analyzer which operates 24 h. Liver Function Test identifies the presence of problem but not problem itself. Abnormal results can be meaningful only when used with clinical data, radiological findings. The study includes 75 post LTx patients in three groups adults (non ACR), Pediatrics and ACR. All recipients were on immunosuppressive therapy (tacrolimus, mycophenolate and methylprednisolone), antiviral (ganciclovir), antiprotozoal, antibacterial and antifungal (fluconazole). 5 mL of blood was drawn in plain vacutainer from the post LTx patients every day for 15 days and LFT and GGT was done. Routinely performed liver function tests correlates well with clinical complications involving liver in the transplant patients. Instead of daily testing, may be alternate day analysis of LFT should be sufficient for effective monitoring of patients. The total protein and albumin and the transaminases offer little help in monitoring LFT post LTx. The elevated levels of serum GGT and ALP may be related to chronic immune damage to the transplanted liver. Serum GGT and ALP can be used as early markers for diagnosing biliary complications and can be used to asses adequacy of endoscopic treatment in the group of patients presenting early. Thus, most of the problems can be satisfactorily assed with a panel of routine LFTs generated quickly, cheaply on analyzer which operates 24 h each day. However, it must be emphasized that LFTs may identify the presence of problems but not the problem itself and the abnormal results are meaningful only when correlated with other clinical information.
RESUMO
BACKGROUND: The success of an immunosuppressive drug therapy depends on the extent of exposure to the drugs (the blood levels and duration), which is measured as the area under the curve (AUC). Tacrolimus shows considerable variability in its pharmacokinetics, with poor correlation between the tacrolimus trough level and systemic exposure, as measured by the AUC of concentration time. Monitoring trough levels helps not only in reducing nephrotoxiicity but also in reducing the chances of acute rejection; although there is no international consensus, the trough concentration is used to determine dosing and the AUC for calculating the exposure of the patient to the drug. The major objective of this study was to find the best sampling time for an abbreviated AUC0-6 (area under the concentration time curve) to predict the total body exposure to tacrolimus in adult renal transplantation recipients. METHODS: The study involved retrospective analysis of 14 renal transplant patients (2 female and 12 male) that were on triple immunosuppressive therapy, methyl prednisolone, mycophenolate mofetil and tacrolimus. To determine trough concentrations, blood samples were collected before administration of tacrolimus (0 h) and at fixed time points of 2 h, 4 h and 6 h after administration of oral tacrolimus and analyzed in duplicate by microparticle enzyme immunoassay. AUC0-6 was determined using the linear trapezoidal rule. The association between the blood concentration and AUC6 were evaluated by the Pearson correlation coefficient. All statistical analyses were performed using the SPSS software (IBM Corp., NY, USA) program. RESULTS: Trough levels were fairly consistent at 7.9-18 ng·h/mL in all the patients included in this study, and this did not show variation with age or sex. The AUC0-6 was higher [202-290 ng/mL at 3-8 mg bis-daily (b.d.) dosage] in patients who received kidneys from cadavers compared to recipients from live donors (60.5-171 ng/mL at 3-8 mg b.d. dosage), but the clinical significance of this is not known. The highest AUC0-6 was 246 ng/mL, observed at 4.5 mg b.d. dosage. Dosages higher than 2 mg b.d. did not result in a noticeable increase in AUC0-6. Peak blood levels of tacrolimus were obtained 4 h after administration. CONCLUSIONS: Trough level determination and a C2, C4 two-point limited sampling strategy may be useful to plan the dosing strategy and estimate the exposure of renal transplant patients to tacrolimus.