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Mycophenolate mofetil (Mycophenolate mofetil, MMF) is an immunosuppressant used in organ transplant recipients, a microbial products from Penicillium fungi extracted, purified and mycophenolic acid (to mycophenolic acid MPA), 2 - ethyl ester derivatives, MMF absorption of the human body through the role of plasma esterases quickly and completely hydrolyzed into its active metabolite MPA, MPA is a selective and efficient, reversible, non-competitive hypoxanthine single-monophosphate dehydrogenase (IMPDH) inhibitor, can inhibit the de novo synthesis of guanine nucleotide depletion of lymphocytes within GMP and GTP, blocking DNA synthesis, inhibition of T and B lymphocyte proliferation thus play immunosuppressive efficacy. IMPDH type Ⅰ and type Ⅱ two isomers, MPA inhibition of type Ⅱ isomer than type Ⅰ isomer strong 4-5 times the resting state, gene expression in human lymphocytes dominant IMPDH type I isomer, when human lymphocyte activation type IMPDH II gene expression is significantly increased, while essentially the same the type Ⅰ enzyme gene expression, lymphocyte IMPDH type II gene expression-based, so the MPA on lymphocytes activation, proliferation, there is a very strong inhibition. T lymphocytes and B lymphocytes purine synthesis is fully dependent on the de novo synthesis pathway, and in the de novo synthesis of purine mitogen stimulation significantly increased, other cells of purine synthesis, except de novo synthesis, can also be synthesized via the salvage pathway, MPA can be selectively to suppress the activation and proliferation of T lymphocytes and B lymphocytes, while the other non-lymphocyte cell (e.g. inhibiting proliferation of the endothelial cells, white blood cells, sperm cells, fibroblasts, etc.) the effect is relatively weak, or even no inhibition. In addition, MPA can also be achieved by influencing the body cells and humoral immune process immunosuppressive role: MPA through selective inhibition of IMPDH, depletion of intracellular GMP and GTP, also inhibited fucose and mannose (these two substances must peripheral lymphocyte activation) transformed into glycoproteins, reduced lymphocyte adhesion molecule expression by inhibition of protein glycosylation, so as to achieve the role of the immune suppression. In addition, studies have shown that, MPA can be induced by activated T lymphocyte apoptosis, thus inhibiting the synthesis of NO, interfere with the body's immune status, the inhibition of reactive T lymphocytes of the heterologous cells and other antigens by the selective inhibition of iNOS. 1960s people MMF treated as anticancer drug research, clinical success, and later found to have immunosuppressive effects, Sollinger first reported in the 1990s using MMF prevention of rejection after renal transplantation to be successful, Following in the large-scale double-blind randomized study confirmed MMF combined with cyclosporine (CsA) and prednisone prevention and treatment of acute renal transplant rejection with good effect, MMF was then widely used in the prevention and treatment of organ transplant rejection after become an organ transplant, and one of the most widely used immunosuppressant in autoimmune diseases. View of the early use of safety MMF in renal transplantation, no significant toxicity, no need to monitor their blood concentration, MMF applications gradually extensive clinical experience constantly enrich people recognize MMF metabolic individual differences in the prevalence of fixed dose administered to bring about differences in efficacy and unnecessary toxicity. Clinical often can be seen even in the conventional dose, the proportion of patients still toxicities occurred, and the reduction of medication or multiple the most toxicity after medication can disappear or remission; while some patients may be due to immunosuppressant dosage acute rejection. Shows that there is obviously insufficient dosing regimen of single dose, and the launching of individualized treatment with immunosuppressants, people want to adjust the dosage according to the blood of patients with MPA concentration, minimize the risk of organ transplant rejection and toxicity . In this paper, as the research object to the center line of the 107 cases of renal transplantation patients, monitoring of the blood of patients with mycophenolic acid (MPA-C0), trough concentrations using the enzyme amplification immunoassays (enzyme multiplied immunoassay technique, EMIT), and occurred exclusive events and toxicity of event records, analysis of renal transplant patients with MPA-C0 correlation between response and drug toxicity and acute rejection after renal transplantation, in order to evaluate drug monitoring of mycophenolate mofetil (MMF) significance . Objective To analyze the renal transplant patients MPA-C0 correlation between response and drug toxicity, acute rejection in order to evaluate the significance of renal transplant recipients on MMF drug monitoring. Methods 107 patients with renal graft at our center from February 2009 to April 2010, 68 cases of male and 39 females, aged 18-69 years old, weighing 38-92kg, an average of 58kg, all patients were the line law hemodialysis or peritoneal dialysis, pregnancy test (-), basic laboratory markers of liver function normal, hepatitis B surface antigen (-), hepatitis C antibody (-), PRA negative. After January, February, March, 4-June ,7-12 month time period laboratory MPA-C0, and records of patients during acute rejection and drug toxicity events, based on the occurrence of acute rejection and drug toxicity or not the patients were divided into rejection group (I group), drug toxicity group (Ⅱ group), the normal group (III group). Rejection group and the normal group, the toxicity and the normal group period MPA-Co level compared using a two-sample t-test; judgment in patients with acute rejection or toxicity events MPA-Co truncated value using ROC curve analysis. All the data use spss13.0 statistical software analysis, p lt; 0.05 with statistical significance. Results 72 patients were followed up for at least 1 year, 35 patients were followed up for at least six months, during a total of 13 patients with acute rejection episode, rejection incidence of 12.1%, 38 patients with drug toxicity events occurred in 62 cases, the incidence of drug toxicity 35.5% Of these, 11 patients with leukopenia, a total of 20 cases; 14 patients with MMF-associated diarrhea, a total of 23 cases; nine patients with infection, a total of 15 cases (cytomegalovirus pneumonia:; cards Pneumocystis carinii pneumonia: 1 up; herpes simplex virus infection: 7 cases; zoster virus infection: 2 cases), four patients suffered liver damage from 4. Ⅰ and group Ⅲ (January), group II and III level of MPA-C0 significant difference; ROC curve shows: MPA-C0 level of 1.55 mg / L is best cutoff value to identify rejection occurred ( sensitivity 69.2%, specificity 65.6%); MPA-C0 level of 2.50 mg / L identify toxicity is best cutoff value (sensitivity 67.7%, specificity 72.9%). Conclusion taking MMF patients after renal transplantation monitoring MPA-C0 favor MMF dosage individualized, conducive to the prevention of rejection reactions and drug toxicity, reduce complications and improve graft survival.
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