Correlation Of Plasma Concentration Of Immunosuppressants And Diarrhea After Kidney Transplantation

Objective To explore the relationship between plasma concentration of mycophenolate mofetil?MMF?and tacrolimus?FK506?and diarrhea after renal transplantation and to evaluate the role of drug concentration monitoring of mycophenolate mofetil?MMF?in renal transplantation patients.Then to provide reference for the diagnosis and treatment of immunosuppressive drug-related diarrhea after kidney transplantation.Methods1.By measuring the plasma concentration of MPA and FK506 in the recipients?MPA-C0 and FK506-C0?,the occurrence of diarrhea after medication was recorded,including the occurrence time,frequency,duration and nature of diarrhea.According to whether diarrhea occurred or not,the included recipients were divided into diarrhea group and non-diarrhea group,and correlation and interaction analysis was performed.At the same time,the determined concentration results were stratified according to the postoperative different time?1 month,1-3 months,3-6 months,more than 6 months?.2.The preliminary study of the research group was used to determine the plasma concentrations at 1h,4h,and 8h after taking the drug,and the area under the drug curve was estimated according to the simplified formula 4.74+4.65C4+1.656C1+4.538C8.At the same time,liver and kidney function,blood routine and other clinical effect observation indicators were detected.According to whether diarrhea occurred or not in the early postoperative period,the recipients were divided into diarrhea group and non-diarrhea group.Correlation analysis was conducted to further explore the correlation between MPA-AUC and diarrhea after renal transplantation.Results1.The 146 renal transplant patients were followed up for 0.2 to 23.2 months.A total of63?43.15%?patients experienced 88 episodes of diarrhea During follow-up.Among them,53 episode?60%?occurred within 1 month after transplantation.2.In 2015.8²017.8,there were 489 cases of mycophenolic acid trough concentrations in follow-up patients.The difference in MPA-C0 between diarrhea and non-diarrhea groups was not statistically significant?P=0.642?;A stratified analysis of the 4 different time periods after kidney transplantation revealed that the MPA-C0 differences between the diarrhea group and the non-diarrhea group were also not statistically significant?P>0.05?.3.A total of 624 tacrolimus drug trough concentrations were detected in follow-up patients.FK506-C0 was significantly different between diarrhea and non-diarrhea patients?P=0.000?;A stratified analysis of the 4 different time periods after kidney transplantation revealed that there was a significant difference between FK506-C0 in the diarrhea group and the non-diarrhea group Within 1 month?P=0.017?.However FK506-C0 difference was not statistically significant in other time periods?P>0.05?;Furtherly Based on the analysis of FK506 concentration in ROC curve,found that the ROC curve of FK506-C0 at 1 month after transplantation was statistically significant?area under the curve 0.607,P=0.017?.FK506 C0 less than 11.15 ng/mL was the best cut-off value of diarrhea.4.Logistic regression model was used to analyze the interaction of MPA and FK506drug trough concentrations on the occurrence of diarrhea.The results showed that the P values of the main effect analysis and interaction terms were all greater than 0.05,indicating that there was no significant correlation between FK506-C0 or MPA-C0alone and diarrhea?P>0.05?and there was no synergistic interaction between them?P>0.05?.5.40 cases of MPA-AUC_0-12h were measured in 39 renal transplant recipients.The doses of MMF taken by 40 renal transplant recipients were 0.25g¹.5g/d at early stage,and the MPA-AUC_0-12h range was estimated to be 9.69⁸0.47mg·L^-1·h^-1.With the increase of exposure,the incidence of diarrhea also increased,but there was no statistical difference in the incidence of diarrhea between different exposures?P=0.615?.6.According to the occurrence of diarrhea or not,40 cases of MPA-AUC_0-12h results were divided into diarrhea group and non-diarrhea group.However diarrhea group MPA-AUC_0-12h were higher than non-diarrhea group,the difference was not statistically significant?P=0.714?;C1 and C4 were higher in the diarrhea group than in the non-diarrhea group?P>0.05?,yet the difference was not statistically significant?P=0.714?.Conclusions1.MPA-C0 was not associated with the occurrence of diarrhea,and FK506-C0 was associated with the occurrence of diarrhea.There is also no synergistic interaction between MPA and FK506.2.Clinically,in the presence of immunosuppressant-associated diarrhea,first consider reducing the blood concentration beyond the target concentration FK506 dose,if it does not exceed the target concentration,reduce or even stop the use of mycophenolate mofetil in the case of closely monitoring renal function.3.The limited sampling method established earlier in the research group can better estimate the area under the curve of mycophenolic acid.This monitoring index has a certain guiding significance for clinical dose adjustment of mycophenolate mofetil.However,it is necessary to further expand the sample size and conduct stratified studies on postoperative different time periods and different dosing schedules.4.MPA-C1,C4,C8 and MPA-AUC0-12h were not associated with the occurrence of diarrhea after renal transplantation.