The Immune Indexes Effects Of Tacrolimus In Kidney Transplant Recipients And Kidney Disease Patients And Its Steady-state Trough Concentration Ranges Was Optimized

Objective: To detect of tacrolimus steady-state concentration?FK506 C₀?in renal transplant recipients and kidney patients by Chemiluminesent Microparticle Immunoassay?CMIA?,and combine with incidence of rejection reactions and toxic reactions of statistical analysis,to optimize the therapeutic window range of tacrolimus.To investigate the effects of tacrolimus the proportion of T lymphocyte subsets?CD3⁺,CD4+,CD8⁺,CD4+/CD8⁺?,B cells?CD19⁺?and NK cells?CD?16+56?+?of the kidney transplant recipients and kidney patients.And to examine the correlation between the levels of lymphocyte and tacrolimus steady-state concentration?FK506 C₀?,liver and renal function were analyzed respectively.Methods:1 To optimize the tacrolimus steady-state concentration ranges of kidney transplant recipients and kidney patientsRetrospective analysis of 354 tacrolimus C₀ in 59 kidney transplant recipients and 40 kidney patients from March 2014 to March 2015 was made.Including kidney transplant recipients and kidney patients' sex,age,biochemical parameters,after renal transplantation time,combined with 354 parts of FK506 C₀ results and toxic reactions and rejection of the case,examine the reasonableness of FK506 C₀.2 The immune indexes effects of tacrolimus kidney transplant recipients A total of 6 health controls and 29 kidney transplant recipients with FK506 and FK506+MMF as the main immunosuppressant regimens were enrolled in this study.The kidney transplant recipients were divided into two groups with immunosuppressive regimen,group A: n=8,taking FK506 recipients;group B:n=21,taking FK506+MMF recipients.The taking FK506+MMF recipientswere divided into three groups with different survival,group?: n=7,0-1 years of post-operation;group ?: n=7,1-5 years of post-operation;group ?:n=7,>5 years of post-operation.Detection control group and experimental group in peripheral blood T lymphocyte subsets?CD3⁺,CD4+,CD8⁺,CD4+/CD8⁺?,B cells?CD19⁺?,NK cells?CD?16+56?+?and liver and kidney function index and statistical analysis.Inclusion criteria: All patients with stable renal function;infection and rejection were not present during the test subject.Exclusion criteria: infection and excluded occur during the test;pregnant or lactating female recipients;clinical data incomplete and halfway lost to follow;the subject could not be measured by a blood sample.3 The immune indexes effects of tacrolimus in kidney patientsA total of 6 health controls and 25 kidney patients with FK506 and FK506+Wuzhi capsules as the main immunosuppressant regimens were enrolled in this study.The kidney patients were divided into two groups by immunosuppressant regimens,group A: n=13,taking FK506 kidney patients;group B: n=12,taking FK506+Wuzhi capsules.FK506 initial dose of0.05⁰.075 mg/?kg?d?,2 times/day,Wuzhi capsules 2 piece/times,3 times/day.Inclusion criteria: Disease with kidney patients be controlled or improved,stable renal function.Exclusion criteria: pregnant or lactating female recipients,clinical data incomplete and halfway lost to follow,the subject could not be measured by a blood sample.Results:1 To optimize the tacrolimus steady-state concentration ranges of kidney transplant recipients and kidney patients219 FK506 C₀ in 59 kidney transplant recipients and 135 FK506 C₀ in 40 kidney patients were determined by CMIA.The blood trough level of FK506 was 8.6±2.7 ng/mL within the first three months,6.8±2.5 ng/mL from the third month after transplantation.And there were 12 case-times of drug toxicity and acute rejection after kidney transplantation.The blood trough level of FK506 was 5.3±2.8 ng/m L from the kidney patients,and the clinicalremission rate was 97.77%.According to the FK506 C₀ values,kidney transplant recipients and kidney patients with rejection and toxic reactions,combined with domestic scholars,and "China adult nephrotic syndrome immunosuppressive therapy expert consensus",so the FK506 C₀ reference range was adjusted as following: 5¹2 ng/mL within the first three months,3⁸ ng/mL from the third month after transplantation,and 2⁸ ng/mL in the kidney patients.2 The immune indexes effects of tacrolimus kidney transplant recipientsCompared with the control group,CD8⁺ T cells in group A and B were significantly higher?PA?CD8⁺?=0.019<0.05;PB?CD8⁺?=0.006<0.05?;the ratio of CD4+/CD8⁺ in group B and CD19⁺ B cells in group A and B were decreased?PB?CD4+/CD8⁺?=0.006<0.05,PA?B?=0.017<0.05,PB?B?=0.003<0.05?.Compared with the control group,CD8⁺ T cells in group?and ? were significantly higher?P??CD8⁺?=0.009<0.01;P??CD8⁺?=0.023<0.05?;the ratio of CD4+/CD8⁺ in group?and ? and CD19⁺ B cells in group?and ? were decreased?P??CD4+/CD8⁺?=0.018<0.05,P??CD4+/CD8⁺?=0.007<0.01,P??B?=0.004<0.01,P??B?=0.001<0.01?.Compared with group B,CD19⁺ B cells in group ?was significantly decreased?P=0.049<0.05?.There was linear correlation between CD8⁺ T cells and ALT levels in group A?r=-0.933,P=0.002?.And There was linear correlation between the ratio of CD4+/CD8⁺ and Cr,ALT,AST levels in group A?rCr=-0.717,PCr=0.045;rALT=0.777,PALT =0.040;rAST=0.841,PAST=0.018?.There was linear correlation between CD3⁺ T cells,CD4+ T cells,the ratio of CD4+/CD8⁺,CD19⁺ B cells and CRE levels in group B?rCD3⁺=0.483,PCD3⁺=0.050;rCD4+=0.578,PCD4+=0.015;rCD4+/CD8⁺=0.540,PCD4+/CD8⁺=0.025;rB=-0.492,PB=0.045?.And There was linear correlation between CD19⁺ B cells and UREA levels in group B?r=0.484,P=0.049?.3 The immune indexes effects of tacrolimus in kidney patientsCompared with the control group,CD3⁺ T cells and CD8⁺ T cells in group A was significantly higher?PCD3⁺=0.015<0.05,PCD8⁺=0.044<0.05?;CD?16+56?+ NK cells in group B was significantly reduced?PCD?16+56?+=0.016<0.05?;compared with group B,CD19⁺B cells in group A was significantly decreased?P=0.032<0.05?.There was linear correlation between the ratio of CD4+/CD8⁺,CD19⁺B cells and FK506 C₀?rCD4+/CD8⁺=0.448,PCD4+/CD8⁺=0.025;rB=0.633,PB=0.001?.There was linear correlation between CD4+T cells,CD?16+56?+ NK cells and ALB levels?rCD4+=-0.441,PCD4+=0.031;rCD?16+56?+=0.461,PCD?16+56?+=0.023?,and between CD3⁺T cells and TBIL levels?r=-0.537,P=0.012?.Conclusion:1 To optimize the tacrolimus steady-state concentration ranges of kidney transplant recipients and kidney patientsThe reference range of tacrolimus C₀ by CMIA should be ajusted as follows: 5¹2 ng/mL within the first three months,3⁸ ng/mL from the third month after liver transplantation,2⁸ ng/mL in the kidney patients.2 The immune indexes effects of tacrolimus kidney transplant recipientsIt is no significantly influence of the taking FK506 recipients and taking FK506+MMF recipients.Recipients as long FK506 C₀ decreases,immune cells become normal levels.The monitoring of FK506 C₀,immune cells and CRE,UREA may be further reacted immune status of recipients.It would be helpful for the therapeutic regimens with the monitoring of tacrolimus.3 The immune indexes effects of tacrolimus in kidney patientsThe levels of CD19⁺B cells and CD?16+56?+NK cells were inhibited by FK506 in kidney patients,and the levels of CD3⁺T cells,CD8⁺T cells were increased.The monitoring of FK506 C₀ and peripheral blood CD3⁺ T cells,CD4+ T cells,the ratio of CD4+/CD8⁺,CD19⁺ B cells,CD?16+56?+NK cells and ALB,TBIL may be further reacted immune status of patients.Wuzhi capsules with FK506 can make CD19⁺B cells expressing lower.