| Kidney transplantation is an ideal supplementary therapy for patients with end stage renal disease.The early six-month renal acute rejection(AR) rate has been reduced from43.5%in the1990s to13.5%of the early new century for the advances in transplant immunology and pharmacotherapy. However,AR may lead to graft loss either immediately or chronic allograft nephropathy,which continues to be a Significant problem after transplantation.Intensity of acute rejection and effect of treatment have direct impact on the long-term outcome of the graft.The half-life of graft in recipients experienced posttransplantation acute rejection is only increased1.8years,as compared with5.9years for those without AR.Acute rejection,the most important complication following renal transplantation,has been widely studied.In current clinical practice,conventional rejection diagnosis,such as serum creatinine measurement,clinical manifestations,lab assessment,and imaging examination,can’t recognize rejection at an early stage.It may also delay treatment because of lacking specificity and sensitivity.Moreover,typical clinical manifestations of acute rejection,such as pain of renal region,oliguria,hematuria, fever,hypertension have changed with modern immunosuppression.Besides,the concentration of serum creatinine will not increase as soon as allograft immunity is activated.It was reported that the concentration of serum creatinine doesn’t determine the intensity of acute rejection.30%of patients with stable renal function may suffer subclinical rejection,with no creatinine level increase.Ultrasonic examination by Doppler’s method is a conventional posttransplantation monitoring tool.Despite the resistant index(R1) can reflect a blood decrease during relaxing period in most cases,it is not specific enough for the diagnosis of AR.Needle biopsy,the gold standard in diagnosis,is limited by biopsy-associated complications,such as sampling errors, hematuria, bleeding, arteriovenous fistulas, and even graft loss can occur.And it needs experieneed pathologists and multitude samples to make accurate diagnosis.The development of noninvasive techniques community with high specificity and sensitivity for the early detection of acute rejection would be desirable in the transplantation.Posttransplantation monitoring of neopterin and other immunologic mediators,such as soluble interleukin2receptor and soluble tumor necrosis factor receptor,are limited intheir use because urinary retention or dialysis significantly affects serum levels of these proteins. CD30,a large transmembrane glycoprotein,was identified on the surface of T cells.After activation of CD30+T cells,a soluble form of CD30(sCD30) is released into the bloodstream.The concentration of sCD30in blood serum is significantly related with CD30level.It is reported that sCD30measurement before transplantation could be used for the prediction of kidney graft outcome except panel reactive antibodies(PRA).The new teehnique is especially effective in patients without PRA.The aim of the present study was to determine whether monitoring of sCD30during the early posttransplantation period can be used to differentiate patients with an acute allograft rejection and evaluate the therapeutic effect of AR.The following4parts have studied relationship between serum sCD30level and acute rejection,long term survival,chronic rejection,and also sCD30with immunosuppressants.Part1Evaluation of pre-and posttransplant soluble CD30for predicting acute renal allograft rejectionObjective To evaluate the relationship between the level of pre2and posttransplant soluble CD30(sCD30) and the occurrence of acute renal allograft rejection.Methods The level of pre-and posttransplant sCD30in the serum from69 recipients (PRA<10%) was detected by enzyme-linked immune sorbnent assay (ELISA).Results In group of positive sCD30(n=11),acute rejection occurred in6patients. In group of negative sCD30(n=58),acute rejection occurred only in5patients. There was a significant difference between two groups (P<0.01). On the day5after transplantation, there was significant difference in sCD30between acute allograft rejection group and control group (P<0.05).Conclusion The level of pre2and posttransplant sCD30,especially detected pretransplant and on the posttransplant day5,is of important value for predicting acute renal allograft rejection.Part2Relationship between posttransplant soluble CD30and chronic renal allograft rejectionObjective To study the relationship between sCD30and chronic rejectionMethods All recipients were from the first affiliated Hospital of Nanjing Medical University,and the renal transplant operation had been passed over three years,according to Banff pathology diagnostic standards,72recipients were chronic rejection group(CR),and212recipients who had normal allografts function were Selected into the control group.The blood samples of chronic group were collected while the allografts were biopsied,and the blood samples of the control group were taken randomly when the recipients came to check at our outpatient.Firstly,we detected sCD30by the means of ELISA,then retrospectively analyzed the difference of sCD30levels between the CR group and the control group.The statistical method was "t" test between two separate samples,The difference was significant when P<0.05.Results There was significant difference in sCD30levels between the CR group and the control group,the CR group sCD30was (192.14±17.63)U/ml,the control group sCD30was (67.45±18.12)U/ml,the statistic values were(t=34.982,P=0.000). According to ROC curve analyse,serum sCD30critical point of statistical Value is135.50U/ml.Conclusions Abnormal elevated postoperation serum sCD30is associated with chronic rejection,it is helpful for us to determine and predict the chronic rejection that is happening.And our investigation may provide clinical data about sCD30critical point.Part3Influence of pre-transplant serum leve1of soluble CD30on the long-term survival rates of kidney transplant recipients and graftsObjective To investigate the influence of pre-transplant sCD30level on the long-term survival rates of kidney transplant recipients and grafts among Chinese.Methods A retrospective cohort of202patients undergoing cadaver renal transplants between Jan.2003and Aug2006,145males and57females, aged43±11, with their blood samples preserved was studied. The plasma levels of sCD30were determined by ELISA.Results The5-year graft survival/functional rates of the high sCD30group were78.7%±3.5%/84.9%±3.2%, significantly lower than those o f the low and intermediate groups,84.7%±2.1%/98.4%±1.1%and87.1%±2.9%/94.4%±1.6%respectively (a11P<0.05). The5-year recipient survival rate of the intermediate sCD30group was92.5%±1.6%, higher than those of the low and high sCD30 groups,84.8%±3.9%and87.2%±2.7%respectively with a significant differencebetween the intermediate and high sCD30groups (P=0.032).Conclusions Pre-transplant serum level of sCD30reflects the immune status. Recipients with high sCD30are prone to rejection while those with low sCD30are prone to infections.Part4Association of sCD30Levels With Immunosuppressive Therapies After Renal TransplantationObjective To analyze the relationship between sCD30levels and immunosuppressive therapies after renal transplantation and find out its clinical application.Methods We retrospectively investigated112patients who underwent allograft kidney transplants between April2007and December2010.Pre and post-transplant serum samples were tested for sCD30content using an enzyme-linked immunosorbent assay(ELISA). The recipients were divided into Cyclosporine A(CsA) and Tacrolimus(FK506) group according to their immunosuppressive regimens. Relevant clinical date including serum creatinine and drug concentration was collected for statistical analysis.Results We could demonstrate there exists a significant association in statistic between sCD30level and the age as compared to the other characteristics(P=0.038).There is no difference in pre and post-transpant sCD30levels between CsA and FK506groups. Also,serum creatinine level of two groups has no difference after long terms of immunosuppressive therapies(month3,6,24)(P>0.05) except the first month(P=0.019). There is significant correlation between pretransplant sCD30levels and serum creatinine levels at post-transplant the24th month in the linear regression analysis(CsA group:P<0.001;FK506group:P=0.010). sCD30level decreased and had shown statistical significance since the7th day after surgery(P<0.05). The correlation between serum drug concentration and sCD30level is significant.Conclusion Both immunosuppressive regimens can reduce post-transplant sCD30level and they have no difference in their impact on renal function.But, pre-transplant sCD30level may affects renal function and serum drug concentration of CsA/FK506.
|
PDF Full Text Request