The Impact Of Immunosuppression Therapy On PRA Level After Kidney Transplantation Failure

BackgroundKidney transplantation has been achievable since the introducing of immunosuppression and the concepts of immunology and rejection been widely accepted.The short outcome of renal transplantation has been greatly improved based on the employment of CsA with vastly declined rejection rate and prolonged graft survival.Calcineurin inhibitors are the basement of triple immunosuppression after kidney transplantation nowadays.However,on the one hand,new immunosupprants are been studied and tested,on the other hand,the optimal employment of current immunosuppressive drugs attract constant interest.Worldwide standard focusing the use of immunosuppression is still lacking after kidney allograft failure.For the recipients who lost their first kidney allograft, maintenance of immunosuppression may help retainning residual renal function,and avoiding the incidence of allograft nonadherence and the adrenal insufficiency symptoms(AIS),but in the meantime, the risk of diatebets and vascular complications rises,infection and malignancy are easier to occur; on the contrary, immunosuppression withdrawal may lead to fever,hematuria,and kidney allograft nonadherence.In 2002, Jassal found a survival benefit in patients who maintained immunosuppression after allograft failure analysising the United States Renal Data System(USRDS), the mean survival had been prolong from 5.3 years to 5.8 years comparing with patients weaned immunosuppression after gfart failure.In 2010, Pham revealed an increasing rate of Kaposi sarcoma because the drugs used after renal allograft failure in his research. As we can tell in the research above, whether to withdrawal immunosuppression when kidney allograft fails is still controversial. Bayliss made a questionnaire focusing the employment of immusuppression after renal allograft failure among 93 transplant centers in America. Most(75.3%) centers questioned said the decision to stop or continue immunosuppression therapy was made by physician as opposed to prorocol driven(24.7%).Thus, criteria guiding the use of immunosuppression is still lacking after kidney allograft failure.Furthermore, as the need for retransplantation is rising, studies were undertaken focusing on the factors that affect the. PRA level before retransplantation though the outcomes vary. We found that in researchs that approving the impact the nephrectomy had on PRA level, immunosuppression was usually withdrawaled, and in the meanwhile, immunosuppression itself was not considered a significant factor of PRA level. We therefore came up with hypothesis that immunosuppression withdrawal leads to PRA level rising after kidney allograft failure other than nephrectomy.We carried out a retrospective study focusing the contention above trying to(Dexplore the effect of the immunosuppression withdrawal on the PRA level after kidney allograft failure, ②investigate and explore the adequate employment of immunosuppression therapy after kidney allograft failure..Objective1. Analysis the ratio and reason of nephrectomy of a failed kidney.2. Analysis the employment of immunosuppression after kidney allograft failure.3. Investigate the changing of PRA level after kidney allograft failure.4. Factors that affect the level of PRA after kidney allograft failure.Methods1. Subject enrollmentSubjects had a failed kidney transplantation between 2005 and 2014 were enrolled using filing system from three transplant center:Nanfang Hospital,Zhujiang Hospital, 303 Hospital of People s Liberation Army. Exclusion criteria including: ①Delayed graft function(DGF) after kidney transplantation,③AR after transplantation,③graft survival less than 12 months, ④retransplantation, ⑤combined transplantation,⑥ missing data. Fifty eight subjects were enrolled in this study.2. GroupingSubjects were divided into two groups:Group A, immunosuppression was maintained after graft failure (n=25), Group B, either CNI or MMF was withdrawaled (n=33).3. Data collecting3.1 Data before first transplantation:age at first transplant, gender, PRA level before first transplant, history of pregnancy in female subjects, history of dialysis and blood transfusion.3.2 Data after transplant failure:graft survival, nephrectomy, PRA level after transplant failure.4. End pointFor the subjects received retransplantation afterwards, end point was re-evalutation before retransplantation, for those who didn’t, end point was set on the last follow up of this study.5. Statistics5.1 Student T test was used to analyse the overall change of PRA level for the whole cohort and the PRA level, age at first kiney transplant,graft survival between two groups.5.2 X2 test were used to analyse the ratio of gender, pregnancy, nephrectomy of the failed allograft between two groups.5.3 Logistic regression test was used to indicate the risk factor for high sensitization after transplant failure, and the protective factor for non-sensitization status. Software SPSS 19.0 was employed doing statistics above.6. DenifitionConcept of sensitization was based on studies as following, PRA (class I or II)> 60% was defined as high sensitization, PRA (class I and II) 0% was defined as non-sensitization status.①Casey MJ, Wen XR, Kayler LK, et al. Prolonged immunosuppression preserves nonsensitization status after kidney transplant failure.Transplantation 2014,98(3):306-11.②Augustine JJ, Woodside KJ, Padiyar A, et al. Independent of nephrectomy, weaning immunosuppression leads to late sensitization after kidney transplant failure. Transplantation 2012; 94:738-743.P value less than 0.05 was defined as statistically significant.Result1. Thirteen subjects (22%) had undertaken nephrectomy based on the reason of infection (n=4), pain(n=3), hemorrhage(n=3), and others(n=3).2. Subjects enrolled in this research,15(26%) were partiallly weaned off immunosuppression,18(31%) were totally weaned of immuosuppression.3. An overall rise was observed in PRA level after kidney transplant failure.4. Immunosuppression withdrawal but not nephrectomy was an independant risk factor (OR=12.2, p=0.04) for high sensitization after transplant failure by Logistic regression test.5. Continued immuosuppression had a independent influence on the maintenance of nonsensitization status by Logistic regression test, nephrectomy was not relevant.ConclusionImmunosuppression withdrawal but not nephrectomy leads to high sensitization after kidney transplantation failure, nonsensitization status was maintained when immunosuppression was continued after kidney allograft failure.