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Variation Of SCD30 Levels Of Renal Graft Recipients In Early Period Post-transplant And Its Application As A Predictor Of Acute Renal Allograft Rejection

Posted on:2008-07-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:D WangFull Text:PDF
GTID:1114360242455217Subject:Surgery
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Objective:①New immunosuppressive agents and regimens have achieved lower rates of acute renal rejection, however, acute rejection episode (ARE) is still a leading cause of early graft dysfunction and late renal graft loss. To prevent irreversible graft damage, it is important to diagnose and treat ARE in its earliest phase. Needle biopsy of graft, the most reliable method for the diagnosis of acute rejection in current clinical practice, is an invasive technique and cannot be performed daily. The recognition of ARE at an early stage continues to pose a problem. CD30 is a member of the tumor necrosis factor receptor (TNFR) superfamily. After activation of CD30+ cells, a soluble form of CD30 (sCD30) is released proteolytically. Recently, several reports have suggested that elevated pre- and post-transplantation levels of sCD30 molecule might be predictive for an increased incidence of ARE and worse renal graft prognosis. In our study, sCD30 levels were measured in 231 renal graft recipients before transplantation, and variation of sCD30 levels was monitored in another 70 renal graft recipients post-transplant. Variation characteristic of sCD30 levels was analyzed and the feasibility of serum sCD30 levels as predictor of ARE in early period post-transplant was also investigated.Methods:①Two hundred and thirty-one patients were included into the study, whose blood samples were obtained on day 0 before transplantation and day 5 and 10 after transplantation. Then blood samples were centrifuged within 2 hours and plasma was separated from cells. Human sCD30 instant ELISA kits were used to measure serum levels of sCD30. Samples were also obtained from 49 age-matched healthy individuals as normal control. After one month follow-up, they were divided into three groups according to the clinical course of one month post-transplant: Group AR (n=49), Group DGF (n=11) and Group UC (n=171).②Blood samples of another 70 patients were obtained on day 0 before transplantation and on day 1, 3, 5, 7, 10, 14, 21, and 30 after transplantation. Then blood samples were centrifuged within 2 hours and plasma was separated from cells. Human sCD30 instant ELISA kits were used to measure serum levels of sCD30. Samples of 49 age-matched healthy individuals mentioned above were used as normal control. Those patients were followed up for six months and then were divided into Group AR (n=11) and Group UC (n=59) according to their clinical course.Results:①Significant decrease of sCD30 was detected on 5 and 10 day post-transplantation respectively (178±79 U/ml before transplantation vs. 52±30 U/ml 5 day vs. 9±5U/ml 10 day post-transplantation, P <0.001). Compared with Group UC and DGF, patients of Group AR had higher sCD30 values on 5 day post-transplantation (92±27 U/ml vs. 41±20 U/ml and 48±18 U/ml, P<0.001). However, sCD30 levels were virtually similar in three groups before transplantation and on 10 day post-transplantation (P>0.05). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on 5 day post-transplantation could differentiate patients who subsequently suffered ARE from others (area under ROC curve 0.95). According to ROC curve, 65 U/ml may be the optimal operational cut-off level to predict impending ARE (specificity 91.8%, sensitivity 87.1%).②70 patients showed significantly higher sCD30 levels than healthy people (147±77U/ml vs. 41±13U/ml,P<0.001). A significant decrease of sCD30 was observed on the first day and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC (P <0.001). Patients of Group AR also had higher sCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 (P <0.001). The sCD30 levels presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value.Conclution:①Renal graft recipients have higher sCD30 levels than heathy people. Measurement of soluble CD30 on 5 day post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.②Soluble CD30 level may be a good marker of increased alloreactivity and of significant predictive value. Monitoring of variation of sCD30 may be helpful for evaluating the risk of impending AR episodes in early period post-transplant.
Keywords/Search Tags:Soluble CD30, Acute rejection, Sensitivity, Specificity, Kidney transplantation, ELISA
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