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Objective:To explore the value of detecting plasma donor-derived free DNA (dd-cfDNA) fraction in distinguishing antibody mediated-rejection (ABMR) and T cell-mediated rejection (TCMR) of renal allografts.Methods:Patients with acute rejection confirmed by allograft biopsy in the First Affiliated Hospital of Medical College of Zhejiang University from December 1, 2017 to July 18, 2019 were retrospectively included. Based on pathological classification of Banff renal allograft rejection in 2017, the patients were divided into ABMR group and TCMR group, and the latter was subdivided into TCMR Ⅰ subgroup and TCMR Ⅱ subgroup. The second generation sequencing and target region capture were used to detect candidates' peripheral blood dd-cfDNA. The demographic and clinicopathological data of the two groups were compared. The receiver operating characteristic curve (ROC) was used to evaluate the differential value of plasma dd-cfDNA and serum creatinine levels in two kinds of acute renal allograft rejection.Results:A total of 60 patients with acute rejection of renal transplantation were enrolled in this study, including 42 patients in TCMR group and 18 patients in ABMR group. The plasma dd-cfDNA percentage (%) in the ABMR group was significantly higher than that in the TCMR group [2.33(1.19, 4.30)% vs 0.98(0.50, 1.82)%, P=0.001]. The absolute value of dd-cfDNA in ABMR group was obviously higher than that in TCMR group [0.94(0.60, 2.27) ng/ml vs 0.43(0.20, 0.96) ng/ml, P=0.003]. ROC analysis to discriminate TCMR from ABMR showed that, the area under the curve ( AUC) of dd-cfDNA% was 0.76(95% CI 0.64-0.88), when the threshold was 1.11%, the sensitivity and specificity were 88.89% and 59.52%, respectively; the AUC of absolute value of dd-cfDNA was 0.74(95% CI 0.61-0.86), when the threshold was 0.53 ng/ml, the sensitivity was 88.89% and the specificity was 54.76%. TCMR subgroups were further analyzed, there was no significant difference between TCMR subgroups on the absolute value and percentage of dd-cfDNA (both P>0.05); dd-cfDNA% in ABMR group was apparently higher than that in TCMRⅠ subgroups ( P=0.008) and TCMRⅡsubgroup ( P=0.030). The absolute value of dd-cfDNA in ABMR group was significantly higher than that in TCMRⅠsubgroups ( P=0.003). Conclusion:Plasma dd-cfDNA level may help to distinguish between ABMR and TCMR rejection.
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BK polyomavirus-associated nephropathy (BKPyVAN) is a common cause of allograft failure. However, differentiation between BKPyVAN and type I T cell-mediated rejection (TCMR) is challenging when simian virus 40 (SV40) staining is negative, because of the similarities in histopathology. This study investigated whether donor-derived cell-free DNA (ddcfDNA) can be used to differentiate BKPyVAN. Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function, 22 with type I TCMR, 21 with proven BKPyVAN, and 5 with possible PyVAN. We found that urinary ddcfDNA levels were upregulated in recipients with graft injury, whereas plasma ddcfDNA levels were comparable for all groups. The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients (10.4 vs. 6.1 ng/mL,
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Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.
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Objective To compare the clinical outcomes of low-dose rabbit antithymocyte globulin (rATG ) vs basiliximab as induction therapy in recipients of ABO-incompatible kidney transplantation (ABOi-KT) .Methods Retrospective analysis was conducted for e the clinical data of 40 ABOi-KT recipients between March 2017 and March 2019 .17 recipients of them received induction therapy with basiliximab (basiliximab group) while another 23 recipients received low-dose rATG (rATG group ,rATG 25 mg/d × 3 d) .During a median follow-up period of 282 days , the data of serum creatinine and eGFR at 1 week and 1 month ,graft survival rate and complication rate of two groups were compared .Results No significant difference existed in age ,gender ,dialytic modality/ duration , blood groups of recipients , HLA mis-match , blood group antibody titers , dose of rituximab ,blood groups of donors or donor age ( P > 0 .05 ) . The times of double filtration plasmapheresis in Basiliximab group were more (P< 0 .05) .No significant difference existed in serum creatinine and eGFR at 1 week or 1 month ( P > 0 .05 ) . No significant difference existed in graft survival rate . No significant difference existed in rate of acute rejection ,parvovirus B19 infection , urinary tract infection or hematoma .Conclusions Low-dose of rATG is as effective as basiliximab for ABOi-KT recipients .And rATG does not increase the rate of infection .
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Objective To investigate the clinical efficacy and safety of double filtration plasmapheresis (DFPP) pretreatment combined with CD25 monoclonal antibody inducible therapy for sensitized recipients of cadaver kidney transplantation.Method The clinical data of 45 sensitized recipients who received the pretreatment with DFPP and CD25 monoclonal antibody from November 2011 to January 2012 were retrospectively analyzed.Panel reactive antibody (PRA) was examined by using ELISA.Before the DFPP combined with CD25 monoclonal antibody,the PRA was (56.5 ± 19.9) ％ (＞ 20％),and after the pretreatment,the PRA level was decreased to (18.9 ± 19.1)％.HLA mismatch of recipients and donators was (2.1 ± 0.7),and the lymphocytotoxic crossmatch tests before operation were negative.The incidence of patient/kidney survival,transplantation rejection and pulmonary infection were observed.All the patients were followed up for 12 months.Result During the follow-up period,no patient died,and transplanted kidney dysfunction occurred in 2/45 recipients.Twelve months after months,the survival rate was 100％ and transplanted kidney survival rate was 95.6％ (43/45).One (2.2％) of 45 recipients had hyperacute rejection during the operation,and was given plasmapheresis after the resection of the transplanted kidney.Twelve (26.7％) of 45 recipients had acute rejection:11 recipients completely recovered after methylprednisolone and ATG therapy,and 1 recipient given plasmapheresis for kidney dysfunction.Four (8.9％) had the pulmonary infection after operation,and all of them recovered after antiinflammation treatment.Conclusion DFPP pretreatment before kidney transplantation combined with CD25 monoclonal antibody inducible therapy is safe and effective,specially for sensitized recipients.