| PART I Prognostic analysis of ABO-incompatible living kidney transplantation: a retrospective cohort study Background and objectiveABO-incompatible living kidney transplantation(ABO-ILKT)has undergone decades of development.At present,the overall prognosis is comparable to that of ABO-compatible living kidney transplantation(ABO-CLKT),which is widely carried out in various countries.However,due to the different perioperative treatment regimes and regional populations,the prognosis of the centers varies.We conduct this study to better understand the prognosis of ABO-ILKT of domestic population and explore whether C4 d deposition is a risk factor for its prognosis.MethodsThis study conducted prognostic follow-up of patients undergoing living donor kidney transplantation at our center between March 2017 and March 2019.The follow-up endpoint was February 28,2020.A total of 39 patients with ABO-ILKT and 340 patients with ABO-CLKT were included.ABO-ILKT was divided into C4 d +(n = 22)and C4d-(n = 9)subgroups based on whether C4 d was deposited in the 1-year transplantation biopsy.And we compared human and graft survival rate,rejection,BK-associated nephropathy(BKAN),and 17 follow-up laboratory indicators between groups.ResultsABO-ILKT patients have benefited from lowered blood cholesterol,but their graft function,anti-infective ability,hemoglobin and coagulation function are worse than ABO-CLKT patients.The incidence of rejection at 1 year after surgery in ABO-ILKT patients,including antibody mediated rejection(AMR)(p = 0.009),T cell mediated rejection(TCMR)(p = 0.004),and the incidence of borderline change(p <0.001)were higher than those in ABO-CLKT patients.Graft loss of ABO-ILKT patients was also significantly higher than that of ABO-CLKT patients(p= 0.001),but there was no statistical difference in 1-year survival rate between the two groups.C4d deposition in patients with ABO-ILKT has no clear association with clinical prognosis including BKAN,acute rejection,graft survival,and patient survival rate.However,the positive rate of urinary protein in the C4 d + group after 1 year was significantly higher than that in the C4d-group(p = 0.008).ConclusionABO-ILKT is worse in clinical prognosis than ABO-CLKT patients,but the overall prognosis is well.C4 d deposition is not a risk factor for the prognosis of ABO-ILKT.PART II Exploration of predictors of antibody-mediated rejection after ABO-incompatible living kidney transplantationBackground and objective AMR is one of the most common complications after ABO-ILKT,which can affect renal function and human survival rate.However,the diagnosis relies on the renal graft biopsy,which is an invasive procedure,and the noninvasive measurement of peripheral blood for early AMR prediction and diagnosis has a good prospect.The purpose of this study is to determine the diagnostic value of 17 cytokines associated with kidney injury in the AMR of ABO-ILKT patients,and to further understand the intrinsic relationship between C4 d deposition and the development of AMR.Methods This study included patients who did not develop AMR after ABO-ILKT in our center from March 2017 to March 2019(graft biopsy C4 d + 19 cases,C4d-9 cases),and patients with AMR(n = 18)as well as patients with a good prognosis(n = 10)after ABO-CLKT conducted from 2010 to 2019.The levels of 17 cytokines including CCL2 and TNF-alpha in peripheral blood obtained at the admission of renal graft biopsy were measured and compared between groups.Results There was no significant difference between the C4 d + and C4d-group in ABO-ILKT patients;the CCL2 level of the ABOi-C4 d + non AMR group was significantly higher than that of the ABO compatible(ABOc)-AMR group(p = 0.0074);the TNF-alpha level of the ABOi-C4 d + non AMR group was significant higher than the control group(p = 0.0009);TNF-alpha(p = 0.0016)and CXCL10(p = 0.0311)levels in the ABOc-AMR group were significantly higher than those in the control group;TNF-alpha levels in the ABOi-C4d-non AMR group were significantly higher than control group(p = 0.0110).Conclusion TNF-alpha has certain diagnostic utility for AMR in ABO-CLKT patients.Patients who did not have AMR after ABO-ILKT had massive chemokines in their bodies,but the extent of damage was limited downstream.PART III Evaluation of immune status in patients with ABO-incompatible living kidney transplantationBackground and objective AMR is a major risk factor for prognosis after kidney transplantation.However,effective non-invasive diagnostic methods are currently lacking.In this study,the immune status of patients with ABO-ILKT after surgery was identified by establishing an immune repertoire of B cell antigen receptor(BCR)in order to achieve the early prevention and diagnosis of AMR.Methods This study included patients who had not undergone AMR after ABO-ILKT surgery conducted in our center from March 2017 to March 2019(graft biopsy C4 d + 17 cases,C4d-9 cases),and 10 patients with biopsy-proved AMR who underwent ABO-CLKT from 2010-2019.We conducted high-throughput BCR sequencing of peripheral blood mononuclear cells obtained at the admission of renal graft biopsy.Results The clonal abundance of ABOi-C4d-patients was significantly lower than the other two groups.The similarity of clone diversity between ABOc-AMR group and ABOi-C4d-group was 93.2%.Compared with the ABOi-C4 d + non AMR group,the most significantly expanded specific IGHV genes of the ABOc-AMR group were: IGHV3-43,IGHV4-4,IGHV1-46,IGHV1-2,IGHV3-53;Compared with the ABOi-C4d-group,the most significantly expanded specific IGHV genes of the ABOi-C4d+non AMR group were IGHV1-24,IGHV3-48,IGHV2-26,IGHV3-20,and IGHV3.66.Conclusion BCR sequencing can reflect the immune status of patients after ABO-ILKT by clone diversity,clone expansion and specific clone expression. |
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