A Retrospective Clinical Study Of A Novel Protocol For Presensitized Kidney Transplantation

Objective : With the improvement of kidney transplantation technology and immunosuppressants,more and more uremic patients choose kidney transplantation to improve their quality of life.However,some of the patients in waiting list developed anti-human leukocyte antigen(HLA)antibodies due to previous transplantation,blood transfusion and pregnancy.The HLA pre-sensitization not only reduces the success rate of donor-recipient HLA-matching,but also increases the risk of acute rejection after transplantation.At present,there is no very effective desensitization method in the world.The purpose of this study is to explore a safe and effective treatment to deal with preexisting anti-HLA donor-specific antibody(DSA),in order to shorten the waiting time of these patients and improve their success rate of kidney transplantation.Methods: From January 1,2012 to December 31,2019,22 pre-sensitized patients(PRA positive)were divided into DSA negative group(n=11)and DSA positive group(n=11)according to the presence of DSA.Flow test of complement-dependent-cytotoxicity(CDC)to donor lymphocytes was performed in the 22 patients before transplantation,and the results were all negative.In the DSA negative group,on the basis of the routine methods reported in the literature [induction therapy with anti-CD20 monoclonal antibody and rabbit anti-human thymus immunoglobulin(r ATG)],intravenous immunoglobulin(IVIG)was used daily within 2 weeks after operation.In the DSA positive group,on the basis of the above regimen,the necessary plasma exchange was added before operation according to the individual condition.In this study,we retrospectively compared and analyzed the results of renal transplantation between the two groups,including the recovery of early postoperative renal function,the changes of postoperative DSA and the incidence of acute rejection,the survival rate of renal allografts and the transplant recipients.Results: There was no primary non-function(PNF)or delayed graft function(DGF)in DSA negative group,and DGF was found in 1 case in DSA positive group(9.1%,p >0.05).T cell mediated rejection(TCMR)occurred in 6 cases(54.5%)in DSA negative group,and the median time was 15 days after operation(12 ~ 18 d),).In the DSA positive group,7 cases(63.6%)had 9 episodes of acute rejection,including 5 cases of TCMR only(45.4%,p>0.05)and 4 cases of AAMR(36.4%,p<0.05).The median time of TCMR was 13.5 days(12-18 days),and the median time of AAMR was 11 days(9-45 days).Among the 4 cases of AAMR,3 cases recovered after plasmapheresis / IVIG treatment for 4 times(3-5 times),and 1 case recovered after 10 times of low-dose splenic irradiation in addition to multiple plasmapheresis / IVIG.Within one month after transplantation,one patient in DSA positive group developed de novo DSA(9.1%),while none of the patients in DSA negative group had de novo DSA.The median follow-up tine of the recipients in the two groups was 27 months and 51 months,respectively,and the survival rates of renal allografts and recipients were both 100%.Conclusion: The incidence of early posttransplant acute cellular rejection in pre-sensitized recipients was high,which could be reversed by timely treatment.The incidence of AAMR in preexisting DSA positive recipients was significantly higher than that in DSA negative recipients,but could be reversed by a treatment regimen consisting plasma exchange combined with IVIG and adjuvant splenic irradiation.After the novel treatment regimen including 2 weeks of IVIG and strict monitoring after transplantation,the preexisting DSA positive recipients can obtain satisfactory intermediate-term outcome of renal transplantation,and the long-term results need further follow-up observation.