Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption

Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From March 2007 to December 2016, 58 sensitized living donor kidney transplant candidates were identified and 38 patients eventually included in the study: 36 patients (95%) had pre-transplant and pre-desensitization Luminex-detected donor-specific HLA antibodies (DSA), and 17/36 patients (47%) in addition had a positive crossmatch result. Two patients had no detectable DSA but a positive CDC B-cell crossmatch result. Patients were treated with pre- and post-transplant apheresis and powerful immunosuppression including the anti-CD20 antibody rituximab (N = 36) in combination with thymoglobulin (N = 20) or anti-IL2 receptor antibody (N = 18). The results of the 38 successfully desensitized and transplanted patients were retrospectively compared to the results of 76 matched standard-risk recipients. Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients (P = 0.55 and P = 0.16, respectively). There was a trend toward reduced death-censored graft survival in desensitized patients (P = 0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed (P = 0.43). The incidence of rejection episodes without borderline changes were in desensitized patients with 21% similar to the 18% in standard-risk patients (P = 0.74). Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85 and 81%, respectively, during pre-transplant desensitization (P < 0.001 for both). On day 360 after transplantation, 20 of 36 (56%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent and de novo DSA during year 1; 2 (40%) of whom lost their graft due to AMR. Eleven (31%) patients with persistent DSA but without de novo DSA had an AMR rate of 18% without graft loss while one patient lost her graft without signs of AMR. Our desensitization protocol for pre-sensitized living donor kidney transplant recipients with DSA resulted in good graft outcomes with side effects and rejection rates similar to that of standard-risk recipients. Adequate patient selection prior to transplantation and frequent immunological monitoring thereafter is critical to minimize rejection episodes and subsequent graft loss.

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P1647CHANGES IN CAUSES OF EARLY GRAFT LOSS IN LIVING DONOR KIDNEY TRANSPLANT RECIPIENTS, 1972-2018

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1647 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Kenta Futamura ◽

Goto Norihiko ◽

Hiroki Fukuhara ◽

Takaaki Nawano ◽

Akiko Kanda ◽

...

Keyword(s):

Risk Factors ◽

Kidney Transplantation ◽

Living Donor ◽

Graft Loss ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Donor Kidney ◽

Donor Kidney Transplantation ◽

Living Donor Kidney Transplant ◽

Living Donor Kidney

Abstract Background and Aims In living donor kidney transplantation, the progress of immunosuppressants in recent decades has led to an average graft survival period more than 15 years. However, the rate of graft loss (GL) within 5 years is still about 5%. Since the incidence of early GL is low, clinical evidence of causes and risk factors are limited and it remains unclear whether early GL was predictable before transplantation. Our purposes were to characterize a patient population with GL, to identify risk factors associated with early (<5 years) GL. Method The subjects were 1,779 patients who underwent living donor kidney transplantation at Japanese Red Cross Nagoya Daini hospital and Masuko Memorial Hospital from January 1, 1972 to December 31, 2018 (former group (1972-1999) : 503, latter group (2000-2018) : 1,276). We retrospectively examined patient characteristics, timing and causes of GL in 445 cases with GL by December 31, 2019 (GL cases in former group : 335, GL cases in latter group : 110). Results The 5- and 10-year graft survival rates were on an increasing trend, with 74.7% and 58.3% in former group and 95.2% and 88.7% in latter group, respectively. In latter group, T cell-mediated rejection and recurrence of primary diseases were significantly more frequent in GL cases within 5 years after transplantation than over 5 years (10% vs 0%, p=0.02 and 6% vs 0%, p=0.04). Although not significant, GL due to antibody-mediated rejection tended to more frequent in over 5 years after transplantation (22% vs 45%). Compared the causes of GL within 5 years after transplantation between GL cases in former group and latter group, rate of allograft rejection significantly reduced (88％ vs 44%, p<0.001), and infections (especially BK polyomavirus infection), medication nonadherence and recurrence of primary diseases tended to increase (0%, 4% and 3% vs 8%, 16% and 8%, respectively). Conclusion Our analysis suggests that management of infections, medication nonadherence and recurrence of primary diseases have become more important for living donor kidney transplant recipients in recent years with improved immunosuppressants.

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