A2/A2B to B kidney transplantation outcomes: A single center 7-year experience.

INTRODUCTION: Data on long-term outcomes following A2/A2B to B kidney transplants since the 2014 kidney allocation system (KAS) changes are few. The primary aim of this study is to report our 7-year experience with A2/A2B to B kidney transplants and to compare post-transplant outcomes of A2/A2B to a concurrent group of B to B kidney transplants. Additionally, the study evaluates the impact of pre-transplant anti-A1 titers on survival outcomes in A2/A2B transplants. METHODS: This retrospective, single-center analysis included all adults who received A2/A2B to B deceased donor kidney transplants from December 2014 to June 2021 compared to B to B recipients. The effects of pre-transplant IgM/IgG titers, stratified as ≤1:8 and ≥1:16, on death-censored, rejection-free, and overall graft survival were tested. RESULTS: Fifty-three A2/A2B and 114 B to B adults were included with a median follow-up time of 32 months. Overall graft survival, patient survival, and rejection-free graft survival did not differ between the two groups. There were no differences between the groups' overall kidney function values (p > .80) or their temporal trajectories (time by group interaction p > .11). Unadjusted death-censored graft survival was lower in A2/A2B to B compared to B recipients (p = .03), but the effect was not significant (p = .195) after adjusting for any readmissions (p = .96), rejection episodes (p < .001) or BK infection (p = .76). We did not detect an effect of pre-transplant titer group on death-censored (p = .59), rejection-free (p = .61), or overall graft survival (p = .26) CONCLUSIONS: A2/A2B to B kidney transplants have comparable overall patient and graft survival, rejection-free graft survival, and longitudinal renal function compared to B to B transplants at our center. Allograft survival outcomes were not significantly different between patients with low and high pre-transplant anti-A1 IgM/IgG titers.

Accommodation in ABO-incompatible organ transplants.

Accommodation refers to a condition in which a transplant (or any tissue) appears to resist immune-mediated injury and loss of function. Accommodation was discovered and has been explored most thoroughly in ABO-incompatible kidney transplantation. In this setting, kidney transplants bearing blood group A or B antigens often are found to function normally in recipients who lack and hence produce antibodies directed against the corresponding antigens. Whether accommodation is owed to changes in anti-blood group antibodies, changes in antigen or a change in the response of the transplant to antibody binding are critically reviewed and a new working model that allows for the kinetics of development of accommodation is put forth. Regardless of how accommodation develops, observations on the fate of ABO-incompatible transplants offer lessons applicable more broadly in transplantation and in other fields.

Pilot conversion trial from mycophenolic acid to everolimus in ABO-incompatible kidney-transplant recipients with BK viruria and/or viremia.

Immunosuppression using everolimus (EVR) plus low-dose tacrolimus (Tac) is commonly used in organ transplantation. EVR has potential antiviral effects. Herein, the long-term outcomes and impacts of Tac-EVR on the BK virus are reported in ABO-incompatible kidney-transplant recipients. The initial immunosuppressive regimen combined steroids, Tac, and mycophenolic acid (MPA). At a median of 141 (34-529) days post-transplantation, seven stable ABO-incompatible kidney-transplant recipients were converted from MPA to EVR because of active BK replication, and compared with a reference group of fourteen ABO-incompatible patients receiving classical Tac plus MPA. At 1 month before conversion, at 1, 3 months after, and at last follow-up, clinical and biological parameters were monitored. The median time from conversion to the last follow-up was 784 (398-866) days. Conversion to EVR caused no change to rejection episodes or immunological status (isoagglutinin titers, anti-HLA antibodies). At last follow-up, median eGFR was similar in the Tac-MPA versus Tac-EVR group (40 [range: 14-56] vs. 54.5 ml/min/1.73 m(2) [range: 0-128], P = 0.07). The major adverse event was dyslipidemia. Interestingly, conversion from MPA to EVR decreased BK viral load in five patients. ABO-incompatible kidney-transplant recipients with an active BK virus infection may benefit from conversion to EVR.

Transfusion Support for ABO-Incompatible Progenitor Cell Transplantation.

ABO-incompatible transplants comprise up to 50% of allogeneic progenitor cell transplants. Major, minor and bidirectional ABO-incompatible transplants each have unique complications that can occur, including hemolysis at the time of progenitor cell infusion, hemolysis during donor engraftment, passenger lymphocyte syndrome, delayed red blood cell engraftment, and pure red cell aplasia. Appropriate transfusion support during the different phases of the allogeneic progenitor cell transplant process is an important part of ABO-incompatible transplantation.

Unconventional Strategies for Solid Organ Transplantation and Special Transplantation Scenarios.

Solid organ transplantation is the only long-term therapeutic option for patients with end-organ failure but cadaveric and living donor transplant pools are unable to meet the demand for organ transplantation. Newer techniques, innovative strategies and altruistic donors can help bridge this wide gap between the number of organ donors and recipients. Domino liver transplantation, paired organ donation, and ABO incompatible transplants are some of the ways to ensure increased transplant organ availability. Split liver transplantation and ex vivo liver resection and auto transplantation are considered surgically challenging but are being done at tertiary transplant centers.

Accommodation in allogeneic and xenogeneic organ transplantation: Prevalence, impact, and implications for monitoring and for therapeutics.

Accommodation refers to acquired resistance of organs or tissues to immune or inflammatory reactions that might otherwise cause severe injury or rejection. As first observed in ABO-incompatible kidney transplants and heterotopic cardiac xenografts, accommodation was identified when organ transplants continued to function despite the presence of anti-graft antibodies and/or other reactants in the blood of recipients. Recent evidence suggests many and perhaps most organ transplants have accommodation, as most recipients mount B cell responses specific for the graft. Wide interest in the impact of graft-specific antibodies on the outcomes of transplants prompts questions about which mechanisms confer protection against such antibodies, how accommodation might be detected and whether and how rejection could be superimposed on accommodation. Xenotransplantation offers a unique opportunity to address these questions because immune responses to xenografts are easily detected and the pathogenic impact of immune responses is so severe. Xenotransplantation also provides a compelling need to apply these and other insights to decrease the intensity and toxicity of immunosuppression that otherwise could limit clinical application.

Immunoadsorption Column Reuse.

INTRODUCTION: Selective immunoadsorption (IA) is a technique to remove preformed Anti-ABO antibodies in ABO-incompatible renal transplants (ABOiRT). Since the cost of a single IA column is high and single use rarely achieves the target anti-ABO titers, its use is not widely spread. We studied the safety and efficacy of the reuse of IA columns in ABOiRT. METHODS: Single-center, retrospective analysis of all patients who underwent ABOiRT with IA column reuse from January 2016 to July 2018. The column was reused after sterilization with ethylene oxide and flushed with normal saline before use. Target titers (IgG) were 1:4 preoperatively. Baseline IgG titers, plasma volume processed in each session, postoperative titer rebound were recorded. The primary outcome was IgG titer reduction after each use and adverse reaction during the IA column reuse. Patients were followed up until 1 year. RESULTS: 16 patients underwent ABOiRT using IA columns. Baseline IgG titer ranged from 1:32 to 1:512. Reuse of IA column was done 23 times and underwent 2nd reuse for 9 times. The average plasma volume treated was 22 L. Efficacy of the IA column in log titer reduction of anti-ABO titer was 4 logs after the first use, 3 logs after 1st reuse, and 1.5 logs after 2nd reuse. 12 (75%) patients successfully reached the target IgG titer of ≤1:4 solely with column reuse. One patient received a single session of plasma exchange before transplantation. Postoperatively, one patient received one session of plasma exchange due to a rebound in anti-ABO antibodies. No serious side effects were noted during the reuse. CONCLUSION: IA column reuse up to two times showed efficacy in the successful reduction of antibody titers. Column reuse was not associated with any significant side effects.

Challenges in living donor liver transplantation.

Living donor liver transplantation is a procedure that has waned in its application over the past decade but remains a beneficial procedure for properly selected candidates. This review discusses some of the newer, relevant studies in the field, focusing on outcomes with hepatocellular carcinoma, ABO-incompatible transplant, and issues in donor complications and safety.

Cascade plasmapheresis (CP) as a preconditioning regime in ABO-incompatible live related donor liver transplants (ABOi-LDLT).

BACKGROUND: ABO-incompatible live donor liver transplant (ABOi-LDLT) is being widely done to bridge the gap of demand and supply of organs. Different desensitization regimes are being used to reduce titer of blood group antibodies for successful transplant and accommodation of graft. The authors used cascade plasmapheresis (CP) to bring down titer of naturally occurring blood group antibody to 16 or lower. MATERIAL AND METHODS: Four recipients of ABOi-LDLT were of blood groups O, O, B, and B while donors were of blood groups B, A, AB, and AB, respectively. Desensitization protocol included immunosuppressive drugs and plasmapheresis. CP consisted of separating patient's plasma as the first step and passing it through pore size based filter column as the second step. The first step was performed using disposable kit (PL1, Fresenius Kabi, Germany) with minor modification on apheresis equipment COM.TEC (Fresenius Kabi, Germany). Pore size based filter column used was 2A column (Evaflux, Kawasumi Laboratories, Japan). Blood group antibody titer (immunoglobulin G (IgG)) was done by column agglutination technology (Ortho-Clinical Diagnostics). RESULTS: Cases 1, 2, 3, and 4 with pre-CP titer of 1,024, 512, 32, and 64 required four, three, one, and one CP procedures, respectively. No signs of antibody-mediated rejection were exhibited on histopathological evaluation by any of the patients. Successful organ engraftment occurred as documented by post-operative liver function tests and liver biopsy. CONCLUSION: Cascade plasmapheresis offers a cost-effective and efficient way to decrease blood group antibody titer and helps in successful transplant.