ABO-incompatible Renal Transplantation Research Articles

#2917 Desensitization techniques in ABO-incompatible renal transplantation: efficacy and analysis of complications

Abstract Background and Aims Living donor transplantation is the best optimal choice for the vast majority of patients with terminal renal insufficiency. However, it is limited by the AB0/ HLA incompatibility between donor and receptor. The resolution of this inconvenient relies on desensitization of isoagglutinins (anti-AB0 immunoglobulins depletion); thus transplantation could be performed safely. For desensitization there are two techniques: specific adsorption (S) and non-specific (NS) techniques, including centrifugal therapeutic plasma exchange (cTPE) and membrane-based therapeutic plasma exchange (mTPE). The aims are to evaluate the efficacy of apheresis techniques: specific versus non-specific, and identify their complications. Secondary objectives include analyzing the acute rejection rate (RR), graft survival, and complications of each technique. Method A retrospective cohort study was conducted on AB0-incompatible living donor transplantation patients at our center (Bellvitge's Hospital) from 2014 to 2022. All patients (except 1) received rituximab and induction treatment by Thymoglobulin or Basiliximab, followed by maintenance treatment (Steroids, Mycophenolate, and calcineurin inhibitors). During follow-up, protocol renal biopsies (RB) were taken at one month and between 3-6 months post-transplantation. Complications were defined as significant haematological alterations, bleeding, or major infections requiring hospitalization. According to the technique used, two cohorts were identified: specific (Glycosorb®/Vitrosorb® columns) and non-specific: mTPE (prismaflex TPE2000) and cTPE (Spectra/Optia®). Both were anticoagulated with heparin or citrate randomly. An expert nurse supervised the technique. To calculate the efficacy we considered the percentual reduction of isoagglutinins in the first session. T-student test was used to calculate the percentage of complication and compare the results. Results A total of 50 patients were selected with a mean age (MA) of 49.5 ± 11.8. Four of these did not require apheresis due to lower title isoagglutinins (<1/8). Each cohort included 23 patients: specific with MA 49.5 vs non-specific 48.4, with a mean isoagglutinin titles in specific of 61.65 vs non-specific 11.8 (p = 0.05). Isoagglutinin clearance were higher in specific techniques with 73% vs 59% non-specific (p < 0.03). Due to the dispersion in the number of sessions, results are expressed with the median (4 sessions in specific vs 3 non-specific). Total renal graft survival rate is 93.4%. At one month, it was diagnosed by biopsy an acute renal rejection rate of 16.7% in non-specific vs 18.2% specific (p > 0.05). Considering complications, they are higher with non-specific 41.7% vs specific 18% (p < 0.05). Regarding infectious issues, there are no differences in cytomegalovirus or polyomavirus infections, but there are differences in urinary infections observing in non-specific 79.2% vs specific 63% (p < 0.05). Conclusion Specific techniques are more effective in reducing isoagglutinins, show a lower rate of complications and post-transplant infections, providing greater benefit to the patient.

Incidence of postoperative cytomegalovirus and BK-polyoma virus infections and graft loss in ABO-incompatible renal transplant recipients: a multicenter retrospective study.

The current study aimed to examine the incidence of perioperative infections and graft viability in ABO-compatible and ABO-incompatible renal transplant recipients. We included 643 living donor renal transplant recipients registered in the Michinoku Renal Transplant Network from 1998 to 2021. Patients were divided into the ABO-compatible and ABO-incompatible kidney transplantation groups. We compared the characteristics of the two groups and evaluated the incidence of postoperative viral infections (cytomegalovirus and BK virus), graft loss-free survival, and overall survival between the two groups. Of 643 patients, 485 (75%) and 158 (25%) were ABO-compatible and ABO-incompatible renal transplant recipients, respectively. Postoperative viral infections, rituximab use, and plasma exchange were significantly more common in ABO-incompatible than in ABO-compatible transplant recipients. However, there were no significant differences in terms of other background characteristics. The ABO-incompatible group was more likely to develop viral infections than the ABO-compatible group. Graft loss-free survival and overall survival did not significantly differ between the two groups. According to the multivariate Cox regression analysis, ABO compatibility was not significantly associated with graft loss-free survival and overall survival. Although the incidence of postoperative viral infections in ABO-incompatible renal transplant recipients increased, there was no significant difference in terms of rejection events, graft loss-free survival, and overall survival.

I-JAMM-(I): A survey providing an insight into the practices of isoagglutinin titration in ABO incompatible kidney and liver transplantation

Background and objectivesABO-incompatible transplantations allow patients to receive timely transplants. Isoagglutinin titration to ascertain levels of incompatible antibodies in the recipient is important in determining patient selection and transplant survivability. To find out the prevalent trends in India, the largest, first of its kind survey was carried out among the transplant centers regarding their practices in isoagglutinin titration. MethodsThe survey was drafted by a working group of Transfusion and Transplant Immunology specialists from six different centers. Data was obtained via the use of an online questionnaire. ResultsResults were categorized into four categories, Hospital information, Titration methodology, Role of transfusion specialists and cut-off titers. Most centers had a well-established solid-organ transplant program with considerable number of ABO-incompatible transplantations. Most centers performed isoagglutinin titration in Transfusion Medicine department. Column Agglutination Technique (CAT) was the most common method, using EDTA blood samples and freshly-prepared in-house pooled cells. Most centers had a turn-around time of less than 12 h. While the policy for ascertaining baseline and threshold titers is well-defined in ABO-incompatible renal transplants, variations from center to center still exist for ABO-incompatible liver transplants. Most centers required a Transfusion Medicine consultation for the patients before such transplants. ConclusionWith increasing ABO-incompatible kidney and liver transplants across the country, the role of Transfusion medicine specialists has become vital in pre-conditioning regimes enabling the viability and success of such transplants. This was a unique survey that provided a snapshot of current trends and practices of isoagglutinin titration for ABO-incompatible transplants in India.

ABO Incompatible Kidney Transplant in a Patient With Atypical Hemolytic Uremic Syndrome: Case Report

Kidney transplant (KT) or renal transplant is 1 of the preferred treatment options for patients with end-stage renal disease, but the presence of atypical hemolytic uremic syndrome (aHUS) further increases the risk of reoccurrence with graft rejection, and poor outcomes. ABO incompatibility further adds to the rejection risk. Here, we present a case of a young adult with a history of aHUS undergoing a successful ABO-incompatible (ABOi) renal transplant. ABO incompatibility desensitization was carried out, and the antibody titer was reduced to nullify the risk of rejection. Graft acceptance was facilitated by triple immunosuppression (steroid, tacrolimus, and mycophenolate mofetil), and 4-month serum creatinine follow-up indicated the absence of antibody-mediated rejection and recurrence of aHUS. This case demonstrates that in patients with aHUS, ABOi renal transplant can be performed successfully.

Double filtration plasmapheresis for children with different types of critical kidney diseases: a single-center retrospective cohort study.

Double filtration plasmapheresis (DFPP) was initially used to facilitate the conduction of ABO-incompatible renal transplantation. The applicability of DFPP has recently expanded to cover the removal of various antibodies in adults with immune-mediated diseases. However, DFPP is seldom used in children, with few reports addressing its efficacy and safety in this population. This study aimed to explore the efficacy and adverse effects of DFPP for pediatric patients with renal indications. Children who received DFPP between December 2017 and December 2020 at Tongji Hospital were retrospectively studied, and sub-grouped for analysis according to the types of disease. All children received 3 to 6 DFPP sessions within 2 to 3 weeks, and were assessed for clinical outcomes according to glomerular filtration rate, proteinuria and extra-renal symptoms. Pre- and post-DFPP plasma were collected to measure the levels of pathogenic autoantibodies, immunoglobulins, fibrinogen, albumin, calcium, etc. In-hospital complications were also recorded. Totally there were 10 children receiving 44 sessions of DFPP, including 2 males and 8 females, with a median age of 11.2 years old (5-13 years) and a median weight of 42.1 kg (20-59 kg). Five patients were treated for systemic lupus erythematosus (SLE), three patients for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), one for C3 glomerulopathy and one for ABO-incompatible renal transplantation. Plasma autoantibodies decreased substantially by 93% and 89% in those with SLE and AAV after the last session, respectively. Complete or partial responses were achieved in 80%, 33.3%, 100% and 100% of patients with SLE, AAV, C3 glomerulopathy, and ABO-incompatible renal transplantation, respectively. The proportion of cumulative IgG, fibrinogen, and albumin removal at the end of the last sessions were 58.8%, 67.69%, and 14.05% respectively. The removal of calcium, potassium and creatinine were not statistically significant. A few episodes (4.55%) of hypotension were observed when fresh frozen plasma was used as the replacement fluid, and no bleeding nor severe anaphylaxis was noted. The efficacy and safety of DFPP treatment in children with SLE, AAV, C3 glomerulopathy and ABO-incompatible renal transplantation were described in the present study. DFPP is proven to be a safe apheresis method for children weighing more than 20 kg.

ABO-incompatible renal transplant: a single center experience from India

Vaibhav Tiwari, Nikita Pawar, Anurag Gupta, Shiv Chadha, Vinant Bhargava, Manish Malik, Ashwani Gupta, Anil Kumar Bhalla, Devender Singh Rana. Korean J Transplant 2022;36:26. https://doi.org/10.4285/ATW2022.F-1208

P8.093: ABO Incompatible Renal Transplantation in Argentina: Experience in a Tertiary Referral University Hospital

Introduction: ABO-incompatible renal transplant (ABOiTr) is little used in Argentina despite being able to increase the pool of donors. We report our experience with this modality in the period Jul/2014 – Mar/2022. Study population and Methods: 177 living transplant donor were performed in the studied period of which 23 were ABOi (13%). Age of TrABOi: 48 years (20-76), 10 female (43%), second Tr 6/23 (26%), time on dialysis 21.8 months (3-60), preemptive 26%, non-related donor 52%, HLA missmatch 3.7 (0-6), presence of DSA in 22%. Median pre-Tr donor anti-group agglutinins: IgG 1/16 (0-1028), IgM 1/8 (0-256). Pre-Tr conditioning therapy included rituximab in 22/23 and plasmapheresis (PF) in 20/23 with a median of 4 sessions (range 1-9). Two patients received PF post ABOi Tr. All received immunosuppression with tacrolimus and mycophenolate one month pre-Tr and continued post-Tr. Intravenous immunoglobulin (IVIG) was used in all patients post last PF and antithymocyte globulin as induction in 20/23 patients. Results: Mean follow-up post-Tr was 37.4 months (1-92). Six patients developed acute rejection (AMR: 4, TCMR: 2). Rejection treatment included corticosteroids pulses and IVIG in all cases. Bortezomib was used in one case and PF in another. All patients except one responded to treatment. The most frequent post-Tr complications were: urinary tract infections in 7 patients one of them with sepsis, BK reactivation in 2 cases and 1 case of immediate post-Tr hemorrhage. Nine patients developed COVID infection (39%), 3 of them required hospitalization. One graft loss was recorded at 6 months post-Tr due to refractory AMR. Three patients died in the study period, two deaths related to COVID infection (1 and 33 months post-Tr) and one death was related to PTLD (49 months post-Tr), all deaths were with a functioning kidney (median patient survival 89%). Creatinine level in last control was 1.53 mg/dl (0.90-2.70 mg/dl) and P/C 0.18 (0.1-1.0). Conclusion: ABOiTr is a feasible alternative in our country, these preliminary results suggest that it should be offered more extensively to recipients who do not have an ABO compatible donor. Fundación Nefrológica de Córdoba.

423.11: Long-term Compromised Immune Regulation After Rituximab Induction in Blood Group Incompatible Living-Donor Renal Transplantation - 5 Year Results of a Prospective Pilot Study

Background: An increased frequency of severe infectious diseases and BK viremia has been described after ABOi renal transplantation. As rituximab induction may alter immunoregulation in these patients, we analyzed clinically relevant immune parameters in a prospective renal transplant study up to 5 years posttransplant. Materials and Methods: Mononuclear cell subsets (peripheral blood; lymph nodes taken during transplant surgery), intracellular cytokine responses, CD4 helper function and in-vitro B cell responses were assessed pretransplant and up to 5 years posttransplant in 85 renal transplant recipients (living donation: n=25 ABO incompatible (ABOi) and n=30 ABO compatible (ABOc); deceased donation (DD): n=30, all ABO compatible). Results: Severe infectious diseases occurred more often in ABOi than ABOc recipients within 2 years posttransplant (11/24 (46%) versus 6/30 (20%), P=0.042) but not beyond. The incidence of BK viremia was significantly enhanced in rituximab versus non-rituximab treated patients (1 year: 9/29 (31%) versus 4/54 (7%), P=0.009; 5 years: 10/30 (33%) versus 7/53 (13%), P=0.029). After rituximab induction in ABOi recipients, counts of peripheral blood B cell subsets were profoundly downregulated even 3 years posttransplant and reached the level of non-ABOi recipients after 4 years (memory B cells after 5 years). T-dependent and T-independent B cell responses were significantly impaired in ABOi patients up to 2 years posttransplant (P=0.010 and P=0.053, respectively) whereas CD4 helper activity was not compromised. CD4+ T cell counts were significantly lower in ABOi compared to ABOc recipients at 3 and 6 months (P=0.025 and P=0.046, respectively), but showed no differences in the percentage of Tregs. In regional lymph nodes of ABOi patients, we found a significant downregulation of CD20+ but not CD19+ B cells (P<0.0005), of naive B cells (P=0.031) and short lived plasma cells (P<0.0005) at the time of transplantation. Conclusion: An increased frequency of severe infectious diseases and BK viremia in rituximab treated ABOi renal transplant recipients may be explained by significantly downregulated CD4+ T cell counts up to 6 months and a profoundly delayed B cell repopulation, most pronounced with regard to memory B cells, together with compromised B cell responses up to 2 years posttransplant. IL-10, as a key player in chronic BK virus infection, was not upregulated in rituximab-treated ABOi transplant recipients.

Role of Double-Filtration Plasmapheresis in ABO- and Human Leukocyte Antigen-Incompatible Kidney Transplant

Kidney transplant has significantly improved the quality of life in end-stage renal disease patients compared to maintenance hemodialysis. Recipients can receive a living-donor or a deceased-donor kidney transplant. However, the presence of donor specific anti human leukocyte antigen (HLA) antibodies or anti A or B antibodies in the recipient makes the transplant incompatible and provokes to cause hyperacute, acute, or chronic rejection. Desensitization which is usually applied before to reduce incompatibility can be achieved by apheresis and preventing donor-specific antibody resynthesis by targeting both T and B cells. Here, we present two such cases transplanted successfully by desensitizing with double-filtration plasmapheresis (DFPP). Case 1 which was a female with high-titer anti-HLA antibody was managed with rituximab, 4 sessions of DFPP, antithymocyte globulin, and posttransplant Tacrolimus (Tac). Case 2 who had both high-titer anti-HLA and anti-A (IgG 1:256) antibody was managed with rituximab, 3 sessions of DFPP, and posttransplant Tac. In both cases, perioperative complications due to DFPP such as bleeding, thrombocytopenia, hypotension, and need of transfusion was minimal. These cases point toward successful application of DFPP in desensitization protocol, leading to successful HLA antibody-incompatible and ABO-incompatible renal transplant with minimal adverse incident and cost.

Laboratory assessment in ABO-incompatible renal transplant

Background: In ABO-incompatible renal transplants, reliable ABO antibody titre measurements are crucial in managing humeral rejection and graft failure. There is a paucity of published studies comparing the different laboratory methods of pre-transplant ABO antibody titre measurement.

Establishment of a Hyperacute Rejection Model of ABO-Incompatible Renal Transplantation in Nonhuman Primates.

The establishment of a hyperacute rejection (HAR) model of ABO-incompatible kidney transplantation (ABOi-KTx) in nonhuman primates is of great significance for the study of the relevant clinical pathophysiological processes and related interventions in ABOi-KTx. In this study, blood group B cynomolgus monkeys were presensitized with synthetic blood group A-antigen conjugated to keyhole limpet hemocyanin (A-KLH) to boost circulating anti-A antibody levels. The serum anti-A antibody levels were measured by flow cytometry using type A human reagent red blood cells (RBCs) or monkey primary renal tubular epithelial cells (RTECs) as target cells. ABOi-KTx was performed in type B monkeys using type A monkeys as donors. After 14 days of A-KLH sensitization, 12 of 16 (75%) type B monkeys had significantly elevated anti-A antibody levels. We found that in order to avoid irregular results in the detection of blood group antibodies by flow cytometry, it was more effective to use RTECs rather than RBCs as target cells. In the absence of presensitization, ABOi-KTx in three monkeys with relatively high levels of natural anti-A antibodies did not produce HAR. However, when four Type B monkeys with significantly increased anti-A antibodies after presensitization were randomly selected as recipients for ABOi-KTx, the allografts in all four monkeys developed HAR with typical pathologic characteristics. Thus, we have successfully established a monkey model of HAR in ABOi-KTx via blood group antigen presensitization, which will be helpful for the further study of rejection, accommodation, and clinical intervention in ABOi-KTx.

Challenges in antibody titration for ABO-incompatible renal transplantation.

Accurate and regular monitoring of anti-A and anti-B titres pre- and post-transplantation plays a crucial role in the clinical management of patients receiving ABO-incompatible renal transplants. There is no standardized protocol or an external quality assurance program (EQA) currently available for this testing in Australia. The aim of this study was to investigate the diversity of techniques, test platforms and reagents that were currently in use in various laboratories with the aim of developing an EQA. An online survey was sent to the participants enrolled with the Royal College of Pathologists of Australasia Quality Assurance Program (RCPAQAP) to assess their interest in participation in the pilot study. A total of 24 participants who expressed interest were sent the group O plasma, A1 , A2 and B cells to perform ABO titration using their own methods. Participants reported a wide range of titre results, from 8 to 1024 for the anti-A titre using A1 cells, from 2 to 128 for anti-A titre using A2 cells and from neat to 32 for anti-B titre using B cells. There was a wide variation in titre results between and within different technologies. These findings demonstrate the need for an ABO titration EQA. Development of a standard technique and participation in an EQA program should, over time, reduce variation and enable transferrable results across testing centres, which will assist in consistent clinical interpretation and better outcomes for patients.

Renal Biopsy and Clinical Outcomes in Patients With ABO-Incompatible Renal Transplant: Experience From a Tertiary Care Hospital.

Renal transplant with ABO-incompatible donors expands the donor pool. Earlier studies have focused the use of protocol biopsies in ABO-incompatible transplant patients. Our study described outcomes of indication (for cause) renal biopsies and clinical outcomes in patients with ABO-incompatible renal transplant. This retrospective study included 164 patients from January 2012 to June 2019. Biochemical parameters, serial immunoglobulin G anti-ABO titers, and class I and II donor-specific antibody findings were obtained from hospital records, and renal graft biopsies were reviewed according to the Banff 2017 update. We analyzed the results of 65 biopsies from 54 patients. Biopsy-proven acute antibody-mediated rejection (12.8%) was found to be more prevalent than acute cellular rejection (1.8%). Patients with antibodymediated rejection all had microvascular inflammation (g+ptc score of 2 or more, where g+ptc is the sum of the glomerulitis and peritubular capillaritis scores) and were positive for C4d. Acute tubular injury per se was seen in 10.3% of patients; 65% of these patients had C4d positivity in peritubular capillaries, and only 1 patient developed chronic active antibody-mediated rejection on follow-up. Patient and death-censored graft survival rates were 92% and 98% at 1 year after transplant and 88% and 91% at 3 years, respectively. Patients with an episode of antibody-mediated rejection had lower rates of patient (76.5%) and deathcensored graft survival (84.6%) at 1 year. The microvascular inflammation score (g+ptc score of 2 or higher) is more reliable than diffuse C4d positivity to determine antibody-mediated rejection in ABO-incompatible transplants because diffuse C4d positivity may also be seen in etiologies unrelated to antibody-mediated rejection. Acute tubular injury with C4d positivity without microvascular injury does not confirm antibody-mediated rejection. We suggest that Banff classification be updated in ABO-incompatible transplants to include diagnostic criteria for the diagnosis of antibody-mediated rejection.

POS-759 HISTOLOGICAL ANALYSIS OF 3 AND 6 MONTH PROTOCOL BIOPSIES AND OUTCOME SIN ABO INCOMPATIBLE RENAL TRANSPLANTS

Renal transplant is the best renal replacement therapy for patients with ERnd stage renal disease. ABO incompatible renal transplant increases chances to undergo renal transplant but has higher chance on infections and rejections compared to ABO compatible renal transplant. To analyse histological changes at 3 and 12 month protocol biopsies in ABO incompatible renal transplants (ABOiRTX) and correlate them with clinical outcomes at 1 year.

Impact of rituximab on the T-cell flow cytometric crossmatch

Rituximab is frequently used in the setting of ABO-incompatible renal transplants, and highly sensitized patients. Its interference with B-cell flow cytometric crossmatch (B-FCXM) is well known. However, its effect on the T-cell flow cytometric crossmatch (T-FCXM) has not been described. We aimed to evaluate the effect of rituximab on the T-FCXM using non-pronase and pronase treated donor lymphocytes and compare results with the single antigen bead (SAB) assay. In this retrospective study, 28 patients on rituximab therapy were evaluated against 30 donors. Using non-pronase treated donor lymphocytes, all 30 FCXMs showed strong B-cell positivity {median (IQR) B-cell ratio: 184.65 (253.17)} which significantly reduced {1.0 (1.18); p < 0.00001} with pronase treatment. ‘T-cell tailing’ phenomenon was observed in 17/30 FCXMs in the non-pronase group as a ‘tail of T-cells’, indicating a rare sub-population. However, it disappeared in the pronase-treated group. SAB assay did not show donor-specific antibodies (DSA) in all 17 patients with ‘T-cell tailing’ phenomenon. Although, rituximab is described to impact only B-FCXM, we have consistently found ‘T-cell tailing’ in 57% of T-FCXMs, which clears with pronase treatment. The ‘T-cell tailing’ led to weak positive T-FCMX ratios due to increased MFI in the FL1 channel. However, the absence of DSA in all recipients reinforces the fact that this is a false positive finding and should not be misconstrued as a possible class I DSA. Structural homology of Fc receptors on activated T-cells to CD20 could be a possible explanation of the same and provide insight into a novel mechanism of action of rituximab.

Outcome of desensitization in human leukocyte antigen and ABO incompatible living donor kidney transplantation: Single center experience of first 200 incompatible transplants.

Although desensitization is well established, concerns about graft outcome, patient survival and rejection still exist. The present study aims at comparing outcomes of renal transplant recipients across simultaneous ABO and human leukocyte antigen (HLA) incompatibility barriers to those with ABO or HLA incompatibility alone. This was a retrospective study conducted from October 2015 to December 2018. All patients with a clinical diagnosis of chronic kidney disease, who were prospective HLA incompatible (HLAi) and/or ABO incompatible (ABOi) renal transplant recipients were included. A total of 400 cases including 36 ABOi transplants, 154 HLAi transplants, 10 simultaneously ABO and HLA incompatible transplants, and 200 ABO (ABOc) and HLA (HLAc) compatible kidney transplants from living donors were included. There were significantly more number of blood transfusions, previous transplants and pregnancies in HLAi transplant recipients relative to the ABOi or the control group. Mean number of therapeutic plasma exchange procedures per patient and mean plasma volume processed per procedure were slightly higher in the ABOi + HLAi category. The incidence of graft dysfunction due to suspected antibody-mediated rejection during first year was highest in the ABOi + HLAi group, followed by ABOc + HLAi and ABOi + HLAc, lowest in the ABOc + HLAc category. Mean time to first episode of graft dysfunction was significantly shorter with incompatible transplants. There were no kidney transplant recipient deaths in the study. Patient outcome and graft outcomes observed with incompatible transplants were not worse than those observed with compatible transplants.

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.

Clinical outcome of living donor kidney transplantation across simultaneous ABO and HLA incompatibility: Single center experience of first ten cases

Background and aimsPreconditioning using different protocols has been tested to prevent antibody mediated rejection (ABMR) individually for ABO and HLA incompatibility. However, simultaneous presence of both barriers is still less explored. The aim of this study was to report outcomes of institutional desensitization protocol in renal transplant recipients with simultaneous ABO and HLA incompatibility. Materials and methodsThis was a retrospective study conducted from October 2015 to December 2018. All patients with a clinical diagnosis of dialysis dependent chronic kidney disease (CKD), who were prospective coexistent HLA and ABO incompatible renal transplant recipients were included in the study. Patients were followed up and graft function and patient survival was assessed at 1 y from the date of transplant. ResultsMedian and mode baseline anti-A titers were 64, while median and mode baseline anti-B titers were 256. All recipients were discharged by tenth postoperative day. None of the patients had any bleeding complications. Post transplant infection rate was found to be 20 %. A total of 54 therapeutic plasma exchange (TPE) procedures were performed before transplant and 8 were performed after transplant. Graft survival and patient survival was 100 % at 3, 6, 9, and 12 months. Range and mean follow-up period was 15–42 months and 23 months respectively. Mean glomerular filtration rate (GFR) at 1 y using the CKD-EPI equation was 85.25 ± 13.76 mL/min. Biopsy proven ABMR was observed in one case only which was managed with TPE and immunosuppression. ConclusionSimultaneous ABO and HLA incompatibility in renal transplant recipients can be managed successfully with adequate preconditioning and careful monitoring.

The suppressive effect on CD4 T cell alloresponse against endothelial HLA-DR via PD-L1 induced by anti-A/B ligation.

While donor-specific human leukocyte antigen (HLA) antibodies are a frequent cause for chronic antibody-mediated rejection in organ transplantation, this is not the case for antibodies targeting blood group antigens, as ABO-incompatible (ABO-I) organ transplantation has been associated with a favorable graft outcome. Here, we explored the role of CD4 T cell-mediated alloresponses against endothelial HLA-D-related (DR) in the presence of anti-HLA class I or anti-A/B antibodies. CD4 T cells, notably CD45RA-memory CD4 T cells, undergo extensive proliferation in response to endothelial HLA-DR. The CD4 T cell proliferative response was enhanced in the presence of anti-HLA class I, but attenuated in the presence of anti-A/B antibodies. Microarray analysis and molecular profiling demonstrated that the expression of CD274 programmed cell death ligand 1 (PD-L1) increased in response to anti-A/B ligation-mediated extracellular signal-regulated kinase (ERK) inactivation in endothelial cells that were detected even in the presence of interferon-γ stimulation. Anti-PD-1 antibody enhanced CD4 T cell proliferation, and blocked the suppressive effect of the anti-A/B antibodies. Educated CD25+ CD127- regulatory T cells (edu.Tregs ) were more effective at preventing CD4 T cell alloresponses to endothelial cells compared with naive Treg ; anti-A/B antibodies were not involved in the Treg -mediated events. Finally, amplified expression of transcript encoding PD-L1 was observed in biopsy samples from ABO-I renal transplants when compared with those from ABO-identical/compatible transplants. Taken together, our findings identified a possible factor that might prevent graft rejection and thus contribute to a favorable outcome in ABO-I renal transplantation.

P1778PROFILE OF NON-BACTERIAL INFECTIONS SPECIFIC TO RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims Infections in renal transplant recipients are a major cause of morbidity and mortality. It is the one of the major cause of patient death with functioning graft. Hence this project was done to study the profile of non-bacterial infections specific to renal transplant recipients and to determine the risk factors associated with such infections. Method Renal-transplant recipients admitted to the department of nephrology with suspected infection were included in the study. Results : A total of 342 patients were included in the study. The mean age of the patients was 45.2 ± 13.3 years. 17.5% had ABO incompatible renal transplant. 91% (87% received leukocyte depleting and 4% received non-leukocyte depleting agents) had received induction as majority had three or more HLA mismatch (70%) and the most common donor was wife. 12.8% had history of graft rejection. A total of 147 infectious episodes were encountered in 121 patients. The incidence of non-bacterial infections was 35% (121/342). Viral infections (68/147 = 46%) and invasive fungal infections (44/147 = 30%) were the most common. Cytomegalovirus infection was the most common 35%. Other viral infections encountered were BK virus associated nephropathy (2.3%) and reactivation of Hepatitis B or C virus (2.6%). The most common site of invasive fungal infection were lower respiratory tract, urinary tract, CNS cryptococcosis, soft tissue infection or cellulitis and oesophageal candidiasis in 41%, 32%, 9%, 9% and 9% respectively. Aspergillus (61%) and Rhizopus (33%) was the most common organism causing fungal pneumonia. Four patients were diagnosed with Pneumocystis jirovecii pneumonia. Majority (60%) of the infections were detected after one year post-transplant. Risk factors found to have statistically significance were ABO incompatibility, diabetes mellitus (pre or post-transplant) and history of graft rejection. Nine patients (7%) died of non-bacterial infections specific to renal transplant recipients. Conclusion Non-bacterial infections are not uncommon in Indian scenario and the timeline of such infections has changed.