Non-antigen-specific Immunoadsorption Is a Risk Factor for Severe Postoperative Infections in ABO-Incompatible Kidney Transplant Recipients.

ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABO-compatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb® ABO columns to reusable non-antigen-specific Immunosorba® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004-2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3-8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx.

Therapeutic apheresis in renal transplantation: An update.

Therapeutic apheresis (TA) plays a significant role in various aspects of renal transplantation. It has been a necessary preconditioning component in ABO incompatible kidney transplants and an important modality in the removal of anti-human leukocyte antigen (HLA) antibodies both in the context of desensitization protocols that have been developed to allow highly sensitized kidney transplant candidates to be successfully transplanted and as treatment of antibody mediated rejection episodes post transplantation. In addition, TA has been used with various results for the management of recurrent focal segmental glomerulosclerosis. The purpose of this review is to examine the evidence supporting the application of TA as an adjunctive therapeutic option to immunosuppressive agents in protocols both before and after kidney transplantation.

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

BACKGROUND AND OBJECTIVES: ABO-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. METHODS: The 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. RESULTS: Results 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. CONCLUSION: With 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.

Therapeutic apheresis in renal transplantation: An update.

Therapeutic apheresis (TA) plays a significant role in various aspects of renal transplantation. It has been a necessary preconditioning component in ABO incompatible kidney transplants and an important modality in the removal of anti-human leukocyte antigen (HLA) antibodies both in the context of desensitization protocols that have been developed to allow highly sensitized kidney transplant candidates to be successfully transplanted and as treatment of antibody mediated rejection episodes post transplantation. In addition, TA has been used with various results for the management of recurrent focal segmental glomerulosclerosis. The purpose of this review is to examine the evidence supporting the application of TA as an adjunctive therapeutic option to immunosuppressive agents in protocols both before and after kidney transplantation.

Hyporesponsiveness against donor's ABO antigens of renal grafts after ABO-incompatible kidney transplantation.

BACKGROUND: ABO antigens expressed on the red blood cells (RBCs) are not identical to those expressed on the renal endothelial cells. The isohemagglutinin assay employing the RBCs is the gold standard for evaluating anti-ABO antibody (Ab) levels. However, it remains unclear whether the anti-ABO Abs detected by the isohemagglutinin assay after ABO-incompatible (ABOi) kidney transplantations (KTx) that are not associated with antibody-mediated rejection can bind to renal graft endothelial cells. METHODS: Ninety plasma samples were collected from patients with stable graft function after ABO-compatible (ABOc) or ABOi KTx. Anti-ABO Ab titers were examined by both the isohemagglutinin assay and the CD31-ABO microarray, which was developed as a mimic of the ABO antigens expressed on the renal endothelial cells. RESULTS: The antibody titers detected by the isohemagglutinin assay and the CD31-ABO microarray after the ABOc KTx relatively correlated with each other. However, the CD31-ABO microarray results showed low antibody levels against donor blood group antigens after ABOi KTx and did not correlate with the isohemagglutinin assay. In contrast, the antibody levels against non-donor blood group antigens after ABOi KTx were comparable to those after the ABOc KTx. Fourteen patients received graft biopsies, and no antibody-mediated rejection was observed in ABOi KTx recipients, except for two patients who had anti-donor-HLA Abs. CONCLUSION: The present study suggested that the anti-ABO Abs detected by the isohemagglutinin assay after ABOi KTx with stable graft function were hyporeactive to the ABO antigen of graft renal endothelial cells.

A Novel Method of CD31-Combined ABO Carbohydrate Antigen Microarray Predicts Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.

Isohemagglutinin assays employing red blood cells (RBCs) are the most common assays used to measure antibody titer in ABO-incompatible kidney transplantation (ABOi KTx). However, ABO antigens expressed on RBCs are not identical to those of kidney and antibody titers do not always correlate with clinical outcome. We previously reported that CD31 was the main protein linked to ABO antigens on kidney endothelial cells (KECs), which was different from those on RBCs. We developed a new method to measure antibody titer using a microarray of recombinant CD31 (rCD31) linked to ABO antigens (CD31-ABO microarray). Mass spectrometry analysis suggested that rCD31 and native CD31 purified from human kidney had similar ABO glycan. To confirm clinical use of CD31-ABO microarray, a total of 252 plasma samples including volunteers, hemodialysis patients, and transplant recipients were examined. In transplant recipients, any initial IgG or IgM antibody intensity >30,000 against the donor blood type in the CD31-ABO microarray showed higher sensitivity, specificity, positive predictive value, and negative predictive value of AABMR, compared to isohemagglutinin assays. Use of a CD31-ABO microarray to determine antibody titer specifically against ABO antigens expressed on KECs will contribute to precisely predicting AABMR or preventing over immunosuppression following ABOi KTx.

ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies: a propensity-matched analysis.

Kidney transplant candidates are blood group incompatible with roughly one out of three potential living donors. We compared outcomes after ABO-incompatible (ABOi) kidney transplantation with matched ABO-compatible (ABOc) living and deceased donor transplantation and analyzed different induction regimens. We performed a retrospective study with propensity matching and compared patient and death-censored graft survival after ABOi versus ABOc living donor and deceased donor kidney transplantation in a nationwide registry from 2006 till 2019. 296 ABOi were compared with 1184 center and propensity-matched ABOc living donor and 1184 deceased donor recipients (matching: recipient age, sex, blood group, and PRA). Patient survival was better compared with deceased donor [hazard ratio (HR) for death of HR 0.69 (0.49-0.96)] and non-significantly different from ABOc living donor recipients [HR 1.28 (0.90-1.81)]. Rate of graft failure was higher compared with ABOc living donor transplantation [HR 2.63 (1.72-4.01)]. Rejection occurred in 47% of 140 rituximab versus 22% of 50 rituximab/basiliximab, and 4% of 92 alemtuzumab-treated recipients (P < 0.001). ABOi kidney transplantation is superior to deceased donor transplantation. Rejection rate and graft failure are higher compared with matched ABOc living donor transplantation, underscoring the need for further studies into risk stratification and induction therapy [NTR7587, www.trialregister.nl].

Safety and Efficacy of Tandem Hemodialysis and Selective Plasma Exchange in Pretransplant Desensitization of ABO-Incompatible Kidney Transplantation.

INTRODUCTION: In patients requiring both hemodialysis (HD) and apheresis, the 2 treatments can be performed simultaneously. At our hospital, selective plasma exchange (SePE) is often performed along with HD for removal of isoagglutinins before ABO-incompatible (ABOi) kidney transplantation. The 2 treatments can be completed within the HD schedule, which allows the treatment time to be shortened. This approach is also less stressful for patients because fewer punctures are required. In this study, we investigated the safety and efficacy of tandem HD and SePE. METHODS: A total of 58 SePE sessions in 30 ABOi kidney transplant recipients were investigated. The SePE circuit was connected in parallel with the HD circuit, and tandem HD and SePE therapy was performed using filtration methods. The SePE sessions were divided into 2 groups: those with SePE monotherapy (group S, n = 20) and those with tandem therapy (group T, n = 38). Changes in transmembrane pressure (TMP), arterial pressure (AP), venous pressure (VP), and decrease in isoagglutinin titers over time were compared between the groups with adjustment for background data. RESULTS: The internal pressures (AP and VP) were higher in group T, and there were significant differences in changes of TMP and AP over time between groups T and S. Membrane exchange was required in 1 case in group T due to coagulation. There was a more significant decrease of immunoglobulin G isoagglutinin titers in group T compared to group S. No case had antibody-mediated rejection after transplantation. DISCUSSION/CONCLUSION: In HD/SePE tandem therapy, internal pressures were higher and TMP and AP tended to increase more compared to SePE monotherapy, but we were able to perform the 2 treatments without any functional problems. Tandem therapy was also effective in decreasing isoagglutinin titers, which suggests that this may be a beneficial treatment modality as apheresis before ABOi kidney transplantation.

Comparison of three modalities of plasmapheresis on coagulation: Centrifugal, single-membrane filtration, and double-filtration plasmapheresis.

BACKGROUND: Plasmapheresis can deplete pathogenic antibodies and allow ABO- and/or HLA-incompatible transplantation. AIM: To determine the impacts of three modalities of plasmapheresis (centrifugal plasmapheresis [cTPE], single-filtration plasmapheresis [mTPE], double-filtration plasmapheresis [DFPP]) on hemostasis parameters and thrombin generation. MATERIALS/METHODS: Prospective, comparative study on 21 patients that received three modalities of plasmapheresis (7 patients/group). Hemostasis (prothrombin time [PT], activated partial thromboplastin time [aPTT], procoagulant factors and natural anticoagulants) were measured before and after the first plasmapheresis session. Thrombin generation was also assessed in platelet-poor plasma using an STA-Genesia (Stago) analyzer and Thromboscreen reagents (Stago) in 4-5 patients from each group. RESULTS: Both cTPE and mTPE resulted in high decreases in proteins, whatever their molecular weights. Median post/pre ratios were 0.27 to 0.55 for cTPE for most proteins (except FVIII [0.64] and VWF [0.57]). Median post/pre-ratios of mTPE were 0.28 to 0.56 for all proteins. DFPP decreased high-molecular-weight proteins (fibrinogen, FV, FVIII, FXI, VWF) and proteins strongly bound to large molecules (protein SandTFPI). Median post/pre ratios with cTPE and mTPE were similar to DFPP for fibrinogen and FXIII. Regarding thrombin generation, cTPE and mTPE did not significantly modify endogenous thrombin potential (ETP) and DFPP induced a slight decrease in ETP (median post/pre ratio at 0.73) in the absence of thrombomodulin. ETP inhibition by thrombomodulin was decreased for all procedures. CONCLUSIONS: DFPP depleted high molecular-weight proteins in contrast to cTPE and mTPE, which significantly decreased all proteins. Regarding thrombin generation, depletion of procoagulant factors was counterbalanced by a decrease in some natural anticoagulants whatever plasmapheresis method used; with all methods, fibrinogen and FXIII were highly depleted.

Early necrotic skin lesions after a ABO-incompatible kidney transplantation: The threat of Cunninghamella Spp.

A 49-year-old man underwent ABO-incompatible kidney transplantation with a living donor. At day 33 post-transplantation, he presented with undiagnosed epilepsy with generalized tonic-clonic seizures. At day 44 post-transplantation, he developed left-sided pneumonia attributed to Aspergillus fumigatus and treatment with liposomal amphotericin B was initiated. At day 51 post-transplantation, necrotic skin lesions appeared. DNA sequencing in a fresh cutaneous biopsy finally identified Cunninghamella Spp., a member of the order Mucorales. Unfortunately, the necrotic lesions spread, and the patient died at day 60 post-transplantation. This case report highlights the infectious risk related to ABO-incompatible kidney transplantation and suggests a requirement for rapid identification of every skin lesion, even in the early phases of immunosuppression.

Single cohort study: ABO-incompatible kidney transplant recipients have a higher risk of lymphocele formation.

PURPOSE: Since 2004, ABO-incompatible kidney transplantation (ABOi KTx) became an established procedure to expand the living donor pool in Germany. Currently, ABOi KTx comprises > 20% of all living donor KTx. Up to September 2015, > 100 ABOi KTx were performed in Freiburg. Regarding lymphocele formation, only scarce data exist. METHODS: Between April 2004 and September 2015, 106 consecutive ABOi and 277 consecutive ABO-compatible kidney transplantations (ABOc KTx) were performed. Two ABOi and 117 ABOc recipients were excluded due to differences in immunosuppression. One hundred-four ABOi and 160 ABOc KTx patients were analyzed concerning lymphocele formation. RESULTS: The incidence of lymphoceles in ABOi KTx was 25.2% and 10.6% in ABOc KTx (p = 0.003). A major risk factor appeared the frequency of ≥ 8 preoperative immunoadsorption and/or plasmapheresis sessions (OR 5.61, 95% CI 2.31-13.61, p < 0.001). Particularly, these ABOi KTx recipients had a distinctly higher risk of developing lymphocele (40.0% vs. 19.2%, p = 0.044). IA/PE sessions on day of transplantation (no lymphocele 20.0% vs. lymphocele 28.6%, p = 0.362) or postoperative IA/PE sessions (no lymphocele 25.7% vs. lymphocele 24.1%, p = 1.0) showed no influence on formation of lymphoceles. CONCLUSION: In ABOi KTx, the incidence of lymphocele formation is significantly increased compared to ABOc KTx and leads to more frequent surgical reinterventions without having an impact on graft survival.

Analysis of the prevalence of systemic de novo thrombotic microangiopathy after ABO-incompatible kidney transplantation and the associated risk factors.

OBJECTIVES: To analyze the prevalence of systemic de novo thrombotic microangiopathy in ABO-incompatible kidney transplantation and risk factors associated with this condition. METHODS: A total of 201 patients who received living-donor kidney transplantation (114 patients with ABO-identical kidney transplantation and 87 patients with ABO-incompatible kidney transplantation) were retrospectively analyzed. Systemic de novo thrombotic microangiopathy was diagnosed clinically according to the presence of thrombocytopenia with microangiopathic hemolytic anemia and pathological findings of thrombotic microangiopathy. Anti-A and anti-B antibodies were purified from human plasma, and these antibodies' bindings to human kidney were investigated in vitro. RESULTS: ABO-incompatible kidney transplantation was a significant risk factor of systemic de novo thrombotic microangiopathy (odds ratio 55.9, 95% CI 1.8-8.9, P < 0.001) after transplantation. Multivariate logistic regression analysis showed that non-use of mycophenolate mofetil, pretreatment immunoglobulin G antibody titer ≥64-fold and pretransplant immunoglobulin M antibody titer ≥16-fold were significant risk factors for systemic de novo thrombotic microangiopathy in ABO-incompatible kidney transplantation. Microvascular inflammation of 1-h post-transplant biopsy could be observed more frequently in thrombotic microangiopathy patients than in non-thrombotic microangiopathy patients. Anti-A and anti-B antibodies purified from human plasma showed a strong in vitro reaction against human kidney when the antibody titer was ≥16-fold. CONCLUSIONS: Antibody titer should be decreased to ≤16-fold until the day of ABO-incompatible kidney transplantation by desensitization therapy including mycophenolate mofetil. The 1-h biopsy results might help to diagnose systemic de novo thrombotic microangiopathy.

Early post-transplant diagnosis of cytomegalovirus esophagitis in an ABO-incompatible kidney transplant recipients: A case report.

Cytomegalovirus (CMV) is a common infectious pathogen in kidney transplant patients. Here, we present a case of CMV esophagitis with antigenemia, that developed within 3 days of kidney transplantation, a timeline generally considered to be too early for development of a CMV infection. Intense immunosuppressive therapy for desensitization in ABO-incompatibility or in the presence of donor-specific antibody can increase the risk for significant opportunistic infection immediately after or even before transplantation.

Favorable results in ABO-incompatible renal transplantation without B cell-targeted therapy: Advantages and disadvantages of rituximab pretreatment.

The effectiveness of desensitization with rituximab in ABO-incompatible renal transplantation (ABO-I) has been widely reported. However, ABO-I outcomes are still worse than those of ABO-identical or ABO-compatible renal transplantation (ABO-Id/C). We retrospectively examined the outcomes in consecutive living donor ABO-Id/C (n = 412) and ABO-I (n = 205) cases to elucidate the causes of inferiority in ABO-I. ABO-I cases included recipients treated with rituximab (RIT, n = 131), splenectomy (SPX, n = 21), or neither because of low anti-A/B antibody titers (NoR/S, n = 53). Graft survival, infection, and de novo HLA antibody production were compared for ABO-I and ABO-Id/C, followed by stratification into RIT and NoR/S groups. Propensity score-based methods were employed to limit selection bias and potential confounders. Overall graft survival for ABO-I was significantly lower than that for ABO-Id/C (92.8% vs 97.2% after 5 years, P = .0037). Graft loss due to infection with ABO-I was significantly more frequent than that with ABO-Id/C, whereas acute antibody-mediated rejection (AMR) caused no graft failure in ABO-I recipients. Stratified analysis demonstrated significantly higher infection risk with RIT than with NoR/S. Safe reduction or avoidance of rituximab in desensitization protocols might contribute to further improvement of ABO-I outcome.

VDJ gene usage among B-cell receptors in ABO-incompatible kidney transplantation determined by RNA-seq Transcriptomic analysis.

BACKGROUND: Studies on B-cell subtypes and V(D)J gene usage of B-cell receptors in kidney transplants are scarce. This study aimed to investigate V(D)J gene segment usage in ABO-incompatible (ABOi) kidney transplant (KT) patients compared to that in ABO-compatible (ABOc) KT patients. METHODS: We selected 16 ABOi KT patients with accommodation (ABOiA), 6 ABOc stable KT patients (ABOcS), and 6 ABOi KT patients with biopsy-proven acute antibody-mediated rejection (ABOiR) at day 10, whose graft tissue samples had been stored in the biorepository between 2010 and 2014. Complete transcriptomes of graft tissues were sequenced and analyzed through RNA sequencing (RNA-seq). The international ImMunoGeneTics information system (IMGT®) was used for in-depth comparison of V(D)J gene segment usage. RESULTS: The mean age of the 28 KT recipients was 43.3 ± 12.8 years, and 53.6% were male. By family, IGHV3, IGHJ4, IGLV2, and IGLJ3 gene segments were most frequently used in all groups, and their usage was not statistically different among the three patient groups. While IGKV3 was most frequently used in both the ABOiA and ABOiR groups, IGKV1 was most commonly used in the ABOcS group. In addition, while IGKJ1 was most commonly used in the ABOiA and ABOcS groups, IGKJ4 was most frequently used in the ABOiR group. According to individual gene segments, IGHV4-34 and IGHV4-30-2 were more commonly used in the ABOiR group than in the ABOiA group, and IGHV6-1 was more commonly used in the ABOcS group than in the ABOiR group. IGLV7-43 was more commonly used in the ABOcS group than in the ABOi group. However, technical variability, small sample size, and potential confounding effects of Rituximab or HLA mismatching are limitations of our study. CONCLUSIONS: Our findings suggest that RNA-seq transcriptomic analyses can provide information on the V(D)J gene usage of B-cell receptors and the mechanisms of accommodation and immune reaction in ABOi KT.

One hundred ABO-incompatible kidney transplantations between 2004 and 2014: a single-centre experience.

BACKGROUND: ABO-incompatible kidney transplantation (ABOi KTx) expands the living donor transplantation options. However, long-term outcome data, especially in comparison with ABO-compatible kidney transplantation (ABOc KTx), remain limited. Since the first ABOi KTx in Germany on 1 April 2004 at our centre, we have followed 100 ABOi KTx over up to 10 years. METHODS: One hundred ABOi KTx and 248 ABOc KTx from 1 April 2004 until 28 October 2014 were analysed in this observational, single-centre study. Three ABOi KTx and 141 ABOc KTx were excluded because of cyclosporine A-based immunosuppression, and 1 ABOc KTx was lost to follow-up. RESULTS: Median estimated 10-year patient and graft survival in ABOi KTx was 99 and 94%, respectively, and surpassed ABOc-KTx patient and graft survival of 80 and 88%, respectively. The incidence rate of antibody-mediated rejections was 10 and 8%, and that of T-cell-mediated rejections was 17 and 20% in ABOi KTx and ABOc KTx, respectively. Infectious and malignant complications in ABOi KTx were not more common than in ABOc KTx. However, postoperative lymphoceles occurred more frequently in ABOi KTx. Subgroup analysis of ABOi-KTx patients revealed that patients with high-titre isohaemagglutinins before transplantation had equal long-term results compared with low-titre isohaemagglutinin patients. CONCLUSION: Taken together, long-term outcome of ABOi KTx is not inferior to ABOc KTx. Incidences of rejection episodes, infectious complications and malignancies are not increased, despite the more vigorous immunosuppression in ABOi KTx. Our data provide further evidence that ABOi KTx with living donation is a safe, successful and reasonable option to reduce the organ shortage.

De novo mTOR inhibitor-based immunosuppression in ABO-incompatible kidney transplantation.

ABO-incompatible (ABOi) kidney transplantation (KTx) has become an accepted therapeutic option in renal replacement therapy for patients without a blood group-compatible living donor. Using different desensitization strategies, most centers apply B-cell depletion with rituximab and maintenance immunosuppression (IS) with tacrolimus and mycophenolic acid. This high load of total IS leads to an increased rate of surgical complications and virus infections in ABOi patients. Our aim was to establish ABOi KTx using an immunosuppressive regimen, which is effective in preventing acute rejection without increasing the risk for viral infections. Therefore, we selected a de novo immunosuppressive protocol with low-dose calcineurin inhibitor and the mTOR inhibitor everolimus for our ABOi program. Here, we report the first 25 patients with a complete three-yr follow-up treated with this regimen. Three-yr patient survival and graft survival were 96% and 83%. The rate of acute T-cell-mediated rejections was low (12%). Cytomegalovirus (CMV) infection was evident in one patient only (4%). Surgical complications were common (40%), but mild in 80% of cases. We demonstrate that ABOi KTx with a de novo mTOR inhibitor-based regimen is feasible without severe surgical or immunological complications and a low rate of viral infections.

An update on ABO-incompatible kidney transplantation.

ABO-incompatible kidney transplantation is nowadays a well-established procedure to expand living donor transplantation to blood group incompatible donor/recipient constellations. In the last two decades, transplantation protocols evolved to more specific isohaemagglutinin elimination techniques and established competent antirejection protection protocols without the need of splenectomy. ABOi kidney transplantation associated accommodation despite isohaemagglutinin reappearance, C4d positivity of peritubular capillaries as well as the increased incidence of bleeding complications is currently under intense investigation. However, most recent data show excellent graft survival rates equivalent to ABO-compatible kidney transplantation outcome.

ABO-incompatible kidney transplant recipients have a higher bleeding risk after antigen-specific immunoadsorption.

Pretransplant removal of antiblood group ABO antibodies is the cornerstone of all current ABO-incompatible (ABOi) transplantation programmes. In our protocol, plasmapheresis (PP) is performed with a plasmafilter followed by immunoadsorption (IA) of anti-ABO antibodies. The bleeding complications of this technique are not known. We analysed the data of all 65 consecutive ABOi kidney transplantations between March 2006 and October 2013 and compared these with matched 130 ABO-compatible (ABOc) kidney transplantations. Cases differed from controls in the pre-operative regimen, which included IA-PP and rituximab, tacrolimus, mycophenolate mofetil, prednisone and immunoglobulines. Data on platelet count, blood loss and red blood cell (EC) transfusions during 48 h postoperatively were collected. ABOi patients received EC transfusions more frequently than controls (29% vs. 12%, P = 0.005). Intra-operative blood loss was higher (544 vs. 355 ml, P < 0.005) and they experienced more major bleeding (≥3 EC within 24 h, 15% vs. 2%, P < 0.0005). Platelet count decreased by 28% after the pre-operative IA. In a multivariate model, only the number of pre-operative IAs was associated with the number of ECs given (OR per IA 1.9, P < 0.05). ABOi kidney transplant recipients have a high postoperative bleeding risk, correlating with the number of pre-operative IA sessions performed.