ABO-incompatible Patients Research Articles

Incidence and Outcome of C4d Staining With Tubulointerstitial Inflammation in Blood Group-incompatible Kidney Transplantation.

The last Banff 2013 report recognizes acute/active antibody-mediated rejection (ABMR) and C4d staining without evidence of rejection. The goal of our study was to analyze the incidence of C4d deposition after ABO-incompatible transplantation and assess outcomes in patients with ABMR, C4d staining without evidence of rejection (all acute Banff scores = 0), and C4d staining with tubulointerstitial inflammation (i > 0 with or without tubulitis). Three-months 'For cause' or protocol biopsies in 50 ABO-incompatible patients were rescored and were correlated with clinical outcomes and antibody titres. Active/acute ABMR was found in 23 patients (46%), C4d staining without evidence of rejection in 7 patients (14%), C4d staining with tubulointerstitial inflammation in 6 patients (12%), tubulointerstitial inflammation in 6 patients (12%), and no evidence of rejection in 8 patients (16%). Patients with active/acute ABMR had a 3-month estimated glomerular filtration rate (median,: 43 mL/min) lower than patients with no evidence of rejection (median, 61 mL/min; P = 0.01). However, after 3 months, a progressively declining estimated glomerular filtration rate was observed more frequently in patients with C4d staining and tubulointerstitial inflammation when compared to patients with no evidence of rejection (100% vs 25%, P = 0.03). Finally, independently of C4d status, interstitial inflammation occurred more frequently in patients with a pretransplant ABO antibody titre higher than 16 and/or posttransplant ABO antibody increase. Whereas isolated C4d deposition and isolated interstitial inflammation appear to be benign lesions, C4d deposition in association with interstitial inflammation is the biopsy finding most strongly associated with the development of chronic graft dysfunction.

The Reuse of Immunoadsorption Columns in ABO-Incompatible Kidney Transplantation Is Efficient: The Swiss Experience.

We developed a multicentric Swiss protocol for ABO-incompatible kidney transplantation including immunoadsorption column reuse. The aim of this study was to assess efficacy and safety of immunoadsorption column reuse in ABO-incompatible kidney transplantation. We performed a multicentric prospective trial including all ABO-incompatible kidney transplantations in Switzerland from 2005 to 2011. Patients received rituximab and standardized immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. Antigen-specific perioperative immunoadsorption was performed. Immunoadsorption columns were reused after restoration. Graft survival, patient survival, kidney function, rejections, number of columns, adverse events after column reuse, and anti-A/anti-B antibody titers were assessed. Seventy-one ABO-incompatible patients underwent antigen-specific immunoadsorption and could be transplanted across the blood group barrier. Kaplan-Meier estimates for both, patient-censored and death-censored graft survivals were both 97.2% at 5 years. Allograft function was excellent with a mean estimated glomerular filtration rate of 54 mL per min after 1 year. The median number of pretransplant immunoadsorptions was 5. All centers performed column reuse. A total of 394 immunoadsorption procedures were performed with reused filters. Patient survival, graft survival, and adverse events did not differ when filters were reused. Column reuse resulted in cost savings of 21,458 USD per patient. We have introduced a national protocol for ABO-incompatible kidney transplantation including immunoadsorption column reuse. Column reuse was efficient and safe.

A Systematic Review of the Use of Rituximab for Desensitization in Renal Transplantation

Rituximab is a B lymphocyte-depleting agent used to treat lymphoma and autoimmune diseases. Recently, it has been used for desensitization therapy in ABO-incompatible and highly sensitized recipients undergoing renal transplantation. A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Four databases and three trial registries were searched for studies comparing rituximab with non-rituximab desensitization protocols. A lack of randomized evidence precluded meta-analysis, and thus a narrative review was conducted. Forty-five records met the inclusion criteria, relating to 21 individual studies (two randomized controlled trials and 19 retrospective cohort studies). Ten studies investigated the use of rituximab in ABO-incompatible patients; most found no significant differences in patient and graft outcomes when compared most frequently to splenectomy-based protocols. Nine studies of limited quality focused on highly sensitized recipients (positive cross-match, donor-specific antibody, and elevated panel reactive antibody) and demonstrated some benefits in graft survival, acute and chronic rejection, and sensitization levels with rituximab. The remaining two studies combined ABO-incompatible and highly sensitized recipients and found no statistically significant increase in infectious complications with rituximab. Evidence of limited quality was identified to support the use of rituximab desensitization in highly sensitized recipients. Among ABO-incompatible recipients, rituximab was found to be equivalent to splenectomy, indicating that this invasive surgical procedure is not necessary. Further randomized controlled trials are required to better define the efficacy, long-term safety, and optimal dosing regimen of rituximab in this setting.

OR52: DE-NOVO DEVELOPMENT OF DONOR MISMATCHED HLA IS SIGNIFICANTLY REDUCED IN ABO-INCOMPATIBLE RENAL TRANSPLANT RECIPIENTS: IMPLICATION FOR LONG TERM ALLOGRAFT FUNCTION

Aim To determine whether the abrogation of development of donor specific antibodies (DSA) following ABO incompatible (ABOi) transplants is due to “accommodation” resulting in better graft outcome of ABOi renal transplants in comparison to ABO compatible (ABOc) renal transplants (RTx). Method RTx recipients with ABOi (n = 18) and ABOc (n = 47) with similar demographics were selected for this study [Table 1]. Pre and post-transplant sera were analyzed for DSA to Class I and II human leukocyte antigen (HLA) using LabScreen Single Antigen assay. Both groups had no detectable HLA and were crossmatch compatible. ABOi patients underwent plasmaheresis, intravenous immunoglobulin and Rituximab to reduce antibodies to blood group antigens, while ABOc patients received intravenous thymoglobulin in the immediate post-transplant period. Both groups were maintained on identical immunosuppressive regimen with triple therapy. Results Allo-immune response in ABOi and ABOc RTx patients was analyzed by measuring de novo development of DSA. None of the ABOi group developed DSA either to HLA Class I or Class II. In contrast, ABOc recipients developed DSA, 11 of 47 (23%). It is of significance that ABOi recipients with similar HLA mismatches to ABOc recipients failed to develop any detectable DSA which may account for lower incidence of acute rejection in ABOi group. In the ABOi only 2 of 18 (11%) developed acute rejection episodes which were reversible compared to 9 of 47 (20%) in the ABOc group. At the end of one year, glomerular filtration rate was also significantly better (p Conclusion Our study demonstrates that desensitization using Rituximab, intravenous immunoglobulin and plasmapheresis for depleting antibodies in ABOi RTx patients prior to transplantation abrogates de novo development of DSA, likely due to accomodation, may account for the better outcome of the ABOi renal transplants.

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 48h 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. 355ml, P<0.005) and they experienced more major bleeding (≥3 EC within 24h, 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.

ABO-Incompatible Kidney Transplantation Outcomes: A Single Center Experience.

Background In recent years, ABO-incompatible kidney donor protocols have been developed, allowing more patients access to kidneys from a living donor. However, it is still unclear what the long-term outcomes of ABO-incompatible kidney transplantation are. Methods We conducted a single center case control study comparing 10 ABO-incompatible (ABO-i) kidney transplantations to 40 ABO-compatible (ABO-c) kidney transplantations. Controls were matched by gender, age and follow-up period. ABO-i recipients were treated with a single dose of rituximab four weeks before transplantation and started triple immunosuppressive treatment (prednisone, mycophenolate mofetil and tacrolimus) two weeks before transplantation. All ABO-incompatible recipients received IVIG preoperatively. Immunoadsorption was conducted at least four times preoperatively, with additional sessions being performed if the target anti donor blood type IgG ≤ 1:8 had not been reached. Postoperatively, 3 immunoadsorptions were conducted. Results ABO-i and ABO-c patients were followed for a median period of 2,25 vs. 2,5 years respectively. There was no significant difference in patient and graft survival. Kidney function (as measured by creatinin clearance, MDRD and proteinuria) was also not significantly different, although there was a trend toward a lower kidney function in ABO-i patients. ABO-i patients had more biopsy-proven rejection episodes (50% in ABO-i vs. 15% in ABO-c, p=0,018) for which they received additional immunosuppressive treatment. This resulted in significantly more infections (1,7 infections per ABO-i patient vs. 0,9 infections per ABO-c patient, p=0,045). The number of days in the hospital in the first year post-transplantation was also higher in the ABO-i group (24 vs. 15,5 median days). In linear regression analysis, higher baseline anti donor blood type IgG were predictive of a lower kidney function during follow-up. Conclusion ABO-i transplantations can be performed successfully, without a significant difference in patient and graft survival after a median follow-up of 2,25 years. However, patients are at increased risk of rejections and infections. Patients with high anti donor blood type IgG are not suitable candidates for ABO-i kidney transplantation.

Low Titer Group O Whole Blood in Emergency Situations

In past and ongoing military conflicts, the use of whole blood (WB) as a resuscitative product to treat trauma-induced shock and coagulopathy has been widely accepted as an alternative when availability of a balanced component-based transfusion strategy is restricted or lacking. In previous military conflicts, ABO group O blood from donors with low titers of anti-A/B blood group antibodies was favored. Now, several policies demand the exclusive use of ABO group-specific WB. In this short review, we argue that the overall risks, dangers, and consequences of "the ABO group-specific approach," in emergencies, make the use of universal group O WB from donors with low titers of anti-A/B safer. Generally, risks with ABO group-specific transfusions are associated with in vivo destruction of the red blood cells transfused. The risk with group O WB is from the plasma transfused to ABO-incompatible patients. In the civilian setting, the risk of clinical hemolytic transfusion reactions (HTRs) due to ABO group-specific red blood cell transfusions is relatively low (approximately 1:80,000), but the consequences are frequently severe. Civilian risk of HTRs due to plasma incompatible transfusions, using titered donors, is approximately 1:120,000 but usually of mild to moderate severity. Emergency settings are often chaotic and resource limited, factors well known to increase the potential for human errors. Using ABO group-specific WB in emergencies may delay treatment because of needed ABO typing, increase the risk of clinical HTRs, and increase the severity of these reactions as well as increase the danger of underresuscitation due to lack of some ABO groups. When the clinical decision has been made to transfuse WB in patients with life-threatening hemorrhagic shock, we recommend the use of group O WB from donors with low anti-A/B titers when logistical constraints preclude the rapid availability of ABO group-specific WB and reliable group matching between donor and recipient is not feasible.

Application of complement component 4d immunohistochemistry to ABO-compatible and ABO-incompatible liver transplantation

Antibody-mediated rejection (AMR) is difficult to diagnose after ABO-compatible or ABO-identical (ABO-C) liver transplantation. To determine whether complement component 4d (C4d) immunostaining would be useful for diagnosing AMR, we compared the results of C4d immunohistochemistry for allograft biopsy samples with assays for anti-donor antibodies performed at the time of biopsy. One hundred fourteen patients with ABO-C grafts and 29 patients with ABO-incompatible (ABO-I) grafts were included. Linear C4d endothelial staining (identifiable with a 4× objective lens) or staining seen in 50% or more of the portal tracts was considered positive. Five of the 114 patients (4%) with ABO-C grafts and 15 of the 29 patients (52%) with ABO-I grafts showed C4d positivity. In the ABO-C cases, C4d positivity in late biopsy samples (≥30 days after transplantation) was associated with stage 2 or higher fibrosis (METAVIR score; P = 0.01) and with the presence of donor-specific anti-human leukocyte antigen DR antibodies (HLA-DR DSAs) with a mean fluorescence intensity > 5000 according to the Luminex single-antigen bead assay (P = 0.04). Conversely, the presence of HLA-DR DSAs was associated with the presence of stage 2 or higher fibrosis, acute cellular rejection, and C4d positivity. During the 2-year follow-up, neither C4d positivity nor HLA-DR DSAs were related to graft loss. Among ABO-I patients, C4d positivity was not associated with allograft dysfunction or fibrosis. Only 3 of the 15 C4d-positive patients (20%) showed periportal hemorrhagic edema, which could be a histological sign of AMR in ABO-I grafts, and they were the only cases associated with elevations in anti-donor A/B antibody titers. In conclusion, C4d endothelial positivity among ABO-C patients is an uncommon event that could be associated with chronic graft damage with or without clinical AMR. C4d positivity is common among ABO-I patients and may not be associated with allograft dysfunction if alloantibody titers are not elevated.

Plasma exchange in small intestinal transplantation between ABO-incompatible individuals: A case report

The aim of this study was to investigate the application of plasma exchange in small intestinal transplantation between ABO blood type-incompatible patients. A small intestinal transplantation case between ABO-incompatible individuals is hereby presented and analyzed. The main treatment included plasma exchange, splenectomy and immunosuppression. The patient undergoing small intestinal transplantation exhibited stable vital signs. A mild acute rejection reaction developed ~2 weeks after the surgery, which the patient successfully overcame. The subsequent colonoscopy and pathological examination revealed no signs of acute rejection. In conclusion, plasma exchange in combination with anti-immune rejection therapy proved to be an effective scheme for the management of small intestinal transplantation between ABO-incompatible patients.

Randomized comparative trial of mizoribine versus mycophenolate mofetil in combination with tacrolimus for living donor renal transplantation

Mizoribine (MZR) was approved in 1984 in Japan for the suppression of rejection in renal transplantation with an approved administration dosage of 1-3mg/kg/day. The action of MZR resembles that of mycophenolate mofetil (MMF), but MZR dosing is markedly lower than that of MMF. To examine whether higher dosing of MZR could obtain efficacy similar to MMF in renal transplantation, we conducted a comparative study of MZR and MMF using a high daily dose of MZR. A prospective, randomized comparative study of MZR versus MMF using tacrolimus (FK) and steroids as the base was conducted in 35 patients who had undergone living-donor renal transplantation (ABO-incompatible patients were not included) at 8 institutions in Japan between July 2005 and June 2007. Starting doses were 12mg/kg/day for MZR and 2g/day for MMF. Dosages of FK and steroids were set according to the protocol of each institution. Patient and graft survival rate at 1year after transplantation was 100% in each group, with no significant difference in rejection rate apparent between groups. Adverse events found in both groups were characteristic, frequently involving infection and digestive organ disorder in the MMF group and elevated uric acid levels in the MZR group. Based on these results, MZR and MMF are considered almost equivalent in terms of efficacy and safety.

BK Virus Allograft Nephropathy: Enhanced Risk for ABO-Compared to HLA-Incompatible Kidney Transplantation

Introduction: It has been observed in some studies that ABO-incompatible kidney transplant recipients have a higher incidence of BK virus allograft nephropathy (BKVAN) compared to ABO-compatible recipients. This could be related to desensitisation and induction protocols or a greater risk for rejection treatment. It is unclear whether HLA-incompatible kidney recipients, who share similar treatment protocols, share this risk or whether this phenomenon is unique to ABO-incompatible patients. Methods: We analysed adult incompatible kidney transplant recipients from a prospectively kept database. 68 ABO-incompatible and 221 HLA-incompatible, transplanted between 1998 and 2010, formed the patient cohort. Patients transplanted against both immunological barriers were excluded from analysis. Protocol biopsies were performed for all incompatible patients on months 1, 3, 6 and 12 post-transplantation and indication biopsies in the context of transplant dysfunction (creatinine rise greater than 20% from baseline and/or new-onset proteinuria). All incompatible patients diagnosed with BKVAN on biopsy (protocol or for cause) were identified. Multivariable logistic regression analysis was used to identify independent risk factors for development of BKVAN. Results: Risk of BKVAN was greater amongst ABO-incompatible compared to HLA-incompatible patients (17.7% versus 5.9%, p=0.008). This compared to the BKVAN rate of 3.0% observed amongst all kidney transplant recipients, compatible or not, at this transplant centre. 42% of BKVAN cases were subclinical and diagnosed on protocol biopsy. ABO-incompatibility, male sex and age were independent predictors for development of BKVAN on multivariable logistic regression. C4d deposition without histologic features of rejection (the typical ABO-incompatible graft ‘accommodation’ phenotype) on 1-year protocol biopsies of ABO-incompatible patients, with and without BKVAN, was 40% versus 75.8% respectively (p=0.040), a putative pathophysiological mechanism. At median follow up of 1399 days post-transplantation, ABO-incompatible patients with BKVAN had death-censored graft survival of 91% and serum creatinine of 1.8 mg/dl amongst surviving kidneys. For HLA-incompatible patients, at median of 1017 days post-transplant death-censored graft survival was also 91% and serum creatinine 1.8 mg/dl amongst surviving kidneys. In contrast compatible kidney recipients, at a median of 1117 days post-transplantation, death-censored graft survival were 69% and serum creatinine 2.6 mg/dl amongst surviving kidneys. Conclusion: This study suggests that ABO-incompatible patients have an elevated risk of developing BKVAN unrelated to desensitisation, intensity of immunosuppression or risk of antibody-mediated rejection. However risk of BKVAN related graft loss is negligible, contrary to compatible kidney transplant recipients, which we hypothesise is due to early sub-clinical detection using protocol biopsy surveillance. Thus ABO-incompatible patients may have unique risk profiles and mechanisms for development and progression of BKVAN but this speculation requires further investigation.

Intentional ABO-incompatible heart transplantation: A case report of 2 adult patients

In 2009, we started to screen all patients on the heart transplant waiting list for the presence of blood group anti-A or anti-B antibodies. From our experience with ABO-incompatible kidney transplantation, we know that transplantation can safely be performed if the antibody level is reduced to a titer of immunoglobulin G (IgG) 1:8. We decided to accept all patients with anti-A or anti-B antibody titer ≤1:8 for ABO-incompatible heart transplantation without any special pre-treatment and patients with antibody titers of IgG 1:16 and 1:32, provided 1 apheresis session could be performed immediately before transplantation. We found 6 of 13 patients were suitable for this program, and 2 ABO incompatible patients underwent successful transplantation with a follow-up of 1 year. In heart transplant candidates where there are problems obtaining a compatible heart and who are not suitable for ventricular assist device support, ABO-incompatible heart transplantations can be considered using our protocol, provided that the levels of anti-A or anti-B antibodies are low.

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Aim Virtual cross matches (VXMs) are key to the success of KPD by aiding identification of compatible donors for sensitized candidates. We evaluated the success of unstandardized VXMs combined with donor preselection by National Kidney Registry (NKR) centers in a population of mostly sensitized and/or ABO incompatible patients. Methods The NKR initiated 437 match offers among 62 US transplant centers based on acceptable VXMs between 3/14/2011 to 3/31/2012. We evaluated the accuracy of the VXM by examining whether or not offers were declined due to positive final XMs. The VXM considered antibodies to HLA-A, B, C, DRB1/3/4/5, DQB1 and DPB1 detected by Single Antigen assays and donor HLA typing. Each center established its own immunological criteria for donor acceptability. To reduce late stage match failures online pre-selection of donors was introduced in July 2011 which allowed centers to accept potential donors based on HLA types and other characteristics prior to a match run. Results NKR centers achieved a 92% VXM accuracy rate and completed 181 transplants; 32% of these had PRA > 80%. Only 29 (8%) offers were rejected by the recipients’ center due to an unacceptable positive final crossmatch. In most cases, the discrepancy with the VXM was due to DSA at or near the center’s threshold or to multiple DSAs when each fell below the threshold of unacceptability. Other cases were due to DQA antibodies (3), non-HLA antibodies (3), a change in antibody profile (1), and data entry error (1). Interestingly, the rate of false negative VXM remained unchanged after the implementation of the pre-selection strategy, while the rate of late-stage cancellations due to unacceptable donors decreased from 5% to 2%. Conclusions Access to transplant for sensitized patients with minimal disruption of chains has improved by pre-selection of acceptable pairs, optimizing data entry for the VXM, frequent antibody monitoring following sensitizing events and good communication between transplant centers and their labs. Sinacore: NKR: Employee.

Incidence and Outcomes of BK Virus Allograft Nephropathy among ABO- and HLA-Incompatible Kidney Transplant Recipients

ABO-incompatible kidney transplant recipients may have a higher incidence of BK virus allograft nephropathy (BKVAN) compared with ABO-compatible recipients. It is unclear whether HLA-incompatible recipients share this risk or whether this phenomenon is unique to ABO-incompatible recipients. DESIGN, SETTING, PARTICIPATION, MEASUREMENTS: This study analyzed adult incompatible kidney transplant recipients from 1998 to 2010 (62 ABO-incompatible and 221 HLA-incompatible) and identified patients in whom BKVAN was diagnosed by biopsy (per protocol or for cause). This was a retrospective analysis of a prospectively maintained database that compared BKVAN incidence and outcomes between ABO- and HLA-incompatible recipients, respectively. BKVAN link to rejection and graft accommodation phenotype were also explored. The Johns Hopkins Institutional Review Board approved this study. Risk for BKVAN was greater among ABO-incompatible than HLA-incompatible patients (17.7% versus 5.9%; P=0.008). Of BKVAN cases, 42% were subclinical, diagnosed by protocol biopsy. ABO-incompatibility and age were independent predictors for BKVAN on logistic regression. C4d deposition without histologic features of glomerulitis and capillaritis (graft accommodation-like phenotype) on 1-year biopsies of ABO-incompatible patients with and without BKVAN was 40% and 75.8%, respectively (P=0.04). Death-censored graft survival (91%) and serum creatinine level among surviving kidneys (1.8 mg/dl) were identical in ABO- and HLA-incompatible patients with BKVAN (median, 1399 and 1017 days after transplantation, respectively). ABO-incompatible kidney recipients are at greater risk for BKVAN than HLA-incompatible kidney recipients. ABO-incompatible recipients not showing the typical graft accommodation-like phenotype may be at heightened risk for BKVAN, but this observation requires replication among other groups.

ABO-incompatible heart transplantation: Analysis of the Pediatric Heart Transplant Study (PHTS) database

ABO incompatible (ABOi) heart transplantation is an accepted approach to increasing organ availability for young patients. Previous studies have suggested that early survival for ABOi transplants is similar to ABO compatible (ABOc) transplants. We analyzed the Pediatric Heart Transplant Study (PHTS) database from 1/96 to 12/08 to further assess this strategy. We analyzed the numbers of ABOi and ABOc done at the PHTS centers. We then compared the clinical characteristics, and short-term freedom from death, rejection and infection in the ABOi patients with the patients that had an ABOc heart transplant during the same period. All patients were less than or equal to 15 months of age at listing (the age of the oldest ABOi patient). We adjusted for co-variates shown to increase risk for mortality (age less than 1 month, extracorporeal membrane oxygenation (ECMO), ventilator, previous sternotomy, and congenital heart disease). There were 931 total transplants done at 34 PHTS centers during the 12 year time period in patients ≤15 months of age. Of these, 502 transplants were performed at 20 PHTS centers that did at least one ABOi heart transplant. Eighty-five of the 502 (17%) were ABOi. At time of transplant, ABOi recipients compared with ABOc were more likely to be on a ventilator (49.4% vs 36.5%, p=0.025), and more often supported with ECMO (23.5% vs 13.4%, p=0.018). There was similar survival at 12 months (82% vs 84%, p=0.7). In risk adjusted analysis ABOi status was not associated with 1 year mortality (HR 0.85, 95% CI 0.45-1.6, p=0.61). The ABOi patients had greater freedom from rejection when compared with ABOc patients for all 34 centers (75% vs 62%, p=0.016), but the difference was not significant when limited only to the 20 centers doing ABOi transplants (75% vs 69%, p=0.4). The ABOi cohort had lower infection rates (23.5% vs 37.9%, p = 0.013). This difference remained after adjusting for center and other covariates. In center and risk adjusted analysis, young children who received an ABOi transplant had equivalent one-year survival and freedom from rejection compared with those who received an ABOc transplant. In spite of the favorable outcome for ABOi recipients, many centers appear to reserve ABOi transplantation for sicker patients. These data mandate reexamination of the current United Network for Organ Sharing (UNOS) policy that gives priority to ABOc over ABOi transplantation in the United States.

Successful ABO-Incompatible Kidney Transplantation with Antibody Removal and Standard Immunosuppression

ABO-incompatible (ABOi) kidney transplantation is an established therapy, though its implementation to date has been in part limited by the requirement for additional immunosuppression. Here, we describe the outcomes of 37 patients undergoing ABOi kidney transplantation utilizing perioperative antibody depletion and receiving an identical tacrolimus-based immunosuppressive regimen to contemporaneous ABO-compatible (ABOc) recipients, with the exception that mycophenolate was commenced earlier (7-14 days pretransplant). Antibody depletion was scheduled according to baseline anti-ABO antibody titer (tube IAT method: median 1:128, range 1:8 to 1:4096). Patient and graft survival for the 37 ABOi recipients was 100% after a median 26 months (interquartile range [IQR] 18-32). Eight rejection episodes (two antibody-mediated and six cellular) in ABOi recipients were successfully treated with biopsy-proven resolution. Latest median eGFR is 50 mL/min × 1.73 m² (IQR 40-64) for ABOi patients and 54 mL/min × 1.73 m² (IQR 44-66) in the ABOc patients (p = 0.25). We conclude that ABOi transplantation can be performed successfully with perioperative antibody removal and conventional immunosuppression. This suggests that access to ABOi transplantation can include a broader range of end-stage kidney disease patients.

Short-term results of ABO-incompatible living donor kidney transplantation: comparison with ABO-compatible grafts

PurposeABO incompatible (ABOi) kidney transplantation (KT) has been increasing to compensate for the shortage of organ donors. However, detailed comparative analyses of ABOi KT with ABO compatible (ABOc) KT are still rare.MethodsThis retrospective study compared 12 consecutive ABOi KTs to 50 ABOc KTs that employed the same maintenance immunosuppressive agents during the same period. Comparisons of patient survival, graft survival, graft function, and complications were made until post-transplant day 90.ResultsBaseline characteristics of the two groups were similar except for the positivity of panel reactive antibody (12% in the ABOc group vs. 42% in the ABOi group; P = 0.029). There were no significant differences in patient survival, graft survival, post-operative renal function, incidence of acute rejection, infections, or medical and surgical complications. However, bleeding complications were more common in the ABOi group (25%) than versus the ABOc group (6%) (P = 0.08). The preoperative and total hospital stay of the ABOi patients was significantly longer than the ABOc patients (P = 0.001).ConclusionABOi KT is a viable and safe option for patients whose only donor is blood incompatible, despite the longer preoperative hospital stay for preparation.

Equivalent Outcomes for Pediatric Heart Transplantation Recipients: ABO-Blood Group Incompatible versus ABO-Compatible

ABO-blood group incompatible infant heart transplantation has had excellent short-term outcomes. Uncertainties about long-term outcomes have been a barrier to the adoption of this strategy worldwide. We report a nonrandomized comparison of clinical outcomes over 10 years of the largest cohort of ABO-incompatible recipients. ABO-incompatible (n = 35) and ABO-compatible (n = 45) infant heart transplantation recipients (< or =14 months old, 1996-2006) showed no important differences in pretransplantation characteristics. There was no difference in incidence of and time to moderate acute cellular rejection. Despite either the presence (seven patients) or development (eight patients) of donor-specific antibodies against blood group antigens, in only two ABO-incompatible patients were these antibodies implicated in antibody-mediated rejection (which occurred early posttransplantation, was easily managed and did not recur in follow-up). Occurrence of graft vasculopathy (11%), malignancy (11%) and freedom from severe renal dysfunction were identical in both groups. Survival was identical (74% at 7 years posttransplantation). ABO-blood group incompatible heart transplantation has excellent outcomes that are indistinguishable from those of the ABO-compatible population and there is no clinical justification for withholding this lifesaving strategy from all infants listed for heart transplantation. Further studies into observed differing responses in the development of donor-specific isohemagglutinins and the implications for graft accommodation are warranted.

Comparative Outcome Analysis of ABO-Incompatible and Positive Crossmatch Renal Transplantation: A Single-Center Experience

ABO-incompatible (ABOi) and positive crossmatch (XM) renal transplants pose special immunologic challenges. It is important to compare outcomes, study resource utilization, and attempt to risk stratify patients in these higher risk transplant settings. We compared apheresis utilization and transplant outcomes in ABOi, XM, and combined ABOi-XM renal transplants. We also analyzed multiple parameters, including patient and laboratory variables, to identify predictors of transplant outcome. Incidences of early (< or =30 days posttransplant) antibody-mediated rejection (AMR) and acute cellular rejection (ACR) were similar among the three incompatible groups whereas they differed in allograft rejection for late (>30 days posttransplant) AMR and ACR. Notably, there were no episodes of late AMR among ABOi patients. Patients treated with more than four pretransplant plasmapheresis/intravenous immunoglobulin (PP/IVIg) had a greater likelihood of experiencing early AMR. The median number of posttransplant PP/IVIg treatments was greater than twofold higher in ABOi-XM and XM patients compared to ABOi patients. Patients who required more than five posttransplant PP/IVIg procedures and those with one or more prior renal transplants had higher incidences of late ACR. Our analysis aids in defining apheresis resource utilization and helps in risk stratification of incompatible renal transplantation. It also aids in predicting allograft rejection and provides an opportunity for preemptive monitoring and treatment.

ABO Incompatible Living Renal Transplantation With a Steroid Sparing Protocol

ABO incompatible (ABOi) live-donor renal transplantation is a successful and accepted form of treatment for patients with renal failure. Although there is significant controversy as to how antiblood group antibodies should be removed and their resynthesis prevented, subsequent immunosuppressive regimes have all involved steroids. We and other groups have successfully used steroid sparing regimes for conventional ABO compatible transplantation and this study describes the use of our steroid sparing protocol in ABOi transplantation. We have transplanted 10 ABOi patients using 1 week of steroids (prednisolone 1 mg/kg for 4 days, 0.5 mg/kg for 3 days and then stopped), tacrolimus and mycophenolate mofetil. Steroids were reintroduced in the event of rejection. Patient- and allograft-survival 1 year posttransplantation is 100%. Three patients experienced antibody-mediated rejection within 2 weeks of transplantation, which was successfully reversed. There has been no late rejection. Allograft function was similar to our live-donor ABO compatible transplant patients receiving a similar steroid sparing regime (12-month mean creatinine 131+/-15 micromol/L vs. 138+/-48 micromol/L; mean CrCl 63.2+/-22 mL/min vs. 56.7+/-20 mL/min). This study shows that ABOi live-donor transplantation can be successfully accomplished using a steroid-sparing protocol.