Pretransplant Blood Transfusions Research Articles

The Risk of Pretransplant Blood Transfusion for Primary Graft Dysfunction After Lung Transplant

BackgroundPrimary graft dysfunction (PGD) is the leading cause of short- and long-term mortality associated with lung transplantation. The impact of pretransplantation blood transfusions for recipients is not fully elucidated. MethodsThis is a retrospective review of 206 consecutive lung transplantations performed at a single academic center (Northwestern University Feinberg School of Medicine, Chicago, IL) from January 2018 to July 2022. Data on patient characteristics, pretransplantation laboratory values, transfusion requirements, and intraoperative and postoperative outcomes were collected. ResultsPGD grade 3 (PGD 3) occurred in 13.2% of the cohort (n = 28). A total of 33 patients received a blood transfusion within 4 weeks, whereas 21 patients received a blood transfusion a week before their lung transplant. Pretransplantation transfusions were strongly associated with a higher incidence of PGD 3 (48.5% vs 6.9%; P < .001). There was no significant difference in 1-year survival between the pretransplantation transfused group and the nontransfused group (77.7% vs 88.0%; P = .478). The 1year survival was reduced in recipients with PGD 3 compared with recipients without PGD 3 (63.5% vs 89.9%; P = .0012). In univariate analysis, pretransplant and intratransplant predictors of PGD 3 included younger age (P < .01), pretransplant extracorporeal membrane oxygenation (ECMO) use (P < .001), higher lung allocation score (P < .001), coronavirus disease 2019 (COVID-19)–related acute respiratory distress syndrome (P < .01), blood transfusion within 4 weeks (P < .001), longer operative time (P < .001), intratransplant blood transfusion (P < .001), and intratransplant venoarterial ECMO use (P < .001). ConclusionsPretransplantation blood transfusions could be associated with a higher rate of PGD. The findings indicated the potential risks of pretransplantation blood transfusions in lung transplant recipients.

Does Overnight Heart Transplantation Lead to Worse Outcomes? Results from a High Volume Transplant Center

<h3>Purpose</h3> Prior studies showed an association between nighttime surgery and worse outcomes after kidney and liver transplants. We evaluated if outcomes are inferior after nighttime heart transplants. <h3>Methods</h3> An institutional registry identified 1087 adult heart transplants between 2010 and 2020. Overnight transplants (incision time 7pm-5am, n=541) were compared to daytime transplants (incision time 5am-7pm, n=546). Outcomes included in-hospital complications, 5-year survival, 5-year incidence of non-fatal major adverse cardiac events (NF-MACE) (myocardial infarction, new congestive heart failure, percutaneous coronary intervention, pacemaker implant, stroke) and treated rejections, with death as a competing risk <h3>Results</h3> Nighttime transplants had similar recipient/donor profile to daytime transplants, except for more pre-transplant blood transfusions (41.2% vs. 33.9%, p=0.01) and geographically closer donors (63, IQR 24-299 vs. 98, IQR 35-348 miles, p=0.02). They had longer aortic cross clamp time (90, IQR 73-111 vs. 86, IQR 70-106 mins, p=0.02) but similar rates of primary graft dysfunction (14.3% vs. 16.5%, p=0.3) and reoperation for bleeding (3.1% vs. 4.2%, p=0.35) compared to daytime transplants. There was no difference in 5-year survival (Figure), NF-MACE (28%, 95% CI 23.4-32.9 vs. 31.4%, 95% CI 26.7-36.3, p=0.33) and rejections (22.9%, 95% CI 19.1-26.9 vs. 19.6%, 95% CI 20.4-28.0, p=0.65) between nighttime and daytime surgery. In multivariate analysis, nighttime surgery was not associated with increased mortality, after adjusting for baseline peripheral vascular disease, multiorgan transplant, urgent status, pre-transplant MCS/inotrope, MELD score, and ischemic time (HR 0.92, 95% CI 0.59-1.42, p=0.69) <h3>Conclusion</h3> Overnight transplants had outcomes comparable to daytime transplants in a high-volume transplant center. We attribute this to system-based practices to improve patient safety.

Redo orthotopic heart transplantation in the current era

ObjectiveThis study aims to investigate the trends, outcomes, and risk factors for mortality after redo orthotopic heart transplantation. MethodsThe United Network for Organ Sharing registry was used to identify adult orthotopic heart transplantation recipients from 2000 to 2020 and stratify into primary and redo cohorts. Five-year post-transplant survival was compared between 2 propensity-matched cohorts. Multivariable modeling was performed to identify risk-adjusted predictors of redo post-transplant mortality, both conditional and nonconditional on shorter-term survival. ResultsA total of 40,711 recipients were analyzed, 39,657 (97.4%) primary and 1054 (2.6%) redo. Redo recipients had a lower median age and were more frequently bridged with intravenous inotropes, intra-aortic balloon pump, or extracorporeal membrane oxygenation (all P < .05). One- and 5-year survivals were lower after redo orthotopic heart transplantation (90.0% vs 83.4% and 77.6% vs 68.6%, respectively) and remained lower after comparing 2 propensity-matched cohorts. Multivariable modeling found factors such as increasing donor age and graft ischemic times, along with pretransplant mechanical ventilation and blood transfusion, to negatively affect 90-day survival. Contingent on 1-year survival, donor factors such as hypertension (hazard ratio, 1.51; 95% confidence interval, 1.15-2.00, P = .004) and left ventricular ejection fraction less than 50% (hazard ratio, 2.22, 95% confidence interval, 1.16-4.24, P = .016) negatively affected survival at 5 years. ConclusionsAlthough infrequently performed, redo orthotopic heart transplantation remains associated with worse post-transplant outcomes compared with primary orthotopic heart transplantation. Although several high-risk features were identified to affect post-retransplant outcomes in the acute perioperative period, donor characteristics such as hypertension and decreased ejection fraction continue to have lasting negative impacts in the longer term.

Effect of donor-specific blood transfusions on allotransplanted teeth in a monkey model: Histoquantification of periodontal healing.

Pre-transplant blood transfusions have previously shown a positive effect on organ allograft survival in humans and various animal species. The aims of this study were, first, to evaluate the effect of pre-transplant donor-specific blood transfusions on periodontal healing of fully developed allotransplanted teeth in monkeys; and second, to investigate the immune response against donor antigens and to determine a possible correlation between alloimmune reactions and histopathological signs of rejection. Twenty monkeys (Cercopithecus aethiops) were divided into ten pairs with similar sizes of incisors. One monkey in each pair gave three transfusions to the other monkey with 1-week intervals. One week after the last transfusion, each pair exchanged simultaneously a central maxillary incisor and a lateral mandibular incisor. The corresponding central maxillary and mandibular lateral incisors were autotransplanted to the contralateral sockets. All teeth were treated endodontically per-operatively. Histocompatibility was evaluated by mixed lymphocyte culture before the first transfusion, while alloantibodies and cell-mediated alloresponses were measured before transfusions and at 2 and 8weeks after transplantation. All animals were sacrificed 8weeks after tooth transplantation. Serial sections of the transplanted teeth were quantified histologically. Mixed lymphocyte cultures showed positive reactions in 19 of 20 cases, indicating incompatibility. The majority of the monkeys developed antibodies towards the tooth donor. Cell-mediated cytotoxicity was negative in all monkeys. Histoquantification revealed a mean score of 70% normal periodontal ligament (PDL) in autotransplanted teeth, with 5% ankylosis. The allografts had a mean score of 17% normal PDL and 63% ankylosis, with no significant influence of transfusion. However, in the mandibular grafts, a tendency towards a positive transfusion effect was seen. Donor-specific blood transfusion did not reduce ankylosis in tooth allografts. The healing of mandibular incisor tooth allografts was improved, but not that of maxillary incisors. Donor-specific antibodies showed no effect on the survival of allograft PDL.

Böbrek Nakli Olan Hastalarda Nakil Sonrasında Oluşan Anti-HLA Antikorlarının Saptanması ve Çeşitli Parametrelerle İlişkisinin Değerlendirilmesi

Aim: In this study, it was aimed to evaluate the immunological response to graft and its association with related factors in the sera samples collected periodically from patients transplanted from deceased or alive donors in Izmir Tepecik Education and Research Hospital.Material and Method: Anti-HLA antibody screening and identification tests of 31 patient sera samples were performed by flow cytometric method. The sera samples were collected periodically (1st day, 1st week, 2nd week, 4th week, 12th week, 24th week and 52nd week) after transplantations in our hospital. After the screening of all samples, anti-HLA antibodies of PRA positive samples were identified. All of procedures were performed according to the manufacturer’s instructions. The other parameters were statistically evaluated by Pearson correlation test.Results: Of the patients, 12.9% and 6.45% were only class I and II positive in the post-transplant 52nd week, respectively. None of the patients was class I and II positive. It was found that antibodies were not produced against mismatched antigens on the 1st day, 1st, 2nd, 4th, and 12th weeks after transplantation. The antibodies were produced 24 weeks after transplantation in some cases. However, the results could not be evaluated statistically because of the small patient group. There were statistically significant correlations between last creatinine levels-donor ages and GFR values-patient ages (p&amp;lt;0.001, p&amp;lt;0.01, respectively), whereas there was no significant association between antibody production and creatinine levels. Conclusion: It was observed that anti-HLA antibodies were produced before transplantation in a patient with pre-transplant blood transfusion. The antibodies were produced in 24th week in five patients. Therefore, anti-HLA antibody screening tests to be performed on the 12th week after transplantation may be important for the treatment protocol.

P164 Role of anti-mica antibodies in graft survival of renal transplant recipients of India: A single centre experience

Aim To find the incidence of MHC class I chain-related chain A (MICA) alloantibodies in patients undergoing live related donor (LRD) renal transplantation and their association with short-term graft survival. Methods Pre-transplant, consecutive, serum samples of ESRD patients undergoing first renal allograft transplantation were tested for anti-MICA antibodies. Association of various demographics, HLA-A + B + DRB1 mismatches and HLA antibody screen with MICA antibodies was assessed using Pearson’s Chi-square test. A multivariate analysis was also performed to check for potential confounders. The effect of pre-transplant blood transfusions on antibodies against HLA Class 1 & class II, or MICA was studied. Results Out of 646 serum samples for MICA antibodies, 94 (14.6%) were positive and 552(85.4%) negative for MICA antibodies. Patients with MICA antibody had a graft survival 89.3% as compared to 94.7% in patients without MICA antibody (P = 0.01). The hazards ratio for all patients was 3.744 (P = 0.01). MANOVA effect was determined for three factors (HLA antibody, MICA antibody & HLA mismatch) and Graft survival which was statistically significant. Two of the three ANOVA’s were statistically significant viz. MICA antibody and presence of HLA antibody. Conclusions MICA antibodies were present in 14.6% of the patients. Preformed MICA antibodies independently increase the risk of kidney rejection and therefore a guideline should be made for mandatory testing of these antibodies prior to transplant.

Frequency of the Original Kidney Disease and Its Effect on the Outcome of Kidney Transplant in the Urology-Nephrology Center Mansoura University.

Renal allograft function and graft survival depends on many factors, including the source of the graft, immunologic matching between donor and recipient, incidence of acute rejection, and recurrence of the original kidney disease. This work aimed to evaluate the effects of the original kidney disease on patient and graft survival. This was a retrospective, single-center study that included 2189 kidney transplant recipients who were transplanted at The Urology and Nephrology Centre, Mansoura University, between 1976 and 2010. Of 2189 recipients, 1350 patients with unknown original kidney disease were excluded, with the remaining 839 patients divided into 4 groups according to their original kidney disease. We found pretransplant dialysis and blood transfusion to be statistically significant among the 4 groups. Regarding induction immunosuppressive therapy, a statistical significance was found between the 4 groups regarding the presence and type of induction therapy, with no statistical significance regarding the type of maintenance immunosuppression. There was no statistical significance between the 4 groups regarding the incidence of acute and chronic rejection. We also found recurrence of original kidney disease to be statistically significant in the 4 groups, particularly in the group that included patients with glomerular disease, where the highest rate of recurrence was reported in patients with focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis, and patient and graft survival was also statistically significant. The original kidney disease has an effect on renal allograft function and graft and patient survival.

Associations of pre‐transplant anemia management with post‐transplant delayed graft function in kidney transplant recipients

Delayed graft function (DGF) complicates kidney allograft outcomes in the immediate post-transplantation period. We hypothesized that in hemodialysis patients more severe anemia, iron deficiency, the requirement for higher doses of erythropoietin-stimulating agents (ESA), or blood transfusions prior to transplantation are associated with higher risk of DGF. Linking five-yr hemodialysis patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, we identified 11 836 hemodialysis patients. Using logistic regression analyses we examined the association between pre-transplant parameters and post-transplant DGF. Patients were 49 ± 14 (mean ± SD) yr old and included 38% women, 27% blacks, and 26% diabetics. After adjusting for relevant covariates, pre-transplant blood transfusion was associated with 33% higher DGF risk (odds ratio [OR] = 1.33; 95% confidence interval [CI]: 1.19-1.48); and each 5000 U/wk increase of pre-transplant ESA dose with 5% higher DGF (OR = 1.05; 95% CI: 1.02-1.09). Compared to pre-transplant blood hemoglobin of 12-12.99 g/dL, there was 25% higher risk of DGF with blood hemoglobin 10-10.99 g/dL (OR = 1.25; 95% CI: 1.01-1.55), whereas blood hemoglobin ≥13 g/dL exhibited 15% higher risk of DGF (OR = 1.15; 95% CI: 0.98-1.34). Pre-transplant blood transfusion, higher ESA dose, and either high or low blood hemoglobin but not iron markers are associated with higher risk of DGF.

Evaluation of live-donor kidney transplant survival in low body weight Egyptian children: 25 year-experience

Identification of problems associated with kidney transplantation in small weight children is an essential step toward improving graft function and patient survival. This study comprised 63 renal transplant children weighing 25 kg or less at time of renal transplantation. All children have received living-donor renal allotransplant between December 1984 and March 2009. These children were retrospectively evaluated regarding their survival, grafts survival as well as associated risk factors. Our patient and graft survival rates at 1, 5 and 10 years were (98.4%, 96.8%, and 96.8%) and (94.9%, 82.6%, and 58.4%), respectively. Significant better graft survival was obtained in cases with non-glomerular etiology of the end-stage renal disease, pre-emptive transplantation and when the aorta was used for arterial vascular anastomosis. Significant worse graft survival was documented among those who experienced pre-transplant hypertension, pre-transplant blood transfusion, post-transplant acute rejection, chronic rejection, hypertension and graft obstruction. The outcome of live donor renal transplantation in children weighing 15–25 kg in our locality as a developing country is comparable to other reports. Better graft survival rates might be obtained by adopting pre-emptive transplant policy, avoiding pre-transplant blood transfusions, using aorta for arterial vascular anastomosis in addition to adopting recent tacrolimus-based immunosuppressive regimens that is associated with reduced incidence of post-transplant acute rejection and graft dysfunction. La identificación de los problemas asociados con el trasplante de riñón en niños de bajo peso corporal es un paso esencial para mejorar la función del injerto y la supervivencia de los pacientes. El presente estudio incluyó a 63 pacientes sometidos a un trasplante de riñón cuyo peso era ≤25 kg en el momento del trasplante renal. Todos habían recibido un alotrasplante renal de donante vivo entre diciembre de 1984 y marzo de 2009. Estos niños se valoraron retrospectivamente con respecto a la supervivencia, supervivencia del injerto, al igual que factores de riesgo asociados. Las tasas de supervivencia de nuestros pacientes y del injerto a los 1, 5 y 10 años fueron del 98,4%, 96,8% y 96,8%, y del 94,9%, 82,6% y 58,4%, respectivamente. Se obtuvo una supervivencia del injerto significativamente mayor en los casos sin etiología glomerular de la nefropatía terminal, trasplante preferente y cuando se usó la aorta para la anastomosis vascular arterial. Entre los niños que experimentaban hipertensión pretrasplante, se sometieron a transfusión de sangre pretrasplante, experimentaron rechazo agudo postrasplante, rechazo crónico, hipertensión y obstrucción del injerto, se documentó una supervivencia del injerto significativamente más breve. El desenlace del trasplante renal de donante vivo en niños cuyo peso corporal es de 15–25 kg en nuestro centro en un país en vías de desarrollo es comparable al descrito en otras publicaciones. Además de adoptar las pautas inmunosupresoras recientes basadas en tacrólimo, que se asocian con una disminución de la incidencia de rechazo agudo postrasplante y disfunción del injerto, pueden obtenerse mayores tasas de supervivencia del injerto adoptando una política de trasplante preferente, evitando las transfusiones de sangre pretrasplante, utilizando la aorta para la anastomosis vascular arterial.

537 Contrary to Popular Belief, Pre-Transplant Blood Transfusions Are Uncommon Sensitizing Events in Patients Awaiting Heart Transplantation

Sensitization is the development of circulating antibodies in patients awaiting heart transplantation. Sensitization in these patients can mean a longer waiting time to transplant in order to find a compatible donor organ. One of the major causes of sensitization is the administration of blood transfusions in the pre-transplant time period. However, it is not known what the risk of individual blood transfusions is in terms of causing sensitization. We sought to determine the risk of separate blood transfusions in patients awaiting heart transplantation.

The impact of hepatitis C virus infection on long-term outcome in renal transplant patients

The aim of this study was to determine the effect of hepatitis C virus infection on patient and graft survival and liver function in renal transplant patients. 1811 renal transplant patients were included in this study. One hundred renal transplant patients (5.5%) were anti-hepatitis C virus-positive. We evaluated demographic, clinical, biochemical, and serological data of patients and compared patient and graft survivals between hepatitis C virus-positive and -negative renal transplant patients. The median follow-up period was 35.7 months. One hundred (5.5%) patients were anti-hepatitis C virus-positive. There were no differences between anti-hepatitis C virus-positive and -negative renal transplant patients regarding age, etiology of renal disease, number of pre-transplant blood transfusions, and hepatitis B virus coinfection rate. Rate of graft loss in anti-hepatitis C virus-positive renal transplant patients was significantly higher than in anti-hepatitis C virus-negative patients (16.0% vs. 9.2%, p=0.026). Survival analysis revealed that patient survival was similar between anti-hepatitis C virus-positive and -negative renal transplant patients. Graft survival was lower in the anti-hepatitis C virus-positive group than in anti-hepatitis C virus-negative patients, especially after the fifth year of renal transplant (p<0.001). Thirty-three percent of anti-hepatitis C virus-positive patients were positive for hepatitis C virus RNA. Twenty-seven percent of anti-hepatitis C virus-positive patients had persistent alanine aminotransferase elevation. None of the patients developed cirrhosis during the follow-up period. Our findings suggest that hepatitis C virus infection in renal transplant patients does not adversely affect patient survival. Long-term graft survival seems to be lower in hepatitis C virus-positive compared to hepatitis C virus-negative renal transplant patients. Nevertheless, renal transplant can be considered as a safe and effective treatment modality in anti-hepatitis C virus-positive patients with end-stage renal disease.

Transfusion sanguine et transplantation

Pretransplant blood transfusion remains a controversial subject and its history can summarize the last 40 years of transplantation. Until 1971, transfusions were widely used in patients awaiting transplantation, especially due to the anemia induced by the chronic renal dysfunction. Then, a noxious effect of preformed anti-HLA antibodies on renal grafts survival was reported and pretransplant transfusions were stopped. Between 1972 and 1977, improvement of renal graft survival in patients who received pretransplant transfusions was noted. Therefore, from 1978 on, a systematic policy of pretransplant transfusions was adopted by almost all centres of transplantation. During the eighties, it was again abandoned for several reasons: absence of graft survival improvement in patients treated by cyclosporine, HLA immunization leading to an increased incidence of acute graft rejection, risk of viral diseases transmission and human recombinant erythropoietin development. The lack of improvement in graft survival for ten years has been leading the transplant community to look for antigen-specific immunosuppressive strategies to achieve transplantation tolerance. Donor-specific transfusion may have clinical benefits, as long-term grafts survival improvement, through modulation of the recipient's cellular immune system and has been recently reconsidered, especially before living donor transplantation. The immunological mechanisms inducing a tolerance-gaining effect of transfusions are still misunderstood, but the recent discovery of immunomodulatory effects of the apoptotic cells present in cellular products could enlighten our comprehension of pretransplant transfusions benefits and could help to develop specific tolerance induction strategies in solid organ transplantation.

Differential Effect of Pretransplant Blood Transfusions on Immune Effector and Regulatory Compartments in HLA-Sensitized and Nonsensitized Recipients

Blood transfusion (BT) may elicit both harmful and beneficial immune responses against a subsequent organ graft. Immune parameters of a single, non leukocyte-depleted BT were investigated in two groups: non-human leukocyte antigen (HLA)-sensitized recipients with a one-HLA-DR matched donor (protocolled BT [PBT]) and females with previous exposure to HLA alloantigens through pregnancy (donor-specific transfusion [DST]). Thirty-five percent of DST recipients and 9.5% of PBT recipients developed HLA antibodies after BT.Phenotypic and functional analyses were performed in pre-BT, 2 weeks post-BT, and more than 10 weeks post-BT samples (PBT: n=10; DST: n=14). The number of donor-reactive interferon-γ-producing memory T cells increased 2 weeks post-BT, but only in the DST group, increased frequencies persisted beyond 10 weeks (P0.004). In the DST recipients, the proportion of natural killer cells (CD3(-)CD56(+)) significantly increased after BT (P=0.01), whereas in PBT recipients, the proportion of regulatoryT cells (CD4(+)CD25(+)Foxp3(+)CD127 low) significantly increased at 2 weeks post-BT (P=0.039). Microarray analysis confirmed increased activity of genes involved in function of natural killer cells,Tcells, and Bcells in DSTrecipients and increased expression of immune regulatory genes (galectin-1, Foxo3a, and follistatin-like 3) in PBT recipients. Galectin-1 expression by quantitative polymerase chain reaction was significantly enhanced in peripheral blood cells after PBT (P0.05). Decreased immune effector mechanisms combined with an increased immune regulatory cell signature after HLA-DR-matched BT in nonsensitized patients is in line with clinical observations of improved outcome of a subsequent graft. Previous sensitization, however, may lead to HLA antibody formation and prolonged donor-specific memory T-cell reactivity after BT.

64-OR: Differential Effect of Pre-Transplant Blood Transfusions on Immune Effector and Regulatory Compartments in HLA-Sensitized- and Non-Sensitized Recipients

64-OR: Differential Effect of Pre-Transplant Blood Transfusions on Immune Effector and Regulatory Compartments in HLA-Sensitized- and Non-Sensitized Recipients

Forty Years of Publication of Transplantation Proceedings—The Second Decade: The Cyclosporine Revolution

With surgical tools in place, increased knowledge concerning immunogenetics and alloimmunity as well as improved management of immunocompromised patients, the foundations were lain for the rapid development of the transplantation enterprise. In contrast to pre-transplant conditioning by thoracic duct drainage or total lymphoid irradiation, which were too cumbersome for routine execution among the burgeoning recipient pool, cyclosporine was a facile method to produce immunosuppression de novo after transplantation. On the one hand, clinical data confirmed the potency of cyclosporine in a variety of clinical settings. On the other hand, a pleiotropic array of side effects, particularly nephrotoxicity, beclouded the regimens, even when used in reduced doses in combination with azathioprine or together with rigorous individualization of therapy by concentration control. The advent of cyclosporine condemned conditioning by pretransplant blood transfusions and donor-recipient HLA matching to therapeutic obsolescence. However, cross-matching achieved greater significance particularly due to the development of flow cytometry methods to detect modest amounts of anti-donor antibody. Adjunctive treatments with polyclonal preparations or monoclonal antibodies were developed to provide an additional layer of security during the critical induction phase of immunosuppression and for treatment of rejection episodes refractory to high dose steroid therapy. Active immunologic investigation was stimulated by antibodies that discriminated CD4+ versus CD8+ T cells, leading to dissection of their numbers of precursors or mature elements as well as their distinct activities. The search for methods to induce, maintain and detect the state of transplantation tolerance continued. The encouraging results in clinical transplantation raised a variety of ethical concerns related to public attitudes; to retrieval, distribution, and allocation of the limited supply of deceased donor organs; the increased utilization of living persons; the opportunities for commerce; the quasi-righteous requests for organ gifts by unrelated individuals and the scant financial resources for long-term treatment with costly immunosuppression. Transplantation had now achieved its rightful place in the clinical armamentarium.

Pre-kidney-transplant blood transfusions do not improve transplantation outcome: a Dutch national study

Female renal transplant candidates are prone to be sensitized by prior pregnancies, and undetected historical sensitization might decrease transplantation outcome. Hypothesis of our study was that pre-transplant blood transfusions (PTFs) can elucidate historical sensitization and that the avoidance of the associated antigens can improve transplantation outcome. Data from all female non-immunized renal transplant candidates who received a random PTF (rPTF) (n = 620), matched PTF (mPTF) (one HLA-A and B and one HLA-DR match) (n = 86) or donor-specific blood transfusion (DST) (n = 100) between 1996 and 2006 were collected. Complement-dependent cytoxicity was used to detect anti-HLA antibodies. Sensitization and transplantation outcomes after a PTF were analyzed. Non-immunized female renal transplant recipients who did not receive a PTF were used as the control group. In 165 patients, anti-HLA antibodies (IgG) were detected after the PTF. Both historical and primary sensitizations were found. A DST induced donor-specific anti-HLA antibodies in 25% of the DST recipients. Our policy did not improve transplantation outcome in recipients of a kidney from a deceased donor (n = 368) or in recipients of a living donor [DST (n = 49) and mPTF (n = 66)]. A PTF did elucidate historical sensitization but induce primary sensitization as well. No beneficial effect of PTFs on transplantation outcome was found, and PTFs with the intention to detect historical sensitization are therefore not suggested.

Hemolytic anemia after ABO nonidentical living donor kidney transplantation

ABO compatible non-identical kidney transplants are used frequently. Acquired hemolytic anemia has been reported after ABO mismatched transplantation. Patients of A, B or AB blood groups may receive organs from ABO-compatible, but non-identical donors, mostly from O blood group donors. It may also occur in patients of the AB blood group who receive a kidney from a donor of the A or B blood groups. ABO non-identical living donor kidney transplantation was done in 214 cases. All studied patients received kidneys from one haplotype HLA mismatched living donors and had pretransplant non-specific blood transfusions. There were 164 males and 50 females with a mean age of 30 years. Ten patients with cyclosporine (CsA)-based therapy developed hemolysis. CsA was stopped in patients maintained on triple immunosuppression (pred, CsA, AZA) and shifted to azathioprine in patients maintained on pred CsA therapy. In all patients pretransplant antibody screen, direct antiglobulin test (DAT) and cytotoxic cross match were all negative. The prognosis was excellent in nine patients, and one died from severe hemolysis. Hemolytic anemia was more frequent among blood group A recipients (60% of our cases) and more severe among recipient blood group B. Six patients received antigen-negative packed RBCs. Univariate analysis demonstrated significant impact for recipient age, donor sex, number of pretransplant blood transfusions, primary immunosuppression, time to onset of diuresis, recipient and donor blood groups. Multivariate analysis restricted the significance to blood group of donor and recipient, time to onset of diuresis and primary immunosuppression. Post transplant hemolysis is infrequent after renal transplantation; however, it may occur with compatible, non-identical ABO blood group donors. Blood group of donor and recipient, time to onset of diuresis and primary immunosuppression (mainly CsA) were significant risk factors in hemolytic anemia in patients after ABO non-identical living donor kidney transplantation. The condition is usually mild and self limited, and change of immunosuppression (stop CsA) can treat the condition.

Immunological Consequences of Apoptotic Cell Phagocytosis

Cells undergo apoptosis in development, tissue homeostasis, and disease and are subsequently cleared by professional and nonprofessional phagocytes. There is now overwhelming evidence that phagocyte function is profoundly altered following apoptotic cell uptake, with consequences for the ensuing innate and adaptive immune response. Pathogens and tumors exploit the changes in macrophage function following apoptotic cell uptake. Here, we will outline the consequences of apoptotic cell phagocytosis and illustrate how apoptotic cells could be used to manipulate the immune response for therapeutic gain.

Determinants of graft survival in pediatric and adolescent live donor kidney transplant recipients: A single center experience

To study the independent determinants of graft survival among pediatric and adolescent live donor kidney transplant recipients. Between March 1976 and March 2004, 1600 live donor kidney transplants were carried out in our center. Of them 284 were 20 yr old or younger (mean age 13.1 yr, ranging from 5 to 20 yr). Evaluation of the possible variables that may affect graft survival were carried out using univariate and multivariate analyses. Studied factors included age, gender, relation between donor and recipient, original kidney disease, ABO blood group, pretransplant blood transfusion, human leukocyte antigen (HLA) matching, pretransplant dialysis, height standard deviation score (SDS), pretransplant hypertension, cold ischemia time, number of renal arteries, ureteral anastomosis, time to diuresis, time of transplantation, occurrence of acute tubular necrosis (ATN), primary and secondary immunosuppression, total dose of steroids in the first 3 months, development of acute rejection and post-transplant hypertension. Using univariate analysis, the significant predictors for graft survival were HLA matching, type of primary urinary recontinuity, time to diuresis, ATN, acute rejection and post-transplant hypertension. The multivariate analysis restricted the significance to acute rejection and post-transplant hypertension. The independent determinants of graft survival in live-donor pediatric and adolescent renal transplant recipients are acute rejection and post-transplant hypertension.

The Putative Mechanism of the Immunomodulating Effect of HLA-DR Shared Allogeneic Blood Transfusions on the Alloimmune Response

Pretransplant blood transfusions have shown to improve organ allograft survival. However, the immunologic mechanism leading to this beneficial effect in clinical transplantation is still not clear. The observation that blood transfusions sharing an HLA-DR antigen with the recipient are more effective than HLA mismatched transfusions has led to the hypothesis that CD4(+) regulatory T (Treg) cells that recognize a foreign peptide in the context of the shared HLA-DR molecule play an important role in down-regulation of the immune response toward the graft. Available experimental evidence supports this hypothesis. Furthermore, these CD4(+) Treg cells are able to modulate antigen-presenting cells, which in their turn will induce Treg cells. As long as clinical transplantation tolerance by blood transfusions is not a reality, further studies on the mechanisms of the beneficial effect of pretransplant allogeneic blood transfusions are needed to obtain an effective protocol for the induction of clinically relevant Treg cells.