A comparison of 2 protocols for living-related renal transplantation in children: donor-specific transfusions versus cyclosporine

We analyzed the results obtained with protocols for immunosuppression of pediatric recipients of haploidentical living-related renal transplants. In the donor-specific transfusion group transfusion of blood products obtained from the prospective organ donor was performed before transplantation, and at transplantation maintenance immunosuppression of azathioprine and prednisone was begun. In the cyclosporine group donor-specific transfusion was not used, and maintenance immuno-suppression of cyclosporine and azathioprine was begun 1 week before transplantation, with the addition of prednisone at transplantation. Of 24 donor-specific transfusion recipients 3 had circulating cytotoxic antibodies to the prospective donor for an incidence of 12%. There was no significant difference between groups with respect to 1-year actual patient and graft survival (100 and 89 versus 100 and 86%, respectively), 1-year mean serum creatinine level (1.1 versus 1.2 mg./dl.), rejection treatments per patient (2.5 versus 2.6) and total days hospitalized during year 1 after transplantation (27 versus 18), with donor-specific transfusion data presented first. Initial hospitalization was significantly shorter (10 versus 16 days, p less than 0.05) and the incidence of rejection crises within 3 months was significantly less (68 versus 94%, p less than 0.05) in the cyclosporine group. We believe that cyclosporine and azathioprine pre-treatment of pediatric recipients of haploidentical living-related renal transplants with the addition of prednisone at transplantation is preferable to a donor-specific transfusion protocol because there is no risk of recipient sensitization to the prospective donor, and patient and graft survival is not adversely affected.     

Mismatched living, related donor renal transplantation: a prospective, randomized study

A prospective, randomized study of 49 mismatched living, related donor renal transplants was undertaken to compare the effect of donor-specific transfusions (DST) combined with conventional immunosuppressive therapy (azathioprine, prednisone, and antilymphoblast globulin) to cyclosporine and prednisone with and without use of prior DST. The results demonstrated that cyclosporine and prednisone without DST have equal patient and graft survival rates after transplantation and an equal incidence of infectious complications and rejection episodes when compared with recipients who received DST and conventional therapy. Patients who received DST and subsequent cyclosporine had poor graft survival rates with more rejection episodes and infectious complications. Hospitalization and the relative cost of transplantation were decreased when recipients received cyclosporine without prior DST. It is concluded that cyclosporine allows easier access to transplantation, is more cost effective in the initial posttransplant period, and does not subject the recipient to the risk of donor sensitization as is seen with DST recipients given conventional therapy. The nephrotoxic side effects of cyclosporine have been minimal and renal function remains excellent in the recipients treated with cyclosporine.     

Are blood transfusions beneficial in the cyclosporine era?

In patients treated with conventional immunosuppression (azathioprine and prednisone) after renal transplantation, there is a beneficial effect of pre-transplant blood transfusions on graft survival; in patients treated with cyclosporine, this effect may be lost. In 66 children who received living-related donor transplants after donor-specific transfusions (DST) and were treated with azathioprine-prednisone in our center, 1- and 5-year graft survival rates were 99% and 77% respectively. These rates were similar to those reported for children who did not receive DST but were treated with cyclosporine in other centers. There were 634 adult and pediatric recipients of cadaver transplants in our center who were treated with cyclosporine and prednisone (non-sequential therapy,n=89) or antilymphoblast globulin, azathioprine preduisone, and cyclosporin (sequential therapy,n=545). When all patients were considered, graft survival rates were higher in transfused than in non-transfused patients at 3–5 years, but in the sequential therapy group, there were no differences in graft survival rates between transfused and non-transfused patients. The results suggest that transfusions do not improve cadaver graft survival in patients receiving optimal cyclosporine therapy and that equally good related donor graft survival can be achieved with DST and conventional immunosuppression or no DST and cyclosporine.     

Declining incidence of wound infection in cadaveric renal transplant recipient

Over a five-year period 100 cadaveric renal transplants were performed. In 91 of these recipients, a prophylactic parenteral antibiotic (cefoperazone) was administered and closed wound drainage was used. Of these 91 patients, 33 received azathioprine/prednisone immunosuppression, whereas cyclosporine/prednisone with or without azathioprine was used in the remaining 58. The incidence of wound infections was significantly reduced from 12 per cent (4/33) in the azathioprine group to 1.7 per cent (1/58) in the cyclosporine group (p less than 0.01). When conventional immunosuppression (azathioprine/prednisone) is employed in renal transplantation, triple antibiotic prophylaxis that includes an aminoglycoside is most effective in preventing wound infections. A single non-nephrotoxic antibiotic, cefoperazone, offers similar protection in the cyclosporine/prednisone-treated renal transplant recipient.     

The current role of pre-transplant blood transfusions and tissue typing in cadaveric renal transplantation

In a retrospective analysis of 74 consecutive cadaveric renal transplants performed at our center during a 38-month period we assessed the influence of random blood transfusions and tissue matching on graft and patient survival. All patients received cyclosporine and low dose prednisone with or without azathioprine as immunosuppressive therapy. Actual patient survival was 100 per cent at 1 year and actuarial 1-year graft survival was 82 per cent. Random blood transfusions and histocompatibility matching at the HLA-DR locus did not influence graft survival. Matching at 2 or more HLA-A and B loci was associated with a significant detrimental influence (p less than 0.05) on graft survival. We conclude that the use of cyclosporine-based immunosuppression overcomes much of the adverse effect of poor tissue matching and may obviate the need for random blood transfusions in cadaveric renal transplantation during the first year of engraftment.     

Benefits of quadruple immunosuppressive therapy in recipients of living related donor kidneys. A review of 855 operations.

Eight hundred fifty-five living related donor transplant recipients were analyzed according to 15 potential risk factors with regard to patient and graft survival according to immunosuppression. Group I, 1968 to 1983, (n = 440 patients) received azathioprine and prednisone; group II, 1984 to 1987, (n = 229 patients) received triple therapy--azathioprine, prednisone, and cyclosporine; and group III, 1988-1991, (n = 186 patients), quadruple therapy--azathioprine, prednisone, cyclosporine, and Minnesota antilymphocyte globulin. Three important risk factors included immunosuppression, tissue typing, and race. Groups II and III had improved allograft survival over group I (p = 0.03). Patients with two haplotype matches had similar survival in all three groups. Kidney survival in one-haplotype-matched recipients improved in group II and was equal to that of the two-haplotype-matched patients in group III. Cyclosporine improved allograft survival in both races when combined with azathioprine and prednisone. Quadruple therapy improved early survival in one-haplotype black patients, even though long-term results remained better in whites. Cyclosporine did not improve graft survival in two-haplotype recipients. The addition of cyclosporine and quadruple therapy did not increase morbidity and mortality rates.     

Repeat cadaver kidney transplantation using cyclosporine A immunosuppression

Repeat cadaver kidney transplantation using azathioprine immunosuppression carried a higher risk of graft loss than primary transplants. We analyzed the results of repeat cadaver kidney grafting with cyclosporine A immunosuppression. A total of 33 cyclosporine A-treated patients received the second kidney transplant at varying intervals after failure of the first transplant. Graft survival at 1 year was 66 per cent. A concurrent group of 189 cyclosporine A-treated first cadaver kidney recipients had a 1-year graft survival rate of 75 per cent, although this better result was not statistically significant (p greater than or equal to 0.25). A historical group of 31 azathioprine-treated second graft recipients had a significantly worse 1-year graft survival rate of 45 per cent compared to the cyclosporine A second graft group (p less than 0.1). Patient age, sex, early first graft loss, interval between transplants and the presence of panel reactive antibodies were not factors in predicting second graft outcome. A complete DR mismatch appeared to worsen the second transplant survival. These findings indicate that early graft survival of cyclosporine A-treated repeat cadaveric transplants is acceptable and is better than azathioprine-treated first or second grafts.     

A seven-year experience with donor-specific blood transfusions. Results and considerations for maximum efficacy

Two hundred thirty-nine transplants have been performed following donor-specific blood transfusions (DSTs) since 1978. Graft and patient survival in 1- and 0-haplotype-matched transplants with DST pretreatment is comparable to HLA-identical results through 4 years. Graft survival in 174 consecutive nondiabetic, non-HLA-identical DST recipients shows that the transfusion effect persists for at least 4 years, with graft survival of 88 +/- 3% at that time, compared with 83 +/- 4% in the concurrent HLA-identical group. Graft function, as determined by serum creatinine, was the same in both groups. Graft and patient survival in 20 0-haplotype matched pairs with DST pretreatment is 100% at 2 years. Low-dose Imuran coverage during DST administration (n = 91) was compared with a concurrent group with no Imuran (n = 93). Imuran had its maximum effect in patients undergoing their first transplant and with a pre-DST PRA less than 10% (12% vs. 21% sensitization rate in the no-Imuran group). Imuran did not appear to confer any beneficial effect in primary transplants with high PRAs and in patients undergoing a second or third transplant. The majority of patients formally excluded from transplantation because of a post-DST positive B-warm crossmatch can now be successfully transplanted with the use of flow cytometry analysis to rule out previously undetectable low levels of anti-T-lymphocyte antibodies. Of 62 patients with a positive B-warm crossmatch alone since 1982, 73% had a subsequent negative fluorescence-activated cell sorter (FACS) crossmatch permitting transplantation. Preliminary results of a DST and cyclosporine treatment study are described. In conclusion, a long-term immunologic effect of DST has been confirmed and the indications and considerations for optimum use of the DST protocol have been more clearly defined.     

Incidental and purposeful random donor blood transfusion. Sensitization and transplantation

We conducted a prospective study to gauge the frequency and degree of sensitization by transfusion and/or pregnancy in 797 candidates for first renal transplants. Sensitization was proportional to the number of blood transfusions. Multiple transfusions or a history of pregnancy without transfusions had similar effects on sensitization. The combination of transfusion and prior pregnancy resulted in sensitization of 1/3 of the candidates. Patients who were not sensitized and were accepted for 1-haplotype living-related donor grafts or first-cadaver donor grafts were transfused to receive a total of 5 units of packed red blood cells. Parous patients had an undue rate of antibody formation and alternate means of selecting and managing parous women are described. Nonparous candidates had a low rate of sensitization (8%) that did not prove an impediment to obtaining a transplant. Only 2% of prospective LRD graft recipients developed antibody against their intended donor. Transplant patients were generally managed with azathioprine and prednisone. One-haplotype LRD graft survival of protocol patients was 93.7% one year posttransplant, and 82.1% at 5 years. One-year CD graft survival was 77%. There was no reduction in graft survival when the interval between transfusion and transplantation exceeded one year. Random donor transfusion is effective in improving renal graft survival. Some recent multiinstitutional reports indicate a reduction or absence of the transfusion effect with current immunosuppression. Discarding blood transfusion as a preparation for transplantation may be ill-advised pending a prospective study.     

Pretransplant cytotoxic conditioning produces effects consistent with clonal deletion mechanisms

A rat cardiac allograft model (ACl to Lewis) was used to investigate the clonal deletion theory. Twelve groups of Lewis recipients received various combinations of donor-specific blood transfusions (DSTs), immediate post-DST immunosuppression with azathioprine/prednisone, and low-dose cyclosporine (1 mg/kg/day) posttransplant. DSTs and cyclosporine together gave modest prolongation of graft survival (from 6.0 to 17 days). DSTs plus immediate post-DST immunosuppression followed by low-dose cyclosporine prolonged graft survival to an average of 45 days. Third-party transfusions alone and in combination with immunosuppression did not significantly prolong allograft survival. Postoperative cyclosporine was required for the expression of this effect suggesting that clonal depression rather than clonal deletion had occurred. Combining DSTs with brief but intense preoperative immunosuppression may be a more effective method of pretransplant conditioning than DSTs alone.     

Pretransplant blood transfusions with cyclosporine in pediatric renal transplantation

Pretransplant transfusions were repeatedly shown to be associated with improved graft survival in the ”pre-cyclosporine era,” and have recently been shown to be beneficial in patients on modern immunosuppressive regimes. In an attempt to improve this transfusion effect and minimize the potential development of cytotoxic antibodies, we have given these transfusions, with concomitant cyclosporine cover, prior to transplantation. Ninety-two renal transplantations were performed in 91 children in the study group (group 1) and all received pretransplant transfusions with cyclosporine cover. Results were compared with a preceding group of 102 children (104 transplantations) who had received pretransplant transfusions without cyclosporine cover (group 2). There were 70 cadaver and 22 living-related donor (LRD) transplants in group 1, and 88 cadaver and 16 LRD transplants in group 2. Graft survival rates (1- and 5-year) for cadaver transplantation were 96% and 90% in group 1 compared with 78% and 64% in group 2 (P=0.001). For LRD transplantation, these figures were 95% and 87% in group 1 and 81% and 69% in group 2. There was no difference between the two groups in terms of age at transplantation, sex, donor age, HLA-A, -B, -DR mismatches, or cold and warm ischemia times. All cadaver graft recipients received quadruple, sequential immunosuppression post transplant. However, 9 patients in group 1 were changed to tacrolimus for recurrent rejection episodes. No patient developed persistent lymphocytotoxic antibodies post transfusion or side effects of cyclosporine. Cyclosporine can be safely given with whole blood prior to transplantation with no adverse effect and no sensitization. Graft survival was significantly improved in this group of patients and graft loss due to rejection was exceptional. This effect should be further evaluated in prospective studies. Received: 10 June 1999 / Revised: 9 March 2000 / Accepted: 10 March 2000     

Heart transplantation in patients over 54 years of age with triple-drug therapy immunosuppression.

Between April 1, 1986, and December 31, 1989, 206 patients received orthotopic heart transplants with triple-drug therapy immunosuppression (cyclosporine, azathioprine, prednisone). Forty-six patients were aged 55 years or more at the time of transplantation and 160 patients were less than 55 years of age; these two groups were compared. Selection criteria and treatment regimen were the same in both groups. In our experience, although both groups had good postoperative survival, older patients had higher mortality rates early after transplantation, particularly from rejection and infection. Patients over 55 years of age had similar nonfatal rejection rates and were no more likely to have infectious episodes than younger patients. As demand for heart transplantation increases and waiting lists lengthen, the age of potential recipients should be an important factor in deciding how to allocate scarce donated organs, although age should not be exclusive.     

Hemolytic anemia after ABO nonidentical living donor kidney transplantation

Introduction  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. Patients and methods  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. Results  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. Conclusions  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.     

Successful transplantation of cyclosporine-treated haploidentical living-related renal recipients without blood transfusions

A protocol of cyclosporine and prednisone immunosuppression was used in 36 consecutive haploidentical living-related renal transplant recipients from donors displaying marked proliferation in mixed lymphocyte culture (MLC) reactions. All blood transfusions (random third-party and donor-specific) were withheld once a negative crossmatch with the prospective kidney donor was obtained. With a mean follow-up of 13.6 months, patient survival is 97% (35/36) and graft survival is 92% (33/36). One graft was lost to rejection; two were abandoned because of sepsis. Only 14% (5/36) of patients experienced a rejection episode. No significant differences were evident in graft survival, rejection episodes, or renal function between the 15 recipients who were never transfused and the 21 with a history of previous blood transfusions. These findings suggest that pretransplant blood transfusions not only are unnecessary to achieve excellent graft survival, but also may jeopardize donor availability by donor-specific presensitization.     

Increased septic complications with three-drug sequential immunosuppression for cadaver renal transplants

In 152 renal transplant recipients, the results of immunosuppression with three-drug sequential (Minnesota antilymphocyte globulin, prednisone, azathioprine, and cyclosporine) immunosuppression (n = 107) were compared with those of a two-drug sequential protocol (Minnesota antilymphocyte globulin, prednisone, and cyclosporine) that excluded azathioprine (n = 45). The study groups were comparable by age, sex, etiology of renal failure, incidence of diabetes, and degree of HLA matching. Patient survival at 1 year was not significantly different in the two groups (two drug, 93% versus three drug, 86%; p = 0.19). One-year graft survival was superior in the two-drug group (two drug, 93% versus three drug, 75%; p = 0.02). Analysis of primary transplants only (n = 116) yielded the same results. During the first year, the serum creatinine level remained stable in both groups. As expected, the three-drug therapy group had significantly more bacterial and viral infections. For low-risk primary cadaveric renal transplants, two-drug sequential immunosuppression is superior.     

Cadaveric renal transplantation with quadruple immunosuppression in patients with a positive antiglobulin crossmatch

The significance of the antiglobulin crossmatch in the cyclosporine era remains controversial. Over an 11-month period, 124 recipients of cadaveric renal allografts (109 primary, 15 nonprimary) were retrospectively crossmatched via the antiglobulin technique. Criteria for recipient selection for transplantation included a negative T lymphocytotoxic (CDC) crossmatch for current and historical sera. Fourteen patients (11.3%) underwent transplantation in the setting of a negative T and positive antiglobulin crossmatch. The patient group included 10 female and 4 male patients with a mean age of 43.8 years. All but one patient received a primary transplant, and current sera were positive in the antiglobulin crossmatch in all cases. The mean HLA-ABDR match was 1.4 (range 0-4). Preoperative PRA titers ranged from 0 to 80% (mean 18.3%). All patients underwent successful renal transplantation with quadruple immunosuppression consisting of prednisone, azathioprine, and the sequential use of MALG/cyclosporine. There were no episodes of hyperacute rejection. However, 10 patients (71.4%) experienced acute rejection, including 7 episodes within 4 days of transplant. Early rejection was significantly more common in patients with a positive antiglobulin test (50% vs. 20.9%, P less than 0.05). The mean one-month serum creatinine was 1.7 mg/dl. Actual patient and allograft survival are 92.9% and 85.7%, respectively. Risk factors for a positive antiglobulin crossmatch included female sex and prior sensitization as measured by PRA. Although these patients represent a high-risk group for early rejection, no adverse effect on patient or graft survival was noted with quadruple immunotherapy. In conclusion, a positive antiglobulin crossmatch is no longer a contraindication to renal transplantation with current immunosuppressive strategies.     

Renal transplantation done safely without prior chronic dialysis therapy

The complications, cost, and inconvenience associated with pretransplant hemodialysis and peritoneal dialysis would be minimized if transplantation were instituted without prior dialysis. That preuremic transplantation is safe and efficacious in patients with immanent end-stage renal disease has not been established. All 1742 consecutive primary renal transplants performed at the University of Minnesota during the 16.5 year period from January 1968 through July 1984 were reviewed to determine whether graft and patient survival were adversely affected by transplantation prior to dialytic therapy. In the overall group of primary renal transplants, no differences in actuarial graft or patient survival were noted with or without prior dialysis. Likewise, outcome was not affected by the pretransplant dialysis status in recipients of allografts from HLA-identical mismatched living-related donors. However, in cadaveric transplantation graft function appeared to be adversely affected by transplantation prior to dialysis, with 52% vs. 66% two-year graft function for nondialyzed vs. chronically dialyzed recipients, respectively (P = 0.15). Patient survival was significantly (P = .04) decreased in the nondialyzed group, with 66% vs. 80% two-year survival in the chronic dialysis group. However, nearly all of the nondialyzed, cadaveric recipients were diabetic. The outcome of transplantation was found to be identical in these patients, as compared with chronically dialyzed diabetic recipients of cadaveric grafts. Thus, the apparent detrimental effect of predialytic transplantation in the cadaver group was due to the preponderance of diabetics in the nondialyzed group. Since July 1984, a single-armed therapeutic trial of combination therapy with azathioprine, prednisone, antilymphoblast globulin (ALG), and cyclosporine has been undertaken, Since that time, 36 primary graft recipients were transplanted prior to dialysis. Of these 36, 35 currently have a functioning graft. Thus, transplantation prior to chronic dialysis is safe irrespective of donor source, or choice of immunosuppressive agents.     

Abdominal aortic aneurysm after pulmonary transplantation: a case report

We present the case of a 39-year-old man who underwent repair of a symptomatic 5-cm abdominal aortic aneurysm. This patient had received a bilateral lung transplant for cystic fibrosis 10 years before this event. He was receiving cyclosporine, prednisone, and azathioprine as immunosuppression therapy. To our knowledge, this is the first reported abdominal aortic aneurysm after lung transplantation, and we note that our patient had a rapidly enlarging aneurysm, as seen in recipients of heart transplants. We postulate that immunosuppression may be related to the development and/or rapid growth of abdominal aortic aneurysms.     

Cyclosporine in heart and heart-lung transplantation

At Stanford University Medical Center from January 1968 until January 1984, 288 patients received 313 heart transplants. The immunosuppressive regimen before December 1980 consisted of azathioprine and prednisone, with or without rabbit antithymocyte globulin. After that time cyclosporine replaced azathioprine. In 92 recipients of 95 heart allografts, the 1- and 3-year survival rates were 82% and 65% to 70% respectively. In the 3 years from March 1981 to March 1984, successful heart-lung transplantation was accomplished in 13 of 19 recipients, using cyclosporine-based immunosuppression. Survival ranged from 1 to 38 months. While it is true that cyclosporine has improved survival in heart transplant recipients, has allowed successful heart-lung transplantation to be performed, has shortened intensive care unit and total hospital stays and therefore hospital costs, and has allowed easier management of rejection and infection, several disconcerting problems have not yet been resolved. These include hypertension that is difficult to control and renal dysfunction in all patients, and the fact that cellular and humoral rejection still occurs, as manifested by graft atherosclerosis, bronchiolitis obliterans and classic acute rejection. Better understanding and application of cyclosporine immunosuppression will undoubtedly minimize both cyclosporine- and non-cyclosporine-related postoperative complications and will improve survival even further.     

Failure of anti-CD20 monoclonal antibody therapy to prevent antibody-mediated rejection in three crossmatch-positive renal transplant recipients

There is no optimal desensitization protocol for cadaveric renal transplant recipients who display high levels of donor-specific alloantibodies as defined by a positive T- or B-cell cytotoxic crossmatch. We used anti-CD20 monoclonal antibodies (Rituximab) to try to prevent antibody-mediated rejection in three crossmatch-positive renal transplants recipients (standard and sensitized techniques). The three patients received a first, second, or third cadaveric donor renal transplant. Patient one had an historical positive T- and B-cell cytotoxicity crossmatch: negative T- and B-cell cytotoxicity crossmatch at the day of transplantation. The panel reactive antibody (PRA) level was 100%. Patients 2 and 3 showed positive B-cell cytotoxicity crossmatches: historical and on the day of transplantation; PRA levels were 50% and 71%, respectively. All recipients were treated pretransplant with rituximab (375 mg/m(2)) and 4 days of intravenous immunoglobulin (0.5 g/kg body weight) per day posttransplant plus 5 days of thymoglobulin. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and prednisone. Antibody-mediated rejection occurred in all patients at day 6, day 10, or 8 months after renal transplantation. For patient 1, the rejection was not reversible and the graft was lost at day 15. Patient 2 had poor renal function with an MDRD estimate of glomerular filtration rate at 36 mL/min/1.73 m(2) at 18 months posttransplantation, and the graft of patient 3 was lost at 9 months posttransplantation due to resistant antibody-mediated rejection with thrombotic microangiopathy. In these three cases of crossmatch-positive patients, rituximab failed to prevent antibody-mediated rejection. Others studies will be needed to determine the place of rituximab in these patients.