Overall Incidence Of Acute Rejection Research Articles

P8.052: Long-term Outcomes and Predictors of Graft Function in Living-Donor Preemptive Kidney Transplants

Background: Beyond the new strategies for dialysis treatment, kidney transplantation has already been associated with better outcomes for patients with advanced kidney chronic disease (CKD), and a preemptive kidney transplant seems to be the preferred option for those patients. Thus, this study purposed to evaluate predictors of long-term graft function and unfavorable outcomes in living-donor preemptive kidney transplant recipients. Methods: Single-center cohort study enrolled 222 living-donor preemptive kidney transplant recipients transplanted between 2011 and 2016 and followed up to 2021. Five-year graft function was estimated by CKD-Epi (5-year-eGFR). The primary outcome was composed of death, graft loss, acute rejection, and 5-year-eGFR < 30 mL/min/1.73m2. The multivariable analysis for 5-year-eGFR was performed by linear regression and logistic regression for the primary outcome. Results: Recipients were 40 (31; 48) years old, 59.9% were male, and 35.1% had CKD due to chronic glomerulonephritis. Donors were 48.5 (41.0; 55.2) years old, being most frequently siblings (50%) or parents (28/8%). One-third of patients received ATG as an induction strategy (30.2%), followed by Tacrolimus + azathioprine (59.5%) or cyclosporin + azathioprine (14.4%) or tacrolimus + mycophenolate (11.3%) as the maintenance immunosuppression. The overall incidence of acute rejection, graft loss, and death was 20.3%, 6.3%, and 0.5%, respectively. The median follow-up time was 88.9 months, and the median 5-year-eGFR was 54.7 mL/min. Sixty-five patients presented the primary outcome (29.2%), significantly associated with the HLA compatibility, not using induction therapy and CMV-related event. Compared with identical HLA matches, the OR was 6.81 for haploidentical (P=0.001) and 11.2 for distinct (P<0.001) HLA matches. In addition, the probability for the primary outcome was reduced by 81% (OR= 0.19, p<0.001) for patients who received ATG as induction therapy and 4-fold higher in those who had CMV-related events (OR=4.09; p=0.001). In the linear regression, the association with 5-yr-eGFR was less evident with HLA matches and AR than donor age. Thus, the identical HLA (B= +6.04; p=0.09) match and AR (B=-6.34; p=0.07) tend to be associated with 5-year-eGFR in the linear regression, while donor age (B= -0,69 per year old; p<0.001) presented a significant and inverse association. Conclusion: In recipients of living-donor preemptive kidney transplants, the HLA matches, thymoglobulin induction therapy, and CMV-related events were predictors of composite outcomes of long-term death, graft loss, acute rejection, and low grade of graft function. In addition, only donor age was independently associated with long-term graft function.

316.11: HLA-DPB1 Molecular Mismatches Are Associated With Acute Rejection and Long-term Graft Function in First Kidney Transplants

Introduction: It is generally accepted that HLA-DP mismatches (MM) do not impact the survival of first transplants but that they may exert a deleterious effect in retransplants. This study aimed to investigate the impact of HLA-DPB1 allele and molecular MM (mMM) on the occurrence of acute rejection (AR) and low 5-year graft function (5-yGF) in first kidney transplants (KT). Method: HLA-DPB1 allele and mMM were determined in 130 first KT from deceased donors, performed between 2014 and 2016. The following mMM models were investigated: expression MM, with the high expression G allele in the donor, T cell epitope (TCE) MM, classified as permissive and nonpermissive MM, epitope MM (EMM), considering all six HLA-DPB1 hypervariable regions (EMM-ABCDEF HVR) or only ABEF regions (EMM-ABEF HVR), Eplet MM (EpMM), considering all or only antibody-verified (AbVer) eplets, and solvent accessible amino acid MM (SAMM). EMM, EpletMM and SAMM loads were categorized using thresholds determined by ROC analysis for each outcome. The outcomes were AR and 5-yGF (estimated by CKD-EPI). Logistic and Cox regressions were used to investigate variables associated with 5-yGF and AR, respectively. Results: 119 (91.5%) KT were performed with one or two HLA-DPB1 allele MM. The overall incidence of AR was 17.7% and the median 5-yGF was 40.3 (27.0 - 51.7) mL/min/1.73m2. No association between HLA-DPB1 allele MM and 5-yGF or rejection was observed. Considering only recipients of standard criteria donor, five logistic models for 5-yGF were built including variables that reached a p-value <0.10 in the univariable analysis (age and donor sex, cause of brain death, ABDR MM and AR) and the mMM (TCE, SAMM, all and AbVer EpMM, EMM-ABCDEF and ABEF HVR). In the model 2, variables associated with 5-yGF≤ 40 were donor age (OR=1.08; CI95%=1.02-1.14; p=0.005) and SAMM≥7 (OR=4.40; CI95%=1.56-12.36, p<0.005), while in the model 4, donor age (OR= 1.09; CI95%=1.03-1.15; p=0.003) and EpMM(AbVer≥2 (OR=3.39; CI95%=1.2-9.45, p=0.02) were associated with low GF. The AUC-ROC for predicting 5-yGF was 0.83 (0.75-0.92) for the model 2, and 0.68 (0.57-0.79) for the model 4. Lastly, for the outcome AR in all recipients, beyond the final donor creatinine, the following mMM models were statistically significant: TCE (HR=3.01; CI95%=1.33-6.84; p=0.008), SAMM≥5 (HR=2.69; CI95%=1.10-6.56; p=0.03), AbVerEpMM ≥3 (HR=3.38; 95%CI=1.32-8.70; p=0.01), and EMM-ABCDEF HVR ≥ 6 (HR=5.08; 95%CI=2.19-11.82; p<0.001). Conclusion: To the best of our knowledge, this is the first study that shows that some mMM, in contrast to classical allele HLA-DPB1 MM, are associated with acute rejection and long-term graft function in a population of exclusively first kidney transplants.

Acute Rejection after Pediatric Intestinal Transplantation

Background: Rejection is a major threat to the survival of intestinal allografts. As immunosuppression regimens have improved, the incidence of acute rejection has decreased significantly. The aim of our study is to report incidence and outcomes of acute rejection (AR) in pediatric intestinal transplantation at our center over the last decade. Methods: All pediatric intestinal transplants performed at our program between 2003–2016 were reviewed. Parameters analyzed included patient demographics, incidence, timing, severity, treatment and outcome of AR. Overall patient and graft survival was also analyzed. Results: The records of 111 pediatric intestinal transplants (n = 40, 36% isolated small bowel (SB), n = 49,45% liver-bowel (LB) and n = 22, 18% multivisceral) performed between 2003–2016 were analyzed; 61 (55%) male, median age 2 years (range 0.5 - 18). The most common indication for transplant was short gut secondary to gastroschisis (27, 24%) and necrotizing enterocolitis (19, 17%). Immunosuppression consisted of a combination of tacrolimus, mycophenolate mofetil, sirolimus and steroids. The overall incidence of AR was 34% after a median interval of 250 days (range 14–3,037) from transplant. The incidence of AR was 35% (14/40) in SB, 35% (17/49) in LB and 27% (6/22) in MV. The severity of acute rejection was classified as grade 1 in 34%, grade 2 in 20%, and grade 3 in 46%. The incidence of AR during 2003–2007 was 58% (22/38) with a median time to rejection of 296 days. The incidence of AR during 2008–2011 was 26% (9/35) with a median time to rejection of 362 days. The incidence of AR during 2012–2016 was 16% (6/38) with a median time to rejection of 21 days. Since 2003, the overall patient and graft survival was 81% and 77%, respectively, with patient and graft survival at 1-year reaching 89% and 87%. Conclusions: According to our experience over a thirteen-year time period, the incidence of acute rejection has decreased over time and current survival rates have improved significantly compared to the early era.

Basiliximab induction in kidney transplantation with donation after cardiac death donors.

Basiliximab is a monoclonal antibody that binds to the α-chain of the interleukin (IL)-2 receptor. It is used as induction therapy in kidney transplantation. The objective of the present study was to evaluate induction therapy with single-dose basiliximab (Simulect®) in kidney transplantation with donation after cardiac death (DCD) donors. A total of 33 DCD kidney transplants were performed between December 2010 and July 2013 in patients who received single-dose basiliximab (20 mg) as induction therapy. The maintenance immunosuppression included calcineurin inhibitor (cyclosporine A or tacrolimus), mycophenolate mofetil and corticosteroids. The follow-up time was 1 year. The mean ages of the DCD donors and recipients were 29.3 and 41.1 years, respectively. Within the 1-year follow-up, the overall incidence of acute rejection was 9.1%. There were 10 cases of delayed graft function among the recipients. Mean serum creatinine values at 1 week and at 1, 3, 6, 9 and 12 months post-transplantation were 257.6, 238.2, 194.5, 159.3, 137.9 and 110.8 µmol/l, respectively, with a favorable trend to allograft function recovery over time. The 1-year patient and graft survival rates were 96.9 and 90.9%, respectively, with an infection rate of 24.2%. Increased alanine aminotransferase/aspartate transaminase levels in only 2 patients were considered to be associated with basiliximab. This experience with single-dose basiliximab for induction therapy in DCD kidney transplantation showed that favorable clinical outcomes were achieved in terms of graft survival and function within 1 year.

Genetic polymorphisms in IL‐2,IL‐10,TGF‐β1, and IL‐2RB and acute rejection in renal transplant patients

Acute rejection (AR) remains a concern for kidney transplantation. Cytokines are key mediators in the induction and effector phases of all immune and inflammatory responses. Single nucleotide polymorphisms (SNPs) in cytokines and their receptors may relate to AR. We investigated the relation between AR and SNPs in the genes encoding for IL-2(-330G>T), IL-10(-592C>A and -1082G>A), TGF-β1(915G>C), and IL-2RB(rs228942 C>A and rs228953 C>T) in 325 renal transplant patients during the first year after transplantation. The overall incidence of AR was 15.4%. In multivariate analysis, only the use of induction therapy was correlated with AR (odds ratio 1.9; 95% confidence interval 1.1-3.7; p = 0.04). No statistically significant associations between the SNPs studied and AR were observed. SNPs in the investigated cytokines and their receptors were not associated with the risk of AR. Genotyping patients for these SNPs is unlikely to aid the clinician in adjusting the immunosuppressive therapy for individual patients.

Pancreas transplantation: The Wake Forest experience in the new millennium.

To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression. A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant (SKPT) and solitary pancreas transplant (SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with mycophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide. Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186 (92%) were primary and 16 (8%) pancreas retransplants; portal-enteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed in African American (AA) patients; of the 162 SKPTs, 30 were performed in patients with pretransplant C-peptide levels > 2.0 ng/mL. In addition, from 2005-2008, 46 SKPT patients were enrolled in a prospective study of single dose alemtuzumab vs 3-5 doses of rabbit anti-thymocyte globulin induction therapy. With a mean follow-up of 5.7 in SKPT vs 7.7 years in SPT recipients, overall patient (86% SKPT vs 87% SPT) and kidney (74% SKPT vs 80% SPT) graft survival rates as well as insulin-free rates (both 65%) were similar (P = NS). Although mortality rates were nearly identical in SKPT compared to SPT recipients, patterns and timing of death were different as no early mortality occurred in SPT recipients whereas the rates of mortality following SKPT were 4%, 9% and 12%, at 1-, 3- and 5-years follow-up, respectively (P < 0.05). The primary cause of graft loss in SKPT recipients was death with a functioning graft whereas the major cause of graft loss following SPT was acute and chronic rejection. The overall incidence of acute rejection was 29% in SKPT and 27.5% in SPT recipients (P = NS). Lower rates of acute rejection and major infection were evidenced in SKPT patients receiving alemtuzumab induction therapy. Comparable kidney and pancreas graft survival rates were observed in AA and non-AA recipients despite a higher prevalence of a "type 2 diabetes" phenotype in AA. Results comparable to those achieved in insulinopenic diabetics were found in the transplantation of type 2 diabetics with detectable C-peptide levels. In the new millennium, acceptable medium-term outcomes can be achieved in SKPT and SPTs as nearly 2/3rds of patients are insulin independent following pancreas transplantation.

Acute Rejection as Key Predictor for Long-Term Outcomes after Kidney Transplantation?

Introduction: Type, severity, timing, and clinical course of acute rejection each influence the impact of a rejection episode, and if renal function recovers fully, there appears to be no survival disadvantage (CTS-Study, Opelz). With modern immunosuppressive regimens, the overall incidence of acute rejection may no longer be the most accurate surrogate marker for long-term kidney graft survival. We investigated the specificity of (subclinical) chronic inflammatory responses (SCAR) induced either by not successful treated rejection episodes, by using different CNI's or ongoing activated innate immune responses. We used the high sensitive parameter for inflammation, indoleamine 2,3 dioxygenase (IDO), in patients after renal transplantation in correlation to graft survival and graft function. Patients and methods: In a retro- (A, n=224, up to 12 years) and prospective study (B, n=124, up to 3 years) of renal transplant recipients we evaluated the IDO behavior for the long-term run. Both groups were comparable concerning the basic demographic data (age, time on dialysis, PRA and waiting time). Estimation of IDO was performed via kynurenine measurement. Results: IDO in normal controls (n=257) was 2,5±0,4 μmol/L Kyn, in stabile renal transplanted patients (n=248) 5,8 ±1,8μmol/L. We identified in both groups already end of the first week posttransplant a statistically significant difference (A:17,2 vs. 7,0 (week 1, median, p< .005; 8,1vs.4,8 (w.6, median, p< .001; B:12,3 vs. 7,0 (w.1, median, p< .001); 6,7 vs. 4,2 (w.6, median, p< .001)) in the IDO levels between patients with/without acute rejection. Patients with an IDO-level > 5, 5 in the follow up (min.3 weeks) and after rejection treatment showed a significant lower graft survival. In the cohort A (IDO < 5,0) 1/5/10 year graft survival was 98/88/69% compared to 88/57/34% (survival data death censored). There was no difference between both CNI's. Rejection rate in A was allover 18%, in B 19,5 % (BPAR). Patients with induction or polyclonal rejection treatment showed lower IDO levels and a better long-term survival. Conclusion: Supported by recent publications we found that chronic transplant nephropathy may not be related solely to CNI toxicity. Our data supporting the results, that not the rejection episode itself is leading to a reduced long-term outcome but a subclinical ongoing inflammatory processes. Once the rejection episode is treated successfully - meaning the reestablishment of the inflammatory homeostasis - the chance for a long graft survival is still given. IDO monitoring might be a helpful tool to identify very early subclinical acute rejection, the best rejection treatment and the optimization of immunsuppressive regimen in sense of rejection prophylaxis.

De novo development of circulating anti-endothelial cell antibodies rather than pre-existing antibodies is associated with post-transplant allograft rejection

Anti-endothelial cell antibodies (AECAs) are thought to be involved in the development of renal allograft rejection. To explore this further, we determine whether AECAs play a role both in predicting the incidence of allograft rejection and long-term outcomes by analysis of serum samples from 226 renal allograft recipients for AECAs pre- and post-transplant. Surprisingly, the presence of pre-existing AECAs was not associated with either an increased risk of rejection or a detrimental impact on recipient/graft survival. Subsequent de novo AECAs, however, were associated with a significantly increased risk of early acute rejection. Moreover, these rejections tended to be more severe with a significantly increased incidence of both steroid-resistant and multiple episodes of acute rejection. The acute rejections associated with de novo AECAs did not correlate with C4d deposition at the time of renal biopsy, but did demonstrate an association with the presence of glomerulitis and peritubular capillary inflammation. Significantly more patients with de novo AECAs developed graft dysfunction. Thus, our prospective study suggests the emergence of de novo AECAs is associated with transplant rejection that may lead to allograft dysfunction.

Does donor race still make a difference in deceased-donor African-American renal allograft recipients?

Background Prior studies have demonstrated that African-American (AA) donor kidneys are independently associated with an increased risk for graft loss. Methods We examined outcomes in comparable groups of AA deceased-donor (DD) kidney transplant patients receiving an AA donor (n = 35) versus a Caucasian donor (C group; n = 150) organ. Results There were no differences between AA and C groups in patient survival, new-onset diabetes, or BK nephropathy. The AA group demonstrated a significantly higher 6-month and overall incidence of acute rejection (AR), increased cytomegalovirus (CMV) infection, and decreased graft survival. Recurrent or de novo focal segmental glomerulosclerosis (FSGS) accounted for a significantly higher fraction of graft losses in the AA versus C group. Conclusions AA DD renal allograft recipients have equivalent patient but decreased graft survival when transplanted with an AA versus C kidney using current immunosuppression. This may be the result of increased AR, CMV infection, and recurrence/development of FSGS.

Is acute rejection the key predictor for long-term outcomes after renal transplantation when comparing calcineurin inhibitors?

In the context of modern immunosuppressive regimens, the overall incidence of acute rejection may no longer be the most accurate surrogate marker for long-term kidney graft survival. The type, severity, timing, and clinical course of acute rejection each influence the impact of a rejection episode, and if renal function recovers fully, there appears to be no survival disadvantage. Randomized clinical trials in renal transplant patients have generally shown that there are fewer acute rejection episodes with tacrolimus compared with cyclosporine, although with contemporary regimens, including mycophenolate acid, this difference is less marked than previously. In randomized trials, kidney graft survival rates with cyclosporine and tacrolimus have proven similar. Large-scale registry analyses have consistently shown no graft survival benefit with tacrolimus vs cyclosporine, and indeed, 2 such analyses have reported significantly higher graft survival with cyclosporine-based immunosuppression compared with tacrolimus in living-donor kidney transplant patients receiving mycophenolate mofetil. There are no reports of improved patient survival with either calcineurin inhibitor after kidney transplantation. In conclusion, the perception of better efficacy with tacrolimus vs cyclosporine based on the incidence of acute rejection is not supported by a difference in graft or patient survival after kidney transplantation.

12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients

The proliferation signal inhibitor everolimus (Certican), has demonstrated efficacy with full-dose cyclosporine (CsA) (Neoral). Two multicenter randomized controlled studies were performed to compare 12-month efficacy and safety of everolimus 1.5 and 3.0 mg/day with reduced-dose CsA. Study 1 enrolled 237 de novo renal allograft recipients, randomizing 222 nonblack patients to either everolimus 1.5 or 3.0 mg/day, with the Neoral) dose guided by C(2) (monitoring of CsA concentration 2 h after dosing). Study 2 had a similar protocol, with basiliximab included, enrolling 256 recipients and randomizing 243 nonblack patients. In Study 1, there was a lower incidence of acute rejection in nonblack patients on 3 mg/day (16.4%) compared with 1.5 mg/day (25.9%), P = 0.08. In Study 2, the inclusion of basiliximab lowered the overall incidence of acute rejection; 14.3% of nonblack patients (3 mg/day) and 13.6% of nonblack patients (1.5 mg/day) had acute rejection by 12 months (P =0.891). Renal function was preserved throughout the study, with no differences observed between groups within studies. Everolimus was well tolerated with no significant differences between doses. Everolimus, in combination with reduced-dose Neoral), demonstrated efficacy and was well tolerated. Basiliximab allows for utilization of lower doses of everolimus with reduced dosing of Neoral).

Comparative Study Between Living and Cadaveric Donors in Pediatric Liver Transplantation

We examined whether the results in living-related hepatic transplantation (LRLT) are better than those from a cadaveric donor (CDLT). Material and methods The last 27 consecutive LRLT, performed from 1998 to 2005, were compared with 27 CDLT matched for age, weight, date, and diagnosis. Grafts in LRLT group were left lateral segment ( n = 22), left lobe ( n = 3), and right lobe ( n = 2). In the CDLT group, the grafts were split in situ ( n = 10), hepatic reduction ( n = 9) and whole liver ( n = 8). We analyzed the actuarial survivals (grafts and children), retransplantation, primary nonfunction, initial graft malfunction (liver enzymes >2000 U/L), surgical complications, rejection, and resource consumption. Results Patient survivals at 6 months, 1 year, and 5 years were 100%, 96%, and 96% in LRLT and 100%, 100%, and 100% in CDLT ( P = NS). Graft survivals were 93%, 89%, and 89% versus 96%, 96%, and 96%, respectively ( P = NS). Complications were biliary complications (LRLT, 25% vs CDLT, 3%; P = .021); portal vein thrombosis (LRLT, 7% vs CDLT, 3%; NS), and hepatic artery thrombosis (LRLT, 0% vs CDLT, 3%; NS). The overall incidence of acute rejection was slightly higher (NS) in LRLT (LRLT, 18% vs CDLT, 11%; NS). Liver enzyme levels were higher in the CDLT group, but initial malfunction rate was not statistically different. Regarding resource consumption: blood product needs were higher in LRLT ( P < .05) and hospital stay and ICU stay were longer, although not significantly, among LRLT. Conclusions The results in LRLT among children are similar to those obtained in CDLT. We found a trend towards less initial graft malfunction in LRLT. Blood product needs were higher in LRLT. Hospital and ICU stay were longer, but not significantly different in LRLT. The benefits of LRLT are saving a scarce resource: a cadaveric donor liver graft.

One year complete follow-up of a porspective randomized international investigator driven study comparing Tac and CsA (+MMF/steroids) after lung transplantation in 274 patients

induction in lung transplantation. Methods: The initial randomized, prospective study included fortyfour lung recipients assigned to receive either RATG induction (locally developed preparation dosed at 1.5 mg/kg/d for 3 days) with conventional immunosuppression or conventional immunosuppression alone. These 2 groups were retrospectively analyzed for episodes of biopsy-proven acute rejection, BOS development, and survival. Results: Patients receiving RATG suffered fewer early rejections ( 6 months posttransplant) Grade 2 or higher (5%), compared to those with conventional therapy alone (41%; Fisher’s Test, p 0.01). With a mean follow-up of 4.4 years, the overall incidence of acute rejection between groups did not differ (RATG 62%, Conventional 68%; p 0.52). Median time to rejection was 614 days for the RATG group and 206 days for recipients without induction therapy (p 0.52). Freedom from BOS and survival at five years was 62% and 41% for the RATG group, compared to 34% and 46% for recipients treated conventionally (log-rank, p 0.14 and 0.48, respectively). Conclusion: Although RATG delays the onset of acute rejection and is associated with a trend towards delayed onset of BOS, significant differences were not observed in long-term allograft survival.

Rejeição aguda em transplantação renal. Análise dos factores de risco e sua influência na disfunção crónica.

The aim of this study was to study the incidence and causes of acute rejection (AR) on cadaveric renal transplants under cyclosporine A-based immunosuppression, and to investigate the AR effect on the ocurrence of chronic dysfunction (CD) and on the outcome of transplantation. We analyzed 794 renal transplants from cadaver donor between December, 1985 and December, 1999. We examined the major donor, recipient and graft-related factors and their influence in graft outcome. The diagnosis of AR was in 65% based in clinical and laboratorial findings: fever, decrease of diuresis, graft pain and/or strained and a serum creatinine increase of at least 0,4 mg/dl, and in 35% the diagnosis of AR was biopsy-proven. Statistics included univariate and multivariate analysis. Graft and patient survival rates were calculated by Kaplan-Meier method (with log-rank test). In the 794 renal transplants included in the study, 498 (63%) didn't have AR and 296 (37%) had at least one episode of AR. This overall incidence of AR of 37% is decreasing and in the last two years, 1998 and 1999 remained in 24% and 25%, respectively. The AR was associated with cadaver donor-related factors [ non traumatic cause of death (p=0,018), perfusion with Eurocollins solution (p=0,008) and cold ischemia time > 24 hours (p= 0,032)] and with recipient-related factors [age < 45 years (p=0,000) and immunosuppression with antithymocyte globulin (ATG) + azathioprine (Aza) + prednisone (Pred) + cyclosporine A (CsA) (p=0,006)]. Concerning graft-related factors acute tubular necrosis (ATN) was related with higher incidence of AR (35% of AR without ATN versus 48% of AR with ATN, p= 0,008) and this, was responsible by a significative increase of chronic dysfunction (CD) (p= 0,000) and by the worst graft function at the end of the first year (p= 0,000). Our results also showed that CD as a cause of graft loss increased substantially (23% vs 49%) in the presence of AR. The 1, 3, 5, 10 and 15-year graft survival in the patients with AR were, 94%, 85%, 74%, 50% and 38%, respectively, and in the patients without AR, 97%, 91%, 87%, 77% and 67%, respectively. These results were statistically significant ( p= 0,000). The AR didn't influence patient survival (p= 0,814). Our overall incidence of AR (37%) is decreasing reaching in the last year 25%. The AR incidence increased significantly with grafts from cadaver donors with non-traumatic cause of death, preserved with Eurocollins solution, with cold ischemia times > 24 hours and in recipients with age < 45 years and with ATG+Aza+Pred+CsA immunosuppression regimen. ATN increased the AR incidence and this was associated with a higher ocurrence of CD and a worst graft function at 1 year. The graft lost by CD duplicate in the patients with AR. Graft survival was significantly worse in the patients with AR. The AR did not adversely affect patient survival.

A decade of living lobar lung transplantation: recipient outcomes

Objective Living lobar lung transplantation was developed as a procedure for patients considered too ill to await cadaveric transplantation. Methods One hundred twenty-eight living lobar lung transplantations were performed in 123 patients between 1993 and 2003. Eighty-four patients were adults (age, 27 ± 7.7 years), and 39 were pediatric patients (age, 13.9 ± 2.9 years). Results The primary indication for transplantation was cystic fibrosis (84%). At the time of transplantation, 67.5% of patients were hospitalized, and 17.9% were intubated. One-, 3-, and 5-year actuarial survival among living lobar recipients was 70%, 54%, and 45%, respectively. There was no difference in actuarial survival between adult and pediatric living lobar recipients ( P = .65). There were 63 deaths among living lobar recipients, with infection being the predominant cause (53.4%), followed by obliterative bronchiolitis (12.7%) and primary graft dysfunction (7.9%). The overall incidence of acute rejection was 0.8 episodes per patient. Seventy-eight percent of rejection episodes were unilateral. Age, sex, indication, donor relationship, preoperative hospitalization status, use of preoperative steroids, and HLA-A, HLA-B, and HLA-DR typing did not influence survival. However, patients on ventilators preoperatively had significantly worse outcomes (odds ratio, 3.06, P = .03; Kaplan-Meier P = .002), and those undergoing retransplantation had an increased risk of death (odds ratio, 2.50). Conclusion These results support the continued use of living lobar lung transplantation in patients deemed unable to await a cadaveric transplantation. We consider patients undergoing retransplantations and intubated patients to be at significantly high risk because of the poor outcomes in these populations.

Early steroid withdrawal after liver transplantation: The canadian tacrolimus versus microemulsion cyclosporin a trial: 1-year follow-up

Corticosteroid therapy contributes significant toxicity to liver transplantation. The safety and efficacy of early steroid withdrawal were determined in patients treated with either tacrolimus or microemulsion cyclosporin A (micro-CsA). The primary outcome was the proportion of patients who were steroid-free 1 year posttransplantation. From the seven Canadian adult liver transplant centers, 143 patients were randomly allocated oral treatment with either tacrolimus (n = 71) or micro-CsA (n = 72), together with corticosteroids and azathioprine. Eligibility criteria for steroid withdrawal included freedom from acute rejection for a minimum of 3 months, and prednisone ≤0.15 mg/kg/d. In eligible patients, the daily steroid dose was reduced by 2.5 mg each month until complete discontinuation was achieved. At 1 year after transplantation, 75% of the tacrolimus patients and 63% of the micro-CsA patients were steroid-free (P = .20). Of all of the patients who became eligible for steroid withdrawal, steroid discontinuation was achieved in over 80%. One-year patient survival was 97% with tacrolimus and 89% with micro-CsA (P = .052) . Graft survival was 97% and 86%, respectively (P = .017). The overall incidence of acute rejection during the first year was 35% with tacrolimus and 43% with micro-CsA (P = .26). There was no difference in survival, acute rejection, or rate of steroid withdrawal when adjusting for hepatitis C. All acute rejection episodes experienced during steroid withdrawal were steroid-responsive. Steroid-resistant rejection occurred in 5.6% of the tacrolimus and 9.7% of the micro-CsA patients. One patient, in the micro-CsA group, experienced refractory rejection. Chronic rejection was not observed in either group. The toxicity profiles were similar. Postoperative serum creatinine levels were similar, and dialysis was required in less than 10% of patients in each group. Infectious complications were similar in both groups. Neurotoxicity was a serious adverse event in 13% and 10% of patients receiving tacrolimus and micro-CsA, respectively. Early steroid withdrawal is safe and effective after liver transplantation using either tacrolimus plus azathioprine or micro-CsA plus azathioprine immunoprophylaxis. (Liver Transpl 2003;9:587-595.)

Pediatric renal transplantation: A single Belgian center experience over 20 years

Between 1980 and 2000, 100 renal transplantations were performed in 91 children at the pediatric unit of the University Hospital Leuven. The proportion of living-related donors (LRD) was 20%. Patient survival rates were 94% at 3 yr, 91% at 5 yr, and 87% at 10 yr. The commonest causes of death were bacterial infections and cardiovascular complications, which underscores the need for aggressive preventative procedures in this area after transplantation. The overall actuarial graft survival was 82% at 3 yr (n = 73), 74% at 5 yr (n = 53), and 56% at 10 yr (n = 29). In the LRD group, the graft survival was 10% better than the overall actuarial graft survival rate. The overall incidence of acute rejection was 55% but has shown a decrease to 34% in more recent years (1993-99). The major causes of graft failure were chronic rejection and recurrence of the initial disease, and these remain a major concern. Improvement of these results could be achieved by tight immunosuppression management, early aggressive treatment of infection and rejection, and careful educational and psychological support.

Pediatric renal transplantation: A single Belgian center experience over 20 years

Abstract: Between 1980 and 2000, 100 renal transplantations were performed in 91 children at the pediatric unit of the University Hospital Leuven. The proportion of living-related donors (LRD) was 20%. Patient survival rates were 94% at 3 yr, 91% at 5 yr, and 87% at 10 yr. The commonest causes of death were bacterial infections and cardiovascular complications, which underscores the need for aggressive preventative procedures in this area after transplantation. The overall actuarial graft survival was 82% at 3 yr (n = 73), 74% at 5 yr (n = 53), and 56% at 10 yr (n = 29). In the LRD group, the graft survival was 10% better than the overall actuarial graft survival rate. The overall incidence of acute rejection was 55% but has shown a decrease to 34% in more recent years (1993–99). The major causes of graft failure were chronic rejection and recurrence of the initial disease, and these remain a major concern. Improvement of these results could be achieved by tight immunosuppression management, early aggressive treatment of infection and rejection, and careful educational and psychological support.

AFRICAN-AMERICAN COMPARED TO CAUCASIAN RESPONSE TO CORTICOSTEROID WITHDRAWAL FOLLOWING TACROLIMUS THERAPY FOR REFRACTORY RENAL REJECTION

625 The results of corticosteroid withdrawal (CSWD) following tacrolimus therapy for refractory acute renal allograft rejection (RARAR) have not been defined in prospective clinical trials. The results of a prospective trial of CSWD after tacrolimus therapy for RARAR are presented. Methods: Between Oct '93 and Oct '98, forty-three patients, twenty-nine African-American (AA) and fourteen Caucasian (CA) patients, were enrolled in a trial of tacrolimus therapy for RARAR that included a prospective CSWD protocol. RARAR was defined as biopsy proven acute rejection (by Banff criteria) occurring during or after rejection therapy with an antilymphocyte preparation. Patients with chronic rejection (by Banff criteria) were excluded. Statistical analysis was performed using Z scores. Results: Mean follow-up for the AA and CA populations were 29 and 38 months. Corticosteroids were successfully withdrawn in 9/29 (31%) for the AA group and 12/14 (86%) in the CA group. Eleven grafts were lost in the AA group to acute rejection 5/11 (1 lost to biopsy bleed, 1 to pt noncompliance) and chronic rejection 6/11 (2 lost to pt noncompliance). Graft loss in the CA group was only secondary to chronic renal rejection (2/14). The overall incidence of acute rejection was 15/29 (52%) for the AA group and 4/14 (29%) for the CA group. The AA patients experienced a significantly lower graft survival at both 2 years (54% vs. 80%) and 3 years (40% vs. 79%). (p=0.03). Chronic rejection was diagnosed equally in both groups, AA 4/29 (14%) and CA 2/14 (14%). No significant differences in weight, white blood cell count or the incidence of new onset diabetes between groups were noted. Initiation or increased anti-hypertensive therapy was required in 28% of AA patients and 21% of the CA patients. (p=NS). Tacrolimus dose, tacrolimus levels, azathioprine dosing, and mycophenolate mofetil dosing were not different between groups over the study period. Serum creatinine and creatinine clearances were not significantly different at three years. Conclusions: CSWD can be performed following tacrolimus therapy for RARAR with acceptable long-term recurrent rejection and graft survival rates in caucasian patients. African-American patients, however, experience higher rates of recurrent rejection and lower long-term graft survival.

Pediatric liver transplantation with cadaveric or living related donors: Comparative results in 90 elective recipients of primary grafts

Study design: Between July 1993 and March 1997, 110 children were listed for primary elective liver transplantation with cadaveric (Cad: n = 68) or living-related (LR: n = 42) donors. Pregraft mortality, post-transplant survival, and surgical and immunologic complications were retrospectively compared in both groups. Results: The pregraft mortality rate was 10 (15%) of 68 versus 1 (2%) of 42 in the Cad and LR groups, respectively ( P = .049). Postliver transplantation 1-year patient and graft survival rates were 87% and 75% in the Cad group (n = 49) versus 92% and 90% in the LR group (n = 41), respectively (NS). The incidence of post-transplant complications was as follows: hepatic artery thrombosis (Cad: 16%; LR: 0%, P = .020), portal vein thrombosis (Cad: 8%; LR: 2%, NS), and biliary complications (Cad: 14%; LR: 34%, P = .044). The overall incidence of acute rejection was similar in both groups; however, a lower incidence of acute rejection occurred in LR graft recipients treated with tacrolimus. Conclusions: The introduction of an LR donor liver transplantation program allowed a significant decrease in the pretransplant mortality rate, with a consequent overall improvement in patient survival compared with the Cad series. The incidence of biliary complications was higher in the LR series, whereas better human leukocyte antigen matching in this subgroup did not result in a lower rejection incidence. (J Pediatr 1999;134:280-6)