Significant Difference In Allograft Survival Research Articles

Outcomes of Flow Cytometry Crossmatch-Positive Lung Transplants Using Peri-Operative Desensitization

<h3>Purpose</h3> Successful outcomes among virtual crossmatch (VXM)-positive lung transplant recipients (LTRs) following peri-operative desensitization have been previously reported. However, the subset of flow cytometry crossmatch (FCXM)-positive LTRs, who may be at higher immunologic risk, has not been studied specifically. We conducted a retrospective cohort study to determine the impact of a positive FCXM on allograft survival (death/re-transplant) and chronic lung allograft dysfunction (CLAD)-free survival among LTRs in our program. <h3>Methods</h3> All adult, first-time LTRs from January 2014 to December 2019 with complete crossmatch data were divided into 3 cohorts based on sensitization status at the time of transplant: VXM-negative, VXM-positive/FCXM-negative, and VXM-positive/FCXM-positive. Patients were followed until October 2021. VXM-positive LTRs were routinely desensitized using plasma exchange, intravenous immune globulin, and anti-thymocyte globulin peri-operatively. Patient characteristics were compared using the chi-square test, and Kaplan Meier estimates of allograft survival and CLAD-free survival were compared using the log-rank test. <h3>Results</h3> A total of 902 LTRs were included: 765 (85%) VXM-negative, 63 (7%) VXM-positive/FCXM-negative, and 74 (8%) VXM-positive/FCXM-positive. VXM-positive/FCXM-positive LTRs were more likely to be female (p<0.001) and less likely to have cystic fibrosis/bronchiectasis (p=0.022), but age and urgency status at listing did not differ from the other cohorts. There was no significant difference in allograft survival (p=0.9805) or CLAD-free survival (p=0.9306) among VXM-negative, VXM-positive/FCXM-negative, and VXM-positive/FCXM-positive LTRs (Figure 1). <h3>Conclusion</h3> In the largest study to date of FCXM-positive LTRs, we demonstrate that with our peri-operative desensitization protocol, outcomes are equivalent to other LTRs. Our protocol may be used to facilitate VXM-positive and FCXM-positive lung transplants safely.

Impact of acute kidney injury in donors on renal graft survival: a systematic review and Meta-Analysis

The acute kidney injury (AKI) of deceased donors was an important strategy to address donor shortage. This meta-analysis was conducted to explore the clinical effect of kidney transplantation from donors with AKI. PubMed, Embase, and Cochrane Library were searched through July 2017. Fourteen cohort studies, involving a total of 15,345 donors, were included. Studies were pooled, and the hazard ratio (HR), relative risk (RR), weighted mean difference (WMD), and their corresponding 95% confidence interval (CI) were calculated. The present meta-analysis showed no significant difference in allograft survival between the AKI and non-AKI groups (HR = 1.16, 95% CI = 0.99–1.37, Pheterogeneity = 0.238, I2 = 21.6%) from 12 months to 120 months after kidney transplantation. However, the time of hospital stay was significantly longer (WMD = 2.49, 95% CI = 1.06–3.92, Pheterogeneity = 0.458, I2 = 0%) and the incidence of delayed graft function (DGF) was significantly higher (RR = 1.76, 95% CI = 1.52–2.04, Pheterogeneity < 0.001, I2 = 71.2%) in the AKI group than in the non-AKI group. We concluded that even though hospital stay time was longer and the incidence of DGF was significantly higher in the AKI group, there is no significant difference in allograft survival between the two groups.

Outcomes From Pancreatic Transplantation in Donation After Cardiac Death

Pancreas transplantation remains the gold standard for treatment for type I diabetes providing an insulin-independent, normoglycemic state. Increasingly, donation after cardiac death (DCD) donors are used in view of the organ donor shortage. We aimed to systematically review recipient outcomes from DCD donors and where possible compared these with donor after brain death (DBD) donors. We searched the databases MEDLINE via PubMed, EMBASE, and The Cochrane Library from inception to March 2015, for studies reporting the outcome of DCD pancreas transplants. We appraised studies using the Newcastle-Ottawa scale and meta-analyzed using a random effects model. We identified 18 studies, 4 retrospective and 6 prospective cohort studies and 8 case reports. Our bias assessment revealed that although studies were well conducted, some studies had potential confounding factors and absence of comparator groups. Eight of the 18 studies included a DBD comparison group comprising 23 609 transplant recipients. Importantly, there was no significant difference in allograft survival up to 10 years (hazard ratio, 0.98; 95% confidence interval [95% CI], 0.74-1.31; P = 0.92), or patient survival (hazard ratio, 1.31; 95% CI, 0.62-2.78; P = 0.47) between DCD and DBD pancreas transplants. We estimated that the odds of graft thrombosis was 1.67 times higher in DCD organs (95% CI, 1.04-2.67; P = 0.006). However, subgroup analysis found thrombosis was not higher in recipients whose DCD donors were given antemortem heparin (P = 0.62). Using current DCD criteria, pancreas transplantation is a viable alternative to DBD transplantation, and antemortem interventions including heparinization may be beneficial. This potential benefit of DCD pancreas donation warrants further study.

Timing of Pregnancy After Kidney Transplantation and Risk of Allograft Failure.

The optimal timing of pregnancy after kidney transplantation remains uncertain. We determined the risk of allograft failure among women who became pregnant within the first 3 posttransplant years. Among 21 814 women aged 15-45 years who received a first kidney-only transplant between 1990 and 2010 captured in the United States Renal Data System, n = 729 pregnancies were identified using Medicare claims. The probability of allograft failure from any cause including death (ACGL) at 1, 3, and 5 years after pregnancy was 9.6%, 25.9%, and 36.6%. In multivariate analyses, pregnancy in the first posttransplant year was associated with an increased risk of ACGL (hazard ratio [HR]: 1.18; 95% confidence interval [CI] 1.00, 1.40) and death censored graft loss (DCGL) (HR:1.25; 95% CI 1.04, 1.50), while pregnancy in the second posttransplant year was associated with an increased risk of DCGL (HR: 1.26; 95% CI 1.06, 1.50). Pregnancy in the third posttransplant year was not associated with an increased risk of ACGL or DCGL. These findings demonstrate a higher incidence of allograft failure after pregnancy than previously reported and that the increased risk of allograft failure extends to pregnancies in the second posttransplant year.

Tailoring the Endovascular Management of Transplant Renal Artery Stenosis

In this study we analyze the different types of endovascular interventions (EVIs) in de novo transplant renal artery stenosis (TRAS) and its anatomical subtypes to examine any variation in recovery of allograft function, blood pressure control, EVI patency and allograft survival with respect to EVI type (DES: drug-eluting stent, BMS: bare-metal stent, PTA: percutaneous transluminal angioplasty). Forty-five patients underwent a total of 50 primary EVIs (DES: 18, BMS: 26, PTA: 6). Patients were stratified according to medical co-morbidities, graft characteristics, biopsy results, clinical presentation and TRAS anatomic subtypes (anastomotic: 26, postanastomotic: 17, bend-kink: 2). There was significant improvement in allograft function and mean arterial blood pressure (MAP) control across all interventions (pre-EVI-creatinine [CR]: 2.8 ± 1.4, post-EVI-Cr: 2.1 ± 0.7, p < 0.001; pre-EVI-MAP: 117 ± 16, post-EVI-MAP: 112 ± 17, p = 0.03) with no significant difference among EVI types. There was no significant difference in allograft survival with respect to EVI type. Patency was significantly higher in EVIs performed with DES and BMS compared to PTA (p = 0.001). In the postanastomotic TRAS subtype, patency rates were significantly higher in DES compared to BMS (p = 0.012) in vessels of comparable reference diameter (≤5 mm).

Renal Transplantation With Donors Older Than 70 Years: Does Age Matter?

PurposeThe need for organs for renal transplantation has encouraged the use of grafts from increasingly older donors. Studies of transplantation results with donors older than 70 years are sparse. The main purpose of this study is to compare the results of transplantation with donors older and younger than 70 years old. MethodsThis retrospective study included 1233 consecutive deceased-donor renal transplantations performed between January 1, 2001, and December 31, 2011. We compared outcomes of grafts from donors older than 70 years (group ≥ 70; n = 82) versus donors younger than 70 years (group < 70; n = 1151). ResultsUnivariate analysis of pretransplantation data showed statistically significant differences (P < .05) among the following variables for the group < 70 and group ≥ 70, respectively: recipient age (46 ± 13 versus 61 ± 5 years), donor age (44 ± 16 versus 73 ± 3 years), donor male gender (69.4% versus 47.6%), use of antibody induction immunosuppression (51.7% versus 70.7%), and HLA compatibilities (2.4 versus 2). The group ≥ 70 showed increased postoperative minor complications: bleeding (8.5% versus 3.4%; P = .017), lymphocele formation (3.7% versus 0.5%; P = .011), and incisional hernia (2.4% versus 0.2%; P < .001). Regarding transplantation results, we observed that mean serum creatinine was significantly lower among group < 70, at 1, 3, 6, 12, 24, and 60 months after transplantation (P < .05). Cumulative graft survival at 1, 3, and 4 years was 90%, 85%, and 83% in the group < 70 versus 87%, 79%, and 72% in the group ≥ 70. In the subgroup of recipients younger than 60 years, we did not verify statistically significant differences in allograft survival between group ≥ 70 and group < 70. Using Cox regression for survival analysis, we verified that donor age was not an independent risk factor for graft failure. ConclusionsThe group of patients who received kidneys from donors younger than 70 years achieved better transplantation outcomes. Nevertheless, kidneys from older donors represent an excellent alternative for older recipients.

CD8 Memory T cell Migration to Cardiac Allografts (145.16)

Abstract Memory T cells that recognize donor alloantigen jeopardize the survival of life-saving organ transplants. Although recent publications studied the role of chemokines in effector T cell migration to the allograft, the migratory requirements of memory T cells are not known. Phenotyping of CD8 memory T cell populations demonstrated up-regulation of CXCR3 and CCR5 chemokine receptors. Therefore, we investigated the survival of cardiac allografts (BALB/c, H-2d) transplanted into aly mice (alymphoplastic, no secondary lymphoid organs after splenectomy, H-2b) that received sorted CXCR3-/- or wt CD8+CD44+ memory T cells (C57Bl/6, H-2b, recognizing H-2d) via adoptive transfer. Additionally, a group of mice receiving CXCR3-/- cells was treated with anti-CCR5 antibody. No significant differences in allograft survival could be detected between the groups. Furthermore, flow analysis revealed no difference in the migration of adoptively co-transferred, congenic, CFSE labeled CXCR3-/- and wt CD8+CD44+ memory T cells to the cardiac allograft at 20 hours and 3 days after cell transfer (n=6). Our results show that CD8 memory T cell migration to the allograft is independent of CXCR3 and CCR5. Moreover, the migration requirements for CD8 memory T cells clearly differ from those established for effector T cells highlighting the role of memory T cells in immune surveillance and their threat to transplanted organs.

Treatment with monoclonal antibodies to ICAM-1 and LFA-1 in rat heart allograft rejection.

During allograft rejection, leukocyte infiltration in the graft is regulated by various adhesion molecules. Treatment with monoclonal antibodies to ICAM-1 and LFA-1 (CD11 a) induces specific tolerance after murine heart transplantation. In this study, we investigated the possibility of tolerance induction using these antibodies in a fully incompatible rat heart transplant model. Heterotopic, intra-abdominal heart transplantation was performed using Dark Agouti (DA) rats as donors and Lewis (LEW) rats as recipients. Group A (n = 6) received no immunosuppression and served as controls. In group B (n = 6) 500 micrograms/kg per day 1A29 (anti-ICAM-1) was administered intravenously (i.v.) for 5 days; group C rats received the same dosage of WT.1 (anti-CD11 a) i.v. for 5 days. In group D (n = 6), rats received combined i.v. administration of anti-CD11 a and anti-ICAM-1 (500 micrograms/kg per day of each, for 5 days. The antibodies used were monoclonal mouse anti-rat antibodies produced from hybridomas. Allograft survival was monitored by daily palpation of the graft. There was no statistically significant difference in allograft survival between the groups (A: 5.7 +/- 0.5 days; B: 5.7 +/- 0.5 days; C: 5.7 +/- 0.5 days; D: 6.2 +/- 0.4 days). Treatment with monoclonal antibodies to ICAM-1 and LFA-1 alone or in combination had no effect on allograft survival after heart transplantation between fully incompatible rat strains. We conclude that induction of tolerance using these antibodies seems inconceivable in human heart transplantation.

IMMUNOLOGICAL DONOR PRETREATMENT IN COMBINATION WITH PULSATILE PRESERVATION IN CADAVERIC RENAL TRANSPLANTATION

The extended experience on the efficacy of pretreating the cadaveric renal allograft donor by means of large doses of cyclophosphamide and methylprednisolone (group A, 36 kidneys) was compared with the experience regarding untreated renal allografts (group B, 32 kidneys). Kidneys in both groups were perfused by pulsatile means using cryoprecipitated plasma. There was a significant difference in allograft survival (72% in group A versus 36% in group B at 3 years by actuarial means). Also, large doses of cyclophosphamide and methylprednisolone as pretreatment did not cause any detrimental effect to the allograft kidney when used in combination with cryoprecipitated plasma and pulsatile perfusion.