Difference In Allograft Survival Research Articles

Comparative outcomes of DSA positive, crossmatch negative living donor kidney transplants versus remaining on the waitlist for an HLA compatible deceased donor

IntroductionThe clinical relevance of preformed donor specific antibodies in the setting of a negative crossmatch (DSA + XM-) remains controversial. In this study we investigate the outcomes of patients with a DSA + XM- living donor (LDi) who proceeded with an HLA-incompatible (HLAi) transplant compared with those who waited for an HLA-compatible deceased donor (DDc). Materials and methodsWe investigated 359 patients on the transplant waiting list who had at least one potential HLAi living donor, from which 203 DSA + XM- pairs were identified and outcomes analysed. ResultsOut of 203 patients, 96 (47.3%) received a LD transplant: 52/96 (54.2%) a LDi, and 44/96 (45.8%) an alternative compatible LD. In addition, 107 patients out of 203(52.7%) waited for a DDc, of which 47(43.9%) were subsequently transplanted. Our adjusted analysis showed that the LDi transplantation did not offer a superior patient survival over waiting for a DDc transplant. For those transplanted, there was no difference in patient (p = 0.065) or death censored allograft survival (p = 0.37) between DDc and LDi recipients. However, there was a higher incidence of acute allograft rejection (p = 0.043) and antibody-mediated rejection (p = 0.005) in the LDi group. Having a high pre-transplant calculated reaction frequency and preformed DSA to both class I and class II antigens were associated with inferior outcomes in the LDi transplants. ConclusionsGiven the lack of difference in allograft survival between LDi and DDc transplants, in the absence of an alternative compatible living donor, proceeding with a LDi should be supported despite a higher rejection risk, providing individual risk assessment and shared decision making is undertaken.

427.1: Donor Dendritic Cell Depletion Allows Novel Insights Into the Alloimmune Response Following Murine Composite Tissue and Skin Transplantation

Background: Cell-based therapies in vascularized composite tissue allotransplantation (VCA) have demonstrated promising results with the potential to modify life-long conventional immunosuppression. Dendritic cells (DCs) promote pro-inflammatory, alloimmune responses. Of particular interest is the role of DCs as antigen-presenting cells and potential tolerogenic effects as immature DCs. Material and Methods: Diphteria Toxin Receptor (DTR) transgenic or wild-type (WT) donor mice were used to deplete subsets of DCs or APCs respectively in a fully histoincompatible murine hind limb and skin transplant models; prior to procurement, all donors were either treated with diphteria toxin (DT; at -15 hours) or with clodronate (CL; 8 days prior to Tx). DBA/2J mice served as recipients. Study endpoint was on POD 6. Alloimmune response was assessed sequentially; graft survival, intragraft structural and inflammatory changes were tested serially. Results: The total number of dendritic cells (CD11b- CD11c+ DC) had markedly increased in recipients of skin WT grafts compared to recipients of VCA WT grafts (p<0.0001). The treatment with CL or DT significantly reduced the numbers of maturated and activated DC in the spleen, blood, and LN of mice receiving a skin graft, whereas numbers of CD11b-CD11c+MHCII+ and CD11b-CD11c+CD40+ DC were exclusively reduced in the spleen of VCA recipients after donor pretreatment with DT. cDC 1 subtypes were significantly higher in VCA WT vs. skin WT recipients (p<0.001). Donor pretreatment with DT decreased cDC1 counts only in recipients of VCA grafts (p<0.001).Luminex analysis revealed significantly higher TNF-alpha serum levels in the VCA WT vs. skin WT group (p<0.01). TNF-beta serum levels were significantly decreased in VCA depletion groups vs VCA WT group (p<0.001). Clinical signs of acute rejection among the VCA groups revealed higher rejection grades in the WT compared to the DC depletion group according to the BANFF criteria (grade III vs. grade II). Additional injection of immature DCs did not show any difference in allograft survival (p=ns).Conclusion: This is to our knowledge the first systematic study delineating the role of mature and immature DCs tested across and skin transplants. Those data may help explaining split-tolerance phenomenon in VCA while providing a basic concept for the utilization of mature and immature DCs in modifying alloimmune responses in VCA transplants.

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.

Use and Outcomes of Induction Therapy in Well-Matched Kidney Transplant Recipients.

The optimal induction treatment in low-immune risk kidney transplant recipients is uncertain. We therefore investigated the use and outcomes of induction immunosuppression in a low-risk cohort of patients who were well matched with their donor at HLA-A, -B, -DR, -DQB1 on the basis of serologic typing. Our study was an observational study of first adult kidney-only transplant recipients in the United States recorded by the Organ Procurement and Transplant Network. Among 2976 recipients, 57% were treated with T cell-depleting antibodies, 28% were treated with an IL-2 receptor antagonist, and 15% were treated without induction. There was no difference in allograft survival, death-censored graft survival, or death with function between patients treated with an IL-2 receptor antagonist and no induction therapy. In multivariable models, patients treated with T cell-depleting therapy had a similar risk of graft loss from any cause, including death (hazard ratio, 1.19; 95% confidence interval, 0.98 to 1.45), compared with patients treated with an IL-2 receptor antagonist or no induction. The findings were consistent in subgroup analyses of Black recipients, patients grouped by calculated panel reactive antibody, and donor source. The incidence of acute rejection at 1 year was low (≤5%) and did not vary between treatment groups. Use of induction therapy with T cell-depleting therapy or IL-2 receptor antagonists in first kidney transplant recipients who are well matched with their donor at the HLA-A, -B, -DR, -DQB1 gene loci is not associated with improved post-transplant outcomes.

PULSATILE PERFUSION IN PEDIATRIC KIDNEY TRANSPLANTATION

Introduction: Pulsatile perfusion of deceased donor kidneys is commonly practiced in adult kidney transplantation. We examined the practice of pulsatile perfusion in pediatric patients undergoing kidney transplantation and compared outcomes from preservation using pulsatile perfusion (PUMP) and static cold storage (COLD) in pediatric recipients. Methods: The UNOS database was used to determine outcomes in all pediatric kidney recipients (<18 years) who were transplanted between 1994—2018. Living donor and multi-organ transplant recipients were excluded. Patients were divided according to preservation method into PUMP or COLD groups. Donor and recipient demographic data were examined, as were survival and outcomes. A p-value of <0.05 was considered to be significant. Results: There were 10,045 pediatric kidney transplants performed during the study period, of which 1,619 were PUMP (16.1%) and 8,426 were COLD (83.9%). PUMP donors were significantly younger (22.7 vs. 23.8 years), had a higher KDPI (22.4% vs. 19.7%), longer cold storage time (18.8 vs. 14.1 hours), more frequent donation after cardiac death (DCD) donor status (12.9% vs. 1.3%), and more likely to be an increased risk of disease (IRD) transmission donor (9.1% vs. 4.8%). PUMP kidneys were also more likely to have been biopsied (18.1% vs. 3.3%). There were no differences in donor creatinine (0.99 vs. 0.96 mg/dL). Recipients of PUMP kidneys were significantly older (12.0 vs. 11.6 years), had a shorter wait time (287.7 vs. 320.2 days), and greater HLA mismatch (4.5 vs. 4.3). There were no differences in BMI, initial or final cPRA, length of stay, or serum creatinine at the time of discharge (1.42 vs. 1.42 mg/dL). No differences in allograft survival at 10 years were noted between PUMP and COLD groups (Figure 1). Additionally, delayed graft function (DGF) occurrence (8.5% vs. 12.5%, p<0.05) and rejection rate in the initial 12 months post transplant (11.5% vs. 13.8%) were significantly lower in the PUMP group compared with the COLD group.Conclusions: Despite multiple unfavorable characteristics noted in PUMP donors, recipients of these kidneys have no difference in allograft survival and have a lower DGF rate. These data support the utilization of pulsatile perfusion during the evaluation of higher risk pediatric kidney donors and a possible role in improving outcomes for pediatric kidney transplantation.

Donation after cardiac death kidneys are suitable for pediatric recipients.

Despite the high number of children listed for kidney transplantation and shortage of deceased organ donors, there is reluctance to utilize DCD kidneys in pediatric recipients. We examined outcomes in pediatric kidney transplant patients who received a DCD kidney allograft. UNOS database was queried to examine outcomes in all pediatric kidney transplant recipients from 1994 to 2017. Pediatric status was defined as <18years at the time of transplantation. Recipients were divided by DBD or DCD allograft status. Donor and recipient demographic data were examined. Patient and allograft survival was calculated, and Kaplan-Meier survival curves were generated. A P-value of <0.05 was considered to be significant. A total of 286 pediatric kidney transplant recipients received a DCD allograft. The donors in the DCD group were significantly younger than those in the DBD group (21.7 vs 23.3years), with a higher KDPI (26.5% vs 22.9%). In the DCD group, the average age at transplant was younger (11.6 vs 12.9years), with no difference in cold ischemia time or length of stay between the two groups. Rates of delayed graft function were higher in the DCD group, but despite this, there were no significant differences in allograft or patient survival between the groups. There is no difference in allograft survival in pediatric kidney transplant recipients who receive a DCD kidney allograft. DCD kidney allografts are suitable for transplantation in pediatric patients and can greatly expand the donor pool.

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.

Impact of Deceased Donor Cardiac Arrest Time on Postpancreas Transplant Graft Function and Survival

IntroductionTransplantation of pancreas allografts from donors that have experienced preprocurement cardiopulmonary arrest (PPCA) is not common, though use of PPCA grafts is routine in liver and kidney transplantation. This article reviews a large number of PPCA pancreas grafts at a single center and reports posttransplant outcomes including early graft dysfunction, length of hospital stay, rejection, and early and late graft survival.MethodsPreprocurement cardiopulmonary arrest, arrest time, and donor and recipient pancreatic enzyme levels were collected from electronic and written medical records. The PPCA donors were stratified into 4 groups: none, less than 20 minutes, 20-39 minutes, and 40 minutes or greater. Graft survival was assessed at 7 and 90 days and at 1 year. Long-term graft survival was assessed by Cox regression analysis.ResultsThe records of 606 pancreas transplants were reviewed, including 328 (54%) simultaneous pancreas and kidney transplants. Preprocurement cardiopulmonary arrest occurred in 176 donors (29%; median time, 20 minutes). Median peak donor lipase was higher in PPCA donors (40 μ/L vs 29 μ/L, P = 0.02). Posttransplant, peak recipient amylase, and lipase levels were similar (P = 0.63). Prolonged arrest time (>40 minutes) was associated with higher donor peak lipase and lower recipient peak amylase (P = 0.05 for both). Stratified by donor arrest time, there was no difference in 7-day, 90-day, or 1-year graft survival. Cox regression comparing the 4 groups demonstrated no statistical difference in 10-year survival.ConclusionsThese results support transplantation of pancreas allografts from PPCA donors. Prolonged asystole was associated with higher peak donor serum lipase but lower peak recipient serum amylase. There were no differences in allograft survival.

Characteristics and Performance of Unilateral Kidney Transplants from Deceased Donors.

The fraction of kidneys procured for transplant that are discarded is rising in the United States. Identifying donors from whom only one kidney was discarded allows us to control for donor traits and better assess reasons for organ discard. We conducted a retrospective cohort study using United Network for Organ Sharing Standard Transplant Analysis and Research file data to identify deceased donors from whom two kidneys were procured and at least one was transplanted. Unilateral pairs were defined as kidney pairs from a single donor from whom one kidney was discarded ("unilateral discard") but the other was transplanted ("unilateral transplant"). Organ quality was estimated using the Kidney Donor Risk Index and Kidney Donor Profile Index (KDPI). We compared all-cause graft failure rates for unilateral transplants to those for bilateral transplant Kaplan-Meier methods, and life table methodology was used to evaluate 1-, 2-, 3-, and 5-year survival rates of transplants from bilateral and unilateral donors. Compared with bilateral donors (i.e., both kidneys transplanted) (n=80,584), unilateral donors (i.e., only one kidney transplanted) (n=7625) had higher mean terminal creatinine (1.3±2.1 mg/dl versus 1.1±0.9 mg/dl) and KDPI (67%±25% versus 42%±27%), were older, and were more likely to have hypertension, diabetes, hepatitis C, terminal stroke, or meet Centers for Disease Control and Prevention high-risk donor criteria. Unilateral discards were primarily attributed to factors expected to be similar in both kidneys from a donor: biopsy findings (22%), no interested recipient (13%), and donor history (7%). Anatomic abnormalities (14%), organ damage (11%), and extended ischemia (6%) accounted for about 30% of discards, but were the commonest reasons among low KDPI kidneys. Among kidneys with KDPI≥60%, there was an incremental difference in allograft survival over time (for unilateral versus bilateral transplants, 1-year survival: 83% versus 87%; 3-year survival: 69% versus 73%; 5-year survival: 51% versus 58%). A large number of discarded kidneys were procured from donors whose contralateral kidneys were transplanted with good post-transplant outcomes.

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).

IgG Donor Specific Antibodies [DSAs] in Patients With Transplant Glomerulopathy [TG] Are Associated With Inferior Allograft Survival.

Transplant glomerulopathy (TG) is a manifestation of chronic AMR with a poor prognosis and no specific treatment. Although the association between TG and anti HLA antibodies [Abs] is well known, there are few studies linking the nature of these Abs to outcome. 55 patients with TG (33M, 22F, mean age 47.5±12.1 yrs, mean time to TG diagnosis 9.32±8.37 yrs, mean follow up 26.6±18.0 months) were studied. Stored serum samples from the time of TG diagnosis were analysed for the presence of IgG and IgM HLA, DSA and Complement fixing antibodies. 52/55 (94.5%) patients were HLA Ab+, 3/55 were IgG HLA Ab- and 1 patient was IgM HLA Ab+. 27/55 (49.1%) had IgG HLA DSAs, 2/27 had class I alone, 15/27 had class II alone and 10/27 had both class I+II. Overall 39/55 (69.1%) patients had Abs directed against DQ (21/39 were DSAbs, 18/39 were HLA). 24/55 (43.6%) patients had C1q+ antibodies; 2/24 (8.3%) had a C1q+ class I DSA, 16/24 (66.7%) had a C1q+ class II DSA, 3/24 (12.5%) had a C1q+ class I non DSA HLA and 3/24 (12.5%) had a C1q+ class II non DSA HLA. 16/24 (66.7%) of patients had C1q+ antibodies against DQ. Overall allograft survival was 70.8%, 35.3%, 27.2% and 15.5% at 12, 36, 48 and 60 months respectively, mean 26.4±17.7 months. Allograft survival was significantly worse in IgG DSA+ patients compared with IgG DSA- patients.Figure: No Caption available.(see Figure 1, log rank test p=0.04). The IgG DSA MFI had no effect on allograft survival. There was no difference in allograft survival in C1q+patients (p=0.88) although the presence of C1q+ Ab was associated with the presence of C4d on allograft biopsy (p=0.01).This study shows that the presence of IgG DSAs is associated with inferior allograft survival in patients with TG. This group of patients may benefit from more aggressive therapy. DISCLOSURES:Lawrence, C.: Other, Honoraria from OneLambda, speakers fee from OneLambda.

Postanastomotic Transplant Renal Artery Stenosis: Association With De Novo Class II Donor-Specific Antibodies

In this study, we analyze the outcomes of transplant renal artery stenosis (TRAS), determine the different anatomical positions of TRAS, and establish cardiovascular and immunological risk factors associated with its development. One hundred thirty-seven of 999 (13.7%) patients had TRAS diagnosed by angiography; 119/137 (86.9%) were treated with angioplasty, of which 113/137 (82.5%) were stented. Allograft survival in the TRAS+ intervention, TRAS+ nonintervention and TRAS- groups was 80.4%, 71.3% and 83.1%, respectively. There was no difference in allograft survival between the TRAS+ intervention and TRAS- groups, p = 0.12; there was a difference in allograft survival between the TRAS- and TRAS+ nonintervention groups, p < 0.001, and between the TRAS+ intervention and TRAS+ nonintervention groups, p = 0.037. TRAS developed at the anastomosis, within a bend/kink or distally. Anastomotic TRAS developed in living donor recipients; postanastomotic TRAS (TRAS-P) developed in diabetic and older patients who received grafts from deceased, older donors. Compared with the TRAS- group, patients with TRAS-P were more likely to have had rejection with arteritis, odds ratio (OR): 4.83 (1.47-15.87), p = 0.0095, and capillaritis, OR: 3.03 (1.10-8.36), p = 0.033. Patients with TRAS-P were more likely to have developed de novo class II DSA compared with TRAS- patients hazard ratio: 4.41 (2.0-9.73), p < 0.001. TRAS is a heterogeneous condition with TRAS-P having both alloimmune and traditional cardiovascular risk factors.

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.

The APOL1 Genotype of African American Kidney Transplant Recipients Does Not Impact 5-Year Allograft Survival

Apolipoprotein L-1 (APOL1) gene variants are associated with end-stage renal disease in African Americans (AAs). Here we investigate the impact of recipient APOL1 gene distributions on kidney allograft outcomes. We conducted a retrospective analysis of 119 AA kidney transplant recipients, and found that 58 (48.7%) carried two APOL1 kidney disease risk variants. Contrary to the association seen in native kidney disease, there is no difference in allograft survival at 5-year posttransplant for recipients with high-risk APOL1 genotypes. Thus, we were able to conclude that APOL1 genotypes do not increase risk of allograft loss after kidney transplantations, and carrying 2 APOL1 risk alleles should not be an impediment to transplantation.

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.

RIP2 Is Required for NOD Signaling But Not for Th1 Cell Differentiation and Cellular Allograft Rejection

Two previous reports that receptor-interacting protein (RIP)-2 knockout (RIP2-/-) mice had defective nuclear factor-kappa B (NF-kappaB) signaling and T helper (Th)1 immune responses had led us to believe that this putative serine-threonine kinase might be a possible target for transplant immunosuppression. Thus, we tested whether RIP2-/- mice were able to reject vascularized allografts. Surprisingly, we found that T cells from RIP2-/- mice proliferated and produced interferon (IFN)-gamma after allostimulation in vitro. Moreover, naïve RIP2-/- CD4+ T cells differentiated normally into Th1 or Th2 cells under appropriate cytokine microenvironments. Consistent with these findings, no difference in allograft survival was observed between wild-type and RIP2-/- recipient mice, and rejection had similar pathology and cytokine profiles in both types of recipients. RIP2 deficiency was associated with defective NOD signaling, but this did not affect T-cell receptor (TCR)-dependent activation of the canonical NF-kappaB signaling or expression of NF-kappaB genes in rejecting allografts. Our data demonstrate that RIP2-deficient mice have intact canonical NF-kappaB signaling and can mount Th1-mediated alloresponses and reject vascularized allografts as efficiently as wild-type mice, thus arguing against RIP2 as a primary target for immunosuppression.

Effects of mycophenolate mofetilvscyclosporine administration on graft survival and function after islet allotransplantation in diabetic rats

To develop an experimental model of islet allotransplantation in diabetic rats and to determine the positive or adverse effects of MMF as a single agent. Thirty-six male Wistar rats and 18 male Lewis rats were used as recipients and donors respectively. Diabetes was induced by the use of streptozotocin (60 mg/kg) intraperitoneally. Unpurified islets were isolated using the collagenase digestion technique and transplanted into the splenic parenchyma. The recipients were randomly assigned to one of the following three groups: group A (control group) had no immunosuppression; group B received cyclosporine (CsA) (5 mg/kg); group C received mycophenolate mofetil (MMF) (20 mg/kg). The animals were killed on the 12th d. Blood and grafted tissues were obtained for laboratory and histological assessment. Median allograft survival was significantly higher in the two therapy groups than that in the controls (10 and 12 d for CsA and MMF respectively vs 0 d for the control group, P<0.01). No difference in allograft survival between the CsA and MMF groups was found. However, MMF had less renal and hepatic toxicity and allowed weight gain. Monotherapy with MMF for immunosuppression was safe in an experimental model of islet allotransplantation and was equally effective with cyclosporine, with less toxicity.

HLA‐DQ matching in cadaveric renal transplantation

The impact of matching for the human leukocyte antigen (HLA)‐ DQ phenotype in cadaveric renal transplantation is unclear. We analyzed the effect of matching serologically defined HLA‐DQ phenotypes on renal allograft survival in 12,050 first cadaveric renal transplants (recipients were 63.5% white and 36.5% African‐American). Recipients were entered into the South‐Eastern Organ Procurement Foundation (SEOPF) database between 1 October 1987 and 6 June 1995. A series of life table analyses were done to test the equality of survival curves for HLA‐DQ match, both alone and accommodating for differences in recipient race and HLA‐DR match. Cox regression models were then performed to detect differences in allograft survival based upon HLA‐DQ match. Initial adjustments were done by recipient race. Subsequent adjustments were done by recipient and donor race, age and sex, cold ischemia time (CIT), body mass index (BMI), cyclosporine A (CyA) use, peak panel reactive antibody (PRA) titer, year of transplant, presence of diabetes mellitus (DM), and degree of HLA‐A,B and HLA‐DR match as covariates. The effect of varying degrees of HLADQ match on graft survival were similar between the two races (p=0.87). In all recipients, an 8.3% reduction in graft failure was observed for each increase in HLA‐DQ match using the Cox regression model adjusted only for recipient race (p=0.004). A non‐significant 3.0% reduction in graft failure (p=0.38) was observed for each level of increasing HLA‐DQ match when using the Cox regression model adjusted for recipient and donor race, age and sex, CIT, BMI, CyA use, year of transplant, DM, HLA‐A,B and ‐DR match. In this model, superior HLA‐A,B match and HLA‐DR match, recipient and donor age, male donor sex, shorter CIT, white race of recipient, lower peak PRA, CyA use, and absence of DM significantly improved graft survival (all ≤0.004). We conclude that HLA‐DQ matching does not significantly affect cadaveric renal allograft survival once adjusted for other known predictors of graft outcome.