Standard Donor Research Articles

Prognostic Effect of Mutations in the Splicing Gene Machinery in 339 Patients with MDS or Secondary AML Following MDS After Allogeneic Hematopoietic Stem Cell Transplantation

AbstractAbstract ▪357▪This icon denotes a clinically relevant abstract Introduction:Molecular predictors for treatment outcome after allogeneic hematopoietic stem cell transplantation (HSCT) of MDS and AML patients are limited. Recently, mutations in the splicing gene machinery have been described as frequent aberrations in MDS. The aim of this study was to investigate the prognostic impact of mutations in the splicing genes U2AF1, SRSF2 and SF3B1 in a large cohort of patients with high risk MDS or secondary AML following MDS (sAML) undergoing allogeneic HSCT. Patients and Methods:Patients (n=339) with a diagnosis of MDS (50.1%) or sAML (49.9%) who received allogeneic HSCT at four German university medical centers (Dresden, Düsseldorf, Hamburg and Hannover) between 1996 and 2011 and for whom genomic DNA was available from a time when the disease was active, were evaluated for the presence of mutations in the splicing genes U2AF1, SRSF2, and SF3B1 by direct sequencing. Results:Median follow up from time of transplantation was 3.27 years. Median patient age at time of HSCT was 58 years (range 19–74). 74 patients (21.8%) were in complete remission and 265 patients (78.2%) had active disease before transplantation. Low, intermediate, and high risk cytogenetics according to IPSS were found in 204 (60.2%), 42 (12.4%), and 76 (22.4%) patients, respectively (in 5% cytogenetic information was not available). Related donor HSCT was performed in 82 patients (24.2%), and unrelated donor HSCT in 257 patients (75.8%). Myeloablative preparative regimens were used in 51 patients (15%), and a non-myeloablative regimen was given to 288 patients (85%).Mutations in U2AF1, SRSF2 and SF3B1 were detected in 14 (4.1%), 32 (9.4%) and 18 (5.3%) patients, respectively. SRSF2 and SF3B1 mutations co-occured in two patients, while the other patients had not more than one mutation in the investigated genes. Baseline characteristics were similarly distributed between U2AF1, SRSF2, or SF3B1 mutated and wildtype patients, respectively (sex, MDS vs sAML, cytogenetics, CMV status of patient, type of previous treatment, and remission status prior to transplantation), except a higher median age of U2AF1 mutated compared to wildtype patients (P=.02). There were no differences regarding transplant-related characteristics between patients with mutated or wildtype U2AF1, SRSF2, and SF3B1 (reduced intensity vs standard conditioning, GvHD prophylaxis, donor age, donor sex, CMV and HLA compatibility between recipient and donor).U2AF1 mutations were associated with a significantly shorter overall survival (OS, median 0.58 vs 3.6 years in mutated vs wildtype patients, respectively, HR 2.54; 95%CI 1.41–4.58; P=.002). The cumulative incidence of relapse (CIR) was higher in U2AF1 mutated compared to wildtype patients (3-year CIR 50% vs 22%, P=.002), while non-relapse mortality (NRM) was similar between mutated and wildtype patients (3-year NRM 43% vs 29%, P=.11). Mutations in SRSF2 and SF3B1 were not associated with OS (P=.98 and P=.44, respectively), CIR (P=.19 and P=.19, respectively), and NRM (P=.49 and P=.44, respectively). In multivariate analysis, when considering variables with P<.15 in univariate analysis (age above or below 55 years, karyotype, stage [MDS vs sAML], CMV serostatus of patient, donor type [related vs unrelated], donor sex), U2AF1 mutations independently predicted shorter OS (HR 2.6; 95%CI 1.39–4.85; P=.011) besides karyotype, stage, CMV serostatus, and donor sex. Mutations in U2AF1 independently predicted higher CIR in multivariate analysis (HR 3.02, 95% CI 1.36–6.7, P=.007). The rates of acute and chronic GvHD were similar in U2AF1 mutated and wildtype patients. Summary:U2AF1 mutations independently predicted worse patient outcome after allogeneic HSCT in MDS and sAML patients in our study due to a higher incidence of relapse. The U2AF1 mutation status may become useful to identify patients at high-risk for relapse after transplantation independent of established prognostic factors. Disclosures:Platzbecker:GlaxoSmithKline: Honoraria, Research Funding.

Transplantation From 8/8-Matched or 7/8-Matched Unrelated Donors Compared with HLA-Matched Siblings in Acute Myeloid Leukemia in First Complete Remission

AbstractAbstract 2040▪▪This icon denotes a clinically relevant abstractComparable survival after 8/8-matched unrelated donor (URD) transplantation with HLA-matched siblings (MSD) has been reported in AML from a few multicenter studies. However, the role of 8/8-matched URD in acute myeloid leukemia (AML) with first complete remission (CR1) is uncertain because they applied various methods for HLA typing, such as low or intermediate resolution or partly high resolution (HR) typing, and/or included various disease status at transplantation. Additionally, there have been few studies comparing the clinical outcomes of 7/8-matched URD with current standard donors, such as MSD or 8/8-matched URD, particularly in AML, as a single disease.According to the risk-adapted treatment strategy, AML CR1 with intermediate or adverse cytogenetics received allogenetic transplantation as a post-remission treatment, if MSD or 8/8-matched URD was available. Patients with no available donor received 7/8-matched URD or autologous transplantation (only intermediate cytogenetics). Among 567 consecutive adult patients with AML who underwent transplantation between January 2002 and December 2009, in order to investigate the role of URD type in AML CR1, we assessed the transplantation outcomes of 8/8-matched URD (n=59) or 7/8-matched URD (n=36) classified by HR HLA typing, compared to MSD (n=165). Only intermediate or adverse cytogenetics was included, and we defined high-risk group as having one of the poor risk features, including adverse cytogenetics, hyperleukocytosis at diagnosis (over 100×109/L), older age over 60 years, or AML with myelodysplasia-related changes.In all, multivariate analyses showed that 8/8-matched URD had comparable 5-year disease-free survival (DFS; HR, 0.94; P=0.803), relapse (HR, 1.03; P=0.935), and non-relapse mortality (NRM; HR, 0.62; P=0.294) to MSD, while 7/8-matched URD had higher relapse (HR, 1.95; P=0.034) and a lower trend for DFS (HR, 1.47; P=0.154) than MSD without the difference in NRM (HR, 0.61; P=0.390). The equivalent outcomes of 8/8-matched URD were consistent irrespective of risk groups (high or standard). Particularly, only in standard-risk group, 7/8-matched URD (n=18) failed to show any benefit compared to concurrently performed autologous transplantation (n=67), contrasting to the superior survival of 8/8-matched URD (n=32) as well as MSD (n=108).In conclusion, the equivalent outcomes between MSD and 8/8-matched URD, irrespective of risk-group in AML CR1, suggest that 8/8-matched URD is useful for standard-risk as well as high-risk group of AML CR1, when lacking of MSD. On the other hand, the inferior outcome of 7/8-matched URD raise the necessity of trials comparing with other alternative graft sources, such as umbilical cord bloods or haploidentical family donors, particularly in AML with high-risk group. Disclosures:No relevant conflicts of interest to declare.

MitoQ Blunts Mitochondrial and Renal Damage during Cold Preservation of Porcine Kidneys

Cold preservation has greatly facilitated the use of cadaveric kidneys for transplantation but damage occurs during the preservation episode. It is well established that oxidant production increases during cold renal preservation and mitochondria are a key target for injury. Our laboratory has demonstrated that cold storage of renal cells and rat kidneys leads to increased mitochondrial superoxide levels and mitochondrial electron transport chain damage, and that addition of Mitoquinone (MitoQ) to the preservation solutions blunted this injury. In order to better translate animal studies, the inclusion of large animal models is necessary to develop safe preclinical protocols. Therefore, we tested the hypothesis that addition of MitoQ to cold storage solution preserves mitochondrial function by decreasing oxidative stress, leading to less renal tubular damage during cold preservation of porcine kidneys employing a standard criteria donor model. Results showed that cold storage significantly induced oxidative stress (nitrotyrosine), renal tubular damage, and cell death. Using High Resolution Respirometry and fresh porcine kidney biopsies to assess mitochondrial function we showed that MitoQ significantly improved complex II/III respiration of the electron transport chain following 24 hours of cold storage. In addition, MitoQ blunted oxidative stress, renal tubular damage, and cell death after 48 hours. These results suggested that MitoQ decreased oxidative stress, tubular damage and cell death by improving mitochondrial function during cold storage. Therefore this compound should be considered as an integral part of organ preservation solution prior to transplantation.

Cold ischemic time is critical in outcomes of expanded criteria donor renal transplantation

The outcomes of expanded criteria donor (ECD) kidneys have been reported to be inferior compared with standard criteria donor (SCD) kidneys. However, the graft survival rate of ECD is not so inferior to SCD in Korea. The purposes of this study were to compare the outcomes of ECD kidneys with SCD kidneys and identify the influencing factors. We retrospectively studied 143 deceased donor transplants from August 2006 to June 2010. The patients were divided into SCD (n = 117) and ECD (n = 26) by UNOS criteria. The one- and three-yr graft survival rates of SCD and ECD (99.1% and 94.4% vs. 100% and 92.9%, respectively, p = 0.15) were not significantly different between groups. The mean cold ischemic time (CIT) was 3.8 ± 2.2 h. When compared the outcome of ECD kidneys with data reported by Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients (OPTN/SRTR) (one- and three-yr graft survival rate: 86.7% and 73.2%), the graft survival rate of our center was superior. In OPTN/SRTR data, transplant with CIT shorter than 11 h was only 20%. The outcomes of ECD grafts are outstanding and comparable with SCD grafts in our center, and the only distinguishing factor is markedly short CIT. Finishing the allocation before organ recovery and immediate operations after recovery could shorten the CIT.

Recipients of Kidneys from Expanded Criteria Donors Whose eGFR Does not Drop &gt;30% Between 1-12 Months after Transplantation Have Excellent Long-Term Graft Survival

Purpose: To determine the impact of eGFR drop lower or greater than 30% during the first yr post-kidney transplantation (KTx) on long-term death censored graft survival (DCGS). Methods: We studied 471 KTx recipients of deceased donor kidneys between 1/1990 and 12/2006. 253 pts (53.7%, 82 women, 171 men, 49±12 yrs) received standard criteria donor (SCD) kidneys, and 218 pts (46.3%, 73 women, 145 men, 52±13 yrs) received ECD kidneys. Immunosuppression consisted of ATG induction, CNI and an antimetabolite. CIT was 15.4±8.4 hr. We analyzed an eGFR drop lower or greater than 30% between 1-3, 1-12 and 3-12 months in recipients of SCD and ECD kidneys, with immediate (IGF, Scr decreased ≥20% within 24 hrs post-KTx), slow (SGF, Scr decreased < 20% within 24 hrs post-KTx and no need for dialysis) or delayed graft function (DGF, need for dialysis during the first week post-KTx), on long-term DCGS in pts whose graft survived >1 yr post-KTx. 55 recipients of SCD and 34 recipients of ECD were excluded because of graft loss, death or loss to follow-up during the first yr. Results: The impact of eGFR drop on long-term DCGS is depicted in Figures 1 and 2. There was no difference in pts with SGF. eGFR (mL/min/1.73m2) at 1, 5 and 10 yrs was 71±22, 66±22 and 57±22 respectively, in recipients of SCD and 56±18, 49±23 and 41±20 respectively, in recipients of ECD (P=0.001). An eGFR drop between 1-12 months was associated with lower DCGS (HR 2.16, P=0.02).Figure: [*P=0.002 and **P=0.01 vs. ECD Drop >30%]Figure: [P<0.0001 and **P=0.0003 vs. ECD Drop >30%]Conclusion: Recipients of ECD kidneys without an eGFR drop >30% between 1-12 months post-KTx have excellent long-term DCGS, equivalent to recipients of SCD kidneys.

The Influence of Immediate Outcomes on Long-Term Results in Recipients of Kidney Transplants from Standard Criteria Versus Expanded Criteria Donors

The Influence of Immediate Outcomes on Long-Term Results in Recipients of Kidney Transplants from Standard Criteria Versus Expanded Criteria Donors

A Single Centre Study of Donation after Cardiac Death Kidney Transplantation - Comparison of Outcomes Between Standard and Expanded Criteria Donor Kidneys

Introduction: Kidneys obtained from donors after cardiac-death (DCD) provide outcomes comparable to those obtained from donors after brain-stem death (DBD). In order to expand the donor pool, more DCD kidneys are being used which were previously considered unacceptable. Here, we compare short-term outcomes within DCD transplants of kidneys from expanded criteria donors (ECD) with those from standard criteria donors (SCD). Methods: From our centre's renal database, we collected data on all controlled (Maastricht 3) DCD kidney transplants from 2004 to 2010. Expanded criteria donor was defined according to UNOS criteria (age ≥ 60 years or 50-59 years with 2 of: hypertension, death from cerebrovascular accident, terminal creatinine ≥ 132 μmol/L). Only conventional cold storage was used. Our protocol included ATG followed by tacrolimus, mycophenolate mofetil and prednisolone. Outcomes studied were 1-year graft and patient survival, delayed graft function (DGF), biopsy-proven acute rejection (BPAR) and 1-year estimated GFR (MDRD). Results: Between 2004 and 2010, 112 DCD transplants were performed from 78 SCD and 34 ECD kidneys. Median follow-up time was 41 months for SCD and 21 months for ECD transplants. Tables 1 and 2 show the donor and recipient characteristics respectively.Table: [Donor Characteristics]Table: [Recipient Characteristics]Warm and cold ischemia times were significantly shorter for ECD kidneys. Incidence of DGF (68% vs.72%, p=0.7), median duration of DGF (4 vs. 6 days, p=0.5) and incidence of BPAR (5% vs. 12%, p=0.18) were similar in SCD and ECD groups respectively. There was 1 case of primary non-function in the SCD group and 2 of early transplant nephrectomy in the ECD group. One-year graft survival (SCD 95% vs. ECD 94%, p=0.8) and patient survival (SCD 96% vs. ECD 100%, p=0.2) were similar. Median eGFR at 6 months (50 vs. 40 ml/min, p=0.004) and 1 year (53 vs. 41 ml/min, p=0.003) was lower in the ECD group. Conclusion: The proportion of ECD kidneys is increasing within the DCD cohort. One-year graft survival from ECD kidneys is comparable to that obtained from SCD kidneys when cold ischemia time is short, although the one-year allograft function is inferior. These findings warrant further follow-up to determine long-term outcomes from cardiac-death donor ECD kidneys.

Recipients of Kidneys from Expanded Criteria Donors Whose eGFR Does not Drop >30% Between 1-12 Months after Transplantation Have Excellent Long-Term Graft Survival

Purpose: To determine the impact of eGFR drop lower or greater than 30% during the first yr post-kidney transplantation (KTx) on long-term death censored graft survival (DCGS). Methods: We studied 471 KTx recipients of deceased donor kidneys between 1/1990 and 12/2006. 253 pts (53.7%, 82 women, 171 men, 49±12 yrs) received standard criteria donor (SCD) kidneys, and 218 pts (46.3%, 73 women, 145 men, 52±13 yrs) received ECD kidneys. Immunosuppression consisted of ATG induction, CNI and an antimetabolite. CIT was 15.4±8.4 hr. We analyzed an eGFR drop lower or greater than 30% between 1-3, 1-12 and 3-12 months in recipients of SCD and ECD kidneys, with immediate (IGF, Scr decreased ≥20% within 24 hrs post-KTx), slow (SGF, Scr decreased < 20% within 24 hrs post-KTx and no need for dialysis) or delayed graft function (DGF, need for dialysis during the first week post-KTx), on long-term DCGS in pts whose graft survived >1 yr post-KTx. 55 recipients of SCD and 34 recipients of ECD were excluded because of graft loss, death or loss to follow-up during the first yr. Results: The impact of eGFR drop on long-term DCGS is depicted in Figures 1 and 2. There was no difference in pts with SGF. eGFR (mL/min/1.73m2) at 1, 5 and 10 yrs was 71±22, 66±22 and 57±22 respectively, in recipients of SCD and 56±18, 49±23 and 41±20 respectively, in recipients of ECD (P=0.001). An eGFR drop between 1-12 months was associated with lower DCGS (HR 2.16, P=0.02).Figure: [*P=0.002 and **P=0.01 vs. ECD Drop >30%]Figure: [*P<0.0001 and **P=0.0003 vs. ECD Drop >30%]Conclusion: Recipients of ECD kidneys without an eGFR drop >30% between 1-12 months post-KTx have excellent long-term DCGS, equivalent to recipients of SCD kidneys.

Heat-Stroke as a Cause of Liver Failure and Evaluation for Liver Transplant

Background: Heat stroke is a multiple organ dysfunction syndrome of poorly understood pathogenesis. Potential complications related to severe heat stroke are liver failure, acute renal failure, disseminated intravascular coagulation, rhabdomyolysis, and acute respiratory distress syndrome. Acute hepatic failure is a rare complication of heat stroke with poor prognosis. Here we report two cases of acute liver failure induced by heat stroke. Goal: To report two cases of acute liver failure induced by heat stroke and review the literature. Results: The first patient is a 28-year-old man collapsed after running 15 Km. On his initial presentation he showed hyperthermia acute liver failure, kidney failure associated to rhabdomyolysis, DIC, and change of mental status. AST peaked 12,000 on day 2 and Tbili peaked 21.6 on day 4. The patient fulfilled Kings' college criteria for emergent liver transplantation. However, he was not transplanted because after few days his clinical condition improved. The second patient is a 27-year-old patient collapsed after running 2 Km. He presented with hyperthermia, acute liver failure (MELD 42), kidney failure, DIC, and change of mental status. AST peaked 26,610 on day 2. Creatinine was 7.5 on day 2, Tbili peaked 47.1. The patient fulfilled standard criteria for emergent liver transplantation, but we decided to wait for spontaneous clinical recovery. On day 20, a liver biopsy showed massive necrosis. After failing conservative management, on day 24 post admission, the patient finally underwent combined liver and kidney transplantation from a standard criteria donor (42years old). The post-op course was unremarkable. Discussion: There are less than 20 cases of acute liver failure associated with heat stroke. In 2/3 of cases there was spontaneously recovery and 1/3 died. There are only 4 previous cases of liver transplantation for heat stroke in the literature, and there are no guidelines available to guide transplantation. Out of 4 cases of liver transplant, three of the patients died shortly after transplant. Thus, conservative management appears to be justified in heat-stroke-associated liver failure even in the presence of accepted criteria for emergent liver transplantation. It is of crucial importance to rule-out irreversible brain damage before listing these patients. Long-term neurologic sequelae occur in approximately 20% of patients. Conclusions: Liver failure following heat-stroke is reversible in many cases and conservative management can be successful. If there is no clinical signs of recovery despite optimal conservative treatment, and the liver biopsy shows massive necrosis, liver transplant should be performed during the window of opportunity, before the patients develop complications.

Followup and Outcome of Renal Transplant Patients with Deceased after Cardiac Death Donors (DCD)

Introduction: Renal transplantation is the best cost effective treatment for end-stage renal failure and improves quality of life, when compared with dialysis. Prior to the introduction, in the mid 1970s of legislation defining the diagnosis of brain-stem death, transplant organs were removed from DCD. Despite renewed interest in DCD kidney transplantation, very few clinical programmes have been developed this type of grafting. We analyzed the function and outcome of kidney transplants performed from DCD in our hospital. Patients and methods: From 1999 until december 2011, 35 patients were grafted with kidneys from DCD. This group was compared with recipients of standard criteria donors (SCD) matched for age, sex, number of transplants and HLA. Immunosupression was performed with Basiliximab, Predinisone, Tacrolimus and Micophenolate Mofetil. Acute rejection episodes were treated with Methylprednisolone boluses, and ATG-FRESENIUS® when necessary. Results: The delayed graft function rate was higher on DCD transplants than in SCD graft. Serum creatinine levels was significantly better in the DCD, 1.5 mg/dl versus 1.75 mg/dl. Graft survival at 5 year was 84% in DCD and 85% in SCD. Patient survival in both groups was 100%. Patients grafted with DCD were hospitalized longer and needed more dialysis. Acute rejection episodes were more frequent in DCD. Conclusion: This source of kidneys has evidence of equivalent graft function and survival, compared with SCD and may contribute to expand de donor pool

Use of Expanded Criteria Donors Gives Significantly Poorer Long-Term Graft Survival

Introduction: The use of expanded criteria donor (ECD) kidneys remains controversial as various groups have reported conflicting outcomes in terms of long-term graft outcomes. It is however well-known that ECD kidneys afford shorter graft survival as compared to kidneys from a standard criteria donor (SCD). In Singapore, patients with end stage renal failure (ESRF) must meet strict medical criteria before they are allowed to be placed on the National Transplant Registry to await a deceased donor kidney, including the absence of clinically overt cardiovascular and cerebrovascular disease. The aim of this study was to determine if there is a difference in long-term graft survival between recipients of SCD and ECD kidneys. Methods: A retrospective review was conducted on all deceased donor renal transplants (DDRT) performed at the Singapore General Hospital from 1st January 2000 to 31 December 2010. Results: During this period, 272 adults underwent a DDRT, with 226 (58.7%) receiving an SCD kidney (Group 1), and 46 (12.0%) receiving an ECD kidney (Group 2). The etiology of ESRF was predominantly chronic glomerulonephritis in both groups (83.1% Group 1 vs 73.9% Group 2, p = 0.75). The mean dialysis duration pretransplant was similar in both groups (45.3+8.7 vs. 46.7+9.0 months in Groups 1 and 2 respectively, p=0.28). While an increased incidence of early acute rejection (a rejection episode within 3 months post-transplant), and delayed graft function (a need for dialysis within a week post-transplant), are risk factors for decreased long-term graft function, the incidence of both events was similar in both groups (10.2% vs. 19.6%, p=0.07, and 42.5% vs. 54.4%, p=0.14, in Groups 1 and 2 respectively). Graft survival at 1 year was similar in both groups (96.0% Group 1 and 91.3% Group 2), but at 5 years there was a clear difference in graft survival (97.1% Group 1 and 68.4% Group 2). The 10-year graft survival was significantly reduced in recipients of ECD kidneys (p< 0.001) (Figure 1). Long term graft survival as described by half-lives was less than 6 years for ECD grafts and more than 10years for SCD grafts.[Figure 1]Conclusion: Patients receiving ECD kidneys, regardless of whether they have experienced an early acute rejection episode or delayed graft function, have a significantly reduced long-term graft survival. This is despite being in similar health as SCD recipients, with the absence of clinically overt cardiovascular and cerebrovascular disease pre-transplant. The use of ECD kidneys should be considered only in selected recipients.

The impact of meeting donor management goals on the number of organs transplanted per donor

Many organ procurement organizations have implemented critical care end points as donor management goals in efforts to increase organs transplanted per donor after neurologic determination of death. Although retrospective studies have demonstrated an association between meeting donor management goals and organ yield, prospective studies are lacking. In June 2008, nine donor management goals were prospectively implemented as a checklist and every donor after neurologic determination of death was managed to meet them. The donor management goals represented normal cardiovascular, pulmonary, renal, and endocrine end points. Data were collected for 7 months. Donor management goals "met" was defined a priori as achieving any seven of the nine donor management goals, and this was recorded at the time of consent, 12-18 hrs later, and prior to organ recovery. The primary outcome measure was ≥4 organs transplanted per donor, and binary logistic regression was used to identify independent predictors of this outcome with a p<.05. All eight organ procurement organizations in the five Southwestern United States (United Network for Organ Sharing Region 5). All standard criteria donors after neurologic determination of deaths. Prospective implementation of a donor management goal checklist. There were 380 standard criteria donors with 3.6±1.7 organs transplanted per donor. Fifteen percent had donor management goals met at the time of consent, 33% at 12-18 hrs, and 38% prior to organ recovery. Forty-eight percent had ≥4 organs transplanted per donor. Donors with ≥4 organs transplanted per donor had significantly more individual donor management goals met at all three time points. Independent predictors of ≥4 organs transplanted per donor were age (odds ratio=0.95 per year), final creatinine (odds ratio=0.75 per 1-unit increase), donor management goals "met" at consent (odds ratio=2.03), donor management goals "met" prior to organ recovery (odds ratio=2.34), and a change in the number of donor management goals achieved from consent to 12-18 hrs later (odds ratio=1.13 per additional donor management goal). Meeting donor management goals prior to consent and prior to organ recovery were both associated with achieving ≥4 organs transplanted per donor. However, only 15% of donors have donor management goals met at the time of consent. The donor hospital management of patients with catastrophic brain injuries, before the intent to donate organs is known, affects outcomes and should remain a priority in the intensive care unit.

Ex-vivo lung perfusion

Lung transplant continues to be hampered by the number of available donors. Ex-vivo lung perfusion (EVLP) has emerged as an essential tool for the reassessment, under a controlled scenario, of lungs that initially did not meet transplantation criteria. The purpose of the current study is to review the most recent clinical and research reports and summarize their findings. Several centers have presented positive data when using ex-vivo perfusion to identify better grafts from the higher risk donor pool. The posttransplant results, when using these organs, are not significantly different from those obtained when using standard criteria donors. In addition, a great amount of research reports have emphasized the potential of ex-vivo perfusion as a platform in reducing the injurious effects of ischemia-reperfusion. EVLP has already proved its value as a tool to identify 'good' lungs from the previously rejected pool. But as new therapeutics arise , EVLP will also prove its value as a reproducible platform for their evaluation.

Outcomes of Simultaneous Liver and Kidney Transplantation in Standard Donors Compared to Donation After Cardiac Death Donors

Outcomes of Simultaneous Liver and Kidney Transplantation in Standard Donors Compared to Donation After Cardiac Death Donors

Organ donation: when should we consider intestinal donation

Although more than 2300 intestinal transplantations (IT) have been performed worldwide, a description of intestinal donor criteria is still missing. This causes confusion among transplant coordinators, OPOs, physicians at intensive care unit and transplant surgeons. A Med-line search looking for publications about donor criteria or donor selection in human IT was performed in December 2011. Retrospective analysis of 39 deceased donors from whom, in the period January 2006-December 2011, 20 isolated intestinal grafts and 19 multivisceral grafts were recovered and successfully transplanted. Among 3504 publications about IT, no study reported specifically about intestinal donor profile. The most commonly cited donor criterion was age, while all other criteria were inconsistently discussed. Based on the collected data, we suggest following inclusion criteria for donation of IT grafts: age 0-50 years, ICU-stay <1 week, no blunt abdominal trauma, most recent Sodium <155 mmol/l, no severe ongoing transfusion requirements, standard donor therapy including early enteral nutrition and a compatible donor-recipient size match. By providing simple criteria for intestinal donation from deceased donor, we may help to properly utilize the limited donor pool.

Pretransplant and Protocol Biopsies May Help in Defining Short and Mid-term Kidney Transplant Outcome

Although many variables may affect long-term graft survival no biomarker is available to identify donor kidney with poor quality and with inadequate short and long-term outcome. While in marginal donors pre-transplant renal biopsies are commonly performed to establish if donor kidneys are suitable for transplantation they are not performed in standard donors. In this study we assessed the relevance of pre-transplant morphological features on post-transplant renal function and evaluated the association between perioperative parameters with posttransplant histological and clinical findings. Kidney transplant recipients undergone pre-transplant and post transplant protocol biopsies at 1, 6, and 12 months were enrolled in the study. Perioperative and posttransplant clinical and biochemical parameters were recorded. Semiquantitative analysis of PAS stained kidney sections was used to determine the degree of lesions. Glomerular volume was measured by computed morphometry. A strong inverse correlation was found between donor age and renal graft function at 1, 6, and 12 months after transplantation. A prompt functional recovery was associated with a better renal function at 6 months and one year. Kidneys with higher glomerular volume demonstrated a lower serum creatinine at 1 month. Higher tubulo-interstitial grading at protocol biopsies was associated with a poor renal function at 1 month.Our findings confirm the importance of donor age in kidney transplant long-term outcome and demonstrate that pretransplant and protocol biopsies are valid options to determine graft outcome and to define therapeutic strategies and tailor immunosuppressive regimen for each patient.

Impact of Expanded Criteria Donors on Outcomes of Recipients After Kidney Transplantation

BackgroundAge and comorbidities of brain-dead donors have increased throughout the last decade. The use of expanded criteria donors (ECD) has become a common clinical practice. The objective of the present study was to compare outcomes of patients who underwent kidney transplantation from ECD versus standard criteria donors (SCD). MethodsWe studied 1375 adult recipients of kidney transplantations from 792 deceased donors in six Quebec centers between 2003 and 2009. Patient and graft survivals were analyzed using uni- and multivariate methods in regard to the effects of donor and recipient characteristics. ECD were defined per United Network for Organ Sharing: criteria age >60 years of age or age 50 to 59 years with two of three associated risk factors—history of cerebrovascular accident, hypertension, or elevated serum creatinine Mean follow-up was 3.5 ± 2 years. ResultsAmong the 792 donors, 510 SCD (64%) and 282 ECD (36%) were used for 1375 kidney transplant recipients. ECD had no effect on patient (P = .47) or graft (P = .28) survival. Cox proportional hazards regression analysis showed female donors (relative risk [RR] 1.75, P = .008), recipient age (RR 1.07, P = .0001), and waiting time be for transplantation (RR 1.000, P = .0001) to be associated with a greater risk of death after transplantation. Donor (RR 1.018, P = .0099) and recipient (RR 1.013, P = .0387) age and recipient waiting time for transplantation (RR 1.000, P = .0048) were also associated with a greater risk of graft loss. ConclusionThe use of SCD or ECD had no impact on patient or graft survival after kidney transplantation. Donor and recipient ages as well as waiting time for transplantation were related to graft loss. Waiting time remains a significant factor affecting outcomes; efforts should aim to decrease this period.

The Implications of Acute Rejection for Allograft Survival in Contemporary U.S. Kidney Transplantation

We examined the frequency and clinical impact of acute rejection (AR) in contemporary U.S. kidney transplantation. Data for Medicare-insured kidney transplant recipients in 2000 to 2007 (n=48,179) were drawn from the United States Renal Data System. AR events were ascertained from Organ Procurement and Transplantation Network reports. AR was subclassified as antibody (Ab)-treated AR or other management (non-Ab-treated AR). Associations of AR with subsequent all-cause graft loss were estimated with time-varying Cox regression. Covariates included recipient, donor, and transplant factors in the United Network for Organ Sharing Kidney Allocation Review Committee survival model. The frequencies of non-Ab-treated AR per 100 graft-years at risk among standard criteria donor recipients over the first 6, 12, 24, and 36 months after transplantation were 9.93, 8.43, 5.71, and 4.70, respectively. Non-Ab-treated AR was consistently more than twice as common as Ab-treated AR by risk period and donor type. Development of Ab-treated AR predicted a greater risk of graft loss than non-Ab-treated AR. The relative risk for graft loss from Ab-treated AR continuously increased with later timing of AR after transplantation, whereas risk associated with non-Ab-treated AR peaked for events reported in months 13 to 24 after kidney transplantation. Regardless of the diagnosis time, the relative risk of graft loss was higher in the first 89 days after a given AR report compared with 90 days and beyond. AR events recognized later after transplantation have more serious graft loss implications, especially within the first 89 days after AR reporting. This observation may reflect reduced intensity of monitoring, delays in diagnosis, or clinicopathologic features of late AR.

The Implications of Acute Rejection and Reduced Allograft Function on Health Care Expenditures in Contemporary US Kidney Transplantation

The economic ramifications of acute rejection (AR) are not well characterized in a contemporary population of kidney transplant recipients. Data for Medicare-insured transplant recipients in 2000 to 2007 (n=45,250) were drawn from the United States Renal Data System. AR events were ascertained from the Organ Procurement and Transplantation Network reports covering months 0 to 12 (yr1), 13 to 24 (yr2), and 25 to 36 (yr3) after transplantation. AR was subclassified as antibody (Ab)-treated AR or other management (non-Ab-treated AR). The marginal cost impact of AR events during and before a period of interest was quantified by multivariate linear regression including covariates for recipient, donor, and transplant factors. Among recipients of standard criteria donor allografts, both Ab-treated AR events (yr1, $22,407; yr 2, $18,803; yr3, $13,909) and non-Ab-treated AR events (yr1, $14,122; yr2, $7852; yr3, $8234) were associated with significant increases in the cost of care. Patterns were similar among recipients of living donor and expanded criteria donor transplants. After weighting by population frequency, AR accounted for 2.3% to 3.8% of total costs incurred during 1 year of posttransplantation care. Subanalysis of recipients with yr1 estimated glomerular filtration rate (eGFR) information demonstrated markedly stronger cost variation across eGFR levels. For example, among those with non-Ab-treated AR, adjusted total yr2 costs were $22,747 with eGFR of 60 mL/min/1.73 m or higher but $43,881 with eGFR of 30 mL/min/1.73 m or lower. AR is a significant contributor to individual posttransplantation costs. However, because of its low frequency, AR accounts for a small proportion of posttransplantation costs in the population. Healthcare costs in patients with AR are markedly higher among those with reduced compared with preserved allograft function.

Availability, Utilization and Outcomes of Deceased Diabetic Donor Kidneys; Analysis Based on the UNOS Registry

The number of kidneys obtained from deceased diabetic donors available for transplantation has increased >eightfold increase in the past 15 years. We assessed allograft outcomes associated with deceased diabetic donors and compared them with that of standard and extended criteria donors (ECD) in the UNOS data registry. We identified 1982 recipients of diabetic standard criteria donors over a 10-year period from 1995 through 2004. Both overall and death-censored survival of organs from diabetic standard criteria donors was significantly better than that of organs obtained from nondiabetic ECD while inferior to that from nondiabetic standard criteria donors. Compared with ECD donors, diabetic donors had lower serum creatinine, less cold ischemia and these kidneys were less likely to be pump-perfused. Recipients of diabetic kidneys were younger and less likely to experience delayed graft function compared with recipient of ECD kidneys. More recently, many diabetic donor kidneys have been given to diabetic recipients with early graft survival being similar to that among nondiabetic recipients. These findings demonstrate the potential to expand and to improve utilization of this resource without compromising outcomes for recipients. Improved, evidence-based evaluation and allocation of deceased diabetic donor kidneys is needed to optimize their use.