Months In Recipients Research Articles

232.3: Longitudinal Analysis of Donor-derived Cell-Free DNA (Dd-cfDNA) in En-bloc Kidney Transplantation

Introduction: The longitudinal dd-cfDNA patterns in en-bloc kidney transplant recipients have not been studied. It is unknown how the initial smaller mass of thetwo pediatric organs impacts dd-cfDNA early post-transplant or if the dd-cfDNA rises over time as the organs enlarge. We analyzed dd-cfDNA scores over thefirst 12 months in recipients of pediatric en-bloc kidneys enrolled in the Kidney allograft Outcomes AlloSure Registry (KOAR, NCT03326076). Methods: 16 recipients of pediatric en-bloc kidneys with donors aged ≤7 years old were identified and compared with 931 single, non en-bloc deceased donorrecipients. Patients with rejection were excluded. Results: Of the 16 en-bloc recipients, 56.2% were male with median donor age of 1.4 years and median cold ischemia time (CIT) of 20 hours. None of the en-bloc transplants had delayed graft function. Aside from KDPI, donor age, and recipient age, no other differences were observed between groups (Table 1). Higher median dd-cfDNA values were seen in the en-bloc cohort compared to not en-bloc at month 1 (M1, 1.4% vs 0.4%) and month 2 (0.58% vs 0.23%) aftertransplant (p<0.001) (Figure 1a). Median dd-cfDNA values were comparable for month 3 (0.21% vs 0.16%, p = 0.07) and all subsequent time points (Figure 1a, 1b). Among 8 patients with M1 dd-cfDNA results, there was no significant association between M1 dd-cfDNA and either CIT (r=0.33, p=0.419) or KDPI (r=0.23,p=0.589) (Figure 2). Conclusion: Our results demonstrate higher early post-transplant dd-cfDNA values among en-bloc kidney compared to single kidney recipients however, nodifference or upward trend is observed beyond month 2 and out to 12 months.

Comparison of progression of care-need levels among long-term care recipients with and without advanced care management in a rural municipality of Japan: A population-based observational study

BackgroundLittle is known about the association between advanced care management and patient outcomes in home settings. In 2009, the Japanese government introduced a financial incentive scheme for advanced care management by long-term care agencies with at least one advanced care manager. However, it remains unclear whether advanced care management in rural areas is associated with improved outcomes for recipients. ObjectiveTo compare the progression of care-need levels among long-term care recipients in home settings with and without advanced care management. DesignA population-based observational study. SettingA rural municipality in Japan. ParticipantsRecipients of long-term care (n = 2005). MethodsWe used individual-level secondary data provided from a rural municipal government that was collected as part of the Survey of Long-Term Care Benefit Expenditures and medical care claim records between April 2012 and March 2017. We linked these two databases using unique identifiers. The inclusion criteria for study subjects were that they: (1) were aged ≥65 years; (2) were newly certified as care-need level 1, 2, or 3; and (3) used long-term care insurance services in home settings from April 2012 through March 2017. We excluded individuals using long-term care insurance services for less than six months. Ultimately, we selected 1722 propensity-matched recipients with and without advanced care management, and then conducted Kaplan–Meier survival analyses and a log-rank test. The outcome measure was progression of care-need levels. ResultsThe proportions of five-year cumulative progression-free survival in the groups with and without advanced care management were 50.3% and 42.2% for recipients of care-need level 1 (p < .01), 34.3% and 32.3% for recipients of care-need level 2 (p < .01), and 22.3% and 24.5% for recipients of care-need level 3 (p > .05), respectively. The progression-free period lasted a median of 12 (interquartile range, 10–24) months for recipients of care-need level 1, 14 (interquartile range, 11–28) months for recipients of care-need level 2, and 12 (interquartile range, 10–24) months for recipients of care-need level 3. ConclusionsLong-term care recipients with advanced care management in home settings had a higher probability of progression of care-need levels in a rural municipality of Japan. This finding suggests that the governmental policy of providing financial incentive for advanced care management may not be effective in improving the outcome of long-term care recipients in a rural municipality of Japan.

Living Donor Kidney Transplantation Improves Graft and Recipient Survival in Patients with Multiple Kidney Transplants.

Background: Failed kidney transplant recipients benefit from a new graft as the general incident dialysis population, although additional challenges in the management of these patients are often limiting the long-term outcomes. Previously failed grafts, a long history of comorbidities, side effects of long-term immunosuppression and previous surgical interventions are common characteristics in the repeated kidney transplantation population, leading to significant complex immunological and technical aspects and often compromising the short- and long-term results. Although recipients’ factors are acknowledged to represent one of the main determinants for graft and patient survival, there is increasing interest in expanding the donor’s pool safely, particularly for high-risk candidates. The role of living kidney donation in this peculiar context of repeated kidney transplantation has not been assessed thoroughly. The aim of the present study is to analyse the effects of a high-quality graft, such as the one retrieved from living kidney donors, in the repeated kidney transplant population context. Methods: Retrospective analysis of the outcomes of the repeated kidney transplant population at our institution from 1968 to 2019. Data were extracted from a prospectively maintained database and stratified according to the number of transplants: 1st, 2nd or 3rd+. The main outcomes were graft and patient survivals, recorded from time of transplant to graft failure (return to dialysis) and censored at patient death with a functioning graft. Duration of renal replacement therapy was expressed as cumulative time per month. A multivariate analysis considering death-censored graft survival, decade of transplantation, recipient age, donor age, living donor, transplant number, ischaemic time, time on renal replacement therapy prior to transplant and HLA mismatch at HLA-A, -B and -DR was conducted. In the multivariate analysis of recipient survival, diabetic nephropathy as primary renal disease was also included. Results: A total of 2395 kidney transplant recipients were analysed: 2062 (83.8%) with the 1st kidney transplant, 279 (11.3%) with the 2nd graft, 46 (2.2%) with the 3rd+. Mean age of 1st kidney transplant recipients was 43.6 ± 16.3 years, versus 39.9 ± 14.4 for 2nd and 41.4 ± 11.5 for 3rd+ (p < 0.001). Aside from being younger, repeated kidney transplant patients were also more often males (p = 0.006), with a longer time spent on renal replacement therapy (p < 0.0001) and a higher degree of sensitisation, expressed as calculated reaction frequency (p < 0.001). There was also an association between multiple kidney transplants and better HLA match at transplantation (p < 0.0001). A difference in death-censored graft survival by number of transplants was seen, with a median graft survival of 328 months for recipients of the 1st transplant, 209 months for the 2nd and 150 months for the 3rd+ (p = 0.038). The same difference was seen in deceased donor kidneys (p = 0.048), but not in grafts from living donors (p = 0.2). Patient survival was comparable between the three groups (p = 0.59). Conclusions: In the attempt to expand the organ donor pool, particular attention should be reserved to high complex recipients, such as the repeated kidney transplant population. In this peculiar context, the quality of the donor has been shown to represent a main determinant for graft survival—in fact, kidney retrieved from living donors provide comparable outcomes to those from single-graft recipients.

Transfer and loss of allergen-specific responses via stem cell transplantation: A prospective observational study.

Currently, no estimates can be made on the impact of hematopoietic stem cell transplantation on allergy transfer or cure of the disease. By using component-resolved diagnosis, we prospectively investigated 50 donor-recipient pairs undergoing allogeneic stem cell transplantation. This allowed calculating the rate of transfer or maintenance of allergen-specific responses in the context of stem cell transplantation. Allergen-specific IgE and IgG to 156 allergens was measured pretransplantation in 50 donors and recipients and at 6, 12 and 24months in recipients post-transplantation by allergen microarray. Based on a mixed effects model, we determined risks of transfer of allergen-specific IgE or IgG responses 24months post-transplantation. After undergoing stem cell transplantation, 94% of allergen-specific IgE responses were lost. Two years post-transplantation, recipients' allergen-specific IgE was significantly linked to the pretransplantation donor or recipient status. The estimated risk to transfer and maintain individual IgE responses to allergens by stem cell transplantation was 1.7% and 2.3%, respectively. Allergen-specific IgG, which served as a surrogate marker of maintaining protective IgG responses, was highly associated with the donor's (31.6%) or the recipient's (28%) pretransplantation response. Hematopoietic stem cell transplantation profoundly reduces allergen-specific IgE responses but also comes with a considerable risk to transfer allergen-specific immune responses. These findings facilitate clinical decision-making regarding allergic diseases in the context of hematopoietic stem cell transplantation. In addition, it provides prospective data to estimate the risk of transmitting allergen-specific responses via hematopoietic stem cell transplantation.

Donor Factors Affecting Short Term Graft Outcome in Live Donor Kidney Transplantation

Introduction: Since the beginning of renal transplant, the objective has been to increase the patient and graft survival, both short term and long term. Data relating to donor factors affecting short term survival at 6 months in live donor kidney transplantation has been scarce. This single center study tries to examine the predictors of short term graft outcome at six months in recipients of live donor kidney transplants and explore which donor characteristics are the most useful in predicting the post-transplant graft function in Nepalese population.&#x0D; Methods: All patients who underwent kidney transplantation between May 2015 to July 2016 were included in the study. The patients who expired during follow were excluded. The clinical and laboratory parameters of the donors we rerecorded. The recipients were followed up for six months post transplantation. The eGFR of the recipients and the occurrence of rejection were recorded at the end of six months post transplantation.&#x0D; Results: A total of 82 donor-recipient pairs underwent living donor renal transplantation at our hospital during the studyperiod. One recipient who expired during follow up was excluded. The mean age of donor was 45.20 ± 11.226years of which 55 (67.9%) were female and 26 (32.1 %) were male. The mean eGFR of the donor calculated from Cockcroft Gault equation was 81.98 ± 18.11. The eGFR of the recipient at the end of six months post transplantation calculated form the MDRD equation was 67.76 ± 20.94. A total of 7 patients (8.6%) had rejection that were biopsy proven. Only donor eGFR was found to be significantly associated with eGFR of the recipient at six months post transplantation (p=0.034). Body mass index of the donor was significantly associated with rejection in the recipient at six months post transplantation (p=0.011).&#x0D; Conclusion: Our study demonstrates that the donor eGFR and body mass index are independent and important factors affecting the short term graft outcome at six months post transplantation.

Donor Factors Affecting Short Term Graft Outcome in Live Donor Kidney Transplantation

Introduction: Since the beginning of renal transplant, the objective has been to increase the patient and graft survival, both short term and long term. Data relating to donor factors affecting short term survival at 6 months in live donor kidney transplantation has been scarce. This single center study tries to examine the predictors of short term graft outcome at six months in recipients of live donor kidney transplants and explore which donor characteristics are the most useful in predicting the post-transplant graft function in Nepalese population. Methods: All patients who underwent kidney transplantation between May 2015 to July 2016 were included in the study. The patients who expired during follow were excluded. The clinical and laboratory parameters of the donors were recorded. The recipients were followed up for six months post transplantation. The eGFR of the recipients and the occurrence of rejection were recorded at the end of six months post transplantation. Results: A total of 82 donor-recipient pairs underwent living donor renal transplantation at our hospital during the study period. One recipient who expired during follow up was excluded. The mean age of donor was 45.20 ± 11.226 years of which 55 (67.9%) were female and 26 (32.1 %) were male. The mean eGFR of the donor calculated from Cockcroft Gault equation was 81.98 ± 18.11. The eGFR of the recipient at the end of six months post transplantation calculated form the MDRD equation was 67.76 ± 20.94. A total of 7 patients (8.6%) had rejection that were biopsy proven. Only donor eGFR was found to be significantly associated with eGFR of the recipient at six months post transplantation (p=0.034). Body mass index of the donor was significantly associated with rejection in the recipient at six months post transplantation (p=0.011). Conclusion: Our study demonstrates that the donor eGFR and body mass index are independent and important factors affecting the short term graft outcome at six months post transplantation.

Comparison of Peripheral Blood Stem Cells (PBSC) to Bone Marrow (BM) for T-Replete HLA-Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide

T cell-replete haploidentical donor transplants (HAPLO-HCT) using post-transplant cyclophosphamide for control of alloreactivity is now being increasingly utilized. HAPLO-HCTs were originally performed using BM grafts. However, recently, a few single center studies have reported good outcomes using G-CSF mobilized PBSC grafts for HAPLO-HCT. No prospective randomized comparisons of BM to PBSC grafts for HAPLO-HCT have been performed. Therefore, we analyzed outcomes for 687 adults (496 BM, 191 PBSC) who received HAPLO-HCT for hematologic malignancies using post-transplant cyclophosphamide + mycophenolate + calcineurin inhibitor for GVHD prophylaxis between 2009 and 2014 in the United States. The primary outcome was overall survival. The characteristics of recipients of BM and PBSC were similar except BM recipients were older, more likely to have a performance score ≥90, HCT-CI index ≤2, be CMV seronegative, have a lymphoid malignancy and receive reduced-intensity conditioning. Most PBSC transplants occurred between 2012 and 2014. The median follow-up was 35 and 20 months for recipients of BM and PBSC grafts, respectively. Cox regression models were built to study the effect of graft type adjusted for other significant factors on overall mortality, non-relapse mortality, relapse and graft-versus-host disease (GVHD) and outcomes censored at 2-years to accommodate differential follow-up between treatment groups (Table 1). After adjusting for age, CMV serostatus, disease risk index (disease type/disease status for myeloid and lymphoid malignancy and cytogenetic risk for acute leukemia and myelodysplastic syndrome) and transplant conditioning regimen there were no significant differences in risks for overall mortality (HR 1.00, p= 0.98; 2-year overall survival: 54% and 57%) or non-relapse mortality (HR 0.92, p=0.74; 2-year non-relapse mortality: 17% and 16%) after transplantation of BM compared to PBSC, respectively. However, relapse risks were higher after transplantation of BM compared to PBSC (HR 1.49, p=0.009; 2-year relapse: 45% and 28%). Subset analyses explored the effect of graft type separately for myeloablative and reduced intensity conditioning regimen adjusting for age, CMV serostatus and disease risk index. Consistent with the main analysis there were no differences in overall or non-relapse mortality risks and relapse risks were higher with BM compared to PBSC with myeloablative regimens (Table 1). Although this may in part be explained by lower chronic GVHD risks with transplantation of BM grafts, chronic GVHD was not significantly predictive of relapse risk when modeled as a time-dependent covariate (HR= 0.73, p=0.49). Grade II-IV acute GVHD risks (HR 0.45, p<0.001; 22% and 37%), adjusted for conditioning regimen were lower after transplantation of BM compared to PBSC. Chronic GVHD risks adjusted for age and performance score were also lower after transplantation of BM compared to PBSC (HR 0.35, p<0.001; 20% and 41%) but rates of moderate and severe chronic GVHD were not significantly different (28% and 32%). There were no differences in incidence of hematopoietic recovery by graft type. In conclusion, compared to BM grafts HAPLO-HCT with PBSC are associated with similar overall survival and non-relapse mortality risks but lower relapse risks with myeloablative conditioning regimens. Longer follow up is needed to ascertain whether survival differences may occur later. The observed adverse effect of BM grafts on relapse with myeloablative regimens must be studied further in the setting of carefully controlled trials. [Display omitted] DisclosuresCiurea:Cyto-Sen Therapeutics: Equity Ownership; Spectrum Pharmaceuticals: Other: Advisory Board. Hamadani:Takeda: Research Funding. Soiffer:Kiadis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Juno: Membership on an entity's Board of Directors or advisory committees. Wingard:Ansun: Consultancy; Gilead: Consultancy; Astellas: Consultancy; Fate Therapeutics: Consultancy; Merck: Consultancy.

Cardiomyocytes Derived from MHC-Homozygous Induced Pluripotent Stem Cells Exhibit Reduced Allogeneic Immunogenicity in MHC-Matched Non-human Primates.

SummaryInduced pluripotent stem cells (iPSCs) can serve as a source of cardiomyocytes (CMs) to treat end-stage heart failure; however, transplantation of genetically dissimilar iPSCs even within species (allogeneic) can induce immune rejection. We hypothesized that this might be limited by matching the major histocompatibility complex (MHC) antigens between the donor and the recipient. We therefore transplanted fluorescence-labeled (GFP) iPSC-CMs donated from a macaque with homozygous MHC haplotypes into the subcutaneous tissue and hearts of macaques having heterozygous MHC haplotypes (MHC-matched; group I) or without identical MHC alleles (group II) in conjunction with immune suppression. Group I displayed a higher GFP intensity and less immune-cell infiltration in the graft than group II. However, MHC-matched transplantation with single or no immune-suppressive drugs still induced a substantial host immune response to the graft. Thus, the immunogenicity of allogeneic iPSC-CMs was reduced by MHC-matched transplantation although a requirement for appropriate immune suppression was retained for successful engraftment.

Prevalence of abdominal aortic calcifications in older living renal donors and its effect on graft function and histology.

We assessed the prevalence of abdominal aortic calcification (AAC) in older living kidney donors and its effect on recipient eGFR and graft histology. A total of 292 consecutive living pairs with donor age ≥50 from 2003 to 2013 were identified (mean age 56; range 50-78; F/M: 1.8). Donor AAC was determined by prenephrectomy unenhanced CT. Recipient eGFR and spot urine protein: creatinine ratios (UPCRs) were recorded. A total of 180 recipients had 6-month protocol biopsies. AAC was present in 40.7% of donors, and they were older (58.6 versus 54.7 years old, P < 0.0001) and more likely to be male (77.6% vs. 37.3%, P = 0.004). There was no significant difference in eGFR or spot UPCR up to 36 months in recipients of allografts from donors with versus without AAC. At 6-month biopsy, there was a higher percentage of allografts with vascular fibrous intimal thickening and arteriolar hyaline thickening from donors with versus without AAC (vascular fibrous intimal thickening: 38.8% vs. 7.1% and arteriolar hyaline thickening: 35.8% vs. 7.1%; P < 0.001 for both). The presence of donor AAC predicts the presence of vascular disease [vascular fibrous intimal thickening (OR: 7.2; CI:2.9-17.9) and arteriolar hyaline thickening (OR:5.7; CI:2.3-14.1)] in allografts at 6 months. Donor AAC is predictive of renal vascular disease and may help to improve the screening of potential donors and inform post-transplant management.

Kidney Laterality and the Safety of Hand-assisted Live Donor Nephrectomy: Review of 1000 Consecutive Cases at a Single Center

To determine the feasibility of performing right-sided, hand-assisted, laparoscopic donor nephrectomy (HALDN) and compare with the results of left-sided surgeries in both donors and recipients. Between September 2006 and September 2013, 1000 consecutive patients underwent HALDN at our institution. Patient characteristics and the intraoperative or postoperative parameters of the donors and recipients were retrospectively evaluated. Preoperative data, including relative renal function, vascular anatomy, and parenchymal abnormalities, were evaluated to determine the reasons for harvesting the right kidney. Intraoperative and postoperative data, including pneumoperitoneum time, warm ischemia time, complications, chronic kidney disease stage, and graft function, were compared between donors and recipients who underwent right- and left-sided procurement. Mean follow-up period was 21 months in donor and 42 months in recipient. Right-sided HALDN was performed on 421 patients (42.1%). The most common reasons for selecting the right kidney was reduced right kidney function (53.4%) followed by multiple left renal arteries (34.2%). None of 1000 patients required conversion to open surgery or developed major complications. Serum creatinine concentrations and chronic kidney disease stage at the last follow-up examinations were similar in donors. There were no significant differences in graft function and ureter-related complications between right- and left-sided kidneys at the last follow-up examination. Right-side HALDN is a safe procedure. The donor side can be freely selected using HALDN to benefit both donors and recipients.

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.

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.

Should a Lower Quality Organ Go to the Least Sick Patient? Model for End-Stage Liver Disease Score and Donor Risk Index as Predictors of Early Allograft Dysfunction

BackgroundThere is a global tendency to justify transplanting extended criteria organs (ECD; Donor Risk Index [DRI] ≥1.7) into recipients with a lower Model for End-Stage Liver Disease (MELD) score and to transplant standard criteria organs (DRI < 1.7) into recipients with a higher MELD scores. There is a lack of evidence in the current literature to justify this assumption. MethodsA review of our prospectively entered database for donation after brain death (DBD) liver transplantation (n = 310) between January 1, 2006, and September 30, 2010, was performed. DRI was dichotomized as <1.7 and ≥1.7. Recipients were divided into 3 strata, those with high (≥27), moderate (15–26), and low MELD (<15) scores. The recently validated definition of early allograft dysfunction (EAD) was used. We analyzed EAD and its relation with donor DRI and recipient MELD scores. ResultsThe overall incidence of EAD was 24.5%. Mortality in the first 6 months in recipients with EAD was 20% compared with 3.4% for those without EAD (relative risk [RR], 5.56, 95% confidence interval [CI], 1.96–15.73; P < .001). Graft failure rate in the first 6 months in those with EAD was 27% compared with 5.8% for those without EAD (RR, 4.63; 95% CI, 2.02–10.6; P < .001). In patients with low MELD scores, a significantly increased rate of EAD (25%) was seen in patients transplanted with a high DRI liver compared with those transplanted with a low DRI liver (6.25%; P = .012). In moderate and high MELD recipients, there was no significant difference in the rate of EAD in patients transplanted with a high DRI liver (62%) compared with those transplanted with a low DRI liver (59%). ConclusionThese results suggest that contrary to common belief it is not justified to preferentially allocate organs with higher DRI to recipients with lower MELD scores.

2280 WAIT-TIME VARIES BY BLOOD-TYPE AND CALCULATED PANEL REACTIVE ANTIBODY FOR INCOMPATIBLE PAIRS IN KIDNEY EXCHANGE

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Vascular Surgery II1 Apr 20122280 WAIT-TIME VARIES BY BLOOD-TYPE AND CALCULATED PANEL REACTIVE ANTIBODY FOR INCOMPATIBLE PAIRS IN KIDNEY EXCHANGE Jeff Veale, Marc Melcher, Connie Davis, Elizabeth Berger, Joe Sinacore, Matt Ronin, Garet Hil, and John Milner Jeff VealeJeff Veale LA, CA More articles by this author , Marc MelcherMarc Melcher Stanford, CA More articles by this author , Connie DavisConnie Davis Seattle, WA More articles by this author , Elizabeth BergerElizabeth Berger Maywood, IL More articles by this author , Joe SinacoreJoe Sinacore Babylon, NY More articles by this author , Matt RoninMatt Ronin Babylon, NY More articles by this author , Garet HilGaret Hil Babylon, NY More articles by this author , and John MilnerJohn Milner Maywood, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2458AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Though important, time waiting to kidney transplant has not been a major focus of transplant centers in regard to a potential kidney transplant recipient waiting with an incompatible living donor. The purpose of this study is to report time-waiting-to-transplant in a large, multi-institutional kidney transplant exchange registry. METHODS A 2-year interval from January 2010 to December 2011 was defined to review time waiting to transplant in a prospectively gathered, multi-institutional registry database created for incompatible living donor-recipient pairs seeking a compatible transplant by exchanging donors. The database was reviewed for recipient wait-time from registration to transplants completed during the interval, and further stratified by the blood types of the incompatible living donor and recipient, and the calculated panel reactive antibody of the recipient assessing how these variables influence wait-time. RESULTS During the interval, a total of 190 transplants were performed, 6 via loops, and 184 via chains. 54 chains were active, 50 eventually closing to the standard wait-list, 2 ongoing, and 2 broken when a bridge donor became unavailable. The average wait-time from registration to transplant was 4 months for recipients with a cPRA of 0 (n=80), 5 months for a cPRA of 0-80% (n=46), 6 months for a cPRA of 80-95% (n=35), and 9 months for a cPRA > 95% (n=29), with an overall wait-time for those transplanted of 6 months (n=190). The average wait-time was 4 months (n=7) for blood type AB recipients, 5 months (n=66) for blood type A recipients, 6 months (n=33) for blood type B recipients, and 8 months (n=84) for blood type O recipients. On the other hand, 212 patients were still awaiting transplant with enrollments continuing throughout the interval, 15% having a cPRA of 0% (n=31), 11% a cPRA of 0-80% (n=24), 8% a cPRA of 80-95% (n=16), and 67% a cPRA of >95% (n=141). A majority of patients still waiting had non-blood type O incompatible donors (n=128), and were sensitized with donor specific antibody (n=181). CONCLUSIONS Wait-time increases with increasing recipient cPRA, and varies by the blood type of the incompatible donor and recipient with blood type O recipients waiting longer on average than blood type B recipients, followed by blood type A recipients, with blood type AB recipients waiting the shortest time to exchange transplant. Sensitized patients who register blood type O incompatible donors, and who register more than one incompatible donor may increase their probability of finding a match more quickly. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e919-e920 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jeff Veale LA, CA More articles by this author Marc Melcher Stanford, CA More articles by this author Connie Davis Seattle, WA More articles by this author Elizabeth Berger Maywood, IL More articles by this author Joe Sinacore Babylon, NY More articles by this author Matt Ronin Babylon, NY More articles by this author Garet Hil Babylon, NY More articles by this author John Milner Maywood, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Pretransplant Immune Parameters Associate With Islet Allograft Outcome

Extensive and informative immunological assessments of islet transplant recipients have been limited due, in part, to the smaller numbers of patients transplanted compared with solid organ trials. Limitations related to blood volume and the logistical challenges of collecting multiple posttransplant samples for drug levels as well as clinical and metabolic parameters also pose challenges. Several variables affect islet allograft outcome, including allo- and autoimmune responses to transplanted islets, β-cell mass and islet quality, efficacy of the immunosuppressive regimen and its effect on islet function, as well as glycemic control. In fact, much debate has centered on whether or not islet attrition is due to immune-mediated loss, death of overworked cells caused by insufficient mass, and/or diabetogenic effect of various immune intervention agents. In addition, many of these parameters may have differing effects based on the transplanted mass, with marginal mass transplants being more susceptible to immune-mediated or stress-induced loss. Recently, several studies have demonstrated immunological alterations in islet allograft patients. Posttransplant changes in lymphocytes and lymphocyte subsets were reported to be variable depending on the immune suppression used but have not yet been associated with graft status or specific clinical outcomes (1–4). Higher posttransplant cytotoxic T-cell precursor frequency against donor antigens was associated with poorer outcome at 6 months in recipients treated with sirolimus-based maintenance therapy but not tacrolimus–mycophenolate mofetil (5). In one study, cytokine production in allogeneic mixed lymphocyte reactions (MLRs) was skewed toward …

Active Immunization to Prevent De Novo Hepatitis B Virus Infection in Pediatric Live Donor Liver Recipients

This study aims to evaluate the efficacy of HBV vaccination as an alternative preventive measure against de novo HBV infection in pediatric living donor liver transplantation (LDLT). Sixty recipients were enrolled in this study. Thirty received grafts from anti-HBc(+) donors, and another 30 received grafts from anti-HBc(-) donors. HBV vaccine was given pretransplant to every candidate. Posttransplant, lamivudine was routinely given to recipients receiving anti-HBc(+) grafts for about 2 years. Forty-seven (78%) recipients achieved high levels of anti-HBs titer (>1000 IU/L). Two (3.3%) recipients developed de novo HBV infection where one received an anti-HBc(-) graft and another received an anti-HBc(+) graft. Both recipients were in the lower anti-HBs titer group (<1000 IU/L). The incidence of de novo HBV infection was significantly higher in the lower titer group (15.4% vs. 0%, p = 0.04). The median follow-up period was 51 months in recipients with anti-HBc(-) grafts and 57 months in those with anti-HBc(+) grafts. Active immunization is an effective method to prevent de novo HBV infection. It can result in high levels of anti-HBs titer (>1000 IU/L) which may prevent de novo HBV infection in pediatric patients with efficient primary vaccination undergoing LDLT.

Laparoscopic Live Donor Nephrectomy: A Risk Factor for Delayed Function and Rejection in Pediatric Kidney Recipients? A UNOS Analysis

The impact of laparoscopic (vs. open) donor nephrectomy on early graft function and survival in pediatric kidney recipients (< or =18 years) is unknown. We studied 995 pediatric live donor txs reported to UNOS from January 2000 to June 2002, in two recipient age groups: 0-5 years (n = 212, 44% laparoscopic donors [LapD]) and 6-18 years (n = 783, 50% LapD). Delayed graft function (DGF) rates were higher for LapD versus open donor (OpD) txs (0-5 years, 12.8% vs. 2.5% [p = 0.004]; 6-18 years, 5.9% vs. 2.8% [p = 0.03]). Acute rejection incidence for LapD versus OpD txs was higher at 6 months for recipients 0-5 years (18.6% vs. 5.9%, p = 0.01) and 6-18 years (22.5% vs. 15.6%, p = 0.03), and 1 year for recipients 0-5 years (24.3% vs. 7.9%, p = 0.004). In multivariate analyses, significant independent risk factors for rejection at 6 months and 1 year were recipient age 6-18 years, pretx dialysis, LapD nephrectomy and DGF. Graft survival was similar for LapD versus OpD txs. In this retrospective UNOS database analysis, LapD procurement was associated with increased DGF and an independent risk factor for rejection during the first year, particularly for recipients 0-5-years old. Future investigations must confirm these findings and identify strategies to optimize procurement and pediatric recipient outcome.

Allogeneic Stem Cell Transplant (AlloSCT) for Hodgkin's Lymphoma Which Has Relapsed Following Autologous SCT - Evidence for Potent Graft-Versus-Lymphoma Effect.

With the advent of reduced intensity conditioning regimens, new treatment options are available to patients who suffer relapse of Hodgkin’s lymphoma (HL) following autoSCT, but the efficacy of this procedure is not proven. We retrospectively compared the cohort of adult patients who received alloSCT for relapse of HL following autoSCT to those who did not at a single institution. 64 patients underwent autoSCT for HL between 7/87 and 5/02: 41 for relapsed disease, 16 for primary refractory disease and 7 unclassified. Thirty-five patients (55%) relapsed at a median 12.5 months (range 0.9 to 140) after autoSCT. Eleven patients underwent alloSCT a median of 182 (35 – 645) days after relapse; 7/11 received reduced intensity conditioning, 5/11 received SCT from an unrelated donor. Of 24 patients who had relapsed after autoSCT (and did not receive an alloSCT), 16 survived at least 6 months and were considered in this analysis. Acute graft-versus-host disease (GVHD) &gt; grade 2 occurred in only one patient, 5 /9 evaluable patients developed chronic GVHD (2 extensive). Five recipients of alloSCT have died: 2 with relapsed disease, 2 with disseminated fungal infections and 1 with interstitial pneumonitis. 6 patients remain alive, 5 remain free of disease. Median event free survival is12.5 months for recipients of alloSCT with median follow up of 3.1 years. Median overall survival is 4.1 years (64 days – 12.5+ years) and estimated overall survival is 71% at 3 years. This compares favorably with a median overall survival of 1.4 years in patients who survived at least 6 months, but did not receive alloSCT after relapse. Improved survival in the alloSCT cohort demonstrates that potent graft-versus-lymphoma activity can be achieved against HL without significant GVHD.

THE LIVER TRANSPLANT WAITING LIST—A SINGLE-CENTER ANALYSIS

At this transplant center 1340 patients were entered on the liver transplant waiting list during the first 25 months (October 1987 to November 1989) after the initiation of the UNOS allocation system for liver grafts. Of these 972 (72.5%) of the patients received a graft, 120 (9.0%) died waiting for a graft, 109 (8.1%) remained on the active list as of the study endpoint of December 15, 1989, 123 (9.2%) were withdrawn from candidacy, and 16 (1.2%) received a transplant at another center. A total of 1201 patients were candidates for a first graft. Of the 812 primary candidates who received a graft, 64.8% received their graft within one month of entry on the waiting list. Of the 109 primary candidates who died before a graft could be found, 79.0% died within a month of entry onto the waiting list. At time of transplantation, 135 (16.6%) primary recipients of a graft were UNOS class 1, 326 (40.1%) were UNOS class 2, 190 (23.4%) were UNOS class 3, and 161 (19.8%) were UNOS class 4. Actuarial survival rates (percentage) at 6 months for recipients in UNOS class 1, class 2, class 3, and class 4 were 88.7 +/- 2.9, 82.6 +/- 2.1, 78.4 +/- 3.2, and 68.4 +/- 3.9, respectively (P less than 0.001). At the time of death of recipients who failed to get a graft, 6 (5.5%) were UNOS class 1, 14 (12.8%) were UNOS class 2, 23 (21.1%) were UNOS class 3, and 66 (60.6%) were UNOS class 4. These results indicate that a high proportion of liver transplant candidates are in urgent need of a graft and that the UNOS system succeeds in giving these patients high priority. However patient mortality on the waiting list and after transplantation would lessen significantly if more patients with end-stage liver disease were referred to the transplant center in a timely manner before their condition reaches the point where the probability of survival is diminished.

The Effect of Serum ALG Concentrations on Results Following Renal Transplantation

Seventy-three recipients of renal allografts from cadaver donors, and 121 recipients of kidneys from living related donors were studied to determine whether there were any differences in posttransplant results between patients that had a high average serum concentration of ALG (>/=800 microg/ml) during the two weeks of ALG therapy and patients that had low serum levels (</=799 microg/ml). Cadaver kidney recipients who had high serum ALG levels (average 1126 microg/ml) had significantly fewer rejection episodes three months posttransplant and less kidney loss three and six months posttransplant when compared to patients with low serum ALG concentrations (average 629 microg/ml). The tendencies after three and six months favored the group with high serum ALG levels, but the differences were not statistically significant. There were also significantly fewer rejection episodes and less kidney loss at three months in the group with serum ALG levels >/=800 microg/ml when high risk patients with diabetes mellitus were excluded. There were significantly also fewer rejection episodes at three months in recipients of living related kidney grafts that had serum ALG levels >/=800 microg/ml. When high risk diabetics or patients older than 40 were excluded from the related recipients, the number of rejection episodes was still significantly less in patients with high serum ALG levels. There was significantly less kidney loss 24 and more months posttransplant in recipients of kidneys from living related donors whether or not high risk patients were excluded. These results support previous reports from the University of Minnesota indicating ALG is a safe and effective immunosuppressive agent in renal allograft recipients.