10-year Death-censored Graft Survival Research Articles

Maternal versus paternal living kidney transplant donation is associated with lower rejection in young pediatric recipients: A Collaborative Transplant Study report.

Approximately 1700 children per year with end-stage kidney disease undergo kidney transplantation in Europe and the United States of America; 30%-50% are living donor kidney transplantations. There may be immunological differences between paternal and maternal donors due to transplacental exchange of cells between the mother and fetus during pregnancy leading to microchimerism. We investigated whether the outcome of living-related kidney transplantation in young children is different after maternal compared with paternal organ donation. Using the international Collaborative Transplant Study (CTS) database, we analyzed epidemiological data of 7247 children and adolescents aged <18years who had received a kidney transplant from either mother or father. Risk of treated rejection episodes and death-censored graft failure were computed using the Kaplan-Meier method and multivariable Cox regression. In the recipient age group 1-4years, the rate of treated rejection episodes in recipients of kidneys from maternal donors (N=195) during the first 2years post-transplant was significantly lower (hazard ratio HR=0.47, p=.004) than in patients receiving kidneys from paternal donors (N=179). This association between donor sex and risk of treated rejections was not observed in children aged 5-9years. The 5-year death-censored graft survival in children aged 1-4years with a maternal or paternal donor was comparable. Maternal kidney donation in young pediatric renal transplant recipients is associated with an approximately 50% lower rate of treated rejection than paternal kidney donation. Whether this phenomenon is due to maternal microchimerism-induced donor-specific hyporesponsiveness must be evaluated in prospective mechanistic studies.

Analysis of risk factors for donation after circulatory death kidney transplantation in Japan.

BackgroundIn Japan, donations after circulatory death kidney transplantation are widely performed due to legislation delays. The number of donations after brain death kidney transplantations is increasing, but the target remains unmet. We reviewed the outcomes of donation after circulatory death in Japan.MethodsWe analyzed 2923 deceased kidney transplantations (2239: donation after circulatory death (DCD), 684: donation after brain death (DBD)) performed in Japan from 2000 to 2019. The outcomes of the DCD and DBD groups were compared. We examined the risk factors for graft loss in the DCD group.ResultsThe 5-year patient survival and death-censored graft survival rates of the DCD group, obtained by propensity score matching, were 93.6% and 95.2%, respectively, which were equivalent to 94.2% and 93.8%, respectively, obtained in the DBD group. Older donors (≥ 50 years) and prolonged cold ischemia time (≥ 12 h) were risk factors for graft loss; in the presence of these, graft survival was lower in the DCD group.ConclusionsOlder donors and prolonged cold ischemia time reduced graft survival in the DCD group. Proper evaluation of donors and careful preparation for transplant surgery are, therefore, essential to ensure good transplant outcomes.

Long-Term Outcomes of Kidney Transplants from Older/Marginal Donors: A Cohort Study

Introduction: To safely expand the donor pool, we introduced a strategy of biopsy-guided selection and allocation to single or dual transplantation of kidneys from donors >60 years old or with hypertension, diabetes, and/or proteinuria (older/marginal donors). Here, we evaluated the long-term performance of this approach in everyday clinical practice. Methods: In this single-center cohort study, we compared outcomes of 98 patients who received one or two biopsy-evaluated grafts from older/marginal donors (“recipients”) and 198 patients who received nonhistologically assessed single graft from ideal donors (“reference-recipients”) from October 2004 to December 2015 at the Bergamo Transplant Center (Italy). Results: Older/marginal donors and their recipients were 27.9 and 19.3 years older than ideal donors and their reference-recipients, respectively. KDPI/KDRI and donor serum creatinine were higher and cold ischemia time longer in the recipient group. During a median follow-up of 51.9 (interquartile range 23.1–88.6) months, 11.2% of recipients died, 7.1% lost their graft, and 16.3% had biopsy-proven acute rejection (BPAR) versus 3.5, 7.6, and 17.7%, respectively, of reference-recipients. Overall death-censored graft failure (rate ratio 0.78 [95% CI 0.33–2.08]), 5-year death-censored graft survival (94.3% [87.8–100.0] vs. 94.2% [90.5–98.0]), BPAR incidence (rate ratio 0.87 [0.49–1.62]), and yearly measured glomerular filtration rate decline (1.18 ± 3.27 vs. 0.68 ± 2.42 mL/min/1.73 m², p = 0.37) were similar between recipients and reference-recipients, respectively. Conclusions: Biopsy-guided selection and allocation of kidneys from older/marginal donors can safely increase transplant activity in clinical practice without affecting long-term outcomes. This may help manage the growing gap between organ demand and supply without affecting long-term recipient and graft outcomes.

Research Highlights

Research Highlights

POS-714 POST-TRANSPLANT OUTCOMES IN RECIPIENTS OF LIVING DONOR KIDNEYS AND INTENDED RECIPIENTS OF LIVING DONOR KIDNEYS

Although kidney transplant recipients (KTR) from living donors demonstrate superior post-transplant outcomes compared to deceased donor (DD) recipients, the relative contribution of recipient factors versus donor factors to outcome differences remains unclear. Comparing outcomes in DD recipients with only potential living donors (DD1) to those with actualized living donors (LD) and DD recipients without potential living donors (DD0) may help inform this question. We hypothesized that graft outcomes in the two DD groups (DD0 and DD1) will be similar, but inferior to the LD group. This was a retrospective cohort observational study of KTR presenting to our centre for evaluation between 01/01/06 and 31/12/18, and received a transplant during that time. They were followed to 31/08/19. KT candidates were classified based on whether they identified a potential living donor at evaluation (LD, DD1) or not (DD0), and their ultimate donor source (LD or DD1). Primary outcome was 5-year death-censored graft survival, adjusted for donor and recipient age, race, cause of end-stage kidney disease (ESKD), peak panel-reactive antibody (PRA), dialysis duration, acute rejection (AR), and delayed graft function (DGF). Within-group and between-group comparisons were made using paired/unpaired student t-test or chi-square/Fisher’s exact test. Graft survival was compared by Kaplan-Meier methodology and log-rank test, with independence of predictor variables by multivariate Cox proportional hazards. Significance was taken as p<0.05. There were 471 KTR (LD=152, DD1=85, DD0=234), excluding DD0 candidates becoming LD (N=8). The most common immunosuppressive regimen was tacrolimus, MPA, and prednisone. DD0 and DD1 did not differ in organ characteristics. LD had a higher 5-year eGFR (59.7 v 53.5 and 52.0 ml/min/1.73m2 for LD, DD1, DD0 respectively, p=0.009) and fewer graft losses (N=10, 10, 49). The 5-year graft survival is shown in Figure 1. DD0 trended inferior to DD1 (p=0.07) and was inferior to LD (p=0.002) while DD1 was not (p=0.19). By multivariate Cox regression analysis, LD demonstrated superior graft survival to combined DD (DD0+DD1) (HR 0.40 [95% CI 0.19-0.84], p=0.016) and DD0 (HR 0.34 [0.16-0.72], p=0.005) but not DD1 (p=0.72). AR, DGF, and diabetic ESKD were also significant across models. Adding peak PRA and dialysis duration rendered DD type insignificant. DD recipients are not all the same. DD1 may exhibit less inferior outcomes to LD than DD0 even with biologically equal DD organs. Not having an identified living donor at initial evaluation is a surrogate for factors risking graft survival that require further attention. Distinguishing DD0 from DD1 as a simple pre-transplant variable may permit clinicians to effectively target biological-social interventions and improve overall DD graft survival. Information about potential but non-actualized living donors must transfer to the DD recipient’s post-transplant chart.

Impact of donor obesity on allograft outcomes after kidney transplantation adjusted for kidney donor profile index - a national cohort study.

Obesity in deceased kidney donors is a known risk factor for poor allograft outcomes. The Kidney Donor Profile Index (KDPI) has been introduced to predict graft survival in deceased donor kidney transplantation (DDKT). Obesity, however, is not included in KDPI. We study the impact of donor obesity on DDKT outcomes after adjusting for organ quality by KDPI. The Organ Procurement Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data of DDKT from 2005 to 2017, with donor BMI≥18.5kg/m2 and weight >80kg were included. There was a total of 66382 DDKTs with 10917 death-censored graft failures. For KDPI≤30%, the 10-year death-censored graft survival (DCGS) rates among donor BMI<30, 30-35, 35-40, 40-45 and ≥45kg/m2 groups were 75.9%, 75.4%, 76.1%, 74.9% and 79.6%, respectively. For KDPI>30%, 10-year DCGS rates were 67.5%, 66.1%, 65.9%, 62.6% and 63.2%, respectively. After adjusting for known confounding factors including KDPI, donor obesity was not independently associated with an increased risk for graft failure. In DDKT with donor weight >80kg, donor obesity was not associated with a lower long term DCGS compared to non-obesity when KDPI≤30%.

5-Year outcomes of the prospective and randomized CISTCERT study comparing steroid withdrawal to replacement of cyclosporine with everolimus in de novo kidney transplant patients.

Withdrawal of either steroids or calcineurin inhibitors are two strategies to reduce treatment-related side effects and improve long-term outcomes of kidney transplantation. The CISTCERT study compared the efficacy and safety of these two strategies. In this multicenter, randomized controlled trial, 151 incident kidney transplant recipients received cyclosporine (CsA), mycophenolic acid (MPA), and steroids during three months, followed by either steroid withdrawal (CsA/MPA) or replacement of cyclosporine with everolimus (EVL) (EVL/MPA/steroids). 5-year patient survival (89% vs. 86%; P=NS) and death-censored graft survival (95% vs. 96%; P=NS) were comparable in the CsA/MPA and EVL/MPA/steroids arm, respectively. 51 CrEDTA clearance was comparable in the intention-to-treat analysis, but in the on-treatment population, the EVL/MPA/steroids arm exhibited a superior 51 CrEDTA clearance at 1 and 5years after transplantation (61.6 vs. 52.4, P=0.05 and 59.1 vs. 46.2ml/min/1.73m2 , P=0.042). Numerically more and more severe rejections were observed in the EVL/MPA/steroids arm, which also experienced a higher incidence of posttransplant diabetes (26% vs. 6%, P=0.0016) and infections. No significant differences were observed in cardiovascular outcomes and malignancy. Both regimens provide an excellent long-term patient survival and graft survival. Regarding graft function, EVL/MPA/steroids is an attractive strategy for patients with good tolerability who remain free of rejection. (ClinicalTrials.gov number: NCT00903188; EudraCT Number 2007-005844-26).

Impact of donor kidney weight to recipient body weight ratio on long-term graft outcomes in live donor kidney transplantation

Background: Kidney weight has been suggested as a surrogate marker for nephron numbers and renal function. Small donor kid ney sizes relative to recipient body size is an important contributor to short-term graft renal function, but the impact of size mis matching on long-term graft outcomes remains unknown. This study is aimed to evaluate the impact of the donor kidney weight to recipient body weight ratio (KW/BW) on long-term graft survival in live donor kidney transplantation. Methods: We performed a longitudinal cohort study in 1,397 patients who underwent live donor kidney transplantation between 2000 and 2016 at Severance Hospital. Following cold perfusion and back table surgery, the kidney was weighted on the same electronic weighting scale by the surgeon. Patients were grouped into four groups according to KW/BW quartiles. Results: During a median follow-up period of 127 months, 245 graft losses occurred (172 graft failures and 73 patient deaths). The 10-year death-censored graft survival rates were 86.9% in the lowest quartile, 90.4% in the second quartile, 90.5% in the third quartile, and 92.4% in the highest quartile (P=0.002). Multivariable analysis revealed that the lowest KW/BW (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.33-3.48; P=0.002) and second lowest KW/BW (HR, 1.69; 95% CI, 1.06-2.70; P=0.029) groups were significantly associated with death-censored graft failure compared with the highest KW/BW group. Patients with lower KW/BW exhibited consistently lower estimated glomerular filtration rates than those with higher KW/BW. Conclusions: Low KW/BW ratio is significantly associated with long-term graft outcome in live donor kidney transplantation.

Combined Liver-Kidney Transplantation With Preformed Anti–human Leukocyte Antigen Donor-Specific Antibodies

IntroductionThe impact of preformed donor-specific anti–human leukocyte antigen (HLA) antibodies (pDSAs) after combined liver-kidney transplantation (CLKT) is still uncertain.MethodsWe conducted a retrospective study in 8 European high-volume transplant centers and investigated the outcome of 166 consecutive CLKTs, including 46 patients with pDSAs.ResultsPatient survival was lower in those with pDSAs (5-year patient survival rate of 63% and 78% with or without pDSA, respectively; P = 0.04). The presence of pDSAs with a mean fluorescence intensity (MFI) ≥ 5000 (hazard ratio 4.96; 95% confidence interval: 2.3–10.9; P < 0.001) and the presence of 3 or more pDSAs (hazard ratio 6.5; 95% confidence interval: 2.5–18.8; P = 0.05) were independently associated with death. The death-censored liver graft survival was similar in patients with or without pDSAs. Kidney graft survival was comparable in both groups. (The 1- and 5-year death-censored graft survival rates were 91.6% and 79.5%, respectively, in patients with pDSAs and 93% and 88%, respectively, in the donor-specific antibody [DSA]-negative group, P = not significant). Despite a higher rate of kidney graft rejection in patients with pDSAs (5-year kidney graft survival rate without rejection of 87% and 97% with or without pDSAs, respectively; P = 0.04), kidney function did not statistically differ between both groups at 5 years post-transplantation (estimated glomerular filtration rate 45 ± 17 vs. 57 ± 29 ml/min per 1.73 m2, respectively, in patients with and without pDSAs). Five recipients with pDSAs (11.0%) experienced an antibody-mediated kidney rejection that led to graft loss in 1 patient.ConclusionOur results suggest that CLKT with pDSAs is associated with a lower patients’ survival despite good recipients’, liver and kidney grafts’ outcome.

Clinical outcomes of the first 300 cases of kidney transplantation: a single-center retrospective cohort study

BackgroundKidney transplantation (KT) is regarded as the most effective treatment for end-stage renal disease. The annual number of KT cases in South Korea has increased rapidly as more centers are implementing a transplantation program. The objective of this study was to determine clinical outcomes of the first 300 consecutive cases of KT in a single center.MethodsClinical data of 300 cases of KT at Seoul National University Bundang Hospital from January 2004 to March 2018 were obtained from a prospectively collected database and retrospectively reviewed.ResultsThe mean age of patients was 47.7±12.9 years, and 59% of patients were male. There were 225 living donors and 75 deceased donors. A total of 42 cases were from ABO-incompatible donors. During a mean follow-up of 68.6±43.5 months, 38 patients (12.7%) experienced rejection. The most common cause was acute T-cell mediated rejection (9.0%). Eighteen patients experienced graft loss. One-year and 5-year death-censored graft survival rates were 99% and 96.6%, respectively. One-year and 5-year patient survival rates were 98.3% and 96.6%, respectively. Multivariate analysis revealed that graft weight-to-recipient weight ratio and rejection were significant factors affecting graft survival.ConclusionsThis single-center review demonstrates clinical outcomes comparable to other major centers. Such good outcomes were obtained by good patient selection, dedicated transplant physicians, and adequate use of immunosuppressive therapy.

BARRIERS IN ACCESS TO LIVER TRANSPLANTATION FOR ETHNIC MINORITY CHILDREN IN THE UNITED STATES DO NOT TRANSLATE INTO INFERIOR OUTCOMES

Purpose: Disparities in children undergoing liver transplantation (LT) exist and have been attributed to a combination of racial and socioeconomic circumstances. We sought to evaluate the influence of those barriers in access to LT on graft and patient survival. Methodology: We evaluated data from the U.S. Scientific Registry of Transplant Recipients (SRTR) of all pediatric (<18 years old) LT recipients from 1999 to 2014 and compared outcomes by race or ethnicity: Hispanic, non-Hispanic White (NHW), and non-Hispanic Blacks (NHB). We assessed 1- and 5-year patient survival (PS) and death-censored graft survival (DCGS). Characteristics controlled for included: living or deceased donor, brain- or cardiac-death donor (DCD), graft type (whole, partial, split), recipient age, BMI, primary disease, PELD score, re-transplant status, graft rejection, functional status, and cold ischemia time (CIT). Cox regression analysis was used with an alpha level of 0.05. Results: During the 15-year period, 8,331 (4,876 NHW, 1,522 NHB, and 1,933 Hispanic) pediatric LT procedures were performed in the U.S. Hispanic children were listed and transplanted at a significantly younger age (4.4, 4.8, respectively) than NHW (5.2, 5.6; p<0.001) and NHB children (5.1, 5.5; p<0.001). Compared to NHW (15.3%) and NHB (20.3%), there was a greater proportion of Hispanic children requiring total functional assistance (23.7%; p<0.001) at LT. Additionally, NHB and Hispanic children had exception points approved with lower frequency than NHW (p=0.036). Compared to NHW (14.2%), NHB (7.5%) and Hispanic (11.5%) children were less likely to have a living donor (p<0.001). NHB were more likely to receive a whole deceased donor graft (69.4%) than NHW or Hispanic children (63.4% and 59.6%, respectively; p<0.001). However, Hispanic children were more likely to receive a split deceased donor graft (19.8% for Hispanics, 12.9% for NHW, 14.7% for NHB; p<0.001). Listing PELD was higher for Hispanics (21.1±11.3) and NHB (20.4±10.7), compared to NHW (20.0±10.8; p=0.023). One-year PS for NHW, NHB, and Hispanics was 82.9%, 83.2%, and 83.1%, respectively; one-year DCGS was 82.8%, 83.1%, and 83.0%, respectively. Five-year PS for NHW, NHB, and Hispanics was 60.6%, 58.5%, and 57.9%, respectively; five-year DCGS was 60.6%, 58.5%, and 57.9%, respectively. None of these was significantly different in any two-way comparison.Multivariate analysis of one-year graft loss showed that older recipient age (HR 0.962, 95% CI 0.943-0.982) was protective while re-transplant status (1.554, 1.180-2.048) and the need for functional assistance (3.079, 2.307-4.109) were predictive of graft loss. Conclusion: Barriers exist for minority children to navigate the LT listing process. However, once transplanted, Hispanic and NHB children outcomes are comparable to NHW. Further research is necessary to understand and ease barriers in accessing LT for minority children.

Predictors of long-term renal allograft survival after second kidney transplantation.

Few studies investigate significant perioperative predictors for long-term renal allograft survival after second kidney transplant (SKT). We compared long-term survival following SKT with primary kidney transplant and determined predictors of renal allograft failure after SKT. Outcomes of all primary or second kidney transplant recipients at a national kidney transplant center between 1993 and 2017 were reviewed. The primary outcomes measurements were renal allograft survival for both first and second kidney transplants. Secondary outcome measurements were incidence of delayed graft function (DGF), incidence of acute rejection (AR), and predictors for renal allograft survival in SKT recipients. In total, there were 392 SKTs and 2748 primary kidney transplants performed between 1993 and 2017. The 1-, 5-, and 10-year death-censored graft survival for deceased-donor recipients was 95.3%, 88.7%, and 78.2% for primary kidney transplant and 94.9%, 87.1%, and 74.9% for SKT (P=.0288). Survival of primary renal allograft <6years (HR 0.6, P=.017), AR episodes (HR 1.6, P=.031), DGF (HR 2.0, P=.005), and HLA-DR MM (HR 1.7, P=.018) was independent predictors of long-term renal allograft failure after SKT. These findings may provide important information on long-term survival outcomes after SKT and for identifying patients at risk for long-term renal allograft failure after SKT.

Kidney transplantation in the extremely elderly from extremely aged deceased donors: a kidney for each age.

Advances in life expectancy have led to an increase in the number of elderly people with end-stage renal disease (ESRD). Scarce information is available on the outcomes of kidney transplantation (KT) in extremely elderly patients based on an allocation policy prioritizing donor-recipient age matching. We included recipients ≥75 years that underwent KT from similarly aged deceased donors at our institution between 2002 and 2015. Determinants of death-censored graft and patient survival were assessed by Cox regression. We included 138 recipients with a median follow-up of 38.8 months. Median (interquartile range) age of recipients and donors was 77.5 (76.3-79.7) and 77.0 years (74.7-79.0), with 22.5% of donors ≥80 years. Primary graft non-function occurred in 8.0% (11/138) of patients. Cumulative incidence rates for post-transplant infection and biopsy-proven acute rejection (BPAR) were 70.3% (97/138) and 15.2% (21/138), respectively. One- and 5-year patient survival were 82.1 and 60.1%, respectively, whereas the corresponding rates for death-censored graft survival were 95.6 and 93.1%. Infection was the leading cause of death (46.0% of fatal cases). The occurrence of BPAR was associated with lower 1-year patient survival [hazard ratio (HR) = 4.21, 95% confidence interval (CI) 1.64-10.82; P = 0.003]. Diabetic nephropathy was the only factor predicting 5-year death-censored graft survival (HR = 4.82, 95% CI 1.08-21.56; P = 0.040). ESRD patients ≥75 years can access KT and remain dialysis free for their remaining lifespan by using grafts from extremely aged deceased donors, yielding encouraging results in terms of recipient and graft survival.

Kidneys From Elderly Deceased Donors-Is 70 the New 60?

There is a growing shortage of kidney donors leading to extended transplant waiting times associated with increased mortality. To expand the donor pool, clinicians nowadays regularly accept organs from elderly donors, including those aged ≥70 years. There is only limited and conflicting data whether kidneys from these elderly donors allow for satisfactory allograft outcome rates. To asses this question, the 5-year death censored graft survival of 116,870 adult first deceased donor kidney allograft recipients that were transplanted at European centers between 1997 and 2016 and reported to the “Collaborative Transplant Study” were analyzed using Kaplan–Meier analysis and country stratified Cox regression. The combinations of the two transplant periods 1997–2006 and 2007–2016 with the donor age categories 18–49, 50–59, 60–69, and ≥70 years were considered. From 1997–2006 to 2007–2016, the median donor age increased from 50 to 55 years and the proportion of kidneys from ≥60-year-old donors rose from 24.1 to 38.8%. At the same time, the proportion of kidneys from ≥70-year-old donors more than doubled (6.7 vs. 15.4%). Between 1997–2006 and 2007–2016, the 5-year graft survival improved in all donor age categories. During 2007–2016, the 5-year death censored graft survival of kidneys from ≥70-year-old donors was comparable to that of kidneys from 60 to 69-year-old donors during 1997–2006. This was true both for younger recipients (18–64 years) and older recipients (≥65 years). Among the younger recipients, 45–64-year-old recipients showed the best death censored graft survival rates for kidneys from old donors. In the country-stratified Cox regression analysis, compared to the reference of grafts from 18 to 49-year-old donors, the hazard ratio for grafts from ≥70-year-old donors during 2007–2016 was 1.92, exactly the same as the hazard ratio for grafts from 60 to 69-year-old donors during 1997–2006. Our analysis indicates that within only one further decade (1997–2006 vs. 2007–2016) the 5-year death censored graft survival of kidneys from ≥70-year old donors improved to the level of kidneys from 60 to 69-year-old donors in the previous decade.

Long-Term Outcome of Kidney Retransplantation in Comparison With First Transplantation: A Propensity Score Matching Analysis

BackgroundAdvances in renal transplantation have improved graft survival. However, many patients experience graft failure due to chronic renal allograft nephropathy. Although renal retransplantation is increasingly performed, its outcome is controversial. The aim of this study was to evaluate outcomes of renal retransplantation compared with those of first renal transplantation. MethodsFrom March 1969 to August 2018, there were 3000 cases of renal transplantation performed at Seoul St. Mary’s Hospital, Korea. Because the number of third renal transplantation was too small, only first and second renal transplantation groups were compared using propensity score matching. Outcomes of the third renal transplantation were then added. Graft survival rates were determined using Kaplan-Meier survival curves and assessed for significance using log-rank test. ResultsFive- and 10-year patient-graft survival rates for the first renal transplantation were 82.6% and 72.8%, respectively. Those for the second renal transplantation were 78.4% and 73.9%, respectively (P = .588). Five- and 10-year patient survival rates were 91.2% and 85.1%, respectively, for the first renal transplantation. These were 87.8% and 85.5%, respectively, for the second renal transplantation (P = .684). Five- and 10-year death-censored graft survival rates were 88.8% and 80.6%, respectively, for the first renal transplantation. These were 84.6% and 80.5%, respectively, for the second renal transplantation (P = .564). ConclusionsThis study showed that graft survival of second renal transplantation was not significantly different from that of first renal transplantation. Therefore, renal retransplantation might be a reasonable option for patients who lost the first renal graft.

BK Virus in Renal Transplant Patients Using Alemtuzumab for Induction Immunosuppression.

Alemtuzumab, a monoclonal antibody utilized as induction immunosuppression in renal transplant, targets CD52-positive lymphocytes, causing profound B- and T-cell depletion. The administration of such novel, potent immunosuppressive agents, with the goal of reducing rejection, poses an increased threat of BK virus infection in renal transplant recipients. This internal review boardapproved retrospective analysis included 676 renal transplant patients during a 9-year period. All patients were induced with alemtuzumab, and most received a steroid-minimizing regimen. BK viremia was defined as a clinically significant BK virus infection confirmed by polymerase chain reaction. Of total study recipients, 58 (8.6%) were positive for BK viremia. African American race/ethnicity, age > 65 years, and rejection showed significant associations with BK viremia. Kaplan-Meier analyses demonstrated significant differences in 3-year (P = .032), 5-year (P = .025), and overall rejection (P = .031) between patients with and without BK viremia. Differences were found in overall (P = .002) and 5-year (P = .001) death-censored graft survival for patients positive for BK viremia plus another non-BK infection versus patients without BK viremia or other infection. BK viremia-positive patients with other infections had significantly lower overall (P = .010) and 5-year (P = .010) death-censored graft survival than patients with BK viremia but without other infections. When we excluded other infections, we observed no differences between BK viremia-positive and BK viremia-negative patients. BK viremia incidence following alemtuzumab induction therapy appears to be comparable to that shown in other reports and slightly lower than the incidence in patients receiving non-alemtuzumab immunosuppression. BK virus may increase risk of rejection, and BK virus plus another infection may lead to decreased graft survival. African American patients, patients > 65 years old, and patients with rejection history may be at increased risk of BK virus. Closer screening should be considered in these populations.

Impact of Cold Ischemia Time on Outcomes of Deceased Donor Kidney Transplantation: An Analysis of a National Registry.

Cold ischemia time (CIT) is known to impact kidney graft survival rates. We compare the impact of CIT on graft failure and mortality in circulatory death versus brain death donor kidneys and how it relates to donor age. We used the prospective Dutch Organ Transplantation Registry to include 2153 adult recipients of brain death (n = 1266) and circulatory death (n = 887) donor kidneys after static cold storage from transplants performed between 2005 and 2012. CIT was modeled nonlinearly with splines. Associations and interactions between CIT, donor type, donor age, 5-year (death-censored) graft survival, and mortality were evaluated. The median CIT was 16.2 hours (interquartile range 12.8-20), ranging from 3.4 to 44.7 hours for brain death and 4.7 to 46.6 hours for circulatory death donor kidneys. At >12 hours of CIT, we observed an increased risk of graft failure in kidneys donated after circulatory death versus after brain death. This risk rose significantly at >22 hours of CIT (hazard ratio 1.45; 95% confidence interval, 1.01-2.49; P = 0.043). Kidneys that came from 60-year-old circulatory death donors demonstrated elevated hazard risk at 19 hours of CIT, a shorter timeline than that for kidneys that came from brain death donors of the same age (hazard ratio 1.33; 95% confidence interval, 1.00-1.78; P = 0.045). The additional harmful effects of increased CIT in kidneys from circulatory-death donors were also found for death-censored graft failure but did not affect mortality rates in any significant way. The findings support the hypothesis that prolonged cold ischemia is more harmful for circulatory death donor kidneys that have already been subjected to a permissible period of warm ischemia. Efforts should be made to reduce CIT, especially for older circulatory death donor kidneys.

Contribution of non-HLA incompatibility between donor and recipient to kidney allograft survival: genome-wide analysis in a prospective cohort

The introduction of HLA matching of donors and recipients was a breakthrough in kidney transplantation. However, half of all transplanted kidneys still fail within 15 years after transplantation. Epidemiological data suggest a fundamental role of non-HLA alloimmunity. We genotyped 477 pairs of deceased donors and first kidney transplant recipients with stable graft function at three months that were transplanted between Dec 1, 2005, and April 30, 2015. Genome-wide genetic mismatches in non-synonymous single nucleotide polymorphisms (nsSNPs) were calculated to identify incompatibilities in transmembrane and secreted proteins. We estimated the association between nsSNP mismatch and graft loss in a Cox proportional hazard model, adjusting for HLA mismatch and clinical covariates. Customised peptide arrays were generated to screen for antibodies against genotype-derived mismatched epitopes in 25 patients with biopsy-confirmed chronic antibody-mediated rejection. 59 268 nsSNPs affecting a transmembrane or secreted protein were analysed. The median number of nsSNP mismatches in immune-accessible transmembrane and secreted proteins between donors and recipients was 1892 (IQR 1850-1936). The degree of nsSNP mismatch was independently associated with graft loss in a multivariable model adjusted for HLA eplet mismatch (HLA-A, HLA-B, HLA-C, HLA-DP, HLA-DQ, and HLA-DR). Each increase by a unit of one IQR had an HR of 1·68 (95% CI 1·17-2·41, p=0·005). 5-year death censored graft survival was 98% in the quartile with the lowest mismatch, 91% in the second quartile, 89% in the third quartile, and 82% in the highest quartile (p=0·003, log-rank test). Customised peptide arrays verified a donor-specific alloimmune response to genetically predicted mismatched epitopes. Genetic mismatch of non-HLA haplotypes coding for transmembrane or secreted proteins is associated with an increased risk of functional graft loss independently of HLA incompatibility. As in HLA alloimmunity, donor-specific alloantibodies can be identified against genotype derived non-HLA epitopes. Austrian Science Fund, WWTF (Vienna Science and Technology Fund), and Ministry of Health of the Czech Republic.

A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival.

Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs. To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay. Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P=0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P=0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11). This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term.

Impact of Donor Age on Clinical Outcomes of Primary Single Kidney Transplantation From Maastricht Category-III Donors After Circulatory Death.

BackgroundStandard-criteria donation after circulatory death (DCD) kidney transplants (KTx) have higher primary nonfunction, delayed graft function (DGF), and rejection rates than age-matched donation after brain death (DBD) but similar graft survival. Data on expanded-criteria DCD are conflicting and many centers remain concerned regarding their use.MethodsIn this single-center observational study with 5-year follow-up, we analyzed data from 112 primary DCD Maastricht category-III single KTx receiving similar organ preservation and maintenance immunosuppression. Patients were sorted as young DCD (donor <60 years, 72 recipients) or old DCD (donor ≥60 years, 40 recipients). Old DCD outcomes were compared with young DCD and to a DBD control group (old DBD, donor ≥60 years, 40 recipients).ResultsAfter 5 years, old DCD showed lower patient survival (66% vs 85%; P = 0.014), death-censored graft survival (63% vs 83%; P = 0.001), and Modification of Diet in Renal Disease estimated glomerular filtration rate (34, 27.0-42.0 mL/min per 1.73 m2 vs 45.0, 33.0-58.0 mL/min per 1.73 m2; P = 0.021) than young DCD with higher DGF (70% vs 47.2%; P = 0.029) and graft thrombosis (12.5% vs 1.4%; P = 0.021). Comparison between old DCD and old DBD showed similar 5-year patient survival (66% vs 67%; P = 0.394) and death-censored graft survival (63% vs 69%; P = 0.518) but higher DGF (70% vs 37.5%; P = 0.007) and lower estimated glomerular filtration rate (34, 27.0-42.0 mL/min per 1.73 m2 vs 41, 40.0-42.0 mL/min per 1.73 m2; P = 0.029). Multivariate Cox regression analysis showed that donor 60 years or older (hazard ratio, 3.135; 95% confidence interval, 1.716-5.729; P < 0.001) and induction with anti–IL2-receptor-α monoclonal antibody (hazard ratio, 0.503; 95% confidence interval, 0.269-0.940, P = 0.031 in favor of induction with rabbit antithymocyte globulin) are independent predictors of transplant loss.ConclusionsOverall, single KTx from DCD Maastricht category-III donors 60 years or older have inferior outcomes than KTx from donors younger than 60 years. Comparison with age-matched DBD showed similar patient and graft survivals. However, the discrepancy in graft function between DCD and DBD deserves further investigation.