MO926RAPID VS. LATE RE-TRANSPLANTATION FOR EARLY KIDNEY GRAFT LOSS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Diana Rodríguez Espinosa ◽  
Jose Jesus Broseta Monzo ◽  
Evelyn Hermida-Lama ◽  
Elena Cuadrado ◽  
Jimena Del Risco ◽  
...  

Abstract Background and Aims Early graft failure (EGL) is a devastating complication of kidney transplantation. Patients with EGL have an increased risk of mortality of up to twelve times compared to patients who received grafts that survive beyond 30 days. Moreover, they may have become sensitized to antigens from the failed graft and that human leukocyte antigen antibodies (anti-HLA), identified on single antigen bead assays, may not be reliable until several weeks after transplantation. Thus, if rapid re-transplantation occurs, there is no certainty regarding the recipient's immunological status. Hence, there could be an increased immunological risk with the consequent disturbance of the new graft's survival. Method We performed a retrospective single-center observational study in re-transplanted patients with EGL (defined as graft loss before 30 days from transplant) between January 1977 and November 2019 from our center to analyze the outcomes of rapid re-transplantation (occurred within 30 days of EGL) vs late re-transplantation (occurred beyond those 30 days). Results: T here were 82 re-transplants after EGL. The median overall patient survival after re-transplantation was 32 years. Eight patients died within the first year. Among the mortality causes, there were four septic shocks, one cardiogenic shock, one massive pulmonary thromboembolism, one myocardial infarction, and one unknown cause. When analyzed for periods, death censored graft survival was 89% at one and five years after re-transplantation. One graft was lost at eight days due to antibody-mediated rejection (AMR), while there was one death with a functioning graft three months after re-transplantation secondary to a pulmonary embolism. Seventy-three late re-transplants occurred. When analyzed for periods, death censored graft survival was 81% and 69% at one and five years after re-transplantation, respectively. The median patient survival after late re-transplantation was 32 years. There were fewer deaths after rapid re-transplantation than late re-transplantation, but given the small number of cases in the former, this difference did not reach statistical significance (p = 0.3). There was no association between the timing of re-transplantation and an increased risk of graft failure (HR 0.30 [0.04 – 2.2]). While four rapid re-transplants did not share any incompatibilities between donors, four did share at least one HLA type I incompatibility, and one shared an incompatibility of HLA class I and class II. There were no T-cell mediated rejections (TCMR), and there was only one AMR in the rapid rapid re-transplantation group, whereas there were six TCMRs and fifteen AMRs in the late re-transplantation group (p = 0.03 and p = 0.4, respectively). Conclusion Rapid re-transplantation appears to be safe and does not entail increased rejection risk, nor it diminishes long-term graft survival when compared to late re-transplantation.

2021 ◽  
Vol 8 ◽  
Author(s):  
Gaston J. Piñeiro ◽  
Enrique Montagud-Marrahi ◽  
José Ríos ◽  
Pedro Ventura-Aguiar ◽  
David Cucchiari ◽  
...  

Background: Despite recent advances in immunosuppression treatment, antibody-mediated rejection (ABMR) remains the leading cause of kidney graft loss. Information about prognostic markers and the efficacy of treatment is scarce.Methods: Retrospective study with kidney recipients diagnosed an active ABMR from January 1, 2004 to December 31, 2019 to explore the influence of persistent inflammation in follow-up biopsies on graft survival after ABMR treatment.Results: About 116 patients were included. Active ABMR were treated with a combination of plasma exchange (PE), intravenous immunoglobulin (IVIg), rituximab, and steroids. At 6 months of treatment, 63 (54.3%) patients presented a stabilization or improvement in kidney-graft function. The effectiveness varied depending on the timepoint of the presentation between transplantation and rejection, which is lower for those with late ABMR (63 vs. 21% for early vs. late ABMR, respectively). Ninety patients (77%) underwent a control biopsy after ABMR treatment, from which 46 (51%) responded to the treatment. Microvascular inflammation (MVI) persisted in 64 (71%) biopsies, whereas tubulitis persisted in 17 (19%) biopsies. Death-censored graft survival at 1 year was significantly lower in patients with persistent MVI (86% vs. 95% without persistent MVI, P = 0.002), or with persistent tubulitis (44% vs. 66% without tubulitis, P = 0.02). In the Cox Regression analysis, the persistence of MVI [hazard ratio (HR), 4.50 (95%CI, 1.35–14.96), P = 0.01] and tubulitis [HR 2.88 95%CI (1.24–6.69), P = 0.01) in follow-up biopsies significantly increased the risk of graft failure.Conclusion: Persistent inflammation in follow-up biopsies after ABMR treatment was associated with an increased risk of graft loss, even without meeting Banff rejection criteria.Study Registration: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTRINM-2017-01.


2021 ◽  
Vol 10 (15) ◽  
pp. 3237
Author(s):  
Lukas Johannes Lehner ◽  
Robert Öllinger ◽  
Brigitta Globke ◽  
Marcel G. Naik ◽  
Klemens Budde ◽  
...  

(1) Background: Simultaneous pancreas–kidney transplantation (SPKT) is a standard therapeutic option for patients with diabetes mellitus type I and kidney failure. Early pancreas allograft failure is a complication potentially associated with worse outcomes. (2) Methods: We performed a landmark analysis to assess the impact of early pancreas graft loss within 3 months on mortality and kidney graft survival over 10 years. This retrospective single-center study included 114 adult patients who underwent an SPKT between 2005 and 2018. (3) Results: Pancreas graft survival rate was 85.1% at 3 months. The main causes of early pancreas graft loss were thrombosis (6.1%), necrosis (2.6%), and pancreatitis (2.6%). Early pancreas graft loss was not associated with reduced patient survival (p = 0.168) or major adverse cerebral or cardiovascular events over 10 years (p = 0.741) compared to patients with functioning pancreas, after 3 months. Moreover, kidney graft function (p = 0.494) and survival (p = 0.461) were not significantly influenced by early pancreas graft loss. (4) Conclusion: In this study, using the landmark analysis technique, early pancreas graft loss within 3 months did not significantly impact patient or kidney graft survival over 10 years.


2021 ◽  
Author(s):  
Felix Poppelaars ◽  
Mariana Gaya da Costa ◽  
Bernardo Faria ◽  
Siawosh K. Eskandari ◽  
Jeffrey Damman ◽  
...  

Introduction Improvement of long-term outcomes in kidney transplantation remains one of the most pressing challenges, yet drug development is stagnating. Human genetics offers an opportunity for much-needed target validation in transplantation. Conflicting data exists about the effect of transforming growth factor beta 1 (TGF-beta1) on kidney transplant survival, since TGF-beta1 has profibrotic and protective effects. We therefore the impact of a recently discovered functional TGBF1 polymorphism on long term kidney graft survival. Methods We performed an observational cohort study analyzing recipient and donor DNA in 1,271-kidney transplant pairs from the University Medical Center Groningen in The Netherlands and associated a low-producing TGBF1 polymorphism (rs1800472 C>T) with 5, 10, and 15-year death-censored kidney graft survival. Results Donor genotype frequencies of s1800472 in TGBF1 differed significantly between patients with and without graft loss (P=0.042). Additionally, the low-producing TGBF1 polymorphism in the donor was associated with an increased risk of graft loss following kidney transplantation (HR 2.13 for the T allele; 95%-CI 1.16-3.90; P=0.015). The incidence of graft loss within 15 years of follow-up was 16.4% in the CC-genotype group and 28.9% in the CT-genotype group. After adjustment for transplant-related covariates, the association between the TGBF1 polymorphism in the donor and graft loss remained significant. In contrast, there was no association between the TGBF1 polymorphism in the recipient and graft loss. Conclusion Kidney allografts possessing a low-producing TGBF1 polymorphism have a higher risk of late graft loss. Our study adds to a growing body of evidence that TGFbeta1 is beneficial, rather than harmful, for kidney transplant survival.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Salmir Nasic ◽  
Johan Mölne ◽  
Bernd Stegmayr ◽  
Marie Felldin ◽  
Björn Peters

Abstract Background and Aims Kidney transplantation is frequently used as a treatment in uremic patients. However, long term function is not easily predicted. The aim of this study was to investigate to what extent histological diagnosis in the first registered transplant kidney biopsy is related to clinical outcome. Method Included were data of 1463 patients (36.6 % women, 63.4 % men) that were merged from a kidney transplantation register and a biopsy register. These patients obtained their first registered transplant biopsy during the period January 1, 2007 until July 30, 2017. Fisher’s exact test and χ-2 analyses were used for cross-tabulation of data. Graft- and patient-survival analysis was performed by Kaplan-Meier analysis with log-rank tests comparing different groups and in next step age and gender adjusted analysis were performed by multivariate Cox-regression-analysis. Data are presented as Hazard Ratio (HR) and 95% Confidence Intervals (CI). A two-sided p-value of <0.05 was considered as statistically significant. Results The graft-survival was shorter for patients with biopsy-proven glomerular diseases (HR 8.1, CI 3.1-20.7) and rejections (HR 4.3, CI 1.7 -10.5) compared to normal biopsy findings. Further, there was a shorter graft-survival for those with chronic damages (HR 3.2, CI 1.3-8.0), acute tubular injuries (HR 3.0, CI 1.2-7.8), and borderline changes (HR 2.9, CI 1.1-7.6). The patient-survival was reduced for patients with biopsy-proven hematological diseases (HR 9.6, CI 2.1-44.0). Sub analysis of all types of rejections showed shorter graft-survival for chronic T-cell-mediated rejection (TCMR) (HR 4.8, CI 2.1-11.7), active antibody-mediated rejection (ABMR) (HR 4.4, CI 2.1-9.3), chronic ABMR (HR 3.8, CI 2.2-6.7), combined chronic ABMR and TCMR (HR 4.0, CI 2.4-6.9) and other rejections (HR 3.3, CI 1.1-9.6) compared to acute TCMR. Patients with TCMR Banff grade II rejection had a better graft-survival (HR 0.35, CI 0.20-0.63) compared to other rejections as well as patients with TCMR Banff grade I (HR 0.52, CI 0.29-0.93). 265 patients had graft-loss and 42 of those patients died afterwards (15.8%). Of the 42 who died after graft-loss 9 patients died within 30 days after transplant failure (21.4%). Conclusion A shorter graft-survival was found in kidneys with glomerular diseases, rejections, acute tubular injuries, borderline changes and chronic damages. A shorter patient-survival was noted for patients with transplant kidney biopsies with hematological diseases. Patients with Banff grade II rejection had a better graft-survival compared to all other diagnosis and other rejections. Further, awareness should be given to patients the first month after graft-loss.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Anissa Paschereit ◽  
Klemens Budde ◽  
Michael Dürr ◽  
Marcel Naik

Abstract Background and Aims Dialysis patients (pts) have an increased risk for hepatitis B (HB) infection and impaired response to HB vaccine compared to the general population. As shown in other studies, patient and graft survival in pts with chronic HB is worse. This study assesses the outcome of HBc-positive patients after kidney transplantation (KTx). Method In our retrospective analysis we included all patients >18 years old, who underwent kidney transplantation from 01.01.1990 to 31.08.2019 in our center. Patients were grouped by their serostatus prior to kidney transplantation into “A: naïve” (HB negative), “B: HBc-positive” (non-active HB) and “C: HBsAg-positive” (chronic HB). Primary endpoints included patient and graft survival analyzed with Kaplan-Meier and log-rank test. Regression analysis was applied to determine independent risk factors for the occurrence of primary endpoints. Results In 2487 kidney transplant patients, serologic markers were retrievable. We identified n=2198 HB naïve, n=218 non-active HB and n=75 chronic HB pts. Overall 29.1% (A:27.7%, B:37.6%, C:45.3%) pts died and 20.3% (A:19.1%, B:27.5%, C:37.3%) pts suffered from graft failure. The 5-year pts survival (Fig. 1) was A: 87.0%, B: 82.8%, C: 82.2%. The 10-year pts survival was A: 71.7%, B: 61.1%, C: 64.5% and the 20-year pts survival was A: 43.1%, B: 26.1%, C: 40.9% (p=0.01). Kaplan-Meier-analysis showed a 5-year graft survival (Fig. 2) of 87.7% in the naïve, 86.1% in non-active HB and 84.3% in chronic HB group. The 10-year graft survival was A: 77.3%, B: 64.9%, C: 76% and the 20-year graft survival was A: 59.7%, B: 52.2%, C: 33.4% (p<0.001). The overall 5-year pts and graft survival (Fig. 3) was A: 78.7%, B: 74.2%, C: 68.6%. The 10-year pts and graft survival was A: 59.8%, B: 46.4%, C: 51.8%. The 20-year overall rate was A: 30.8%, B: 26.4%, C: 14.9% (p<0.001). Regression analysis (Table 1) showed that anti-HBs positivity (≥100 IE/l) was a protective factor for graft failure and death (p<0.001). Conclusion HB leads to earlier graft loss and inferior patient survival. Beside the already known negative effect of chronic HB infection, also in patients with non-active HB infection overall survival was significant worse to HB naïve patients. Thus, non-active HB status is an important risk factor for overall transplant outcome. Next, influence of antiviral and immunosuppressive regimens and incidence of HB-reactivation are to be analyzed.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Oliver Beetz ◽  
Juliane Thies ◽  
Clara A. Weigle ◽  
Fabio Ius ◽  
Michael Winkler ◽  
...  

Abstract Background In spite of renal graft shortage and increasing waiting times for transplant candidates, simultaneous heart and kidney transplantation (HKTx) is an increasingly performed procedure established for patients with combined end-stage cardiac and renal failure. Although data on renal graft outcome in this setting is limited, reports on reduced graft survival in comparison to solitary kidney transplantation (KTx) have led to an ongoing discussion of adequate organ utilization. Methods This retrospective study was conducted to evaluate prognostic factors and outcomes of 27 patients undergoing HKTx in comparison to a matched cohort of 27 patients undergoing solitary KTx between September 1987 and October 2019 in one of Europe’s largest transplant centers. Results Median follow-up was 100.33 (0.46–362.09) months. Despite lower five-year kidney graft survival (62.6% versus 92.1%; 111.73 versus 183.08 months; p = 0.189), graft function and patient survival (138.90 versus 192.71 months; p = 0.128) were not significantly inferior after HKTx in general. However, in case of prior cardiac surgery requiring sternotomy we observed significantly reduced early graft and patient survival (57.00 and 94.09 months, respectively) when compared to patients undergoing solitary KTx (183.08 and 192.71 months; p < 0.001, respectively) or HKTx without prior cardiac surgery (203.22 and 203.22 months; p = 0.016 and p = 0.019, respectively), most probably explained by the significantly increased rate of primary nonfunction (33.3%) and in-hospital mortality (25.0%). Conclusions Our data demonstrates the increased rate of early kidney graft loss and thus significantly inferior graft survival in high-risk patients undergoing HKTx. Thus, we advocate for a “kidney-after-heart” program in such patients to ensure responsible and reasonable utilization of scarce resources in times of ongoing organ shortage crisis.


2020 ◽  
Vol 9 (5) ◽  
pp. 1469
Author(s):  
Wisit Cheungpasitporn ◽  
Charat Thongprayoon ◽  
Pradeep K Vaitla ◽  
Api Chewcharat ◽  
Panupong Hansrivijit ◽  
...  

Background: This study aimed to assess the association between the percentage of glomerulosclerosis (GS) in procurement allograft biopsies from high-risk deceased donor and graft outcomes in kidney transplant recipients. Methods: The UNOS database was used to identify deceased-donor kidneys with a kidney donor profile index (KDPI) score > 85% from 2005 to 2014. Deceased donor kidneys were categorized based on the percentage of GS: 0–10%, 11–20%, >20% and no biopsy performed. The outcome included death-censored graft survival, patient survival, rate of delayed graft function, and 1-year acute rejection. Results: Of 22,006 kidneys, 91.2% were biopsied showing 0–10% GS (58.0%), 11–20% GS (13.5%), >20% GS (19.7%); 8.8% were not biopsied. The rate of kidney discard was 48.5%; 33.6% in 0–10% GS, 68.9% in 11–20% GS, and 77.4% in >20% GS. 49.8% of kidneys were discarded in those that were not biopsied. Death-censored graft survival at 5 years was 75.8% for 0–10% GS, 70.9% for >10% GS, and 74.8% for the no biopsy group. Among kidneys with >10% GS, there was no significant difference in death-censored graft survival between 11–20% GS and >20% GS. Recipients with >10% GS had an increased risk of graft failure (HR = 1.27, p < 0.001), compared with 0–10% GS. There was no significant difference in patient survival, acute rejection at 1-year, and delayed graft function between 0% and 10% GS and >10% GS. Conclusion: In >85% KDPI kidneys, our study suggested that discard rates increased with higher percentages of GS, and GS >10% is an independent prognostic factor for graft failure. Due to organ shortage, future studies are needed to identify strategies to use these marginal kidneys safely and improve outcomes.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Michiel G. H. Betjes ◽  
Kasia S. Sablik ◽  
Henny G. Otten ◽  
Dave L. Roelen ◽  
Frans H. Claas ◽  
...  

Background. The presence of donor-specific antibodies (DSAs) against HLA before kidney transplantation has been variably associated with decreased long-term graft survival. Data on the relation of pretransplant DSA with rejection and cause of graft failure in recipients of donor kidneys are scarce. Methods. Patients transplanted between 1995 and 2005 were included and followed until 2016. Donor-specific antibodies before transplantation were determined retrospectively. For cause, renal transplant biopsies were reviewed. Results. Pretransplant DSAs were found in 160 cases on a total of 734 transplantations (21.8%). In 80.5% of graft failures, a diagnostic renal biopsy was performed. The presence of pretransplant DSA (DSApos) increased the risk of graft failure within the first 3 months after transplantation (5.2% vs. 9.4%) because of rejection with intragraft thrombosis (p<0.01). One year after transplantation, DSApos recipients had an increased hazard for antibody-mediated rejection at 10 years (9% DSAneg vs. 15% DSApos, p=0.01) with significant decreased graft survival at 10 years (79% DSAneg vs. 69% DSApos, p=0.02). This could largely contribute to an increased graft loss because of antibody-mediated rejection in the DSApos group. The incidence and graft loss because of T cell-mediated rejection was not affected by the presence of pretransplant DSA. Conclusions. Pretransplant DSAs are a risk factor for early graft loss and increase the incidence for humoral rejection and graft loss but do not affect the risk for T cell-mediated rejection.


2019 ◽  
Vol 14 (7) ◽  
pp. 1056-1066 ◽  
Author(s):  
Malte Ziemann ◽  
Wolfgang Altermann ◽  
Katharina Angert ◽  
Wolfgang Arns ◽  
Anette Bachmann ◽  
...  

Background and objectivesThe prognostic value of preformed donor-specific HLA antibodies (DSA), which are only detectable by sensitive methods, remains controversial for kidney transplantation.Design, setting, participants, & measurementsThe outcome of 4233 consecutive kidney transplants performed between 2012 and 2015 in 18 German transplant centers was evaluated. Most centers used a stepwise pretransplant antibody screening with bead array tests and differentiation of positive samples by single antigen assays. Using these screening results, DSA against HLA-A, -B, -C, -DRB1 and -DQB1 were determined. Data on clinical outcome and possible covariates were collected retrospectively.ResultsPretransplant DSA were associated with lower overall graft survival, with a hazard ratio of 2.53 for living donation (95% confidence interval [95% CI], 1.49 to 4.29; P<0.001) and 1.59 for deceased donation (95% CI, 1.21 to 2.11; P=0.001). ABO-incompatible transplantation was associated with worse graft survival (hazard ratio, 2.09; 95% CI, 1.33 to 3.27; P=0.001) independent from DSA. There was no difference between DSA against class 1, class 2, or both. Stratification into DSA <3000 medium fluorescence intensity (MFI) and DSA ≥3000 MFI resulted in overlapping survival curves. Therefore, separate analyses were performed for 3-month and long-term graft survival. Although DSA <3000 MFI tended to be associated with both lower 3-month and long-term transplant survival in deceased donation, DSA ≥3000 MFI were only associated with worse long-term transplant survival in deceased donation. In living donation, only strong DSA were associated with reduced graft survival in the first 3 months, but both weak and strong DSA were associated with reduced long-term graft survival. A higher incidence of antibody-mediated rejection within 6 months was only associated with DSA ≥3000 MFI.ConclusionsPreformed DSA were associated with an increased risk for graft loss in kidney transplantation, which was greater in living than in deceased donation. Even weak DSA <3000 MFI were associated with worse graft survival. This association was stronger in living than deceased donation.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Rita Leal ◽  
Clara Pardinhas ◽  
Luís Rodrigues ◽  
Maria Guedes Marques ◽  
Lidia Santos ◽  
...  

Abstract Background and Aims Kidney retransplantation confers a robust survival benefit over dialysis in selected patients and recent data has shown second graft outcomes similar to those of a first graft. However, the management of these patients is challenging, particularly due to allosensitization and an increased risk of acute rejection, which are related with poorer graft survival. The recognition of risk factors to acute rejection, dependent on the first and second graft, might help us to personalize standard care and achieve similar graft survival rates to patients with a first transplant. Our aim was to identify risk factors to second graft acute rejection, and the impact of acute rejection in graft failure. Method We performed a retrospective, longitudinal study including all patients submitted to a second kidney transplant between January 2008 and December 2019, excluding patients with more than 2 grafts or multi-organ transplant. Demographic, clinical and histocompatibility data from the donor and receptor were collected from our unit database. Delayed graft function was defined as the need of dialysis in the first week post-transplant. All acute rejection episodes were biopsy proven, according to Banff 2017 criteria. Follow-up was defined at 1st June 2020 for functioning grafts or at graft failure, with a mean time of 94±42 months. Results We included 109 patients of which 70 males (64%), mostly Caucasian (97%), with a mean age of 43±12 years at second kidney transplant. The main causes of end stage renal disease were glomerular disease (37%), undetermined cause (34%), and urological pathology (15%). First kidney transplant was performed before the year 2010 in 95 patients (87%). The median time of first graft survival was 75 months (IQR 58.5-91.4) and the main causes of first graft loss were chronic allograft nephropathy (N=62, 70.5%) and 11 patients (12.5%) presented primary disfunction due to surgical/vascular complications. During follow-up, 20 patients (18%) presented biopsy proven acute rejection: 3 patients borderline changes, 10 patients T cell mediated and 7 patients antibody mediated, the majority during the first-year post-transplant (N=17, 85%). The risk factors for second graft rejection are summarized in table 1. First year graft survival of the second transplant was 90% and survival at follow up was 72.5% (N=79). Acute rejection was an important risk factor for graft loss (OR 6.548 (95%CI[2.292 - 18.703]), p&lt;0.01). Conclusion Worst outcomes in first kidney transplant, such as acute rejection, primary dysfunction and lower graft survival were related with an increased risk of acute rejection in second graft outcomes, and consequently a higher risk of graft failure.


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