scholarly journals Preformed Donor-Specific HLA Antibodies in Living and Deceased Donor Transplantation

2019 ◽  
Vol 14 (7) ◽  
pp. 1056-1066 ◽  
Author(s):  
Malte Ziemann ◽  
Wolfgang Altermann ◽  
Katharina Angert ◽  
Wolfgang Arns ◽  
Anette Bachmann ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Graft Loss ◽  
Hazard Ratio ◽  
Living Donation ◽  
Hla Antibodies ◽  
Transplant Survival ◽  
Antibody Mediated Rejection ◽  
Increased Risk

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.

scholarly journals A functional TGFB1 polymorphism in the donor associates with long-term graft survival after kidney transplantation.

2021 ◽  
Author(s):  
Felix Poppelaars ◽  
Mariana Gaya da Costa ◽  
Bernardo Faria ◽  
Siawosh K. Eskandari ◽  
Jeffrey Damman ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Loss ◽  
Kidney Graft ◽  
Genotype Group ◽  
Transplant Survival ◽  
Increased Risk ◽  
The Impact

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.

scholarly journals Late and Chronic Antibody-Mediated Rejection: Main Barrier to Long Term Graft Survival

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Qiquan Sun ◽  
Yang Yang
Keyword(s):  
Graft Survival ◽  
Graft Loss ◽  
Limited Effect ◽  
Hla Antibodies ◽  
Specific Antibodies ◽  
Antibody Mediated Rejection ◽  
Donor Specific Antibodies ◽  
Main Barrier ◽  
Lines Of Evidence

Antibody-mediated rejection (AMR) is an important cause of graft loss after organ transplantation. It is caused by anti-donor-specific antibodies especially anti-HLA antibodies. C4d had been regarded as a diagnosis marker for AMR. Although most early AMR episodes can be successfully controlled or reversed, late and chronic AMR remains the leading cause of late graft loss. The strategies which work in early AMR have limited effect on late/chronic episodes. Here, we reviewed the lines of evidence that late/chronic AMR is the leading cause of late graft loss, characteristics of late AMR, and current strategies in managing late/chronic AMR. More effort should be put on the management of late/chronic AMR to make a better long term graft survival.

scholarly journals P1646SURVIVAL OF KIDNEY TRANSPLANTS ACCORDING TO PRESENCE OF HLA ANTIBODIES WHEN DONORSPECIFIC ANTIBODIES ARE SCREENED DURING POSTTRANSPLANT FOLLOW-UP

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Inge Derad ◽  
Johanna Busch ◽  
Martin Nitschke ◽  
Malte Ziemann
Keyword(s):  
Risk Factors ◽  
Confidence Interval ◽  
Graft Survival ◽  
Graft Loss ◽  
Immunosuppressive Regimen ◽  
Term Survival ◽  
Hla Antibodies ◽  
Transplant Survival ◽  
The Mean

Abstract Background and Aims Posttransplant kidney survival depends on several risk factors. A careful immunogenetic matching and the absence of HLA donor specific antibodies (DSA) seem to determine the longevity of the transplant. Method Screening the presence of donor specific HLA antibodies in our posttransplant outpatients was implemented in 2010 (every 6 months in case of DSA free patients for two years, then yearly, and every 3 months in case of DSA + patients for two years, then twice a year). At the same time a treatment protocol was implemented, omitting reduction of immunosuppressive drugs in case of newly detected DSA, and most important with preventing steroid withdrawal in this case.The present single center study reports the long-term survival and kidney function from patients undergoing HLA-screening after transplantation between 2010 and 2016 with a follow-up until 2018. Using a Kaplan-Meier analysis patients without HLA antibodies (no HLA-ab), with HLA antibodies but without DSA (NDSA), and with donor-specific HLA antibodies (DSA) were compared by logrank-testing. Results A full dataset was obtained from 318 patients. The mean overall survival (patients and organ function) didn´t differ between the three groups, p=0.318: no HLA-ab 7.2 years (95%confidence interval 6.7;7.6), NDSA 6.6 (5.9;7.2), DSA 6.8 (6.1;7.5), overall 7.0 (6.6;7.3), events are given in Table1. Whereas the mean patient survival didn´t differ between the groups (p=0.715), the mean death-censored graft survival differed significantly, p=0.008, with a reduced transplant survival in the patients with HLA antibodies but without donorspecific antibodies: no HLA-ab 8.0 years (95%confidence interval 7.7;8.3), NDSA 7.0 (6.4;7.6), DSA 7.6 (7.1;8.2), overall 7.7 (7.4;8.0), numbers are given in Table1. Conclusion In conclusion, the presence of HLA antibodies was associated with a reduced transplant survival. Patients with HLA antibodies had a worse survival than patients with DSA undergoing HLA screening with a personalised immunosuppressive regimen. Immunosuppressive regimen of the groups, as well as other known risk factors of graft survival have to be further analysed. The results of these multivariate analyses have to be awaited to determine whether the risk for graft loss inferred by HLA antibodies is independent from other factors.

MO963GRAFT- AND PATIENT-SURVIVAL AFTER FIRST KIDNEY TRANSPLANT BIOPSY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Salmir Nasic ◽  
Johan Mölne ◽  
Bernd Stegmayr ◽  
Marie Felldin ◽  
Björn Peters
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Patient Survival ◽  
Graft Loss ◽  
Glomerular Diseases ◽  
Hematological Diseases ◽  
Antibody Mediated Rejection ◽  
Transplant Kidney ◽  
Grade Ii ◽  
Transplant Biopsy

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 &lt;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.

Reducing calcineurin inhibitor first for treating BK polyomavirus replication after kidney transplantation: long-term outcomes

2018 ◽  
Vol 34 (7) ◽  
pp. 1240-1250 ◽  
Author(s):  
Nicole Bischof ◽  
Hans H Hirsch ◽  
Caroline Wehmeier ◽  
Patricia Amico ◽  
Michael Dickenmann ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Calcineurin Inhibitor ◽  
Graft Loss ◽  
Standard Operating Procedure ◽  
Rejection Rate ◽  
Long Term Outcomes ◽  
Antibody Mediated Rejection ◽  
Bk Polyomavirus

Abstract Background Reducing immunosuppression is the mainstay of treating BK polyomavirus (BKPyV) viraemia after kidney transplantation, but the best approach, efficacy and impact are undefined. We established a standard operating procedure (SOP) treating BKPyV viraemia based on first reducing calcineurin inhibitor (‘CNI first’). The aim of this study was to investigate long-term outcomes in 644 consecutive transplantations using this SOP. Methods Patients were monitored for active BKPyV infection by urinary decoy cells and, if positive, by BKPyV viraemia. In case of sustained BKPyV viraemia >1000 copies/mL, immunosuppression was reduced stepwise according to the SOP. Patients were classified as ‘no decoy cells’ [n = 432 (66%)], ‘decoy cells/no viraemia’ [n = 107 (17%)] and ‘viraemia’ [n = 105 (17%)]. Results At 6-years post-transplant, graft survival was ∼84%, the clinical rejection rate was ∼25% and they were not different among the three groups (P = 0.14; P = 0.91). The median estimated glomerular filtration rate at the last follow-up was similar (range 49–53 mL/min, P = 0.08). Of 105 viraemic patients, 101 (96%) cleared BKPyV viraemia. In 39% of patients, viraemia clearance followed a tacrolimus reduction. A reduction of mycophenolic acid was required in 43% and discontinuation in 3%. No short-term graft loss was directly attributable to BKPyV-associated nephropathy. After a median follow-up of 5 years after clearance of BKPyV viraemia, 11/101 patients (11%) developed clinical rejection: 7 (7%) T-cell-mediated rejection and 4 (4%) antibody-mediated rejection (ABMR). Conclusions Immunosuppression reduction based on ‘CNI first’ leads to similar long-term outcomes in patients with/without BKPyV viraemia and is associated with a low risk for ABMR after clearance of BKPyV viraemia. Randomized trials are needed to compare the risks and benefits of immunosuppression reduction strategies in kidney transplant patients with BKPyV viraemia.

scholarly journals Successful rescue therapy with mycophenolate mofetil in kidney transplantation improves the long-term graft survival

Medicina ◽  
2007 ◽  
Vol 43 (12) ◽  
pp. 953 ◽  
Author(s):  
Jaanus Kahu ◽  
Aleksander Lõhmus ◽  
Madis Ilmoja ◽  
Ülle Kirsimägi ◽  
Gennadi Timberg ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Kidney Transplantation ◽  
Graft Survival ◽  
Cyclosporine A ◽  
Negative Impact ◽  
Rescue Therapy ◽  
Graft Loss ◽  
Graft Function ◽  
Significant Difference

Objective. The aim of this study was to compare the graft survival after kidney transplantation in patients treated with azathioprine (AZA) or mycophenolate mofetil (MMF) and analyze the significance of different risk factors for graft survival. Material and methods. A total of 137 patients, transplanted between January 1996 and June 2001, were retrospectively divided into two groups: patients who received AZA together with cyclosporine A and methylprednisolone (AZA group, n=72) and patients who received MMF either immediately or were switched from AZA to MMF during 3 months (MMF group, n=65). Results. According to Kaplan-Meier analysis, a 1-year graft survival was 79% in the AZA group and 85% in the MMF group; a 6-year graft survival was 51% and 67%, respectively (P=0.046). Multivariate Cox survival model demonstrated that MMF therapy reduced the risk of graft loss by 34% (P=0.028), while delayed graft function increased the risk of graft loss (risk ratio 2.26, P=0.009). A statistically significant difference in total cholesterol level (6.7 vs. 5.7 mmol/L, respectively; P=0.002), mean systolic blood pressure (145 vs. 134 mmHg, P=0.009), and cyclosporine A daily dose (238 vs. 203 mg, P=0.015) between the AZA and MMF groups at 1 year was revealed. Conclusion. MMF rescue therapy improves the long-term graft survival compared to AZA despite high early rejection rate and avoids the negative impact of acute rejections on graft survival.

scholarly journals Antibody-Mediated Rejection in Kidney Transplantation: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Chethan Puttarajappa ◽  
Ron Shapiro ◽  
Henkie P. Tan
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Management Strategies ◽  
Clinical Manifestations ◽  
Allograft Survival ◽  
Current Management ◽  
Antibody Mediated Rejection ◽  
Emerging Issues

Antibody mediated rejection (AMR) poses a significant and continued challenge for long term graft survival in kidney transplantation. However, in the recent years, there has emerged an increased understanding of the varied manifestations of the antibody mediated processes in kidney transplantation. In this article, we briefly discuss the various histopathological and clinical manifestations of AMRs, along with describing the techniques and methods which have made it easier to define and diagnose these rejections. We also review the emerging issues of C4d negative AMR, its significance in long term allograft survival and provide a brief summary of the current management strategies for managing AMRs in kidney transplantation.

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