Tracing clinically relevant HLA antibodies prior to kidney transplantation: Commentary on “Pre-transplant HLA antibodies detected by single antigen bead assay are a risk factor for long-term kidney graft loss even in the absence of donor specific antibodi

2016 ◽  
Vol 29 (9) ◽  
pp. 985-987 ◽  
Author(s):  
Nils Lachmann ◽  
Constanze Schönemann
Keyword(s):  
Risk Factor ◽  
Kidney Transplantation ◽  
Graft Loss ◽  
Kidney Graft ◽  
Hla Antibodies ◽  
Single Antigen

scholarly journals Pretransplant human leukocyte antigen antibodies detected by single-antigen bead assay are a risk factor for long-term kidney graft loss even in the absence of donor-specific antibodies

2016 ◽  
Vol 29 (9) ◽  
pp. 988-998 ◽  
Author(s):  
Rudolf Richter ◽  
Caner Süsal ◽  
Stefanie Köhler ◽  
Sara Qidan ◽  
Alicia Schödel ◽  
...  
Keyword(s):  
Risk Factor ◽  
Human Leukocyte Antigen ◽  
Graft Loss ◽  
Human Leukocyte ◽  
Kidney Graft ◽  
Specific Antibodies ◽  
Leukocyte Antigen ◽  
Single Antigen ◽  
Donor Specific Antibodies

scholarly journals Posttransplant Allosensitization in Low Immunological Risk Kidney and Kidney-Pancreas Graft Recipients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Jorge Malheiro ◽  
Sandra Tafulo ◽  
Leonídio Dias ◽  
La Salete Martins ◽  
Isabel Fonseca ◽  
...  
Keyword(s):  
Risk Factor ◽  
Graft Loss ◽  
Graft Function ◽  
Kidney Graft ◽  
Hla Antibodies ◽  
Luminex Assay ◽  
Screening Protocol ◽  
Antibody Positivity ◽  
Cox Analysis ◽  
Pancreas Graft

Introduction. Posttransplantation allosensitization prevalence and effect on kidney grafts outcomes remain unsettled.Methods. Between 2007 and 2012, 408 patients received a primary kidney graft (with 68 patients also receiving a pancreas graft) after a negative cytotoxic crossmatch. All patients had a pretransplant negative anti-HLA screening and 0% panel reactive antibodies. We analyzed retrospectively the results of anti-HLA antibodies screening by Luminex assay, performed between 6 and 24 months after transplant, and searched for the risk factors for antibody positivity and its impact on kidney graft outcomes.Results. Anti-HLA antibodies prevalence at 6 months was 17.4%. Previous steroid-insensitive acute rejection was the only risk factor for both anti-HLA classes detected antibodies. Antithymocyte globulin induction was also a risk factor for anti-HLA-I antibodies. Antibody positivity status was associated with reduced graft function at 12 months and graft survival at 5 years (91.5% versus 96.4%,P=0.03). In multivariable Cox analysis, delayed graft function (HR = 6.1,P<0.01), HLA mismatches>3 (HR = 10.2,P=0.03), and antibody positivity for anti-HLA class II (HR = 5.1,P=0.04) or class I/II (HR = 13.8,P<0.01) were independent predictors of graft loss.Conclusions. Allosensitization against HLA classII±Iafter transplant was associated with adverse kidney graft outcomes. A screening protocol seems advisable within the first year in low immunological risk patients.

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 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.

Association of Kidney Graft Loss with Posttransplant Presence of Strong HLA Antibodies Detected by Luminex Single Antigen Testing

2012 ◽  
Vol 94 (10S) ◽  
pp. 62
Author(s):  
C. Süsal ◽  
B. Döhler ◽  
A. Ruhenstroth ◽  
S. Scherer ◽  
T. H. Tran ◽  
...  
Keyword(s):  
Graft Loss ◽  
Kidney Graft ◽  
Hla Antibodies ◽  
Single Antigen ◽  
Antigen Testing

Association of Kidney Graft Loss With De Novo Produced Donor-Specific and Non-Donor-Specific HLA Antibodies Detected by Single Antigen Testing

2015 ◽  
Vol 99 (9) ◽  
pp. 1976-1980 ◽  
Author(s):  
Caner Süsal ◽  
Daniel Wettstein ◽  
Bernd Döhler ◽  
Christian Morath ◽  
Andrea Ruhenstroth ◽  
...  
Keyword(s):  
De Novo ◽  
Graft Loss ◽  
Kidney Graft ◽  
Hla Antibodies ◽  
Single Antigen ◽  
Antigen Testing

scholarly journals Thinking Outside the Box: Novel Kidney Protective Strategies in Kidney Transplantation

2021 ◽  
pp. CJN.15070920
Author(s):  
Hassan N. Ibrahim ◽  
Dina N. Murad ◽  
Greg A. Knoll
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Loss ◽  
Lipid Lowering ◽  
Kidney Graft ◽  
Modest Improvement ◽  
Sodium Glucose Cotransporter ◽  
Protective Strategies ◽  
Calcineurin Inhibitor Nephrotoxicity

Despite the reduction in the incidence of acute rejection, a major risk factor for graft loss, there has been only modest improvement in long-term graft survival. Most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or calcineurin inhibitor nephrotoxicity. Distinct immunologic and nonimmunologic factors conspire to lead to a common pathway of allograft fibrosis. It remains plausible that mitigating nonimmunologic damage using strategies proven effective in native kidney disease may yield benefit in kidney transplantation. In this review, we will focus on nonimmunologic aspects of kidney transplant care that may prove to be valuable adjuncts to a well-managed immunosuppression regimen. Topics to be addressed include the roles of hypertension and agents used to treat it, lipid lowering, sodium and water intake, elevated uric acid, metabolic acidosis, and the use of sodium-glucose cotransporter 2 inhibitors on long-term kidney transplant health.

scholarly journals Tumor necrosis factor-α gene polymorphism is associated with short- and long-term kidney allograft outcomes.

2021 ◽  
Author(s):  
Felix Poppelaars ◽  
Mariana Gaya da Costa ◽  
Bernardo Faria ◽  
Siawosh K. Eskandari ◽  
Marc A. Seelen ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Tumor Necrosis Factor ◽  
Graft Survival ◽  
Tumor Necrosis ◽  
Graft Loss ◽  
Tnf Alpha ◽  
Kidney Graft ◽  
Genotype Group ◽  
Necrosis Factor

Introduction Kidney transplantation has excellent short-term results with current immunosuppression regimes, but long-term outcomes have barely improved. Hence, there is a need for new therapeutic options to increase long-term survival of kidney grafts. Drug development for transplantation has slowly plateaued, limiting progress while making drug repurposing an attractive alternative. We, therefore, investigated the impact of tumor necrosis factor-alpha (TNF-alpha) gene (TNF) polymorphisms on kidney graft survival. Methods We performed a prospective cohort study to assess the association of TNF polymorphisms (rs1800629 G>A and rs3093662 A>G) with primary non-function (PNF) and death-censored kidney allograft survival in 1,271 kidney transplant pairs from the University Medical Center Groningen in The Netherlands. Results The G-allele of the TNF rs3093662 polymorphism in donor kidneys was associated with a higher risk of PNF (odds ratio: 2.05; 95%-CI: 1.06-3.97; P = 0.032). Furthermore, the G-allele of this TNF rs3093662 polymorphism in the donor was also associated with worse 5-year, 10-year, and 15-year death-censored kidney graft survival (P<0.05). The cumulative incidence of graft loss was 15.9% in the reference AA-genotype group and 25.2% in the AG/GG-genotype group, respectively. In multivariable analysis, the association between the TNF rs3093662 polymorphism in the donor and 15-year death-censored kidney graft survival remained significant (hazard ratio: 1.51; 95%-CI: 1.05-2.19, P = 0.028). Conclusion Kidney allografts possessing a high-producing TNF polymorphism have a greater risk of immediate and late graft loss. Our study adds to a growing body of literature indicating the potential of TNF-alpha blockade in improving kidney transplantation outcomes.

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