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.

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.

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 The impact of early acute rejection on kidney graft survival after repeat kidney transplantation

2021 ◽  
Vol 13 (3) ◽  
pp. 260-271
Author(s):  
A. V. Pinchuk ◽  
N. V. Shmarina ◽  
I. V. Dmitriev ◽  
E. S. Stolyarevich ◽  
N. V. Natalya V. Zagorodnikova ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Graft Survival ◽  
Postoperative Period ◽  
Kidney Graft ◽  
Group I ◽  
Group Ii ◽  
Kidney Transplantations ◽  
The Impact

Introduction. Despite the improvements in immunosuppressive therapy, the growing number of repeat kidney transplantations and associated risks of acute rejection make it relevant to assess the impact of early acute rejection on a long-term kidney graft survival.Objective. The aim of the study was to evaluate the rate, the clinical aspects of early acute rejection after repeat kidney transplantation and the outcomes of its treatment, to perform the assessment of the impact of rejection episodes on a long-term kidney graft survival.Material and methods. We carried out the retrospective analysis of kidney graft survival after 121 repeat kidney transplantations performed in N.V. Sklifosovsky Research Institute for Emergency Medicine in the period from 2007 to 2018. Group I included 96 recipients after kidney transplantation without acute rejection in postoperative period. Group II consisted of 25 patients with early acute rejection after kidney transplantation. We performed the assessment of the impact of early acute rejection on the kidney graft survival in comparison with recipients with uncomplicated postoperative period. Statistical processing was carried out by nonparametric methods. Survival was assessed using the Kaplan–Meier curves.Results. 1-year and 3-year kidney graft survival rates amounted to 90.3% (95%, confidence interval 85–95) and 85.4% (95%, CI 79–91), respectively, in recipients of Group I; and 72% (95%, CI 58–86) and 60% (95%, CI 46–76) in patients of Group II. Significant differences in 1-year and 3-year kidney graft survival between patients of Group I and II have been noticed (P=0.0022 and P=0.0065, respectively).Conclusions. Patients with early acute rejection after kidney transplantation had poorer kidney graft survival in comparison with patients without rejection episodes in postoperative period.

scholarly journals Impact of Early Pancreatic Graft Loss on Outcome after Simultaneous Pancreas–Kidney Transplantation (SPKT)—A Landmark Analysis

2021 ◽  
Vol 10 (15) ◽  
pp. 3237
Author(s):  
Lukas Johannes Lehner ◽  
Robert Öllinger ◽  
Brigitta Globke ◽  
Marcel G. Naik ◽  
Klemens Budde ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Graft Loss ◽  
Type I ◽  
Kidney Graft ◽  
Landmark Analysis ◽  
Pancreas Kidney Transplantation ◽  
Simultaneous Pancreas Kidney ◽  
Simultaneous Pancreas Kidney Transplantation ◽  
Pancreas Graft

(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.

scholarly journals Progress in Pediatric Kidney Transplantation

2014 ◽  
Vol 7 (1) ◽  
pp. 115-122
Author(s):  
Jodi M. Smith ◽  
Vikas R. Dharnidharka
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Pediatric Population ◽  
Short Term ◽  
Allocation Policy ◽  
Pediatric Kidney Transplantation ◽  
Timely Access ◽  
The Impact ◽  
Made In

Significant progress has been made in pediatric kidney transplantation. Advances in immunosuppression have dramatically decreased rates of acute rejection leading to improved short term graft survival but similar improvements in long term graft survival remain elusive. Changes in allocation policy provide the pediatric population with timely access to transplant but there remains concern about the impact of less HLA matching and a decrease in living donors. This report presents data from North America on these successes and the ongoing challenges that face the pediatric transplant community.

Machine learning support for decision making in kidney transplantation: step-by-step development of a technological solution (Preprint)

2021 ◽  
Author(s):  
François-Xavier Paquette ◽  
Amir Ghassemi ◽  
Olga Bukhtiyarova ◽  
Moustapha Cisse ◽  
Natanael Gagnon ◽  
...  
Keyword(s):  
Neural Networks ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Survival ◽  
The United States ◽  
Technological Solution ◽  
Discriminative Ability ◽  
Potential Donor ◽  
Transplant Survival ◽  
Transplant Outcomes

BACKGROUND Kidney transplantation is the preferred treatment option for patients with end-stage renal disease. To maximize patient and graft survival, the allocation of donor organs to potential recipients requires careful consideration. OBJECTIVE To develop an innovative technological solution to enable better prediction of kidney transplant survival for each potential donor-recipient pair. METHODS We used de-identified data on past organ donors, recipients and transplant outcomes in the United States from the Scientific Registry of Transplant Recipients (SRTR). To predict transplant outcomes for potential donor-recipient pairs, we used several survival analysis models, including regression analysis (Cox Proportional Hazards), Random Survival Forests (RSF) and several artificial neural networks (DeepSurv, DeepHit, Recurrent Neural Networks (RNN)). We evaluated the performance of each model on their ability to predict the probability of graft survival after kidney transplantation from deceased donors. Three metrics were employed: the C-index, the Integrated Brier Score and the Integrated Calibration Index (ICI), along with calibration plots. RESULTS Based on the C-index metrics, the neural network-based models (DeepSurv, DeepHit, RNN) had better discriminative ability than the Cox model and RSF (0.650, 0.661, 0.659 vs 0.646 and 0.644, correspondingly). The proposed RNN model offered a compromise between the good discriminative ability and calibration and was implemented in a technological solution of TRL-4. CONCLUSIONS Our technological solution based on RNN model can effectively predict kidney transplant survival and provide support for medical professionals and candidate recipients in determining the most optimal donor-recipient pair. CLINICALTRIAL Not applicable.

MO939RECURRENCE AND OUTCOME OF ANTI-GLOMERULAR BASEMENT MEMBRANE GLOMERULONEPHRITIS AFTER KIDNEY TRANSPLANTATION: A BELGIAN MULTICENTER STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sophie Coche ◽  
Ben Sprangers ◽  
Steven Van Laecke ◽  
Laurent Weekers ◽  
Vicky De Meyer ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Graft Survival ◽  
Glomerular Basement Membrane ◽  
Kidney Biopsy ◽  
Graft Loss ◽  
Survival Rates ◽  
Kidney Graft ◽  
Clinical Recurrence ◽  
Patient And Graft Survival

Abstract Background and Aims Recurrence of anti-glomerular basement membrane (anti-GBM) glomerulonephritis in the kidney graft is a rare event, described in limited case reports and registry analysis. The aim of this study was to evaluate in a large cohort of patients with detailed data collection and long follow-up the risk of recurrence of anti-GBM disease and graft loss caused by recurrence, the risk factors associated with clinical recurrence and the long-term patient and graft survival. Method Multicenter retrospective study. Inclusion criteria: patients with anti-GBM glomerulonephritis transplanted with a kidney between 1977 and 2015. Exclusion criteria: systemic vasculitis (except ANCA), lupus erythematosus and cryoglobulinemia. Clinical recurrence was defined as reappearance of signs of glomerulonephritis along with histological signs of proliferative glomerulonephritis and linear IgG staining on kidney biopsy, with or without anti-GBM antibodies. Results Fifty-three patients were included. Clinical recurrence in a first kidney transplant occurred in only one patient five years after transplantation -a prevalence rate of 1.9%- in the context of cessation of immunosuppressive drugs. The graft was lost due to recurrence. Histological recurrence with linear IgG staining on kidney biopsy in the absence of histologic signs of proliferative glomerulonephritis was observed in four patients, in the context of cellular rejection. Two patients lost their kidney graft from severe acute rejection; the others fully recovered. Patient survival was 100%, 94% and 89% at 5, 10 and 15 years, respectively. Overall, death-censored first graft survival rates were 88%, 83% and 79% at 5, 10 and 15 years, respectively. Conclusion Recurrence rate of anti-GBM glomerulonephritis after transplantation is very low, and associated with graft loss. The long-term patient and graft survival rates are excellent.

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

2020 ◽  
Vol 9 (7) ◽  
pp. 2118 ◽  
Author(s):  
Maria Irene Bellini ◽  
Aisling E Courtney ◽  
Jennifer A McCaughan
Keyword(s):  
Kidney Transplantation ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Living Donor ◽  
Patient Survival ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

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

scholarly journals P1706THE GRAFT SURVIVAL OF KIDNEY TRANSPLANTATION ACCORDING TO ETHNICITY IN KIDNEY TRANSPLANT RECIPIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yeonsoon Jung ◽  
Jisu Kim ◽  
Haesu Jeon ◽  
Ye Na Kim ◽  
Ho Sik Shin ◽  
...  
Keyword(s):  
African American ◽  
Kidney Transplantation ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Cox Regression ◽  
Patient Survival ◽  
Graft Loss ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Data Set

Abstract Background African American kidney transplant recipients experience disproportionately high rates of graft loss. The aim of this analysis was to use a UNOS data set that contains detailed baseline and longitudinal clinical data to establish and quantify the impact of the current overall graft loss definition on suppressing the true disparity magnitude in US AA kidney transplant outcomes. Methods Longitudinal cohort study of kidney transplant recipients using a data set created by United Network for Organ Sharing (UNOS), including 266,128 (African American 70,215, Non-African American 195,913) transplant patient between 1987 and December 2016. Multivariable analysis was conducted using 2-stage joint modeling of random and fixed effects of longitudinal data (linear mixed model) with time to event outcomes (Cox regression). Results 195,913 non-African American (AA) (73.6%) were compared with 70,215 AA (26.4%) recipients. 10-year-graft survival of AA in all era is lower than that of non-AA (31% in deceased kidney transplants (DKT) AA recipient and 42% in living kidney transplantation (LKT) non-AA recipient). 10-year-patient survival of AA with functioning graft in all era is similar that of non-AA. Multivariate Cox regression of factors associated with patient survival with functioning graft are acute rejection within 6 months, DM, hypertension and etc. Pre-transplant recipient BMI in AA show the trend as a protective factor in patient survival with functioning graft although not significantly in statistics Conclusions African American kidney transplant recipients experience a substantial disparity in graft loss, but not patient death with functioning graft.

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