Effect of initial immunosuppression on long-term kidney transplant outcome in immunological low-risk patients

2018 ◽  
Vol 34 (8) ◽  
pp. 1417-1422 ◽  
Author(s):  
Laura A Michielsen ◽  
Arjan D van Zuilen ◽  
Marianne C Verhaar ◽  
Bram W Wisse ◽  
Elena G Kamburova ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Human Leukocyte ◽  
Low Risk ◽  
Kidney Graft ◽  
Free Survival ◽  
Leukocyte Antigen ◽  
Single Antigen ◽  
Risk Patients

Abstract Background Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients. Methods We performed an analysis on the PROCARE cohort, a Dutch multicentre study including all transplantations performed in the Netherlands between 1995 and 2005 with available pretransplant serum (n = 4724). All sera were assessed for the presence of DSA by a luminex single-antigen bead assay. Patients with a previous kidney transplantation, pretransplant DSA or receiving induction therapy were excluded from the analysis. Results Three regimes were used in over 200 patients: cyclosporine (CsA)/prednisolone (Pred) (n = 542), CsA/mycophenolate mofetil (MMF)/Pred (n = 857) and tacrolimus (TAC)/MMF/Pred (n = 811). Covariate-adjusted analysis revealed no significant differences in 10-year death-censored graft survival between patients on TAC/MMF/Pred therapy (79%) compared with patients on CsA/MMF/Pred (82%, P = 0.88) or CsA/Pred (79%, P = 0.21). However, 1-year rejection-free survival censored for death and failure unrelated to rejection was significantly higher for TAC/MMF/Pred (81%) when compared with CsA/MMF/Pred (67%, P < 0.0001) and CsA/Pred (64%, P < 0.0001). Conclusion These results suggest that in immunological low-risk patients excellent long-term kidney graft survival can be achieved irrespective of the type of initial immunosuppressive therapy (CsA or TAC; with or without MMF), despite differences in 1-year rejection-free survival.

scholarly journals Long-term related kidney graft survival in high-risk patients after monitored donor-specific transfusion protocol

1998 ◽  
Vol 11 (s1) ◽  
pp. S110-S114 ◽  
Author(s):  
A. Padánvi ◽  
A. Horuzsko ◽  
E. Gyódi ◽  
M. Réti ◽  
F. Perner ◽  
...  
Keyword(s):  
High Risk ◽  
Graft Survival ◽  
Kidney Graft ◽  
High Risk Patients ◽  
Risk Patients ◽  
Transfusion Protocol

scholarly journals De Novo Donor-specific HLA Antibodies Reduce Graft Survival and Increase Risk of Kidney Transplant Rejection: A Single-Center Retrospective Study

2020 ◽  
Author(s):  
Wei Liu ◽  
Jie Zhao ◽  
Zhong-Yu Kang ◽  
Yan-Li Xiao ◽  
Li Yang ◽  
...  
Keyword(s):  
Graft Survival ◽  
De Novo ◽  
Transplant Rejection ◽  
Survival Rates ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Complement Dependent Cytotoxicity ◽  
Increase Risk ◽  
The Impact

Abstract Background: This study investigated the impact of posttransplantation de novo donor-specific anti-human leukocyte antigen antibodies (dnDSAs) on long-term death-censored graft survival and renal allograft rejection.Methods: This retrospective cohort study included 121 patients who received kidney transplants from deceased donors with negative complement-dependent cytotoxicity crossmatch. Based on the presence of dnDSAs, recipients were divided into dnDSA+ (n=31) and dnDSA− (n=90) groups. We evaluated the occurrence of rejection and long-term graft survival in the recipients along with pathologic changes in transplanted kidneys.Results: DnDSAs were identified in 31/121 (25.6%) patients, who had lower graft survival rates than patients without dnDSAs (P=0.007). There was no difference in graft survival rate between patients with high (≥4000) and low (<4000) DSA mean fluorescence intensity (P=0.669). The presence of dnDSA in serum was associated with a higher incidence of antigen- and T-cell–mediated rejection (P<0.0001). DnDSA+ and dnDSA− groups differed in terms of Banff score for arterial fibrointimal and arteriolar hyaline thickening (P<0.05).Conclusion: DnDSAs are associated with decreased long-term graft survival and increased rate of rejection, which is often accompanied by microcirculatory inflammation and positive C4d staining.

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 Long-term survival of the transplanted kidney and the clinical relevance of donor-specific antibodies

2020 ◽  
Vol 3 (1) ◽  
pp. 17-22
Author(s):  
Eva Svobodova ◽  
Sarka Valhova ◽  
Ondrej Viklicky ◽  
Ilja Striz ◽  
Jelena Skibova ◽  
...  
Keyword(s):  
Graft Survival ◽  
Solid Phase ◽  
Kidney Graft ◽  
Term Survival ◽  
Specific Antibodies ◽  
Antibody Mediated Rejection ◽  
Number Of Patients ◽  
Single Antigen ◽  
Donor Specific Antibodies

The aim of our study was to evaluate the relevance of donor-specific antibodies (DSA) as defined by solid-phase single-antigen (SA) assays for predicting long-term graft survival after kidney transplantation. Sera from 132 kidney transplant recipients were retrospectively tested before, 3, 6 and 12 months after transplantation. The incidence of rejection and graft survival was followed up for 7 years. We found 29 episodes of acute cellular rejection (CR), 21 cases of antibody-mediated rejection (AMR) and 18 graft failures due to immunological reasons. Pre-transplant DSA and DSA three months after transplantation correlated with an increased rate of AMR and impaired graft function. After the fourth year, recipients with persistent DSA were at a higher risk of graft failure (p = 0.0317). Antibody specificity was prevailingly to HLA class I antigens (66.6% DSA, 75% non-DSA). During the first year after transplantation, the number of patients with non-DSA decreased (30.3% to 10.7%), while, due to de novo production of antibodies, the number of DSA positive patients remained constant. Conclusion: Detection of antibodies to HLA antigens using solid-phase assays, especially single-antigen bead technology before and three months after transplantation is predictive for increased incidence of antibody-mediated rejection and impaired long-term kidney graft survival.

scholarly journals FO048EFFECT OF INITIAL IMMUNOSUPPRESSION ON LONG TERM KIDNEY TRANSPLANT OUTCOME IN IMMUNOLOGICAL LOW RISK PATIENTS

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i39-i39 ◽  
Author(s):  
Laura Michielsen ◽  
Arjan van Zuilen ◽  
Bram Wisse ◽  
Marianne Verhaar ◽  
Elena Kamburova ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Low Risk ◽  
Transplant Outcome ◽  
Risk Patients
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