scholarly journals Combined Immunotherapy With Belatacept and BTLA Overexpression Attenuates Acute Rejection Following Kidney Transplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Hengcheng Zhang ◽  
Zijie Wang ◽  
Jiayi Zhang ◽  
Zeping Gui ◽  
Zhijian Han ◽  
...  
Keyword(s):  
Immune Response ◽  
Kidney Transplantation ◽  
Acute Rejection ◽  
Serum Creatinine ◽  
Graft Survival ◽  
Rat Kidney ◽  
Combined Therapy ◽  
Graft Function ◽  
Kidney Graft ◽  
Term Survival

BackgroundCostimulatory blockade provides new therapeutic opportunities for ensuring the long-term survival of kidney grafts. The adoption of the novel immunosuppressant Belatacept has been limited, partly due to concerns regarding higher rates and grades of acute rejection in clinical trials. In this study, we hypothesized that a combined therapy, Belatacept combined with BTLA overexpression, may effectively attenuate acute rejection after kidney transplantation.Materials and MethodsThe rat kidney transplantation model was used to investigate graft rejection in single and combined therapy. Graft function was analyzed by detecting serum creatinine. Pathological staining was used to observe histological changes in grafts. The expression of T cells was observed by immunohistochemistry and flow cytometry. In vitro, we constructed an antigen-stimulated immune response by mixed lymphocyte culture, treated with or without Belatacept and BTLA-overexpression adenovirus, to observe the proliferation of receptor cells and the expression of cytokines. In addition, western blot and qRT-PCR analyses were performed to evaluate the expression of CTLA-4 and BTLA at various time points during the immune response.ResultsIn rat models, combined therapy reduced the serum creatinine levels and prolonged graft survival compared to single therapy and control groups. Mixed acute rejection was shown in the allogeneic group and inhibited by combination treatment. Belatacept reduced the production of DSA and the deposition of C4d in grafts. Belatacept combined with BTLA overexpression downregulated the secretion of IL-2 and IFN-γ, as well as increasing IL-4 and IL-10 expression. We also found that Belatacept combined with BTLA overexpression inhibited the proliferation of spleen lymphocytes. The duration of the elevated expression levels of CTLA-4 and BTLA differentially affected the immune response.ConclusionBelatacept combined with BTLA overexpression attenuated acute rejection after kidney transplantation and prolonged kidney graft survival, which suggests a new approach for the optimization of early immunosuppression after kidney transplantation.

scholarly journals Ameliorating Metabolic Profiles After Kidney Transplantation: A Protocol for an Open-Label, Prospective, Randomized, 3-Arm, Controlled Trial

2021 ◽  
Vol 8 ◽  
Author(s):  
Saifu Yin ◽  
Ming Ma ◽  
Zhongli Huang ◽  
Yu Fan ◽  
Xianding Wang ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Controlled Trial ◽  
Subcutaneous Fat ◽  
Graft Function ◽  
Metabolic Profiles ◽  
Kidney Graft ◽  
Kidney Transplant Recipients ◽  
Open Label ◽  
Term Survival ◽  
Inflammatory Parameters

Aim: High prevalence of metabolic disorders causes higher risk of cardiovascular diseases after kidney transplantation (KT), which remains the main burden impairing short-term and long-term survival. This open-label, prospective, randomized, 3-arm, controlled trial will evaluate the safety, tolerability and efficacy of metformin and empagliflozin in ameliorating metabolic profiles after KT.Methods: After a screening assessment, eligible patients with an estimated glomerular filtration rate (eGFR) >45 mL/min/1.73m2 are randomly assigned to standard triple immunosuppression alone, standard immunosuppression plus metformin (500 mg twice daily), standard immunosuppression plus empagliflozin (25 mg once daily) from discharge. The primary endpoint is the differences in the visceral-to-subcutaneous fat area ratio over 12 months, evaluated by magnetic resonance imaging (MRI). Secondary outcomes include kidney graft function, glycometabolism, lipid metabolism, and inflammatory parameters. The trial will enroll 105 kidney transplant recipients, providing 90% power to detect the difference at 5% significance.

scholarly journals BELATACEPT COMBINED WITH BTLA PROLONG ALLOGENEIC KIDNEY GRAFT SURVIVAL AND INHIBITED ACUTE REJECTION AFTER KIDNEY TRANSPLANTATION

2020 ◽  
Vol 104 (S3) ◽  
pp. S342-S342
Author(s):  
Hengcheng Zhang ◽  
Hao Chen ◽  
Li Sun ◽  
Zijie Wang ◽  
Zhijian Han ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Graft Survival ◽  
Kidney Graft

scholarly journals The Value of Graft Implantation Sequence in Simultaneous Pancreas-Kidney Transplantation on the Outcome and Graft Survival

2021 ◽  
Vol 10 (8) ◽  
pp. 1632
Author(s):  
Hans-Michael Hau ◽  
Nora Jahn ◽  
Sebastian Rademacher ◽  
Elisabeth Sucher ◽  
Jonas Babel ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Graft Survival ◽  
Graft Function ◽  
Kidney Graft ◽  
Significant Difference ◽  
Pancreas Kidney Transplantation ◽  
Simultaneous Pancreas Kidney ◽  
Graft Implantation ◽  
Simultaneous Pancreas Kidney Transplantation ◽  
Pancreas Graft

Background/Objectives: The sequence of graft implantation in simultaneous pancreas-kidney transplantation (SPKT) warrants additional study and more targeted focus, since little is known about the short- and long-term effects on the outcome and graft survival after transplantation. Material and methods: 103 patients receiving SPKT in our department between 1999 and 2015 were included in the study. Patients were divided according to the sequence of graft implantation into pancreas-first (PF, n = 61) and kidney-first (KF, n = 42) groups. Clinicopathological characteristics, outcome and survival were reviewed retrospectively. Results: Donor and recipient characteristics were similar. Rates of post-operative complications and graft dysfunction were significantly higher in the PF group compared with the KF group (episodes of acute rejection within the first year after SPKT: 11 (18%) versus 2 (4.8%); graft pancreatitis: 18 (18%) versus 2 (4.8%), p = 0.04; vascular thrombosis of the pancreas: 9 (14.8%) versus 1 (2.4%), p = 0.03; and delayed graft function of the kidney: 12 (19.6%) versus 2 (4.8%), p = 0.019). The three-month pancreas graft survival was significantly higher in the KF group (PF: 77% versus KF: 92.1%; p = 0.037). No significant difference was observed in pancreas graft survival five years after transplantation (PF: 71.6% versus KF: 84.8%; p = 0.104). Kidney graft survival was similar between the two groups. Multivariate analysis revealed order of graft implantation as an independent prognostic factor for graft survival three months after SPKT (HR 2.6, 1.3–17.1, p = 0.026) and five years (HR 3.7, 2.1–23.4, p = 0.040). Conclusion: Our data indicates that implantation of the pancreas prior to the kidney during SPKT has an influence especially on the early-post-operative outcome and survival rate of pancreas grafts.

scholarly journals Clinical features of BK-polyomavirus and cytomegalovirus co-infection after kidney transplantation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ulrich Jehn ◽  
Katharina Schütte-Nütgen ◽  
Joachim Bautz ◽  
Hermann Pavenstädt ◽  
Barbara Suwelack ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Multivariable Analysis ◽  
Graft Function ◽  
Single Infection ◽  
Kidney Graft ◽  
Viral Pathogens ◽  
Bk Polyomavirus ◽  
Allograft Function ◽  
Cmv Dnaemia

AbstractBK polyomavirus (BKPyV) and cytomegalovirus (CMV) are the main viral pathogens affecting the graft and recipient outcome after allogenic kidney transplantation. It has recently been found that infection with both viruses has a greater impact on kidney graft function than a single infection. We retrospectively analyzed a cohort of 723 recipients who received kidney transplantation between 2007 and 2015 after living and postmortal donation for differences in risk and outcome parameters regarding BKPyV (DNAemia) and CMV (CMV DNAemia) co-infection compared to sole viremias and to patients without viremia. Of all kidney allograft recipients in our cohort, 8.2% developed co-infection with BKPyV DNAemia and CMV DNAemia, 15.1% showed BKPyV viremia alone and 25.2% sole CMV DNAemia. Acute rejection was closely linked with co-infection (multivariable analysis, p = 0.001). Despite the fact that the estimated glomerular filtration rate of patients with co-infection was noticeably reduced compared to patients with BKV or CMV infection alone, transplant survival and patient survival were not significantly reduced. Co-infection with BKPyV and CMV in kidney transplanted patients is significantly associated with inferior allograft function. Since co-infection is strongly associated with acute rejection, co-infected individuals should be considered a risk collective.

scholarly journals Day-Time Declamping Is Associated with Better Outcomes in Kidney Transplantation: The Circarein Study

2021 ◽  
Vol 10 (11) ◽  
pp. 2322
Author(s):  
David Montaigne ◽  
Nasser Alhawajri ◽  
Mathilde Jacquelinet ◽  
Amandine Coppin ◽  
Marie Frimat ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Ischemia Reperfusion ◽  
Multivariable Analysis ◽  
Graft Function ◽  
Kidney Graft ◽  
Cold Ischemia ◽  
Night Time ◽  
Term Survival ◽  
Transplant Survival ◽  
Post Transplant

Despite improvements in organ preservation techniques and efforts to minimize the duration of cold ischemia, ischemia–reperfusion (IR) injury remains associated with poor graft function and long-term survival in kidney transplantation. We recently demonstrated a clinically significant day-time variation in myocardial tolerance to IR, transcriptionally orchestrated by the circadian clock. Patient and graft post-transplant survival were studied in a cohort of 10,291 patients first transplanted between 2006 and 2017 to test whether kidney graft tolerance to IR depends on the time-of-the-day of clamping/declamping, and thus impacts graft and patient survival. Post-transplant 1- and 3-year survival decreased with increasing ischemia duration. Time-of-the-day of clamping did not influence outcomes. However, night-time (vs. day-time) declamping was associated with a significantly worse post-transplant survival. After adjustment for other predictors, night-time (vs. day-time) declamping remained associated with a worse 1-year (HR= 1.26 (1.08–1.47), p = 0.0028 by Cox multivariable analysis) and 3-year (HR= 1.14 (1.02–1.27), p = 0.021) outcome. Interestingly, the deleterious impact of prolonged ischemia time (>15 h) was partially compensated by day-time (vs. night-time) declamping. Compared to night-time declamping, day-time declamping was associated with a better prognosis of kidney transplantation despite a longer duration of cold ischemia.

scholarly journals A Comparison of Allograft Survival Between Cyclosporine and Tacrolimus Based Immunosuppressive Therapy in Kidney Transplantation: BIRDEM General Hospital Experience

2016 ◽  
Vol 5 (2) ◽  
pp. 78-81
Author(s):  
Palash Mitra ◽  
Md Anisur Rahman ◽  
Muhammad Abdur Rahim ◽  
Mehruba Alam Ananna ◽  
Tasrina Shamnaz Samdani ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Serum Creatinine ◽  
Immunosuppressive Therapy ◽  
Graft Survival ◽  
Graft Function ◽  
Calcineurin Inhibitors ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Group 2 ◽  
Group 1

Introduction and Aims: Calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, are one of the three major components of basic immunosuppressive therapy of kidney transplantation. Our aims were to study and compare the early and long-term graft survival in kidney transplant recipients who were receiving either of these two CNIs.Methods: A questionnaire was formed and data were collected from the hospital records. We divided the patients in group 1 (patients on cyclosporine) and group 2 (patients on tacrolimus). We retrospectively evaluated patients’ clinical and laboratory findings.Results: Group 1 included 50 patients who were on cyclosporine and group 2 included 61 patients who were on tacrolimus. Patients receiving tacrolimus showed almost similar renal function as cyclosporine receiving patients; serum creatinine was 1.27 ± 0.56 versus 1.42 ± 0.91mg/dL (p = 0.258), but they required less time for serum creatinine to become normal (4.71 ± 2.3 versus 7.26 ± 5.6 days, p=0.001) and less duration of post-transplant hospital stay (11.38 ± 3.33 versus 13.65 ± 5.0 days, p = 0.005). New onset diabetes was more pronounced in group 2 (29.5% versus 12 %, p = 0.025). On the other hand, acute rejection was only noted in group 1 (2 versus 0, p = 0.014). One-year and three-year graft survival for cyclosporine was 92.0% and 83.3%, and for tacrolimus was 96.2% and 89.2% respectively.Conclusions: Tacrolimus is relatively favourable to cyclosporine in preventing acute allograft rejection and better immediate post-transplant graft function recovery.Birdem Med J 2015; 5(2): 78-81

Plasmapheresis in HLA-Immunosensitized Patients Prior to Kidney Transplantation

1997 ◽  
Vol 20 (1) ◽  
pp. 51-56 ◽  
Author(s):  
A. Alarabi ◽  
U. Backman ◽  
B. Wikström ◽  
O. Sjöberg ◽  
G. Tufveson
Keyword(s):  
Kidney Transplantation ◽  
Retrospective Study ◽  
Serum Creatinine ◽  
Graft Survival ◽  
Human Lymphocyte ◽  
Immunosuppressive Drugs ◽  
Chronic Hemodialysis ◽  
Kidney Graft ◽  
Hla Antibodies

Immunosensitization against the human lymphocyte antigen (HLA) is a problem in most transplant centers. It prolongs the waiting list time in addition to risk of frequent acute rejections. To avoid these problems, various pretransplantation approaches have been attempted e.g. plasmapheresis (PP). The present retrospective study reports our experience with PP in this respect over a 5 year period. Twenty-three chronic hemodialysis patiens with circulating panel reactive antibodies (≥ 50%) and previous kidney graft rejections were treated with 12 PP each. In addition to this, immunosuppression with cyclophosphamide and prednisolone were administered on the first day of PP and after tapering continued until transplantation. HLA-antibodies, as measured by the panel reactive antibodies and the antibody titer, decreased. from about 70% to 30% (p<0.001) and 5 steps of titerdilution, respectively with PP and immunosuppressive drugs; Twenty-two patients were transplanted with cadaveric grafts. Eight grafts were lost due to irreversible rejection, and one due to the patient's death 2 months after transplantation. The cumulative five-year graft survival at the time of follow-up was 59%. Adequate kidney function (serum creatinine mean 150 μmol/l) was observed in all grafts (n=3) still functioning 60 months posttraplant. We conclude that prestransplantation plasmapheresis together with immunosuppressive drugs (cyclophosphamide and prednisolone) is useful in the removal of HLA antibodies in immunized patients awaiting kidney transplantation. It can be considered a valuable approach to increase the chances of successful transplantations.

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