scholarly journals A Prospective Controlled Trial to Evaluate Safety and Efficacy of in vitro Expanded Recipient Regulatory T Cell Therapy and Tocilizumab Together With Donor Bone Marrow Infusion in HLA-Mismatched Living Donor Kidney Transplant Recipients (Trex001)

2021 ◽  
Vol 7 ◽  
Author(s):  
Rainer Oberbauer ◽  
Matthias Edinger ◽  
Gabriela Berlakovich ◽  
Peter Kalhs ◽  
Nina Worel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kidney Transplant ◽  
Graft Function ◽  
Control Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Donor Bone Marrow ◽  
Living Donor Kidney Transplant

Background: The induction of donor-specific immunological tolerance could improve outcome after kidney transplantation. However, no tolerance protocol is available for routine clinical use. Chimerism-based regimens hold promise, but their widespread application is impeded in part by unresolved safety issues. This study tests the hypothesis that therapy with polyclonal recipient regulatory T cells (Tregs) and anti-IL6R (tocilizumab) leads to transient chimerism and achieves pro-tolerogenic immunomodulation in kidney transplant recipients also receiving donor bone marrow (BM) without myelosuppressive conditioning of the recipient.Methods/design: A prospective, open-label, controlled, single-center, phase I/IIa academic study is performed in HLA-mismatched living donor kidney transplant recipients.Study group: Recipients of the study group receive in vitro expanded recipient Tregs and a donor bone marrow cell infusion within 3 days after transplantation and tocilizumab for the first 3 weeks post-transplant. In addition they are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Starting 6 months post-transplant, sirolimus and steroids are withdrawn in a step-wise manner in stable patients.Control group: Recipients of the control group are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Co-primary endpoints of safety (impaired graft function [eGFR <35 mL/min/1.73 m2], graft-vs.-host disease or patient death by 12 months) and efficacy (total leukocyte donor chimerism within 28 days post-transplant) are assessed. Secondary endpoints include frequency of biopsy-proven acute rejection episodes and subclinical rejection episodes on surveillance biopsies, assessment of kidney graft function, and the evaluation whether the study protocol leads to detectable changes in the immune system indicative of pro-tolerogenic immune modulation.Discussion: The results of this trial will provide evidence whether treatment with recipient Tregs and donor BM is feasible, safe and efficacious in leading to transient chimerism. If successful, this combination cell therapy has the potential to become a novel treatment option for immunomodulation in organ transplantation without the toxicities associated with myelosuppressive recipient conditioning.Trial registration: European Clinical Trials Database EudraCT Nr 2018-003142-16 and clinicaltrials.gov NCT03867617.

scholarly journals Indicators of monocyte-derived component of the immune system in patients with satisfactory renal graft function

2020 ◽  
Vol 22 (2) ◽  
pp. 53-62
Author(s):  
S. V. Zybleva ◽  
S. L. Zyblev
Keyword(s):  
Kidney Transplant ◽  
Negative Correlation ◽  
Graft Function ◽  
Control Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Long Term Follow Up

Objective: to study the indicators of the monocyte-derived component of the immune system in kidney transplant recipients with satisfactory early and delayed renal transplant function. Materials and methods. The study involved 76 kidney transplant recipients. Concentrations of serum creatinine (sCr), serum urea (sUr) and serum cystatin C (sCysC) were measured. CD14+mid/high and CD14+low were isolated from CD14+ monocytes. CD64- and CD86-expressing cell counts were determined for each subpopulation. Immunological examination was performed before surgery, as well as at days 1, 3, 7, 30, 90, 180 and 360 after surgery. Results. There was significant imbalance between the two monocyte subpopulations before transplantation and in the early post-transplant period (first 3 months). By the end of a 6-month follow-up period, the percentage of CD14+ cells had normalized. The dynamics of the subclasses of CD86-expressing monocytes in the post-transplant period is somewhat different from the dynamics of the total count for these monocytes. However, by the end of a 6-month follow-up period, these biomarkers returned to normal for the group of healthy individuals (CD14+mid/highCD86+ p180 = 0.079; CD14+lowCD86+ p180 = 0.789). CD14+lowCD64+ level was significantly higher in the kidney transplant group than in the control group during the entire follow-up period (p0 = 0.0006, p1 = 0.0001, p7 = 0.005, p30 = 0.005, p90 = 0.007, p180 = 0.0002, p360 = 0.001). On the other hand, CD14+mid/highCD64+ count for up to 180 days was not significantly different from that of the control group (p0 = 0.561, p1 = 0.632, p7 = 0.874, p30 = 0.926, p90 = 0.912), with subsequent significant increase by day 360 of follow-up (p180 = 0.01, p360 = 0.003). We observed a negative correlation between CD14+lowCD86+ level at day 0 and sCr levels at day 7 (r = –0.4; p = 0.008) and day 360 (r = –0.34; p = 0.042) and sCysC level at day 7 (r = –0.57; p = 0.014). A negative correlation was also found between CD14+lowCD86+ at day 1 and sCr levels at day 7 (r = –0.4; p = 0.005) and day 360 (r = –0.39; p = 0.02). There was positive correlation between the CD14+lowCD64+ subpopulation index at day 0 and sCr (r = 0.54; p = 0.008) and sCysC (r = 0.6; p = 0.008) levels at day 7, and also between the CD14+lowCD64+ count at day 1 and sCr (r = 0.55; p < 0.0001) and sCysC (r = 0.58; p = 0.004) levels at day 7. CD14+mid/highCD64+ at day 0 negatively correlated with sCysC level at day 360 (r = –0.85; p = 0.015), while CD14+mid/highCD64+ at day 7 positively correlated with sCysC level at day 360 (r = 0.50; p = 0.016). Conclusion. Before transplant surgery, CD14+mid/high, CD14+mid/highCD86+ , and CD14+lowCD86+ counts were reduced, while those of CD14+low, CD14+mid/highCD64+ and CD14+lowCD64+ were increased. By the 6-month follow-up, all these subpopulations except CD14+mid/highCD64+ had reached values for healthy people. Positive correlation between CD14+mid/high, CD14+lowCD64+ , CD14+mid/highCD86+ , CD14+mid/highCD64+ counts in the early post-transplant period and sCr/sCysC levels in long-term follow-up, as well as negative correlation between CD14+low, CD14+lowCD86+ counts in the early post-transplant period and sCr/sCysC levels in long-term follow-up can serve as a predictor of renal graft function.

scholarly journals Associations of pre-transplant anemia management with post-transplant delayed graft function in kidney transplant recipients

2012 ◽  
Vol 26 (5) ◽  
pp. 782-791 ◽  
Author(s):  
Miklos Z. Molnar ◽  
Csaba P. Kovesdy ◽  
Laszlo Rosivall ◽  
Suphamai Bunnapradist ◽  
Junichi Hoshino ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Anemia Management

scholarly journals Graft Function, Albuminuria, and the Risk of Hemorrhage and Thrombosis After Kidney Transplantation

2020 ◽  
Vol 7 ◽  
pp. 205435812095219
Author(s):  
Rachel Jeong ◽  
Robert R. Quinn ◽  
Pietro Ravani ◽  
Feng Ye ◽  
Manish M. Sood ◽  
...  
Keyword(s):  
Cohort Study ◽  
Venous Thrombosis ◽  
Kidney Transplant ◽  
Graft Function ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Increased Risk ◽  
Lower Egfr ◽  
Risk Of Hemorrhage

Background: Compared to the general population, kidney transplant recipients are at increased risk of hemorrhage and thrombosis. Whether this risk is affected by graft function and albuminuria is unknown. Objective: To determine the association between graft function and albuminuria and the risk of post-transplant hemorrhage and thrombosis. Design: Retrospective cohort study. Setting: We used linked health care databases in Alberta, Canada. Patients/sample/participants: We included adult kidney transplant recipients from 2002 to 2015 with a functioning graft at 1 year. Measurements: Estimated glomerular filtration rate (eGFR) and albuminuria measurements at 1 year post-transplant were used to categorize recipients (eGFR: ≥45 vs. <45 mL/min/1.73 m2; albuminuria: absence vs. presence). We determined the rates of post-transplant hemorrhage and venous thrombosis based on validated diagnostic and procedural codes. Methods: We determined the association between categories of eGFR and albuminuria and post-transplant hemorrhage and venous thrombosis using Poisson regression with log link. Results: Of 1284 kidney transplant recipients, 21% had an eGFR <45 mL/min/1.73 m2 and 40% had presence of albuminuria at 1 year post-transplant. Over a median follow-up of 6 years, there were 100 hemorrhages (12.6 events per 1000 person-years) and 57 venous thrombosis events (7.1 events per 1000 person-years). The age- and sex-adjusted rate of hemorrhage and thrombosis was over 2-fold higher in recipients with lower eGFR and presence of albuminuria compared to higher eGFR and no albuminuria (hemorrhage: incidence rate ratio, IRR, 2.6, 95% confidence interval [CI]: 1.5-4.4, P = .001; thrombosis: IRR, 2.3, 95% CI: 1.1-5.0, P = .046). Limitations: Complete relevant medication information, such as anticoagulants, were not available in our datasets. Due to sample size, this study was underpowered to conduct a fully adjusted analysis. Conclusion: Among kidney transplant recipients, lower eGFR and presence of albuminuria at 1 year post-transplant were associated with an over 2-fold higher risk of hemorrhage and venous thrombosis. Graft function and albuminuria at 1 year post-transplant are important prognostic factors in determining risk of post-transplant hemorrhage and venous thrombosis. Further research, including medication data, are needed to further delineate outcomes and safety. Trial registration: Not applicable (cohort study).

scholarly journals Early Acute Microvascular Kidney Transplant Rejection in the Absence of Anti-HLA Antibodies Is Associated with Preformed IgG Antibodies against Diverse Glomerular Endothelial Cell Antigens

2019 ◽  
Vol 30 (4) ◽  
pp. 692-709 ◽  
Author(s):  
Marianne Delville ◽  
Baptiste Lamarthée ◽  
Sylvain Pagie ◽  
Sarah B. See ◽  
Marion Rabant ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Kidney Transplant ◽  
Hla Antigens ◽  
Control Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Serum Samples ◽  
Hla Antibodies

BackgroundAlthough anti-HLA antibodies (Abs) cause most antibody-mediated rejections of renal allografts, non-anti–HLA Abs have also been postulated to contribute. A better understanding of such Abs in rejection is needed.MethodsWe conducted a nationwide study to identify kidney transplant recipients without anti-HLA donor-specific Abs who experienced acute graft dysfunction within 3 months after transplantation and showed evidence of microvascular injury, called acute microvascular rejection (AMVR). We developed a crossmatch assay to assess serum reactivity to human microvascular endothelial cells, and used a combination of transcriptomic and proteomic approaches to identify non-HLA Abs.ResultsWe identified a highly selected cohort of 38 patients with early acute AMVR. Biopsy specimens revealed intense microvascular inflammation and the presence of vasculitis (in 60.5%), interstitial hemorrhages (31.6%), or thrombotic microangiopathy (15.8%). Serum samples collected at the time of transplant showed that previously proposed anti–endothelial cell Abs—angiotensin type 1 receptor (AT1R), endothelin-1 type A and natural polyreactive Abs—did not increase significantly among patients with AMVR compared with a control group of stable kidney transplant recipients. However, 26% of the tested AMVR samples were positive for AT1R Abs when a threshold of 10 IU/ml was used. The crossmatch assay identified a common IgG response that was specifically directed against constitutively expressed antigens of microvascular glomerular cells in patients with AMVR. Transcriptomic and proteomic analyses identified new targets of non-HLA Abs, with little redundancy among individuals.ConclusionsOur findings indicate that preformed IgG Abs targeting non-HLA antigens expressed on glomerular endothelial cells are associated with early AMVR, and that in vitro cell-based assays are needed to improve risk assessments before transplant.

Perioperative donor bone marrow infusion in cadaver kidney transplant recipients

2001 ◽  
Vol 33 (7-8) ◽  
pp. 3840-3843 ◽  
Author(s):  
R.O. Garcia-Morales ◽  
G. Ciancio ◽  
J. Mathew ◽  
Y. Jin ◽  
A. Rosen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Donor Bone Marrow ◽  
Cadaver Kidney ◽  
Marrow Infusion ◽  
Bone Marrow Infusion

scholarly journals The Possible Role of Early Post-Transplant Inflammation in Later Anemia in Kidney Transplant Recipients

2009 ◽  
Vol 9 (4) ◽  
pp. 307-312 ◽  
Author(s):  
Goran Imamović ◽  
Enver Zerem ◽  
Safet Omerović ◽  
Enes Osmanović ◽  
Emir Hodžić
Keyword(s):  
Kidney Transplant ◽  
White Blood Cells ◽  
Graft Function ◽  
Kidney Graft ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Inflammatory State ◽  
Wbc Count ◽  
Clinical Records

Delayed kidney graft function and acute rejection in the early post-transplant period affect both short and long-term allograft survival. Allograft rejection, as an inflammatory state, results in increased eryth-ropoietin resistance, which leads to decreased haemoglobin (Hb) level. We conducted this study to evaluate whether inflammation in the early post-transplant period could predict later anemia.This is a retrospective cohort study based on the analysis of 64 existing clinical records. Predictor. White blood cells (WBC) count obtained by the end of the first week post-transplant (W1). Covariates. Donor’s age, recipient’s age and sex. Outcome. Anemia identified at 12 months (M12) post engraftment.Median WBC count at W1 was 9,5 x103^L (5th - 95th percentile 5,2 x103^L -17,8 x 103/μΚ). Mean Hb values at M12 were 129,9 ± 20,3 g/L, in males 136,2 ± 20,1 g/L and in females 119,4 ± 16,2 g/L. The significant correlation was found between WBC at W1 and Hb at M12. Pearson coefficient of correlation r was -0,26, and 95% confidence interval (CI) for r was -0,47 to -0,015 (p=0,03). Univariate logistic regression showed significant association between WBC at W1 and Hb at M12 (OR 1,20; 95% CI 1,04 to 1,39, p=0,01). After the adjustment for donor’s and recipient’s age by transplantation and recipient’s sex, multiple regression showed that WBC count remained predictive of anemia at M12 (OR 1,17; 95% CI 1,01 to 1,36, p=0,03).Early post-transplant inflammatory response predicts later anemia in kidney transplant recipients. An increase in WBC count in the first week post-transplant by 109/L increases the risk for anemia after twelve months by 17%.

Sign in / Sign up

Export Citation Format

Share Document