scholarly journals The Effect of Induction Therapy on Established CMV Specific T Cell Immunity in Living Donor Kidney Transplantation

2018 ◽  
pp. 251-260 ◽  
Author(s):  
L. STRANAVOVA ◽  
P. HRUBA ◽  
E. GIRMANOVA ◽  
I. TYCOVA ◽  
A. SLAVCEV ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
T Cell ◽  
Living Donor ◽  
T Cell Immunity ◽  
Transplant Recipients ◽  
Donor Kidney ◽  
Cell Immunity ◽  
Dialysis Vintage ◽  
Cmv Prophylaxis ◽  
Living Donor Kidney

Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation. Recipients’ peripheral blood mononuclear cells were stimulated with immediate-early (IE1) and phosphoprotein 65 (pp65) CMV-derived peptide pools and the number of cells producing interferon gamma (IFN-γ) was assessed. Patients received quadruple immunosuppression based either on depletive rabbit antithymocyte globulin (rATG) or non-depletive basiliximab induction and tacrolimus/mycophenolate mofetil/steroids. Patients with rATG induction received valgancyclovir prophylaxis. No effects of different induction agents on CMV specific T cell immunity were found at sixth month after kidney transplantation. There were no associations among dialysis vintage, pretransplant CMV specific T cell immunity, and later CMV DNAemia. Similarly, no effect of CMV prophylaxis on CMV specific T cell immunity was revealed. This study shows no effect of posttransplant immunosuppression on CMV specific T cell immunity in living donor kidney transplant recipients with CMV immunity already established, regardless of lymphocyte depletion and CMV prophylaxis.

scholarly journals Immune Reconstitution in Recipients of Living Donor Kidney/Hematopoietic Stem + Facilitating Cell Transplants

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 191-191
Author(s):  
Joseph R. Leventhal ◽  
Mary J Elliott ◽  
Esma S. Yolcu ◽  
Larry D. Bozulic ◽  
David J Tollerud ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cell ◽  
Living Donor ◽  
Immune Reconstitution ◽  
Transplant Recipients ◽  
Donor Kidney ◽  
Hematopoietic Stem ◽  
Protocol Biopsy ◽  
Donor Chimerism ◽  
Living Donor Kidney

Abstract Solid organ transplant recipients generally require life-long immunosuppressive agents to maintain graft acceptance. This is associated with a number of toxicities, including renal dysfunction, metabolic abnormalities, opportunistic infection and malignancies. Calcineurin inhibitors, the most frequently used agents for immunosuppression, induce nephrotoxicity, with gradual renal decline in many transplant recipients. As a result, approaches to induce tolerance remain a major focus of research. We report here the long-term results from a reduced-intensity nonmyeloablative conditioning approach to establish high levels of donor chimerism without graft-versus-host disease (GVHD) or engraftment syndrome in mismatched related and unrelated recipients of combined living donor kidney/hematopoietic stem cell transplant (HSCT). Recipients were conditioned with 200 cGy total body irradiation plus fludarabine (30 mg/kg day -5, -4, -3) and cyclophosphamide (50 mg/kg days -3 and +3) and administered donor granulocyte colony-stimulating factor mobilized stem cells, enriched for hematopoietic stem cells (HSC) and graft facilitating cells (FCs) and depleted of GVHD-producing cells (FCRx). Subjects ranged in age from 18 to 65 years. All subjects were HLA-disparate from their living kidney/HSCT donors, ranging from 5 of 6 related to 0 of 6 unrelated. Eight were unrelated and 11 related to their donors. Subjects were maintained on tacrolimus and mycophenolate mofetil (MMF) for 6 months. At 6 months, if protocol biopsy is normal and chimerism present, the MMF is discontinued. Similarly, the tacrolimus is discontinued at 12 months if stable renal function, normal protocol biopsy and chimerism are present. 30 subjects have been enrolled and 25 transplanted. Nineteen subjects have > 1 year follow up. Twelve have achieved stable donor chimerism and have been successfully taken off immunosuppression. Time off IS ranges from 8 months to 48 months. None have developed GVHD. We have herein prospectively evaluated immune reconstitution and immunocompetence. Return of CD4+ and CD8+ T central and effector memory cell populations was rapid. Examination for recent thymic emigrants (T cell staining for CD31+ CDRA+, TCR excision circle analysis) indicated that the majority (>97%) of these chimeric cells are being produced de novo. The TCR repertoires post-transplant in chimeric subjects were as diverse as pre-transplant donors and recipients but were distinct from donor or recipient pre-transplant. An increase in the CD4+ regulatory T cell/CD4+ effector T cell ratio was seen early in durably and transiently chimeric patients, suggesting active immunoregulation. Patients have been successfully vaccinated per American Society of Bone and Marrow Transplantation guidelines without loss of chimerism or development of allograft rejection. Of four subjects immunized for hepatitis B and whose donors were not, three retained immunologic memory after transplantation. Most chimeric subjects retained memory for measles, mumps, rubella and varicella. Chimeric subjects generated immune responses to pneumococcal vaccine. Opportunistic viral infections such as BK viremia and cytomegalovirus activation were absent after cessation of immunosuppression. These findings suggest that immunologic recovery is robust in chimeric subjects who receive kidney/FCRx and that durable chimerism is associated with donor-specific tolerance to renal allografts. Disclosures Bozulic: Regenerex, LLC: Employment. Tollerud:Regenerex, LLC: Chief Operating Officer Other. Ildstad:Regenerex, LLC: Chief Executive Officer Other.

P1647CHANGES IN CAUSES OF EARLY GRAFT LOSS IN LIVING DONOR KIDNEY TRANSPLANT RECIPIENTS, 1972-2018

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kenta Futamura ◽  
Goto Norihiko ◽  
Hiroki Fukuhara ◽  
Takaaki Nawano ◽  
Akiko Kanda ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Living Donor ◽  
Graft Loss ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Donor Kidney ◽  
Donor Kidney Transplantation ◽  
Living Donor Kidney Transplant ◽  
Living Donor Kidney

Abstract Background and Aims In living donor kidney transplantation, the progress of immunosuppressants in recent decades has led to an average graft survival period more than 15 years. However, the rate of graft loss (GL) within 5 years is still about 5%. Since the incidence of early GL is low, clinical evidence of causes and risk factors are limited and it remains unclear whether early GL was predictable before transplantation. Our purposes were to characterize a patient population with GL, to identify risk factors associated with early (<5 years) GL. Method The subjects were 1,779 patients who underwent living donor kidney transplantation at Japanese Red Cross Nagoya Daini hospital and Masuko Memorial Hospital from January 1, 1972 to December 31, 2018 (former group (1972-1999) : 503, latter group (2000-2018) : 1,276). We retrospectively examined patient characteristics, timing and causes of GL in 445 cases with GL by December 31, 2019 (GL cases in former group : 335, GL cases in latter group : 110). Results The 5- and 10-year graft survival rates were on an increasing trend, with 74.7% and 58.3% in former group and 95.2% and 88.7% in latter group, respectively. In latter group, T cell-mediated rejection and recurrence of primary diseases were significantly more frequent in GL cases within 5 years after transplantation than over 5 years (10% vs 0%, p=0.02 and 6% vs 0%, p=0.04). Although not significant, GL due to antibody-mediated rejection tended to more frequent in over 5 years after transplantation (22% vs 45%). Compared the causes of GL within 5 years after transplantation between GL cases in former group and latter group, rate of allograft rejection significantly reduced (88％ vs 44%, p<0.001), and infections (especially BK polyomavirus infection), medication nonadherence and recurrence of primary diseases tended to increase (0%, 4% and 3% vs 8%, 16% and 8%, respectively). Conclusion Our analysis suggests that management of infections, medication nonadherence and recurrence of primary diseases have become more important for living donor kidney transplant recipients in recent years with improved immunosuppressants.

Impact of ABO-Incompatible Living Donor Kidney Transplantation on Patient Survival

2020 ◽  
Vol 76 (5) ◽  
pp. 616-623 ◽  
Author(s):  
Allan B. Massie ◽  
Babak J. Orandi ◽  
Madeleine M. Waldram ◽  
Xun Luo ◽  
Anh Q. Nguyen ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Living Donor ◽  
Patient Survival ◽  
Donor Kidney ◽  
Living Donor Kidney Transplantation ◽  
Donor Kidney Transplantation ◽  
Living Donor Kidney
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