Everolimus-Treated Renal Transplant Recipients Have a More Robust CMV-Specific CD8 T-Cell Response Compared With Cyclosporine- or Mycophenolate-Treated Patients

Everolimus-Treated Renal Transplant Recipients Have a More Robust CMV-Specific CD8 T-Cell Response Compared With Cyclosporine- or Mycophenolate-Treated Patients

Consensus Guidelines on the Testing and Clinical Management Issues Associated With HLA and Non-HLA Antibodies in Transplantation

Consensus Guidelines on the Testing and Clinical Management Issues Associated With HLA and Non-HLA Antibodies in Transplantation

OPTN/SRTR 2011 Annual Data Report: Kidney

ABSTRACT  A shortage of kidneys for transplant remains a major problem for patients with end-stage renal disease. The number of candidates on the waiting list continues to increase each year, while organ donation numbers remain flat. Thus, transplant rates for adult wait-listed candidates continue to decrease. However, pretransplant mortality rates also show a decreasing trend. Many kidneys recovered for transplant are discarded, and discard rates are increasing. Living donation rates have been essentially unchanged for the past decade, despite introduction of desensitization, non-directed donations, and kidney paired donation programs. For both living and deceased donor recipients, early posttransplant results have shown ongoing improvement, driven by decreases in rates of graft failure and return to dialysis. Immunosuppressive drug use has changed little, except for the Food and Drug Administration approval of belatacept in 2011, the first approval of a maintenance immunosuppressive drug in more than a decade. Pediatric kidney transplant candidates receive priority under the Share 35 policy. The number of pediatric transplants peaked in 2005, and decreased to a low of 760 in 2011. Graft survival and short-term renal function continue to improve for pediatric recipients. Postransplant lymphoproliferative disorder is an important concern, occurring in about one-third of pediatric recipients.

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Página original: http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.12019

Machine perfusion versus cold storage for the preservation of kidneys from donors >=65 years allocated in the Eurotransplant Senior Programme

Background

In the Eurotransplant Senior Programme (ESP), kidneys from donors aged ≥65 years are preferentially allocated locally and transplanted into patients aged ≥65 years on dialysis. The purpose of this study was to analyse whether the results of transplantation in the ESP can be improved by preservation of organs by hypothermic machine perfusion (MP) compared with simple cold storage (CS).

Methods

Overall, 85 deceased heart-beating donors ≥65 years of age were included in this analysis with follow-up until 1 year post-transplant. For each donor, one kidney was randomly assigned to preservation by CS and the contralateral kidney to MP from organ procurement until transplantation. Delayed graft function (DGF), primary non-function (PNF) and 1-year patient and graft survival rates were evaluated as primary and secondary endpoints.

Results

The median recipient age was 66 years in both groups and the median cold ischaemia time was 11 h for MP and 10.5 h for CS (P = 0.69). The DGF rate was 29.4% for MP and 34.1% for CS (P = 0.58). Only extended duration of cold ischaemia time was an independent risk factor for the development of DGF (odds ratio 1.2, P < 0.0001). PNF was significantly reduced (3.5% MP versus 12.9% CS, P = 0.02). The 1-year patient and graft survival rates were similar for MP and CS (94% versus 95% and 89 versus 81%, P > 0.05). The 1-year graft survival rate was significantly improved after MP in recipients who developed DGF (84% MP versus 48% CS, P = 0.01).

Conclusions

Continuous pulsatile hypothermic MP for kidneys from donors aged ≥65 years can reduce the rate of never-functioning kidneys and improve the 1-year graft survival rate of kidneys with DGF. In this small cohort, the known advantage of MP for the reduction of DGF could not be confirmed, possibly due to relatively short cold ischaemia times.

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Página original: http://ndt.oxfordjournals.org/cgi/content/short/27/12/4458?rss=1

Everolimus-Treated Renal Transplant Recipients Have a More Robust CMV-Specific CD8+ T-Cell Response Compared With Cyclosporine- or Mycophenolate-Treated Patients

Background: In renal transplant recipients, mammalian target of rapamycin (mTOR) inhibitors have been reported to protect against cytomegalovirus (CMV) disease. Here, we questioned whether mTOR inhibitors specifically influence human CMV-induced T-cell responses. Methods: We studied renal transplant recipients treated with prednisolone, cyclosporine A (CsA), and mycophenolate sodium (MPS) for the first 6 months after transplantation followed by double therapy consisting of prednisolone/everolimus, which is an mTOR inhibitor (P/EVL; n=10), prednisolone/CsA (P/CsA; n=7), or prednisolone/MPS (P/MPS; n=9). All patients were CMV-IgG positive before transplantation. CMV reactivation was detectable in the first 6 months after transplantation and not thereafter. None of the patients included in this study suffered from CMV disease. Both CD27-CD8+ and CD27-CD28-CD4+ effector-type T-cell counts, known to be associated with CMV infection, were measured before transplantation and at 6 and 24 months after transplantation. Additionally, we determined both number and function of CMV-specific CD8+ T cells at these time points. Results: The number of total CD8+ T cells, CD27-CD8+ T cells, and CD28-CD4+ T cells increased significantly after switch to therapy with P/EVL but not after switch to P/CsA or P/MPS. Specifically, CMV-specific CD8+ T-cell counts significantly increased after switch to therapy with P/EVL. Furthermore, the mTOR inhibitor sirolimus strongly inhibited alloresponses in vitro, whereas it did not affect CMV-specific responses. Conclusion: We observed a significant increase in (CMV-specific) effector-type CD8+ and CD4+ T-cell counts in everolimus-treated patients. These findings may at least in part explain the reported low incidence of CMV-related pathology in everolimus-treated patients. (C) 2012 Lippincott Williams & Wilkins, Inc.

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Página original: http://pdfs.journals.lww.com/transplantjournal/9000/00000/Everolimus_Treated_Renal_Transplant_Recipients.98779.pdf

Effects of HLA-Matched Blood Transfusion for Patients Awaiting Renal Transplantation

Background: HLA sensitization in potential renal transplant recipients hinders opportunities of receiving suitable organs. To alleviate this, we sought to determine if supplying closely HLA Class I matched leukodepleted blood would minimize sensitization. Methods: Patients received HLA selected or random units of packed red cells. Selected units were sourced from blood donors included in the British Bone Marrow Registry and had no HLA-A and HLA-B mismatches where available, or alternatively, no HLA antigens with more than five immunogenic triplet mismatches as determined by the HLAMatchmaker algorithm. Posttransfusion antibody screening confirmed development of de novo Class I and Class II HLA-specific IgG antibody(s) or increases in preexisting antibody levels of at least 20%. Results: Thirty-seven and 31 patients received HLA selected (mean, 2.5 units) and random (mean, 3.4 units) blood, respectively. A total of 20 of 37 (54.1%) patients receiving selected units and 10 of 31 (32.3%) patients receiving random units were previously sensitized. No patient receiving HLA selected units demonstrated any change in antibody levels. In patients who received random units, 7 of 31 demonstrated changes in antibody levels with three developing de novo HLA-specific antibodies and four an increase in panel reactive antibody (PRA) of at least 20% (P=0.002). Conclusions: The risk of developing HLA-specific antibody is significantly reduced in renal patients awaiting transplantation when transfused with HLA selected units of blood compared with random units. With planning, access to HLA typed blood is achievable as many blood transfusion centers recruit donors for stem cell donor registries.

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Página original: http://journals.lww.com/transplantjournal/Fulltext/2012/12150/Effects_of_HLA_Matched_Blood_Transfusion_for.6.aspx