Willem Weimar

..Only in one patient, who had stopped all his medication, was a rejection episode diagnosed. We conclude that in patients with a low donor-specific CTLp frequency it is safe to reduce the immunosuppression...

..In comparison with natural Tregs, the rATG-induced Tregs are phenotypically distinct but have similar regulatory activities. rATG may beneficially contribute to the mechanisms that control alloreactivity...

..Healthy individuals served as controls...

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..Therefore, we analyzed the gene expression profiles of regulatory and effector T-cell markers during immunological quiescence and acute rejection...

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..Hence, our results indicate the feasibility of their use in autologous cell therapy in patients with renal disease...

..Additionally, the interaction between forkhead box P3+ T cells and kidney injury molecule-1 by activated primary tubular epithelial cells was studied...

..Moreover, discontinuation of CNIs' treatment allows FOXP3+ regulatory T-cells development, resulting in a significant decrease of anti-donor immune reactivity...

..In this study, the immunosuppressive effect of MSC on recipient anti-donor reactivity was examined before and after clinical kidney transplantation...

..Interleukin (IL)-21 is the most recently described cytokine that signals via the common cytokine receptor (gammac), is produced by activated CD4+ T-cells, and regulates expansion and effector function of CD8+ T-cells...

..We investigated the effect of immunosuppressive drugs targeting this pathway, the JAK inhibitor tofacitinib (CP-690,550) and the anti-interleukin (IL)-2R antibody basiliximab, as part of a phase 2 study...

..CONCLUSION.: Analysis of P-STAT5 may, therefore, be used to determine the immunomodulatory effect of CP-690,550 at the cellular level in transplant patients...

..However, it remains to be demonstrated, whether these cells are generated after clinical transplantation...

..No influence of the polymorphism on the development of heart failure, graft survival, acute rejection, or transplant atherosclerosis was found...

..We questioned whether discontinuation of azathioprine (AZA) or mycophenolate mofetil (MMF) influenced T-cell reactivity, circulating dendritic cell (DC) subsets numbers and their maturation status...

..Evidence from animal studies indicate a crucial role for CD25(bright+) regulatory T cells in transplantation tolerance...

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..Furthermore, patients during AR exhibited low proportions of mDCs positive for CD83 or CCR7. These findings suggest peripheral blood mDC depletion in association with selective lymphoid homing of this subset during AR after clinical HTx...

..The transcription factor FOXP3 has been identified as the molecule associated with the regulatory function of CD25+ T cells...

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..No data are available on the need for immunosuppression for these specific patients. We wondered whether their immunosuppressive load could be radically reduced...

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..In conclusion, MSCs can stimulate the activation and proliferation of resting T-cells and generate regulatory T-cells. These findings are important when MSCs are applied in the clinic...

..CD4CD25FoxP3 regulatory T cells are suppressors of antigen-activated immune reactivity. Here, we assessed the clinically relevant role of these cells in the control of immune responses directed to a transplanted heart...

..25mg FTY/day. Elispot assays revealed no IL-4 producing cells and a low frequency of IFN-gamma producing cells. We suggest that both CCR7 dependent and independent mechanisms are involved in the depletion of T cells from peripheral blood...

..In the present prospective and controlled study, we investigated the effect of rATG on the frequency, function and phenotype of peripheral immunoregulatory CD4+ T cells in kidney transplant (KTx) patients...

..In conclusion, expansion of CD4(+)CD28null T cells in CMV-seropositive patients with ESRD associates with increased demand for epoetin...

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..The molecular targets of these drugs are expressed in MSC, but the effect of their inhibition on MSC functioning is unknown...

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..The graft failure risk of deceased donor transplantation is almost twice that of living donor transplantation so that a 60-year-old living donor kidney has the same graft failure risk as a 20-year-old deceased donor kidney...

..We questioned whether stopping CNI had an effect on the donor-specific reactivity, as CNI might hinder immune responses leading to graft acceptance...

..Such changes must be taken into account if RBV measurements are used to improve the haemodynamic tolerance of dialysis...

..Safe tapering of immunosuppression should not result in rejection and high donor-directed T-cell responses. In the present study, we investigated the effect of tapering azathioprine (AZA) on T-cell reactivity...

..Unlimited chain length did not significantly affect the results. The optimal chain length for living donor kidney exchange programs is 3. Longer chains with their inherent logistic burden do not lead to significantly more transplants...

..The data suggest that VZV-reactive EM T-cells are impaired in the elderly and renal transplant recipients...

..Beside increasing LD ABOi transplantation, a new DD allocation model favouring both highly immunised and blood type O patients is essential...

..We investigated which socioeconomic and clinical factors influence who undergoes living or deceased donor kidney transplantation...

..The risk of long-term chronic allograft nephropathy and graft loss after kidney transplantation is increased in patients with a high intrapatient variability of tacrolimus (Tac) clearance...

..Living donor kidney exchange is now performed in several countries. However, no information is available on the practical problems inherent to these programs. Here, we describe our experiences with 276 couples enrolled in the Dutch program...

..These cytokines play key roles in lymphocyte function and homeostasis. As part of a phase 1 trial, we evaluated the effect of CP-690,550 on immune parameters...

..This state of immune incompetence is associated with continuous activation of the immune system. An additional explanation for this state of activation may be the disturbed function of CD4(+)CD25(bright+)FoxP3(+) regulatory T-cells...

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..In conclusion, with the use of anti-IL-2Ra induction and daily therapy with tacrolimus and MMF it is feasible to withdraw steroids at 3 days after renal transplantation...

..Continued discussion is required for definition of safety and eventually efficacy endpoints for MSC therapy in solid organ transplantation...

..The authors studied the influence of these SNPs on CsA pharmacokinetics as well as on the incidence of biopsy-proven acute rejection (BPAR) and renal function after kidney transplantation...

..Laparoscopic donor nephrectomy (LDN) has become the preferred procedure for live donor nephrectomy. Most transplant surgeons are reluctant toward right-sided LDN (R-LDN) fearing short vessels and renal vein thrombosis...

..In contrast, the outcome in obese males seems to be less advantageous, indicating that total LDN in overweight women can be advocated as a routine procedure but in obese men reluctance seems justified...

..Hand-assisted retroperitoneoscopic donor nephrectomy reduces operation and warm ischemia times, and provides at least equal safety. Hand-assisted retroperitoneoscopic may be a valuable alternative for left-sided LDN...

..Pred withdrawal was safe and resulted in a reduction in mean arterial pressure. However, patient and graft survival and renal function 2 yr after RTx were not different among groups...

..We studied whether TAC inhibits p38 MAPK signaling in primary human T cells and ex vivo in healthy volunteers and kidney transplant recipients...

..The feasibility of this method has been demonstrated recently, but as to date there are no data available advocating the use of one technique above the other...

..The low oral bioavailability of calcineurin inhibitors is thought to result from the actions of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and CYP3A5 and the multidrug efflux pump P-glycoprotein, encoded by MDR-1...

..Modulation of the chemokine network could offer interesting novel therapeutic modalities for end-stage HF...

..Vascular endothelial growth factor (VEGF) is crucial for preservation of microvasculature and contributes to cytoprotection of the graft after kidney transplantation...

..In our opinion logistic solutions like paired exchange, list exchange and altruistic donation programs are to be preferred over the more medical demanding programs e.g. desensitization and transplantation across the blood type barrier...

..CONCLUSIONS: Both procedures clearly impact quality of life and fatigue. The beneficial effect on the quality of life and the earlier return to work encourage us to advocate LDN as the surgical approach to be preferred...

..A national donor kidney exchange was considered as a possible solution...

..This may cause a relevant reduction in T-cell immunity, yielding a lowered risk for acute rejection (AR) of kidney allografts...

..Finally, reflecting on these ethical considerations, essential conditions for carrying out such a programme are outlined. The goal is to develop an ethically justified and responsible educational programme...

..In this study, we analysed whether this reduction resulted from CKD or from renal replacement therapy (RRT)...

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..This finding suggests that CsA-mediated inhibition of the biliary excretion of MPAG by the Mrp2 transporter is the mechanism responsible for the interaction between CsA and MMF...

..We wondered whether a low attendance or a high decline of potential non-European donors could explain this difference...

..We evaluated the outcome of vascular imaging and the clinical consequences of multiple arteries and veins...

..In addition, we discuss the importance of the appropriate localization for the control of anti-donor immune reactivity...

..These findings are highly suggestive of repetitive antigenic stimulation of the immune system in patients with end stage disease by subclinical CMV reactivation which might contribute to increased atherosclerotic risk...

..This study investigated attitudes towards the post-transplant regime of immunosuppressive medication among the ever growing population of elderly kidney recipients...

..Elevated growth factor expression levels indicate repair responses after tissue damage due to either the transplantation procedure (surgery, ischemia, reperfusion) or acute allograft rejection...

..CONCLUSION: The surgical technique of live donor nephrectomy varies greatly between transplant centers in European countries. To define the optimal surgical approach a European registration of donor nephrectomies would be helpful...

..The authors determined the CTL precursor frequency (CTLpf) and simultaneously measured the number of IFN-gamma- and GrB-producing cells (pc) by ELISPOT assay...

..Our data suggest that the improvement in diastolic left ventricular function is associated with a general reduction of inflammation within the allograft, rather than related to a specific cytokine expression pattern...

..We speculate that prolonged ischemia and hypoxia time leads to the production of HIF-1alpha, which in turn induces the production of fibrogenic cytokines in the graft...

..To examine whether genetic factors are involved in the development of acute rejection (AR), we investigated a (CA)m(CT)n repeat in the 3'-flanking region of the interleukin (IL)-2 gene...

..Therefore, HTLf-analysis may be a useful tool in monitoring the cellular immune response as an indicator for early graft dysfunction due to rejection in clinical valve transplantation...

..Patients with chronic kidney disease (CKD) with or without chronic intermittent haemodialysis (CIHD) show an impaired immune response. Dysfunction of DCs may underlie this phenomenon...

..We discuss these topics and assess the feasibility of MSCs therapy in organ transplantation...

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..In an attempt to reduce calcineurin inhibitor toxicity, transplant patients treated with tacrolimus can be switched to maintenance treatment with sirolimus...

..The present study aimed to identify young adults at risk for nonadherent behavior by investigating their attitudes about posttransplant health lifestyle...

..To evaluate the effect of corticosteroids on tacrolimus pharmacokinetics...

..In order to evaluate the role of blood DCs in cardiomyopathies of different origins, we examined myeloid (mDC) and plasmacytoid (pDC) subset levels and maturation characteristics, according to HF severity and etiology in humans...

..Uniform treatment regimes according to guidelines are useful but should leave room for adjustment to the needs of individual patients. Longer follow-up studies are needed to decide on the optimal maintenance treatment...

..Assessment of LV diastolic function should not be performed shortly before HD, and its time relation to HD is essential...

..We questioned whether a more sensitive method like the Elispot-assay could be more appropriate...

..For optimal results, both ABO blood type incompatible and cross match positive pairs should participate...

..Nevertheless, it may be difficult to find a living kidney donor. The purpose of this explorative study is to investigate how kidney transplant candidates may, or may not, find a living donor in the Netherlands...

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..In conclusion, MIDN is a safe approach, which reduces blood loss, hospital stay and the number of incision related complications when compared with CL with only a modest increase in operation time...

..In this study, we determined whether cardiac allograft recipients show donor-specific hyporesponsiveness and studied the underlying mechanisms...

..We concluded that whether viewed separately or in combination, these issues do not impede the efficient organization of a crossover program or raise worrying ethical issues...

..Therefore, fresh blood is preferable for monitoring purposes in transplant patients, as only these cells reflect the in vivo immune-status of patients accurately...

..This benefit justifies encouragement of preemptive kidney transplantation...

..To reach target AUC levels as soon as possible in this cyclosporine-treated population, it appears that larger MMF doses as currently recommended are necessary in the first month after transplantation...

..Because alternatives are currently available, we expect that XT will become more popular only if future results of this procedure have proved to be comparable to transplantation with a human donor kidney...

..Since February 1, 2001, kidneys from both heart-beating (HB) and non-heart-beating (NHB) donors in The Netherlands have been indiscriminately allocated through the standard renal-allocation system...

..The results of these surveys are comparable: about a quarter of the population is in favor of this idea, whereas the majority is opposed or undecided...

..Renal dysfunction in everolimus cohorts necessitates close monitoring...