Increased telomere attrition following renal transplantation: impact of anti-metabolite therapy

Background: The uremic milieu exposes chronic kidney disease (CKD) patients to premature ageing processes. The impact of renal replacement therapy (dialysis and renal transplantation [RTx]) or immunosuppressive treatment regimens on ageing biomarkers has scarcely been studied. Methods: In this study telomere length in whole blood cells was measured in 49 dialysis patients and 47 RTx patients close to therapy initiation and again after 12 months. Forty-three non-CKD patients were included as controls. Results: Non-CKD patients had significantly (P <= 0.01) longer telomeres than CKD patients. Telomere attrition after 12 months was significantly greater in RTx patients compared to dialysis patients (P = 0.008). RTx patients receiving mycophenolate mofetil (MMF) had a greater (P = 0.007) degree of telomere attrition compared to those treated with azathioprine. After 12 months, folate was significantly higher in RTx patients than in dialysis patients (P < 0.0001), whereas the opposite was true for homocysteine (P < 0.0001). The azathioprine group had lower levels of folate after 12 months than the MMF group (P = 0.003). Conclusions: The associations between immunosuppressive therapy, telomere attrition, and changes in folate indicate a link between methyl donor potential, immunosuppressive drugs, and biological ageing. The hypothesis that the increased telomere attrition, observed in the MMF group after RTx, is driven by the immunosuppressive treatment, deserves further attention

The technique of prolonged thoracic duct drainage in transplantation

Prolonged thoracic duct drainage as an immunosuppressive adjunct was accomplished in 96 per cent of organ recipients upon whom it was attempted

Platelet-Activating Factor-Induced Reduction in Contact Hypersensitivity Responses Is Mediated by Mast Cells via Cyclooxygenase-2-Dependent Mechanisms

Platelet-activating factor (PAF) stimulates numerous cell types via activation of the G protein-coupled PAF receptor (PAFR). PAFR activation not only induces acute proinflammatory responses, but it also induces delayed systemic immunosuppressive effects by modulating host immunity. Although enzymatic synthesis and degradation of PAF are tightly regulated, oxidative stressors, such as UVB, chemotherapy, and cigarette smoke, can generate PAF and PAF-like molecules in an unregulated fashion via the oxidation of membrane phospholipids. Recent studies have demonstrated the relevance of the mast cell (MC) PAFR in PAFR-induced systemic immunosuppression. The current study was designed to determine the exact mechanisms and mediators involved in MC PAFR-mediated systemic immunosuppression. By using a contact hypersensitivity model, the MC PAFR was not only found to be necessary, but also sufficient to mediate the immunosuppressive effects of systemic PAF. Furthermore, activation of the MC PAFR induces MC-derived histamine and PGE2 release. Importantly, PAFR-mediated systemic immunosuppression was defective in mice that lacked MCs, or in MC-deficient mice transplanted with histidine decarboxylase- or cyclooxygenase-2-deficient MCs. Lastly, it was found that PGs could modulate MC migration to draining lymph nodes. These results support the hypothesis that MC PAFR activation promotes the immunosuppressive effects of PAF in part through histamine- and PGE2-dependent mechanisms

In vitro immunosuppressive effects of FR 900506 on human T lymphocyte alloactivation

FR 900506 (FR) is a new immunosuppressive drug which prolongs allograft survival. Our studies have compared the in vitro inhibitory effects of FR and cyclosporine (CsA) on human lymphocyte proliferation. Considerably lower doses of FR were required to induce inhibition of lymphocyte proliferation induced by concanavalin A (Con A) stimulation or in primary mixed lymphocyte reactions (MLR). Similar differences between FR and CsA were observed with the secondary stimulation of alloactivated T cells generated in MLR or propagated from liver transplant biopsies. These observations provide further evidence that FR is about 500 fold more potent than CsA and may be a useful immunosuppressive agent in organ transplantation

The University of Pittsburgh: a three and three-quarter-year experience with cadaveric renal transplantation under the point system.

Eight hundred and sixty kidney transplants were performed at the University of Pittsburgh over a 3.75-year period between January 1, 1986 and October 19, 1989. Recipient selection was by means of a computerized point system designed to allocate organs equitably. Ninety-three percent 1-year patient survival and 74% 1-year graft survival were obtained in the overall group; 80% 1-year graft survival was obtained in patients receiving immunosuppression with CsA, azathioprine, and prednisone. These data serve as a measure of what can be achieved with an equitably based allocation system and can serve as a basis of comparison with other allocation protocols or new immunosuppressive regimens

Quality of life after liver transplantation : state of the art

Quality of life (QoL) after deceased donor liver transplantation is increasingly recognized as a major outcome parameter. We reviewed recent publications in this rapidly evolving field in order to summarize recent achievements in the field and to define opportunities and perspectives for research and improvement of patient care. QoL does improve after liver transplantation according to a typical pattern. During the first year, there is a significant improvement in QoL. After one year, the improvement does stabilise and tends to decline slightly. In addition to the physical condition, different psychological parameters (such as depression, anxiety, sexual function) and socio-demographic elements (professional state, sex, marital state) seem to impact QoL. Opportunities for further research are the use of dedicated questionnaires and identification of influencing factors for QoL