Transplantation Research

BACKGROUND: The aim of this study is to determine the feasibility of using nuclear magnetic resonance (NMR) tracer studies ((13)C-enriched glucose) to detect ex vivo de novo metabolism in the perfusion fluid and cortical tissue of porcine kidneys during hypothermic machine perfusion (HMP). METHODS: Porcine kidneys (n = 6) were subjected to 24 h of HMP using the Organ Recovery Systems LifePort Kidney perfusion device. Glucose, uniformly enriched with the stable isotope (13)C ([U-(13)C] glucose), was incorporated into KPS-1-like perfusion fluid at a concentration of 10 mM...

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) adversely affects patients' long-term outcome. METHODS: The paired t test and McNemar's test were applied in a retrospective 1:1 matched-pair analysis including 36 patients with PTLD and 36 patients without PTLD after kidney or liver transplantation. Matching criteria were age, gender, indication, type of transplantation, and duration of follow-up. All investigated PTLD specimen were histologically positive for EBV...

BACKGROUND: Over the past three decades, public attitudes to organ donation have been a subject of numerous studies focusing on donor motivation. Here, we present a fresh approach. We suggest focusing on public acceptability instead of motivation. The point is to understand public attitudes well enough to avoid risking public support for organ transplantation. We conducted the study in Denmark because there have been significant developments in public attitudes to organ donation in this country...

ABSTRACT: Ischaemic reperfusion (IR) injury is a major cause of graft loss, morbidity and mortality following orthotopic liver transplantation (OLT). Demand for liver transplantation has resulted in increasing use of marginal grafts that are more prone to IR injury. Remote ischaemic preconditioning (RIPC) reduces IR injury in experimental models, but recipient RIPC has not been evaluated clinically. METHODS: A single-centre double-blind randomized controlled trial (RCT) is planned to test the hypothesis that recipient RIPC will reduce IR injury...

BACKGROUND: The shortage of suitable organs and achieved tolerance are uncontested main concerns in transplantation. Long waiting lists for deceased donors and limited numbers of living donors are the current scenarios. Kidney grafts from living donors have better overall survival compared to cadaveric and require less aggressive immunosuppressive regimens. The human leukocyte antigen (HLA) labs have the key role to test the recipient and donors compatibility based on typing and antibody profile...

BACKGROUND: Tacrolimus is available as twice-daily Prograf® (Tac-BID) and the once-daily formulation, Advagraf® (Tac-OD). Although therapeutically equivalent, some transplant recipients require dose adjustments to achieve similar tacrolimus trough concentrations [Tac C0] after conversion between formulations. Tacrolimus is primarily metabolized by cytochrome P450 3A5 (CYP3A5). We sought to determine whether genetic polymorphisms in the CYP3A5 enzyme; CYP3A5 *1/*1 and CYP3A5 *1/*3 (expressers) compared to CYP3A5 *3/*3 (non-expressers) could account for discrepancies in dose requirements following conversion from Tac-BID to Tac-OD...

BACKGROUND: Silibinin has been shown to have anti-HCV activity and immune-modulating properties by regulating dendritic cell (DC) function. DCs are antigen-presenting cells that, together with regulatory T cells (Treg), play a pivotal role in controlling alloimmune, as well as anti-HCV immune responses. METHODS: Twelve liver transplant patients with HCV recurrence received iv infusion of Silibinin (iv-SIL) for 14 consecutive days. Using flow cytometry, before and at the end of treatment, we determined the frequencies of circulating myeloid (m) and plasmacytoid (p) DC and Treg and the expression of costimulatory/coregulatory molecules by the DC subsets and Treg...

Here, we review 15 years of clinical use of sirolimus in our transplant center, in context with the developing immunosuppressive strategies use worldwide. The majority of studies were conducted in de novo kidney transplant recipients, using sirolimus (SRL) in combination with calcineurin inhibitors (CNIs). We also explored steroid (ST) or CNI-sparing therapies, including CNI minimization, elimination, or conversion strategies in combination with mycophenolate (MMF/MPS). Pooled long-term outcomes were comparable with those obtained with CNI and antimetabolite combination...

Immunosuppressive therapy after kidney transplantation is based on calcineurin inhibitors (CNI). In most cases CNI therapy is combined with mycophenolate and steroids. In spite of good short-term results this therapy is associated with long-term toxicities, graft loss and patient death. Therefore, alternative immunosuppressive strategies are needed that combine excellent efficacy with low incidences of long-term adverse outcomes. This review focuses on the strategies based on mTOR- inhibitors in combination with minimized exposure to CNI...

No abstract text is available yet for this article.

BACKGROUND: Determining eligibility for a kidney transplant is an important decision. Practice guidelines define contraindications to transplantation; however many are not evidence based. Canadian guidelines recommend that patients unlikely to survive the wait period not be evaluated. The purpose of this study was to evaluate what proportion of patients with a contraindication would survive the wait time. METHODS: Consecutive incident dialysis patients (January 2006 to December 2012) with a contraindication, defined using Canadian guidelines, were studied...

Commercial transplant tourism results in significant harm to both kidney donors and recipients. However, proponents of incentives for kidney donation assert that proper oversight of the process prevents these harms and also that transplant numbers can be safely increased so that the moral burden of poor end-stage kidney disease outcomes can be alleviated. In a moral dilemma analysis, the principle of preventing donor harm can be dissociated from the principles of providing benefits to the recipient and to society...

While immunosuppressive agents are necessary to prevent the rejection of transplanted organs, and are a great medical success story for protecting against early allograft loss, graft and patient survival over the long term are diminished by side effects from these same drugs. One striking long-term side effect is a high rate of skin cancer development. The skin cancers that develop in transplant recipients tend to be numerous, as well as particularly aggressive, and are therefore a major contributor to morbidity and mortality in transplant recipients...

BACKGROUND: Determining eligibility for a kidney transplant is one of the most important decisions facing nephrologists. It is assumed that the harm of kidney transplantation is minimal and most will benefit. The purpose of this study was to quantify the probability of 'no benefit' as defined by death on the wait list; 'harm', defined by the probability that a transplanted patient would live less than the average wait listed patient; and 'benefit' for the probability a transplanted patient would outlive the average wait listed patient...

BACKGROUND: Literature on the timing of rabbit antithymocyte globulin (rATG) induction and its effects on kidney transplant outcomes is limited. The manufacturer recommends that the first dose be given intra-operatively, however this may present clinical practice risks and challenges. Our objective was to assess the impact of the timing of the first dose of rATG on kidney transplant outcomes. METHODS: Incident kidney transplant recipients (KTR) from January 2002 to December 2009 receiving the first dose of rATG post-operatively (Post, n = 353) or before reperfusion (Pre, n = 124) were evaluated...

BACKGROUND: Primary graft dysfunction (PGD) is a significant cause of early morbidity and mortality following lung transplantation. Improved organ preservation techniques will decrease ischemia-reperfusion injury (IRI) contributing to PGD. Adult bone marrow-derived adherent stem cells, including mesenchymal stromal (stem) cells (MSCs) and multipotent adult progenitor cells (MAPCs), have potent anti-inflammatory actions, and we thus postulated that intratracheal MAPC administration during donor lung processing would decrease IRI...

BACKGROUND: The effects of pre-transplantation medication for secondary hyperparathyroidism on post-transplantation parathyroid hormone (PTH) and calcium levels have not yet been conclusively determined. Therefore, this study sought to determine the level of off-label use of cinacalcet and to determine predictors of its administration during the long-term follow-up of a cohort of individuals who received deceased-donor renal transplants. Furthermore, safety considerations concerning the off-label use of cinacalcet are addressed...

BACKGROUND: Premature cardiovascular (CV) death is the commonest cause of death in renal transplant recipients. Abnormalities of left ventricular (LV) structure (collectively termed uremic cardiomyopathy) and left atrial (LA) dilation, a marker of fluid status and diastolic function, are risk factors for reduced survival in patients with end stage renal disease (ESRD). In the present analysis, we studied the impact of pre-transplant LA and LV abnormalities on survival after successful renal transplantation (RT)...

BACKGROUND: The failure of a kidney transplant is now a common reason for initiation of dialysis therapy. Kidney transplant recipients commencing dialysis have greater morbidity and mortality than transplant-naïve, incident dialysis patients. This study aimed to identify variables associated with survival after graft failure. METHODS: All recipients of first, deceased donor kidney transplants performed in Northern Ireland between 1986 and 2005 who had a functioning graft at 12 months were included (n = 585)...

BACKGROUND: ABO-incompatible live donor liver transplant (ABOi-LDLT) is being widely done to bridge the gap of demand and supply of organs. Different desensitization regimes are being used to reduce titer of blood group antibodies for successful transplant and accommodation of graft. The authors used cascade plasmapheresis (CP) to bring down titer of naturally occurring blood group antibody to 16 or lower. MATERIAL AND METHODS: Four recipients of ABOi-LDLT were of blood groups O, O, B, and B while donors were of blood groups B, A, AB, and AB, respectively...