Targeted Gene Deletion or Antagonism of the Prostaglandin E2 EP3 Receptor Protects Against Cardiac Injury Postmyocardial Infarction.

Background: Prostaglandin E2 acts through 4 G-protein-coupled receptors (EP1-EP4). We previously reported that activation of the EP3 receptor reduces cardiac contractility, and its expression increases after a myocardial infarction (MI), mediating the reduction in cardiac function. In contrast, cardiac overexpression of the EP4 receptor in MI substantially improves cardiac function.

Prostaglandin E2 affects mitochondrial function in adult mouse cardiomyocytes and hearts.

Prostaglandin E2 (PGE2) signals differently through 4 receptor subtypes (EP1-EP4) to elicit diverse physiologic/pathologic effects. We previously reported that PGE2 via its EP3 receptor reduces cardiac contractility and male mice with cardiomyocyte-specific deletion of the EP4 receptor (EP4 KO) develop dilated cardiomyopathy. The aim of this study was to identify pathways responsible for this phenotype.

Deleterious effects of cardiomyocyte-specific prostaglandin E2 EP3 receptor overexpression on cardiac function after myocardial infarction.

Aims: Prostaglandin E2 (PGE2) is a lipid hormone that signals through 4 different G-protein coupled receptor subtypes which act to regulate key physiological processes. Our laboratory has previously reported that PGE2 through its EP3 receptor reduces cardiac contractility at the level of isolated cardiomyocytes and in the isolated working heart preparation. We therefore hypothesized that cardiomyocyte specific overexpression of the PGE2 EP3 receptor further decreases cardiac function in a mouse model of heart failure produced by myocardial infarction.

Inhibition of spleen tyrosine kinase decreases donor specific antibody levels in a rat model of sensitization.

Antibody mediated rejection is a major cause of renal allograft loss. Circulating preformed donor specific antibodies (DSA) can result as a consequence of blood transfusion, pregnancy or prior transplantation. Current treatment strategies are limited due to partial or transient efficacy, adverse side-effects or patient unsuitability.

Gastrointestinal Bleeding in a Pancreas Transplant Recipient: A Case to Remember.

BACKGROUND Pancreas transplantation has proven to be the most effective therapeutic option for insulin-dependent diabetes mellitus. However, despite advances in surgical technique and continuously improving outcomes, pancreas transplantation has the highest complication rate among all solid-organ transplants. Vascular complications in particular can be catastrophic, with graft- and life-threatening potential.

Transfusion-Dependent Anemia in a Simultaneous Pancreas and Kidney Transplant Recipient.

A case of transfusion-dependent anemia in a simultaneous pancreas and kidney (SPK) transplant recipient that masqueraded as gastrointestinal bleeding (GIB) is described. The anemia was attributed to bleeding from the donor duodenal cuff based on balloon enteroscopy findings. The patient underwent multiple contrast-enhanced computed tomography scans and multiple endoscopies with confounding features until, eventually, the diagnosis was established.

Causes and risk factors for acute dialysis initiation among patients with end-stage kidney disease-a large retrospective observational cohort study.

Background: Patients who require acute initiation of dialysis have higher mortality rates when compared with patients with planned starts. Our primary objective was to explore the reasons and risk factors for acute initiation of renal replacement therapy (RRT) among patients with end-stage kidney disease (ESKD). Our secondary objective was to determine the difference in glomerular filtration rate (GFR) change in the year preceding RRT between elective and acute dialysis starts.

Allosensitization after transplant failure: the role of graft nephrectomy and immunosuppression - a retrospective study.

There are conflicting data about the role of transplant nephrectomy and immunosuppression withdrawal on the development of allosensitization and the impact on re-transplantation. We divided 109 first graft recipients into two groups according to whether they underwent nephrectomy (NX+, n = 61) or their graft was left in situ (NX-, n = 48). Sera were assessed for HLA-A/B/Cw/DR/DQ antibodies at the time of NX/transplant failure and after 3, 6, 12, 24 months.

Dual-balloon assisted super-selective embolisation of high flow arterial venous fistula within a transplant kidney.

Background: In this case report, we describe a novel application of the technique of 'dual-balloon assisted' cannulation and embolisation of a high flow arterial venous fistula (AVF) in transplant kidney, where attempts at standard and previously described embolisation techniques were proving difficult to achieve.

Case Presentation: Seventy year old gentleman with renal transplant presenting with high output cardiac failure and deteriorating renal function. Angiography demonstrated high flow traumatic AV fistula within transplanted kidney, secondary to multiple biopsies.

Successful management of post-transplant focal segmental glomerulosclerosis with therapeutic plasma exchange and rituximab.

Background: Post-transplant focal segmental glomerulosclerosis (FSGS) is associated with renal allograft loss. Currently, optimal treatment remains controversial.

Methods: The aim of our study was to examine the efficacy and safety of therapeutic plasma exchange (TPE), and rituximab (RTX), in the management of post-transplant FSGS.

Shared alloimmune responses against blood and transplant donors result in adverse clinical outcomes following blood transfusion post-renal transplantation.

De novo HLA donor-specific antibodies (DSA) following transplantation are associated with alloimmune injury and allograft failure. Blood transfusions are allogeneic, and when given posttransplant (PTBT) they may independently increase the risk of HLA antibody development. This study aims to analyze the development of HLA transfusion-specific antibodies (TSA) to blood donors of transfusions given posttransplant and examine the impact on clinical outcomes.

Neurological complications of renal dialysis and transplantation.

Neurological complications from renal replacement therapy contribute significantly to morbidity and mortality in patients with renal failure. Such complications can affect either the central or peripheral nervous systems. Most neurological disturbances associated with the uraemic state do not respond fully to renal replacement therapy.

High Intrapatient Variability of Tacrolimus Levels and Outpatient Clinic Nonattendance Are Associated With Inferior Outcomes in Renal Transplant Patients.

Background: Nonadherence to immunosuppressants is associated with rejection and allograft loss. Intrapatient variability (IPV) of immunosuppression levels is a marker of nonadherence. This study describes the impact of IPV of tacrolimus levels in patients receiving a tacrolimus monotherapy immunosuppression protocol.

Terasaki Epitope Mismatch Burden Predicts the Development of De Novo DQ Donor-Specific Antibodies and are Associated With Adverse Allograft Outcomes.

Background: De novo DQ donor-specific antibody (DSA) are associated with antibody-mediated rejection and allograft loss. Given the lack of effective treatment of de novo DQ DSA, their prevention is vital if there is to be an improvement of long-term allograft survival. Using the HLA Matchmaker program, DQ epitope matching has been shown to be superior to HLA antigen mismatching in predicting de novo DQ DSA development.

Alemtuzumab dose adjusted for body weight is associated with earlier lymphocyte repletion and less infective episodes in the first year post renal transplantation - a retrospective study.

The optimal dose of alemtuzumab for renal transplant induction is not known, and the doses reported in the literature vary. This study compares two separate dosing regimens of alemtuzumab in renal transplantation. The first is a standard fixed dose of 30 mg (SD), and the second is a dose adjusted for body weight at 0.

Long-term outcome in biopsy-proven acute interstitial nephritis treated with steroids.

There are no prospective randomized controlled trials describing the outcome of acute interstitial nephritis (AIN) treated with steroids, and retrospective studies are limited. We identified adult patients with a diagnosis of AIN without glomerular pathology over a 14-year period. Treated patients all received oral prednisolone and three also recieved IV methylprednisolone.

Risk factors and outcomes of delayed graft function in renal transplant recipients receiving a steroid sparing immunosuppression protocol.

Aim: To analyse the risk factors and outcomes of delayed graft function (DGF) in patients receiving a steroid sparing protocol.

Methods: Four hundred and twenty-seven recipients of deceased donor kidney transplants were studied of which 135 (31.6%) experienced DGF.

Tubuloreticular Inclusions in Renal Allografts Associate with Viral Infections and Donor-Specific Antibodies.

The presence of tubuloreticular inclusions (TRIs) in native glomerular endothelial cells associates with viral infections and lupus nephritis. However, the associations of TRIs in renal transplant biopsy specimens are not known. We analyzed data from 316 patients who had a transplant biopsy with electron microscopy examination; 41 of 316 (13.

Peritubular Capillary Basement Membrane Multilayering in Renal Allograft Biopsies of Patients With De Novo Donor-Specific Antibodies.

Background: Severe peritubular capillary basement membrane multilayering (PTCBML) is part of the Banff definition of chronic antibody-mediated rejection. We retrospectively investigated whether assessment of the mean number of layers of basement membrane (BM) around peritubular capillaries (PTC) can be used in a cohort of patients with de novo donor-specific antibodies (dnDSA) as an early marker to predict long-term antibody-mediated injury.

Methods: This is a retrospective cohort study with 151 electron microscopy samples from 54 patients with dnDSA, assessed at around 1 year after transplantation, for a mean number of BM layers around PTC and in serial biopsies.

B-lymphocytes support and regulate indirect T-cell alloreactivity in individual patients with chronic antibody-mediated rejection.

We explored how B-lymphocytes influence in vitro T-cell alloresponses in patients with antibody-mediated rejection (AMR), testing whether B-cells would be preferentially involved in this group of patients. Peripheral blood mononuclear cells were collected from 65 patients having biopsy: 14 patients with AMR and 5 with no pathology on protocol; 38 with AMR and 8 with nonimmunologic damage on 'for cause'. Using enzyme-linked immunosorbent spot assays, we found interferon-γ production by indirect allorecognition in 45 of 119 total samples from the 65 patients.

Use of Quantitative Real Time Polymerase Chain Reaction to Assess Gene Transcripts Associated With Antibody-Mediated Rejection of Kidney Transplants.

Introduction: Microarray studies have shown elevated transcript levels of endothelial and natural killer (NK) cell-associated genes during antibody-mediated rejection (AMR) of the renal allograft. This study aimed to assess the use of quantitative real-time polymerase chain reaction as an alternative to microarray analysis on a subset of these elevated genes.

Methods: Thirty-nine renal transplant biopsies from patients with de novo donor-specific antibodies and eighteen 1-year surveillance biopsies with no histological evidence of rejection were analyzed for expression of 11 genes previously identified as elevated in AMR.

Incidence, risk factors, and outcomes of stroke post-transplantation in patients receiving a steroid sparing immunosuppression protocol.

Corticosteroid use after transplantation is associated with an increased incidence of cardiovascular events and death. Cerebrovascular disease is a common cause of morbidity and mortality post-renal transplantation; however, a dedicated analysis of cerebrovascular disease in recipients of a steroid sparing protocol has not been reported. The aim of this study was to examine the incidence, risk factors, and outcomes of CVA in transplant recipients receiving a steroid sparing protocol.

Comparison of Tesio and LifeCath twin permanent hemodialysis catheters: the VyTes randomized trial.

Purpose: Central venous catheters for maintenance hemodialysis (HD) are designed to attain the required dialysis dose through sustained high blood flow rates (BFR). The authors studied the immediate and long-term performance and complications of two twin-catheter systems, the Tesio catheter (TC) and the LifeCath Twin (LC), to inform clinical practice.

Methods: This single-center randomized controlled parallel-group trial allocated 80 incident patients (1:1) to receive either a TC (MedComp) or LC (Vygon).