Inhibition of RIPK1 or RIPK3 kinase activity post ischemia-reperfusion reduces the development of chronic kidney injury.

Ischemia-reperfusion injury (IRI) occurs when the blood supply to an organ is temporarily reduced and then restored. Kidney IRI is a form of acute kidney injury (AKI), which often progresses to kidney fibrosis. Necroptosis is a regulated necrosis pathway that has been implicated in kidney IRI.

Dynamics of necroptosis in kidney ischemia-reperfusion injury.

Necroptosis, a pathway of regulated necrosis, involves recruitment and activation of RIPK1, RIPK3 and MLKL, leading to cell membrane rupture, cell death and release of intracellular contents causing further injury and inflammation. Necroptosis is believed to play an important role in the pathogenesis of kidney ischemia-reperfusion injury (IRI). However, the dynamics of necroptosis in kidney IRI is poorly understood, in part due to difficulties in detecting phosphorylated MLKL (pMLKL), the executioner of the necroptosis pathway.

Retinal microvascular function predicts chronic kidney disease in patients with cardiovascular risk factors.

Background And Aims: Endothelial dysfunction is a precursor to atherosclerosis and is implicated in the coexistence between cardiovascular disease (CVD) and chronic kidney disease (CKD). We examined whether retinal microvascular dysfunction is present in subjects with renal impairment and predictive of long-term CKD progression in patients with CVD.

Methods: In a single centre prospective observational study, 253 subjects with coronary artery disease and CVD risk factors underwent dynamic retinal vessel analysis.

A psychosocial intervention for individuals with advanced chronic kidney disease: A feasibility randomized controlled trial.

Aim: The current study evaluated the feasibility and preliminary efficacy of a psychosocial intervention, the Kidney Optimal Health Program, in reducing symptoms of depression and anxiety in individuals with advanced chronic kidney disease.

Methods: Patients with stage 4 or 5 chronic kidney disease were randomized to either a nine-session psychosocial intervention programme or usual care. Feasibility was assessed through recruitment and retention rates and programme acceptability.

Antigen-specific CD4 CD25 T cells induced by locally expressed ICOS-Ig: the role of Foxp3, Perforin, Granzyme B and IL-10 - an experimental study.

We have previously reported that ICOS-Ig expressed locally by a PIEC xenograft induces a perigraft cellular accumulation of CD4 CD25 Foxp3 T cells and specific xenograft prolongation. In the present study we isolated and purified CD4 CD25 T cells from ICOS-Ig secreting PIEC grafts to examine their phenotype and mechanism of xenograft survival using knockout and mutant mice. CD4 CD25 T cells isolated from xenografts secreting ICOS-Ig were analysed by flow cytometry and gene expression by real-time PCR.

Regulated necrosis in kidney ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) is the outcome of an inflammatory process that is triggered when an organ undergoes a transient reduction or cessation of blood flow, followed by re-establishment of perfusion. In the clinical setting, IRI contributes to significant acute kidney injury, patient morbidity and mortality, and adverse outcomes in transplantation. Tubular cell death by necrosis and apoptosis is a central feature of renal IRI.

Paraneoplastic systemic lupus erythematosus associated with colorectal cancer.

A 64-year-old gentleman initially presented with nephrotic syndrome and membranous nephropathy with positive staining for C1q, which was suspicious for lupus membranous nephritis. Investigation led to the simultaneous diagnosis of colorectal cancer (CRC). The CRC was surgically excised and the patient's nephrotic syndrome resolved.

Lifetime risk of end-stage kidney disease in living donors for paediatric kidney transplant recipients in Australia and New Zealand - a retrospective study.

Living kidney donors (LKD) for paediatric kidney transplant recipients (KTR) have a heightened motivation to donate for emotional reasons and the clear health benefits to the KTR. We hypothesized that the cohort of LKD for paediatric KTR (LKD-P) includes motivated young parents with a higher lifetime end-stage kidney disease (ESKD) risk compared to adult KTR (LKD-A). Data from the Australia and New Zealand Dialysis and Transplant LKD Registry (2004-2015) was analysed to compare baseline characteristics and predonation ESKD risk in LKD-P (n = 315) versus LKD-A (n = 3448).

Carvedilol and Cardiac Biomarkers in Dialysis Patients: Secondary Analysis of a Randomized Controlled Trial.

Background/aims: Cardiac biomarkers are associated with cardiac abnormalities and adverse outcomes in dialysis patients. Our aim was to report the effect of the beta-blocker carvedilol on cardiac biomarkers in adult dialysis patients.

Methods: The Beta-Blocker to Lower Cardiovascular Dialysis Events Feasibility Study was a randomized controlled trial comparing carvedilol to placebo.

Effect of haemodialysis and residual renal function on serum levels of galectin-3, B-type natriuretic peptides and cardiac troponin T.

Aim: Levels of plasma markers of myocardial fibrosis (galectin-3), stretch (B-type natriuretic peptide (BNP)) and injury (high-sensitivity troponin T (hs-TnT)) are affected by haemodialysis, residual renal function (RRF) and cardiac pathology. We aimed to determine the association of RRF, urine output and haemodialysis itself on cardiac biomarkers in haemodialysis patients.

Methods: Adult haemodialysis patients underwent venesection pre- and post-haemodialysis then echocardiography and inter-dialytic urine collection to calculate RRF (mL/min per 1.

Application of an epitope-based allocation system in pediatric kidney transplantation.

Donor-recipient HLA mismatch remains a leading cause for sensitization and graft loss in kidney transplantation. HLA compatibility at an epitope level is emerging as an improved method of matching compared with current HLA antigen allocation. A novel epitope-based allocation approach to prospectively exclude donors with high-level mismatches was implemented for pediatric KTRs on the DD waiting list.

The β-Blocker to Lower Cardiovascular Dialysis Events (BLOCADE) Feasibility Study: A Randomized Controlled Trial.

Background: β-Blocking agents reduce cardiovascular mortality in patients with heart disease, but their potential benefit in dialysis patients is unclear. We aimed to determine the feasibility of a randomized controlled trial (RCT).

Study Design: Pilot RCT.

Nephrologists' management of patient medications in kidney transplantation: results of an online survey.

Rationale, Aims And Objectives: Medication adherence is essential in kidney transplant recipients to reduce the risk of rejection and subsequent allograft loss. The aim of this study was to delineate what 'usual care' entails, in relation to medication management, for adult kidney transplant recipients.

Methods: An online survey was developed to explore how nephrologists promote and assess medication adherence, the management of prescriptions, the frequency of clinic appointments and the frequency of clinical screening tests.

The rationale and design of the Beta-blocker to LOwer CArdiovascular Dialysis Events (BLOCADE) Feasibility Study.

Aims: The Beta-blocker to LOwer CArdiovascular Dialysis Events (BLOCADE) Feasibility Study aims to determine the feasibility of a large-scale randomized controlled trial with clinical endpoints comparing the beta-blocking agent carvedilol with placebo in patients receiving dialysis.

Methods: The BLOCADE Feasibility Study is a randomized, double-blind, placebo-controlled, parallel group feasibility study comparing the beta-blocking agent carvedilol with placebo. Patients receiving dialysis for ≥3 months and who are aged ≥50 years, or who are ≥18 years and have diabetes or cardiovascular disease, were eligible.

Temporal trajectory of B-type natriuretic peptide in patients with CKD stages 3 and 4, dialysis, and kidney transplant.

Background And Objectives: B-type natriuretic peptide (BNP) concentration predicts outcome in patients undergoing dialysis. Because survival and cardiovascular risk change across the CKD continuum, serial changes in BNP were compared in patients at different CKD stages and after kidney transplantation.

Design, Setting, Participants, & Measurements: Patients with CKD stages 3 and 4 (CKD 3-4), dialysis patients, and kidney transplant recipients (KTRs) from one center had two measurements of BNP taken a median of 161 days apart in 2003-2004 and were followed until July 2012.

Angiotensin-converting enzyme 2 activity in patients with chronic kidney disease.

Background: Angiotensin-converting enzyme 2 (ACE2) is a novel regulator of the renin-angiotensin system that counteracts the adverse effects of angiotensin II. In heart failure patients, elevated plasma ACE2 activity predicted adverse events and greater myocardial dysfunction. We aimed to describe plasma ACE2 activity and its clinical associations in patients with kidney disease.

Challenges in blood pressure measurement in patients treated with maintenance hemodialysis.

The association between blood pressure and cardiovascular outcomes in patients undergoing hemodialysis remains controversial. This may relate in part to the technique and device used and the timing of the blood pressure measurement in relation to the hemodialysis procedure. Emerging evidence indicates that standardized hemodialysis unit blood pressure measurements or measurements obtained at home, either by the patient or using an ambulatory blood pressure monitor, may offer advantages over routine hemodialysis unit blood pressure measurements for determining cardiovascular risk and treatment.

Foxp3+ T cells in peripheral blood of renal transplant recipients and clinical correlations.

Aim: Immunophenotype peripheral blood T cells from renal transplant recipients (RTR) using cellular markers of regulatory T cells (Tregs) and flow cytometry, including Foxp3, and correlate these findings with clinical parameters.

Methods: Expression of phenotypic markers of Tregs was assessed by flow cytometric analysis of peripheral blood lymphocytes (PBL) from (i) RTR (n = 95); (ii) patients with end-stage renal failure (ESRF) awaiting transplantation (n = 17); and (iii) normal healthy controls (n = 18).

Results: The percentage of CD4(+) CD25(+) Foxp3(+) cells within the CD4(+) cell population did not significantly alter at different time points post-transplant.

Prolonged xenograft survival induced by inducible costimulator-Ig is associated with increased forkhead box P3(+) cells.

Background: Blockade of the inducible costimulator (ICOS) pathway has been shown to prolong allograft survival; however, its utility in xenotransplantation is unknown. We hypothesize that local expression of ICOS-Ig by the xenograft will suppress the T-cell response resulting in significant prolonged graft survival.

Methods: Pig iliac artery endothelial cells (PIEC) secreting ICOS-Ig were generated and examined for the following: (1) inhibition of allogeneic and xenogeneic proliferation of primed T cells in vitro and (2) prolongation of xenograft survival in vivo.

Approaching the promise of operational tolerance in clinical transplantation.

Long-term acceptance of transplanted organs without requirement for indefinite immunosuppression remains the ultimate goal of transplant clinicians and scientists. This clinical state of allograft acceptance termed "operational tolerance" has been elusive in routine practice. However, there are published reports of recipients where immunosuppression has been discontinued, by intention or patient noncompliance, in which the outcome is a nondestructive immune response and normal function.

Secular trends in cardiovascular mortality rates of patients receiving dialysis compared with the general population.

Background: Cardiovascular mortality rates in the general population have decreased over time. We hypothesized that cardiovascular mortality rates in dialysis patients, which are higher than in the general population, have not decreased as much as those in the general population.

Study Design: Comparison of registry data with population data.

Understanding cardiac biomarkers in end-stage kidney disease: Frequently asked questions and the promise of clinical application.

A novel strategy in the management of cardiovascular disease in patients with end-stage kidney disease is the use of biochemical markers to facilitate the detection of cardiovascular abnormalities in the hope that this will allow effective therapy to be instituted earlier. The cardiac troponins and B-type natriuretic peptide are among the best studied of these biochemical markers of cardiovascular disease. However, controversy remains regarding the interpretation of such results and the subsequent clinical application of these biomarkers, particularly when abnormal in patients with end-stage kidney disease.

Impact of chronic kidney disease on patient outcome following cardiac surgery.

Background: Renal impairment is a major risk factor for cardiovascular disease. This study addressed clinical predictors of outcome following cardiac surgery, focusing on pre-operative renal dysfunction.

Methods: All patients undergoing cardiac surgery at Austin Health from June 1, 2001 to June 30, 2006, were included in the analysis.