Glass Slippers and Glass Cliffs: Fitting In and Falling Off.

Background: A glass ceiling effect exists for women in male-dominated professions. Recent studies also show a glass-cliff effect where senior women can more easily fall from positions of leadership. Transplantation remains a male-dominated specialty.

Administration of erythropoiesis-stimulating agents in patients undergoing haemodialysis: A time and motion study.

Background: International guidelines recommend treatment of anaemia due to chronic kidney disease (CKD) with erythropoiesis-stimulating agents (ESAs).

Objective: To document the time required and the cost in terms of nursing time to prepare and administer ESAs to patients on facility based haemodialysis (HD) with anaemia due to CKD before and after the introduction of long-acting ESAs.

Design: A time and motion study was implemented at four HD units in Australia to determine the time and costs associated with preparing and administering ESAs before and after the introduction of long-acting ESAs.

A Trial of Extending Hemodialysis Hours and Quality of Life.

The relationship between increased hemodialysis hours and patient outcomes remains unclear. We randomized (1:1) 200 adult recipients of standard maintenance hemodialysis from in-center and home-based hemodialysis programs to extended weekly (≥24 hours) or standard (target 12-15 hours, maximum 18 hours) hemodialysis hours for 12 months. The primary outcome was change in quality of life from baseline assessed by the EuroQol 5 dimension instrument (3 level) (EQ-5D).

Comparison of intermittent and continuous extracorporeal treatments for the enhanced elimination of dabigatran.

Context: Severe bleeding associated with dabigatran frequently requires intensive care management. An antidote is currently unavailable and data reporting the effect of dialysis on elimination of dabigatran are encouraging, but limited. Objective.

A systematic review of conversion from calcineurin inhibitor to mammalian target of rapamycin inhibitors for maintenance immunosuppression in kidney transplant recipients.

This was a systematic review of randomized controlled trials comparing delayed conversion of mammalian target of rapamycin inhibitors (mTORi) for calcineurin inhibitors (CNIs) versus CNI continuation in kidney transplantation. Databases (2000-2012) and conference abstracts (2009-2012) were searched giving a total of 29 trials. Outcomes analyzed included GFR, graft loss, rejection and adverse events and were expressed as weighted mean differences (WMDs) or as risk ratios (RRs).

A role for everolimus in post-transplant encapsulating peritoneal sclerosis: first case report.

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD) that carries a high morbidity and mortality. The 'two hit theory' suggests that long term deterioration of the peritoneum combined with intraperitoneal inflammation is needed in the pathogenesis of EPS. For unclear reasons, post transplantation EPS is being increasingly reported in patients previously on PD.

A randomized, controlled trial of everolimus-based dual immunosuppression versus standard of care in de novo kidney transplant recipients.

Kidney transplant recipients receiving calcineurin inhibitor-based immunosuppression incur increased long-term risks of cancer and kidney fibrosis. Switch to mammalian target of rapamycin (mTOR) inhibitors may reduce these risks. Steroid or Cyclosporin Removal After Transplant using Everolimus (SOCRATES), a 36-month, prospective, multinational, open-label, randomized controlled trial for de novo kidney transplant recipients, assessed whether everolimus switch could enable elimination of mycophenolate plus either steroids or CNI without compromising efficacy.

Efficacy of sotrastaurin plus tacrolimus after de novo kidney transplantation: randomized, phase II trial results.

Sotrastaurin, a novel immunosuppressant, blocks early T cell activation through protein kinase C inhibition. Efficacy and safety of sotrastaurin with tacrolimus were assessed in a dose-ranging non-inferiority study in renal transplant recipients. A total of 298 patients were randomized 1:1:1:1 to receive sotrastaurin 100 (n = 77; discontinued in December 2011) or 200 mg (n = 73) b.

Sotrastaurin in calcineurin inhibitor-free regimen using everolimus in de novo kidney transplant recipients.

Sotrastaurin, a novel selective protein-kinase-C inhibitor, inhibits early T cell activation via a calcineurin-independent pathway. Efficacy and safety of sotrastaurin in a calcineurin inhibitor-free regimen were evaluated in this two-stage Phase II study of de novo kidney transplant recipients. Stage 1 randomized 131 patients (2:1) to sotrastaurin 300 mg or cyclosporine A (CsA).

Sirolimus reduces vasculopathy but exacerbates proteinuria in association with inhibition of VEGF and VEGFR in a rat kidney model of chronic allograft dysfunction.

Background: Use of the mTOR inhibitor (mTORi) sirolimus to replace calcineurin inhibitors in kidney transplantation has been associated with improved renal function but, in a proportion of cases, also with de novo or exacerbated proteinuria. Experimental deficiency of vascular endothelial growth factor (VEGF) induces proteinuria and mTOR is required for VEGF production and signalling. We therefore explored the impact of sirolimus on the development of chronic allograft dysfunction (CAD) in the rat, with a focus on VEGF biology.

Enteric-coated mycophenolate sodium in combination with full dose or reduced dose cyclosporine, basiliximab and corticosteroids in Australian de novo kidney transplant patients.

Aim: Cyclosporine (CsA), dosed to achieve C2 targets, has been shown to provide safe and efficacious immunosuppression when used with a mycophenolate and steroids for de novo kidney transplant recipients. This study examined whether use of enteric-coated mycophenolate sodium (EC-MPS) together with basiliximab and steroids would enable use of CsA dosed to reduced C2 targets in order to achieve improved graft function.

Methods: Twelve-month, prospective, randomized, open-label trial in de novo kidney transplant recipients in Australia.

Stimulation of mesangial cells by angiotensin II and lipopolysaccharide increases expression of interleukin-18, but not IL-18 receptor.

Background/aims: Mesangial cell (MC) hyperplasia is associated with several kidney diseases. Experimental studies confirm upregulation of IL-18 in glomerular disease and renal allograft rejection. We evaluated whether MCs express IL-18 and IL-18 receptor-α (IL-18Rα) with and without stimulation by LPS, AngII and PDGF.

Long-term cancer risk of immunosuppressive regimens after kidney transplantation.

Cancer is a widely recognized complication of transplantation, and the effects of various immunosuppressive drugs on cancer risk remains controversial. This randomized trial allocated 489 recipients of first cadaveric renal transplants to one of three groups: Azathioprine and prednisolone, cyclosporine monotherapy, or cyclosporine monotherapy followed by a switch to azathioprine and prednisolone after 3 months. Here, we report cancer outcomes by non-skin cancer (including melanoma) and skin cancer (excluding melanoma) for 481 patients during a median follow-up of 20.

Outcome of parathyroidectomy for patients with renal disease and hyperparathyroidism: predictors for recurrent hyperparathyroidism.

Background: A small group of patients with renal disease-related secondary or tertiary hyperparathyroidism require surgical parathyroidectomy. Among them, 5-20% require further re-exploration and excision of parathyroid tissue because of recurrent disease. The aims of the present study were to review the characteristics and outcomes of patients undergoing parathyroidectomy for renal disease related hyperparathyroidism and to identify the risk factors for recurrent hyperparathyroidism.

Cyclosporine withdrawal improves long-term graft survival in renal transplantation.

Background: The reduction in renal transplant rejection rates achieved over the last 20 years have not translated into a commensurate improvement in long-term graft survival. Cyclosporine has been central to immunosuppressive regimens throughout this period but its effect on long-term transplant outcomes remains unclear.

Methods: This randomized controlled trial allocated first cadaveric renal transplant recipients in seven centers around Australia to three immunosuppressive regimens: azathioprine and prednisolone (AP), long-term cyclosporine alone (Cy), or cyclosporine initiation followed by withdrawal at 3 months and azathioprine and prednisolone replacement (WDL).

Photopheresis therapy for problematic renal allograft rejection.

Background: Photopheresis is an immunomodulatory therapy for the treatment of T cell-mediated disorders. It has been used for rejection prophylaxis in cardiac transplantation, adjuvant treatment of bronchiolitis obliterans in lung transplantation, treatment of graft verse host disease, and in a small number of cases, for treatment of acute rejection in renal transplantation. Little is known of long-term outcomes following the use of photopheresis in solid organ transplantation.

Dentritic cell derived IL-18 production is inhibited by rapamycin and sanglifehrin A, but not cyclosporine A.

Interleukin-18 (IL-18), a product of dendritic cells (DC), is a pro-inflammatory cytokine involved in the pathogenesis of allograft rejection, vascular disease, arthritis and diabetes. Rapamycin (Rapa) is an immunosuppressant that inhibits T cell mTOR kinase activation. In contrast, Sanglifehrin A (SFA), is a cyclophilin-binding immunosuppressant that does not act on calcineurin phosphatases but appears to inhibit IL-2-dependent T cell proliferation.

TLR4 activation mediates kidney ischemia/reperfusion injury.

Ischemia/reperfusion injury (IRI) may activate innate immunity through the engagement of TLRs by endogenous ligands. TLR4 expressed within the kidney is a potential mediator of innate activation and inflammation. Using a mouse model of kidney IRI, we demonstrated a significant increase in TLR4 expression by tubular epithelial cells (TECs) and infiltrating leukocytes within the kidney following ischemia.

Decision-making about suitability for kidney transplantation: Results of a national survey of Australian nephrologists.

Aim: This study aimed to elucidate the factors affecting nephrologists' decision-making on patients' suitability for kidney transplantation. Given the reduced access to transplantation for Indigenous Australians, the role of patient's ethnicity was of particular interest.

Methods: A postal survey of practising nephrologists and trainees was undertaken in Australia.

Anemia after kidney transplantation is not completely explained by reduced kidney function.

Background: Anemia is prevalent among kidney transplant recipients and likely contributes to mortality and morbidity. Prevalence of anemia is associated strongly with degree of kidney graft dysfunction; however, it remains unclear whether additional transplant-associated factors also contribute.

Methods: The aim of this study is to compare the prevalence of anemia between 2 cohorts, 1 of kidney transplant recipients (n = 851) and another from the general population (n = 732), sourced from subjects of the AusDiab study and selected by means of propensity score to provide a cohort matched for kidney function (Cockcroft-Gault creatinine clearance).

12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients.

The proliferation signal inhibitor everolimus (Certican), has demonstrated efficacy with full-dose cyclosporine (CsA) (Neoral). Two multicenter randomized controlled studies were performed to compare 12-month efficacy and safety of everolimus 1.5 and 3.