Anti-coagulation, anti-platelets or no therapy in haemodialysis patients with atrial fibrillation: a decision analysis

BACKGROUND: Optimal treatment of atrial fibrillation (AF) in the haemodialysis population is uncertain due to the exclusion of this group from randomized trials. The risk-benefit profile for anticoagulation and anti-platelet therapy in haemodialysis differs from the general population due to platelet dysfunction from uraemia, altered pharmacokinetics and increased falls risk. METHODS: This decision analysis used a Markov-state transition model that took a patient perspective over a 5 year timeframe. The Markov model compared life-years gained and quality-adjusted life-years gained (QALY) for three AF treatment strategies: warfarin, aspirin and no treatment. The base case was a 70-year-old man on haemodialysis with non-valvular AF. RESULTS: In the base case, the total health outcomes in life-years and QALY were 2.37 and 1.47 respectively for warfarin, 2.38 and 1.61 respectively for aspirin, and 2.39 and 1.61 respectively for no treatment. Thus, warfarin led to 0.14 fewer QALY or 1.7 fewer months of life lived in full health, compared with either aspirin or no therapy. The finding that warfarin generated the lowest expected QALY was robust to one-way, two-way and probabilistic sensitivity analyses. CONCLUSIONS: Our results suggest that warfarin should not be the default choice for older haemodialysis patients with non-valvular AF as it provides the fewest QALY compared with aspirin or no therapy

Anti-coagulation, anti-platelets or no therapy in haemodialysis patients with atrial fibrillation: A decision analysis

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Short-chain fatty acids directly exert anti-inflammatory responses in podocytes and tubular epithelial cells exposed to high glucose

Aims: Gut-microbiome derived short-chain fatty acids exert anti-inflammatory effects and delay progression of kidney disease in diabetic nephropathy. The aim of this study was to examine the impact in vivo and in vitro of short-chain fatty acid treatment on cellular pathways involved in the development of experimental diabetic nephropathy.Methods: To determine the effect of short-chain fatty acids in diabetic nephropathy, we compared wildtype, GPR43−/− and GPR109A−/− mice diabetic mice treated with acetate or butyrate and assessed variables of kidney damage. We also examined the impact of short-chain fatty acid treatment on gene expression in renal tubular cells and podocytes under high glucose conditions.Results: Short-chain fatty acid treatment with acetate or butyrate protected wild-type mice against development of diabetic nephropathy, exhibiting less glomerular hypertrophy, hypercellularity and interstitial fibrosis compared to diabetic controls. Acetate and butyrate treatment did not provide the same degree of protection in diabetic GPR43−/− and GPR109A−/− diabetic mice respectively. Consistent with our in vivo results, expression of pro-inflammatory genes in tubular epithelial cells exposed to high glucose were attenuated by acetate and butyrate treatment. Acetate did not reduce inflammatory or fibrotic responses in glucose stimulated GPR43−/− TECs. Butyrate mediated inhibition of pro-fibrotic gene expression in TECs through GPR109A, and in podocytes via GPR43.Conclusion: SCFAs protect against progression of diabetic nephropathy and diminish podocyte and tubular epithelial injury and interstitial fibrosis via direct, GPR-pathway dependent effects on intrinsic kidney cells. GPR43 and GPR109A are critical to short-chain fatty acid mediated reno-protection and have potential to be harnessed as a therapeutic target in diabetic nephropathy

Interleukin-10 Promoter Polymorphism is Associated with the Predisposition to the Development of IgA Nephropathy and Focal Segmental Glomerulosclerosis in Korea

The roles of interleukin-10 (IL-10) have been emphasized in several models of glomerulonephritis (GN). Three biallelic polymorphisms within the IL-10 promoter region, at positions -1,082, -819, and -592 from the transcription initiation site, were shown to affect the level of IL-10 production. To investigate the effect of IL-10 promoter polymorphisms on the predisposition to development of GN in Korea, IL-10 promoter polymorphisms were assayed by polymerase chain reaction followed by restriction fragment length polymorphism in 108 patients with IgA nephropathy (IgAN), 49 focal segmental glomerulosclerosis (FSGS), and 100 healthy controls. In comparison with the control, the frequency of -1,082*G alleles were lower in IgAN and the frequencies of -592*C and -819*C were lower in FSGS, respectively. As for the haplotype, GCC haplotype was less frequent among IgAN than the control and ATA haplotype was more frequent among FSGS than the control (p<0.05). The frequency of intermediate producer genotypes (GCC/ACC and GCC/ATA) were lower among IgAN or FSGS than the control. Our findings suggested that IL-10 promoter polymorphism predisposed to the development of IgAN and FSGS in Korean patients

Estimating the total incidence of kidney failure in australia including individuals who are not treated by dialysis or transplantation

Background: To date, incidence data for kidney failure in Australia have been available for only those who start renal replacement therapy (RRT). Information about the total incidence of kidney failure, including non-RRT-treated cases, is important to help understand the burden of kidney failure in the community and the characteristics of patients who die without receiving treatment

Comparative Survival and Economic Benefits of Deceased Donor Kidney Transplantation and Dialysis in People with Varying Ages and Co-Morbidities

<div><h3>Background</h3><p>Deceased donor kidneys for transplantation are in most countries allocated preferentially to recipients who have limited co-morbidities. Little is known about the incremental health and economic gain from transplanting those with co-morbidities compared to remaining on dialysis. The aim of our study is to estimate the average and incremental survival benefits and health care costs of listing and transplantation compared to dialysis among individuals with varying co-morbidities.</p> <h3>Methods</h3><p>A probabilistic Markov model was constructed, using current outcomes for patients with defined co-morbidities treated with either dialysis or transplantation, to compare the health and economic benefits of listing and transplantation with dialysis.</p> <h3>Findings</h3><p>Using the current waiting time for deceased donor transplantation, transplanting a potential recipient, with or without co-morbidities achieves survival gains of between 6 months and more than three life years compared to remaining on dialysis, with an average incremental cost-effectiveness ratio (ICER) of less than $50,000/LYS, even among those with advanced age. Age at listing and the waiting time for transplantation are the most influential variables within the model. If there were an unlimited supply of organs and no waiting time, transplanting the younger and healthier individuals saves the most number of life years and is cost-saving, whereas transplanting the middle-age to older patients still achieves substantial incremental gains in life expectancy compared to being on dialysis.</p> <h3>Conclusions</h3><p>Our modelled analyses suggest transplanting the younger and healthier individuals with end-stage kidney disease maximises survival gains and saves money. Listing and transplanting those with considerable co-morbidities is also cost-effective and achieves substantial survival gains compared with the dialysis alternative. Preferentially excluding the older and sicker individuals cannot be justified on utilitarian grounds.</p> </div

The impact of automated eGFR reporting and education on nephrology service referrals

Background. Serum creatinine concentration is an unreliable and insensitive marker of chronic kidney disease (CKD). To improve CKD detection, the Australasian Creatinine Consensus Working Committee recommended reporting of estimated glomerular filtration rate (eGFR) using the four-variable Modification of Diet in Renal Disease (MDRD) formula with every request for serum creatinine concentration. The aim of this study was to evaluate the impact of automated laboratory reporting of eGFR on the quantity and quality of referrals to nephrology services in Southeast Queensland, Australia

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. Patients received cyclosporin, mycophenolate and steroids for the first 14 days then everolimus with mycophenolate and CNIwithdrawal (CNI- WD); everolimus with mycophenolate and steroid withdrawal (steroid-WD); or cyclosporin, mycophenolate and steroids (control). 126 patients were randomized. The steroid WD arm was terminated prematurely because of excess discontinuations. Mean eGFR at month 12 for CNI-WD versus control was 65.1 ml/ min/1.73 m2 vs. 67.1 ml/min/1.73 m2 by ITT, which met predefined noninferiority criteria (P = 0.026). The CNI-WD group experienced a higher rate of BPAR (31% vs. control 13%, P = 0.048) and showed a trend towards higher composite treatment failure (BPAR, graft loss, death, loss to follow-up). The 12 month results from SOCRATES show noninferiority in eGFR, but a significant excess of acute rejection when everolimus was commenced at week 2 to enable a progressive withdrawal of mycophenolate and cyclosporin in kidney transplant recipients.Steven J. Chadban, Josette Marie Eris, John Kanellis, Helen Pilmore, Po Chang Lee, Soo Kun Lim, Chad Woodcock, Nicol Kurstjens, Graeme Rus

Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies

Abstract View references (47) The presence of preformed donor-specific antibodies in transplant recipients increases the risk of acute antibody-mediated rejection (AMR). Results of an open-label single-arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased-donor kidney transplants with preformed donor-specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy-proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow-up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24-70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P <.001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010-019631-35). \ua9 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeon