Dietary habits in Australian, New Zealand and Malaysian patients with end stage kidney failure: A pre-specified cross-sectional study of the FAVOURED trial participants.

BACKGROUND: Dietary management plays an important role in patients with kidney failure. Current dietary habits of Australians and New Zealanders (ANZ) and Malaysians with chronic kidney disease (CKD Stage 4-5) have not been adequately investigated. We report the dietary habits of people with advanced CKD and their adherence to country-specific dietary guidelines. METHODS: Participants with CKD Stage 4-5, enrolled in the Omega-3 Fatty Acids (Fish oils) and Aspirin in Vascular access Outcomes in Renal Disease (FAVOURED) trial, completed a lifestyle questionnaire at baseline on their dietary intake. RESULTS: Of 567 participants, 538 (ANZ, n = 386; Malaysian, n = 152; mean ± SD age 54.8 ± 14.3 years, 64% male) completed the questionnaire. Dietary fruit and vegetable intakes were higher in ANZ participants; 49% (n = 189) consumed ≥2 serves day-1 of fruit and 61% (n = 235) ate ≥2 serves day-1 of vegetables compared to 24% (n = 36) and 34% (n = 52) of Malaysians, respectively (p < 0.0001). Only 4% (n = 15) of ANZ participants met Australian Dietary recommendations of two fruit and five vegetable serves day-1 . Fish consumption was higher in Malaysians with 83% (n = 126) consuming ≥2 serves week-1 compared to 21% (n = 81) of ANZ participants (p < 0.001). Red meat intake was higher in ANZ participants; however, chicken consumption was similar; 48% (n = 185) consumed >2 chicken serves week-1 and 65% (n = 251) ate >2 serves week-1 of red meat compared to 43% (n = 65) and 15% (n = 23) of Malaysians, respectively. CONCLUSIONS: Significant regional variation in dietary intake for fruit, vegetables and animal protein is described that likely reflects cultural and economic differences. Barriers to meeting recommended dietary intakes require further investigation.

Fish oil and aspirin effects on arteriovenous fistula function: Secondary outcomes of the randomised omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) trial.

BACKGROUND: Arteriovenous fistulas (AVF) for haemodialysis often experience early thrombosis and maturation failure requiring intervention and/or central venous catheter (CVC) placement. This secondary and exploratory analysis of the FAVOURED study determined whether omega-3 fatty acids (fish oils) or aspirin affected AVF usability, intervention rates and CVC requirements. METHODS: In 567 adult participants planned for AVF creation, all were randomised to fish oil (4g/d) or placebo, and 406 to aspirin (100mg/d) or placebo, starting one day pre-surgery and continued for three months. Outcomes evaluated within 12 months included AVF intervention rates, CVC exposure, late dialysis suitability failure, and times to primary patency loss, abandonment and successful cannulation. RESULTS: Final analyses included 536 participants randomised to fish oil or placebo (mean age 55 years, 64% male, 45% diabetic) and 388 randomised to aspirin or placebo. Compared with placebo, fish oil reduced intervention rates (0.82 vs 1.14/1000 patient-days, incidence rate ratio [IRR] 0.72, 95% confidence interval [CI] 0.54-0.97), particularly interventions for acute thrombosis (0.09 vs 0.17/1000 patient-days, IRR 0.53, 95% CI 0.34-0.84). Aspirin significantly reduced rescue intervention rates (IRR 0.45, 95% CI 0.27-0.78). Neither agent significantly affected CVC exposure, late dialysis suitability failure or time to primary patency loss, AVF abandonment or successful cannulation. CONCLUSION: Although fish oil and low-dose aspirin given for 3 months reduced intervention rates in newly created AVF, they had no significant effects on CVC exposure, AVF usability and time to primary patency loss or access abandonment. Reduction in access interventions benefits patients, reduces costs and warrants further study.

Omega-3 Polyunsaturated Fatty Acid Supplementation to Prevent Arteriovenous Fistula and Graft Failure: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Arteriovenous access failure frequently occurs in people on hemodialysis and is associated with morbidity, mortality and large healthcare expenditures. Omega-3 polyunsaturated fatty acids (omega-3 PUFA) may improve access outcomes via pleiotropic effects on access maturation and function, but may cause bleeding complications. STUDY DESIGN: Systematic review with meta-analysis. SETTING & POPULATION: Adults requiring hemodialysis via arteriovenous fistula or graft. SELECTION CRITERIA: Trials evaluating omega-3 PUFA for arteriovenous access outcomes identified by searches in CENTRAL, MEDLINE, and Embase to 24 January 2017. INTERVENTION: Omega-3 PUFA. OUTCOMES: Primary patency loss, dialysis suitability failure, access abandonment, interventions to maintain patency or assist maturation, bleeding, gastrointestinal side-effects, all-cause and cardiovascular mortality, hospitalization, and treatment adherence. Treatment effects were summarized as relative risks (RR) and 95% confidence intervals (CI). Evidence was assessed using GRADE. RESULTS: Five eligible trials (833 participants) with a median follow-up of 12 months compared peri-operative omega-3 PUFA supplementation with placebo. One trial (n=567) evaluated treatment for fistulae and four (n=266) for grafts. Omega-3 PUFA supplementation prevented primary patency loss with moderate certainty (761 participants, RR 0.81, CI 0.68-0.98). Low quality evidence suggested, that omega-3 PUFA may have had little or no effect on dialysis suitability failure (536 participants, RR 0.95, CI 0.73-1.23), access abandonment (732 participants, RR 0.78, CI 0.59-1.03), need for interventions (732 participants, RR 0.82, CI 0.64-1.04), or all-cause mortality (799 participants, RR 0.99, CI 0.51-1.92). Bleeding risk (793 participants, RR 1.40, CI 0.78-2.49) or gastrointestinal side-effects (816 participants, RR 1.22, CI 0.64-2.34) from treatment were uncertain. There was no evidence of different treatment effects for grafts and fistulae. LIMITATIONS: Small number and methodological limitations of included trials. CONCLUSIONS: Omega-3 PUFA supplementation probably protects against primary loss of arteriovenous access patency, but may have little or no effect on dialysis suitability failure, access interventions or access abandonment. Potential treatment harms are uncertain.

The pathogenesis of hemodialysis vascular access failure and systemic therapies for its prevention: Optimism unfulfilled.

In patients receiving hemodialysis, the provision of safe and effective vascular access using an arteriovenous fistula or graft is regarded as a critical priority by patients and health professionals. Vascular access failure is associated with morbidity and mortality, such that strategies to prevent these outcomes are essential. Inadequate vascular remodeling and neointimal hyperplasia resulting in stenosis and frequently thrombosis are critical to the pathogenesis of access failure. Systemic medical therapies with pleiotropic effects including antiplatelet agents, omega-3 polyunsaturated fatty acids (fish oils), statins, and inhibitors of the renin-angiotensin-aldosterone system (RAAS) may reduce vascular access failure by promoting vascular access maturation and reducing stenosis and thrombosis through antiproliferative, antiaggregatory, anti-inflammatory and vasodilatory effects. Despite such promise, the results of retrospective analyses and randomized controlled trials of these agents on arteriovenous fistula and graft outcomes have been mixed. This review describes the current understanding of the pathogenesis of arteriovenous fistula and graft failure, the biological effects of antiplatelet agents, fish oil supplementation, RAAS blockers and statins that may be beneficial in improving vascular access survival, results from clinical trials that have investigated the effect of these agents on arteriovenous fistula and graft outcomes, and it explores future therapeutic approaches combining these agents with novel treatment strategies.

Effect of Fish Oil Supplementation and Aspirin Use on Arteriovenous Fistula Failure in Patients Requiring Hemodialysis: A Randomized Clinical Trial.

Importance: Vascular access dysfunction is a leading cause of morbidity and mortality in patients requiring hemodialysis. Arteriovenous fistulae are preferred over synthetic grafts and central venous catheters due to superior long-term outcomes and lower health care costs, but increasing their use is limited by early thrombosis and maturation failure. ω-3 Polyunsaturated fatty acids (fish oils) have pleiotropic effects on vascular biology and inflammation and aspirin impairs platelet aggregation, which may reduce access failure. Objective: To determine whether fish oil supplementation (primary objective) or aspirin use (secondary objective) is effective in reducing arteriovenous fistula failure. Design, Setting, and Participants: The Omega-3 Fatty Acids (Fish Oils) and Aspirin in Vascular Access Outcomes in Renal Disease (FAVOURED) study was a randomized, double-blind, controlled clinical trial that recruited participants with stage 4 or 5 chronic kidney disease from 2008 to 2014 at 35 dialysis centers in Australia, Malaysia, New Zealand, and the United Kingdom. Participants were observed for 12 months after arteriovenous fistula creation. Interventions: Participants were randomly allocated to receive fish oil (4 g/d) or matching placebo. A subset (n = 406) was also randomized to receive aspirin (100 mg/d) or matching placebo. Treatment started 1 day prior to surgery and continued for 12 weeks. Main Outcomes and Measures: The primary outcome was fistula failure, a composite of fistula thrombosis and/or abandonment and/or cannulation failure, at 12 months. Secondary outcomes included the individual components of the primary outcome. Results: Of 1415 eligible participants, 567 were randomized (359 [63%] male, 298 [53%] white, 264 [47%] with diabetes; mean [SD] age, 54.8 [14.3] y). The same proportion of fistula failures occurred in the fish oil and placebo arms (128 of 270 [47%] vs 125 of 266 [47%]; relative risk [RR] adjusted for aspirin use, 1.03; 95% CI, 0.86-1.23; P = .78). Fish oil did not reduce fistula thrombosis (60 [22%] vs 61 [23%]; RR, 0.98; 95% CI, 0.72-1.34; P = .90), abandonment (51 [19%] vs 58 [22%]; RR, 0.87; 95% CI, 0.62-1.22; P = .43), or cannulation failure (108 [40%] vs 104 [39%]; RR, 1.03; 95% CI, 0.83-1.26; P = .81). The risk of fistula failure was similar between the aspirin and placebo arms (87 of 194 [45%] vs 83 of 194 [43%]; RR, 1.05; 95% CI, 0.84-1.31; P = .68). Conclusions and Relevance: Neither fish oil supplementation nor aspirin use reduced failure of new arteriovenous fistulae within 12 months of surgery. Trial Registration: anzctr.org.au Identifier: CTRN12607000569404.

Baseline characteristics of the omega-3 fatty acids (Fish oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study.

AIM: The Fish oils and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) trial investigated whether 3 months of omega-3 polyunsaturated fatty acids, either alone or in combination with aspirin, will effectively reduce primary access failure of de novo arteriovenous fistulae. This report presents the baseline characteristics of all study participants, examines whether study protocol amendments successfully increased recruitment of a broader and more representative haemodialysis cohort, including patients already receiving aspirin, and contrasts Malaysian participants with those from Australia, New Zealand and the United Kingdom (UK). METHOD: This international, randomized, double-blind, placebo-controlled trial included patients older than 19 years with stage 4 or 5 chronic kidney disease currently receiving, or planned within 12 months to receive haemodialysis. RESULTS: Participants (n = 568) were overweight (28.6 ± 7.3 kg/m(2) ), relatively young (54.8 ± 14.3 years), and predominantly male (63%) with a high prevalence of diabetes mellitus (46%) but low rate of ischaemic heart disease (8%). Sixty one percent were planned for lower arm arteriovenous fistula creation. Malaysian participants (n = 156) were younger (51.8 ± 13.6 years vs 57.1 ± 14.2 years, P < 0.001) with a higher prevalence of diabetes mellitus (65% vs 43%, P < 0.001), but less ischaemic heart disease (5% vs 14%, P < 0.01) compared with the combined Australian, New Zealand and UK cohort (n = 228). Protocol modifications allowing for inclusion of patients receiving aspirin increased the prevalence of co-morbidities compared with the original cohort. CONCLUSIONS: The FAVOURED study participants, while mostly similar to patients in contemporary national registry reports and comparable recent clinical trials, were on average younger and had less ischaemic heart disease. These differences were reduced as a consequence of including patients already receiving aspirin.

The Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study: the updated final trial protocol and rationale of post-initiation trial modifications.

BACKGROUND: The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which commenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs) either alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous fistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from additional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial design. METHODS/DESIGN: The original trial protocol published in 2009 has undergone two major amendments, which were implemented in 2011. Firstly, the primary outcome 'early thrombosis' at 3 months following AVF creation was broadened to a more clinically relevant outcome of 'AVF access failure'; a composite of thrombosis, AVF abandonment and cannulation failure at 12 months. Secondly, participants unable to cease using aspirin were allowed to be enrolled and randomised to omega-3 PUFAs or placebo. The revised primary aim of the FAVOURED study is to test the hypothesis that omega-3 PUFAs will reduce rates of AVF access failure within 12 months following AVF surgery. The secondary aims are to examine the effect of omega-3 PUFAs and aspirin on the individual components of the primary end-point, to examine the safety of study interventions and assess central venous catheter requirement as a result of access failure. DISCUSSION: This multicentre international clinical trial was amended to address the clinically relevant question of whether the usability of de novo AVF at 12 months can be improved by the early use of omega-3 PUFAs and to a lesser extent aspirin. This study protocol amendment was made in response to a large trial demonstrating that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Secondly, including patients taking aspirin will enroll a more representative cohort of haemodialysis patients, who are significantly older with a higher prevalence of cardiovascular disease and diabetes which may increase event rates and the power of the study. TRIAL REGISTRATION: Australia & New Zealand Clinical Trial Register (ACTRN12607000569404).