Worldwide, the most common renal replacement therapy is hemodialysis, best performed using a functioning arteriovenous vascular access; aestablishing and maintaining functional arteriovenous vascular access remains a major challenge associated with dialysis care. Dysfunction of arteriovenous fistula (AVF) and graft (AVG) leads to prolonged use of central venous catheters and is associated with repeat hospitalization and procedures as well as higher rates of complications and mortality.
The pathogenesis of arteriovenous access failure is complex and not well understood. Possible explanations include neointimal hyperplasia formation and impaired vascular remodeling, with insufficient vasodilation and vessel wall thickening in response to the increased pressure, shear stress, and oxygen tension that results from redirected arterial flow.
Researchers, led by Andrea K. Viecelli, MD, hypothesized that access outcomes might be improved with omega-3 polyunsaturated fatty acids (omega-3 PUFA) via pleiotropic effects on access maturation and function. However, there may also be an association between omega-3 PUFA and bleeding complications in the patients with end-stage renal disease (ESRD) requiring hemodialysis.
To test the hypothesis and evaluate the benefits and harms of omega-3 PUFA supplementation for arteriovenous access complications, the researchers conducted a systematic review and meta-analysis. Results were reported in the American Journal of Kidney Diseases [2018;72(1):50-61].
The review included a search of MEDLINE (1946 through January 24, 2017); Embase (1980 through January 24, 2017); and the Cochrane Central Register of Controlled Trials (through issue 11 of 12, 2016). Eligible trials were randomized controlled and quasi-randomized controlled comparing omega-3 PUFAs with placebo or no treatment for prevention of AVF or AVG failure. Eligible participants were adults with ESRD receiving or planning to receive hemodialysis using an AVF, AVG, or arteriovenous shunt in the upper or lower limb.
Eligibility requirements were met by six trials involving 865 participants. There was a range of seven to 567 participants assigned to receive treatment in the studies. Duration of treatment ranged from 12 to 52 weeks, and follow-up ranged between 5 and 12 months. Four studies reported the timing in initiation of treatment: within 7 days of access creation in two trials; 2 weeks following access creation in one trial; and 1 day prior to access creation in one trial.
Dosage of omega-3 PUFA varied from 3 grams three times per week to 6 grams daily; content of the two main biologically active components varied (eicosapentaenoic acid [EPA; 0.96-3 g] and docosahexaenoic acid [DHA; 0.6-1.52 g]). The effect of omega-3 PUFA on AVG outcomes was examined in four studies, on AVF outcomes in one trial, and on shunt outcomes in one trial. The remaining study was a crossover trial lacking extractable outcome data reported at the end of the first study phase; there was no data from that trial included in the meta-analysis.
In three trials, 265 participants had primary patency loss due to thrombosis or requiring an intervention to restore patency (761 individuals at risk). Evidence with moderate certainty suggested that patency loss was prevented with treatment with omega-3 PUFA (relative risk [RR], 0.81; 95% confidence interval [CI], 0.68-0.98) using 1.6 to 3.4 grams of EPA and DHA for 12 to 52 weeks. There was no evidence of significant heterogeneity in treatment effects. There was no significant difference between access type in treatment effects on vascular access patency loss (P [for subgroup difference]=.9).
At least one bleeding event occurred in 44 individuals (794 individuals at risk). Evidence with very low certainty suggested there was an uncertain risk for bleeding associated with omega-3 PUFA supplementation (RR, 1.40- 95% CI, 0.78-2.49). There were no data regarding the severity or duration of bleeding episodes with the exception of one participant assigned to treatment with omega-3 PUFA ( 3 g of EPA three times weekly) who required hospitalization for a gastrointestinal bleed.
One trial included data for late dialysis suitability failure, defined as an AVF that was unable to be cannulated for at least eight of 12 consecutive dialysis sessions or was abandoned with 6 months of access surgery. It was not possible to conduct a meta-analysis of that data. In the single trial, there was no statistically significant difference between the RR determined by log-binomial regression analysis and adjusted for use of aspirin between omega-3 PUFA (3.4 g of EPA and DHA daily for 12 weeks) and the placebo arm (78 of 270 [29%] vs 81 of 266 [30%]; RR, 0.95; 95% CI, 0.73-1.24).
One trial representing 536 individuals reported on the need for interventions to restore patency or assist maturation in newly created AVFs, as did one representing 196 individuals in newly created AVGs. Low certainty evidence suggested that treatment with omega-3 PUFA (2.4 to 3.4 g of EPA and DHA daily) may have had little or no effect on the need for access interventions to maintain patency (RR, 0.82; 95% CI, 0.64-1.04). Treatment effects were not different for AVFs and AVGs.
Omega-3 PUFA supplementation (2.4 g to 3.4 g of EPA and DHA daily) may have had little or no effect on arteriovenous access abandonment based on evidence of low certainty (RR, 0.78; 95% CI, 0.59-1.03).
The authors cited some limitations to the findings, including imprecision of risk estimates and the low certainty of evidence for most outcomes due to the small number of trials and events. There was also possible limitation in the ability to detect a significant difference between AVFs and AVGs in treatment effect. In addition, despite a highly sensitive search that included hand-searching and conference abstracts, unpublished studies may have been missed.
In conclusion, the researchers said, “Omega-3 PUFA supplementation started at the time of arteriovenous access surgery, probably prevents primary patency loss within 12 months but may have little or no effect on access interventions, dialysis suitability failure, or access abandonment, and treatment harms are uncertain. Larger randomized controlled trials are required to determine the efficacy and safety of omega-3 PUFA supplementation in patients requiring hemodialysis and to assess novel putative interventions to improve dialysis vascular outcomes. Based on the available evidence, recommendations on the routine use of omega-3 PUFAs for safely preventing arteriovenous access complications cannot be made.”
- Establishing and maintaining functional arteriovenous access is a major challenge in the management of patients with end-stage renal disease requiring maintenance hemodialysis.
- Researchers conducted a systematic review and meta-analysis of randomized controlled trials examining treatment with omega-3 polyunsaturated fatty acids (PUFAs) for arteriovenous access outcomes.
- Supplementation with omega-3 PUFAs likely protects against primary loss of arteriovenous access patency; there may be little or no effect on dialysis suitability failure, access interventions, or access abandonment.