Fish oil for preventing blockage of haemodialysis vascular access in patients with kidney failure

What is the issue?

Patients requiring long-term haemodialysis (HD) because of poorly functioning kidneys need a reliable and efficient method of circulating blood at high flow rates between their bodies and the HD machine. Arteriovenous fistulas (AVFs) and grafts (AVGs) are the two main methods of achieving such long-term vascular access. An AVF is a surgically constructed direct connection (fistula) between a patient's artery and vein. An AVG is a synthetic flexible hollow tubing (graft) that indirectly connects a patient's artery and vein and is usually used when a fistula cannot be created. During HD, the fistula or graft is pierced by needles (cannulated) connected to the dialysis machine. The patency of these artificial connections may be blocked by blood clots (thrombosis) or by a narrowing (stenosis) of the vein. The risk of this occurring is lower for AVFs, making it the method of choice. When a blockage does occur, HD cannot be performed and surgical or radiological salvage procedures will be urgently required. Omega-3 fatty acid fish oils can reduce blood viscosity and might conceivably reduce the risk of blood clots and blood vessel narrowing, hence improving long-term vascular access and quality of HD.

What did we do?

We collected data from studies that tested HD patients with supplements of omega-3 fatty acid fish oils against placebo and that reported results for preventing vascular access blockage and for the following side-effects - death, hospitalisation, cardiovascular events, major bleeding, minor bleeding, gastrointestinal events, and other adverse events. We analysed and reported the results separately for patients with AVFs and AVGs.

What did we find?

We found five randomised controlled trials (RCTs) that studied a total of 833 participants; one was a very small pilot study of seven participants. Four studies involved patients with AVGs; there was only one study of AVFs. The outcomes were measured over a period of six or 12 months. There were reservations about the overall quality of all the studies, making us moderately to highly uncertain about the evidence. In AVF patients, we are moderately certain that fish oil supplements do not prevent blockage nor do they cause additional harm but the evidence only comes from one study. In AVG patients, we are very uncertain of the evidence for preventing blockage or causing serious harm, but there may be an increased risk of mild digestive side-effects such as a sensation of bloatedness, gas or a fishy aftertaste.

Conclusions

There is limited high quality data on the benefits of omega-3 fish oil supplementation for preventing HD blockage in kidney failure patients. We did not find strong evidence that omega-3 fish oil supplements could prevent blockage of HD vascular access or that it increases the risk of serious and non-serious side-effects. All the evidence for preventing blockages come from just one or two studies, so more and better quality studies are needed.

Authors' conclusions: 

In CKD patients with an AVF, there is moderate certainty that ω-3FA supplementation makes little or no difference to preventing patency loss; and in patients with an AVG, it is very uncertain that ω-3FA supplementation prevents patency loss within 12 months.

Read the full abstract...
Background: 

Maintaining long-term vascular access patency is necessary for high quality haemodialysis (HD) treatment of patients with the terminal and most serious stage of chronic kidney disease (CKD) - end-stage kidney disease (ESKD). Oral supplementation with omega-3 fatty acids (ω-3FA) may help to prevent blockage of the vascular access by reducing the risk of thrombosis and stenosis.

Objectives: 

To evaluate the efficacy and safety of ω-3FA supplementation versus placebo or no treatment for maintaining vascular access patency in ESKD patients undergoing HD.

Search strategy: 

We searched the Cochrane Kidney and Transplant Register of Studies up to 23 July 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov.

Selection criteria: 

Randomised controlled trials (RCTs) of omega-3 fatty acids versus placebo that assessed the patency of arteriovenous fistula (AVF) or arteriovenous graft (AVG) types of vascular access in ESKD patients.

Data collection and analysis: 

We assessed the risk of bias of each eligible study using the Cochrane Risk of Bias tool and made separate overall risk of bias judgments for the efficacy and safety outcomes. The certainty of evidence was assessed using the GRADE approach. The primary efficacy outcome was loss of vascular patency and the primary safety outcomes were occurrences of serious adverse events (e.g. death, hospitalisation, cardiovascular events, major bleeding). Secondary outcomes were the occurrence of non-serious adverse events (e.g. minor bleeding, gastrointestinal events and other adverse events). Efficacy effects were reported as risk ratios (RR) and safety effects as risk differences (RD) with 95% confidence intervals (CI). Studies were pooled separately by type of vascular access using a random-effects model.

Main results: 

Five studies (833 participants) were included; one was a very small pilot study of 7 participants. All studies compared oral ω-3FA supplements against placebo. Four studies enrolled participants with arteriovenous grafts (AVGs), and the other had participants with arteriovenous fistulas (AVFs). The risk of bias for both efficacy and safety outcomes was unclear for all studies, due mainly to incomplete reporting for allocation concealment and incompleteness of study follow-up.

In AVF patients, ω-3FA supplementation probably makes little or no difference to the 12-month risk of patency loss (1 study, 536 participants: RR 1.01, 95% CI 0.84 to 1.21; moderate certainty evidence), risk of death (1 study, 567 participants: RD 0.00, 95% CI -0.03 to 0.02; moderate certainty evidence) and risk of hospitalisation (1 study, 567 participants: RD 0.00, 95% CI -0.08 to 0.08; low certainty evidence). There was no information on cardiovascular events and major bleeding.

In AVG patients, it is very uncertain whether ω-3FA supplementation reduces the risk of patency loss within 6 months (2 studies, 41 participants: RR 0.91, 95% CI 0.36 to 2.28; very low certainty evidence) or 12 months (2 studies, 220 participants: RR 0.59, 95% CI 0.27 to 1.31; very low certainty evidence). ω-3FA supplementation may make little or no difference to the risk of death within 6 to 12 months in AVG patients (4 studies, 261 participants: RD 0.01, 95% CI -0.05 to 0.07; low certainty evidence). It is very uncertain if ω-3FA supplementation increases the risk of hospitalisation (3 studies, 65 participants: RD 0.08, 95% CI -0.11 to 0.28; very low certainty evidence), changes the risk of cardiovascular events (4 studies, 261 participants: RD -0.02, 95% CI -0.11 to 0.07; very low certainty evidence), or increases the risk of major bleeding (3 studies, 65 participants: RD 0.08, 95% CI -0.11 to 0.28; very low certainty evidence) within 6 to 12 months in AVG patients. There may be an increase in the risk of mild gastrointestinal adverse reactions (3 studies, 65 participants: RD 0.25, 95% CI 0.07 to 0.43; low certainty evidence) such as a sensation of bloatedness, gas or a fishy aftertaste.

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