Haemodiafiltration, haemofiltration and haemodialysis for end-stage kidney disease

People who have severe loss of kidney function are treated with dialysis or a kidney transplant to remove toxins and fluid. Dialysis removes waste products and fluid by filtering these across a membrane in the dialysis machine (for haemodialysis) or within the body (for peritoneal dialysis). Toxins that build-up in the body when the kidneys fail vary in size and larger molecules are removed less well by standard haemodialysis. Newer dialysis types 'push' water across the dialysis membrane which allows the removal of unwanted molecules more efficiently. Larger molecules are removed better and the dialysis fluid has fewer impurities, leading to the potential for convective dialysis to improve the ways patients feel and survive on dialysis. The three types of convective dialysis therapy are haemodiafiltration, haemofiltration, and acetate-free biofiltration. Use of convective therapy for dialysis is higher in Europe and lower in the USA. Given the difference between regions for uptake of this treatment and the potential benefits on patient outcomes, we have updated this Cochrane review to new additional studies available in 2015.

We identified 40 studies enrolling 4137 adult participants. Of these, 35 studies in 4039 adults compared convective dialysis with standard haemodialysis. Overall the evidence in the studies was low or very low quality due to limitations in the methods used in the research leading to low confidence in the results. Overall, there was no evidence convective dialysis lowered risk of death from any cause but may reduce death due to heart or vascular disease. Overall treating 1000 men and women who have end-stage kidney disease with convective dialysis rather than standard haemodialysis may prevent 25 dying from heart disease. Convective therapy may reduce blood pressure falls during dialysis but there was no evidence that convective dialysis influenced chances of hospital admission or other side-effects, or improved quality of life.

Authors' conclusions: 

Convective dialysis may reduce cardiovascular but not all-cause mortality and effects on nonfatal cardiovascular events and hospitalisation are inconclusive. However, any treatment benefits of convective dialysis on all patient outcomes including cardiovascular death are unreliable due to limitations in study methods and reporting. Future studies which assess treatment effects of convection dose on patient outcomes including mortality and cardiovascular events would be informative.

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Background: 

Convective dialysis modalities (haemofiltration (HF), haemodiafiltration (HDF), and acetate-free biofiltration (AFB)) removed excess body fluid across the dialysis membrane with positive pressure and accumulated middle- and larger-size accumulated solutes more efficiently than haemodialysis (HD). This increased larger solute removal combined with use of ultra-pure dialysis fluid in convective dialysis is hypothesised to reduce the frequency and severity of symptoms during dialysis as well as improve clinical outcomes. Convective dialysis therapies (HDF and HF) are associated with lower mortality compared to diffusive therapy (HD) in observational studies. This is an update of a review first published in 2006.

Objectives: 

To compare convective (HF, HDF, or AFB) with diffusive (HD) dialysis modalities on clinical outcomes (mortality, major cardiovascular events, hospitalisation and treatment-related adverse events) in men and women with end-stage kidney disease (ESKD).

Search strategy: 

We searched the Cochrane Renal Group's Specialised Register (to 18 February 2015) through contact with a Trials' Search Co-ordinator using search terms relevant to this review.

Selection criteria: 

We included randomised controlled trials comparing convective therapy (HF, HDF, AFB) with another convective therapy or diffusive therapy (HD) for treatment of ESKD.

Data collection and analysis: 

Two independent authors identified studies, extracted data and assessed study risk of bias. We summarised treatment effects using the random effects model. We reported results as a risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous data together with 95% confidence intervals (CI). We assessed for heterogeneity using the Chi2 test and explored the amount of variation in treatment estimates beyond that expected by chance using the I2 statistic.

Main results: 

Twenty studies comprising 667 participants were included in the 2006 review. In that review, there was insufficient evidence of treatment effects on major clinical outcomes to draw clinically meaningful conclusions. Searching to February 2015 identified 40 eligible studies comprising 3483 participants overall. In total, 35 studies (4039 participants) compared HF, HDF or AFB with HD, three studies (54 participants) compared AFB with HDF, and three studies (129 participants) compared HDF with HF.

Risks of bias in all studies were generally high resulting in low confidence in estimated treatment effects. Convective dialysis had no significant effect on all-cause mortality (11 studies, 3396 participants: RR 0.87, 95% CI 0.72 to 1.05; I2 = 34%), but significantly reduced cardiovascular mortality (6 studies, 2889 participants: RR 0.75, 95% CI 0.61 to 0.92; I2 = 0%). One study reported no significant effect on rates of nonfatal cardiovascular events (714 participants: RR 1.14, 95% CI 0.86 to 1.50) and two studies showed no significant difference in hospitalisation (2 studies, 1688 participants: RR 1.23, 95% CI 0.93 to 1.63; I2 = 0%). One study reported rates of hypotension during dialysis were significantly reduced with convective therapy (906 participants: RR 0.72, 95% CI 0.66 to 0.80). Adverse events were not systematically evaluated in most studies and data for health-related quality of life were sparse. Convective therapies significantly reduced predialysis levels of B2 microglobulin (12 studies, 1813 participants: MD -5.55 mg/dL, 95% CI -9.11 to -1.98; I2 = 94%) and increased dialysis dose (Kt/V urea) (14 studies, 2022 participants: MD 0.07, 95% CI -0.00 to 0.14; I2 = 90%) compared to diffusive therapy, but results across studies were very heterogeneous. Sensitivity analyses limited to studies comparing HDF with HD showed very similar results. Directly comparative data for differing types of convective dialysis were insufficient to draw conclusions.

Studies had important risks of bias leading to low confidence in the summary estimates and were generally limited to patients who had adequate dialysis vascular access.

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