Is it time to wake up to online Hemodiafiltration?

There has been a lot of interest recently in online Hemodiafiltration (olHDF) with multiple studies  published in the past year. It is a technique which has gained favor in Europe (albeit with a lack of hard evidence) while being not utilized at all in the US for various reasons. HDF involves the addition of convective clearance, hemofiltration, to the diffusive treatment of hemodialysis (HD) which gives better clearance of middle sized uremic toxins. Very large volumes of plasma water are ultrafiltered using a high flux dialyzer with replacement solution needed to maintain fluid balance. As a large volume of fluid is infused directly into the patient, this infusate needs to be ultrapure with low levels of pyrogen and microbial contamination. The development of online generation of ultrapure replacement fluid, directly from the water treatment plant, has facilitated the roll out of olHDF in Europe. Safety concerns have also been addressed. Previously reported benefits, apart from middle molecule clearance, have included better phosphorous removal, improved intra-dialytic blood pressures, lower levels of EPO resistance, improved quality of life among others but hard outcome data has been lacking until recently. The past year has seen the publication of 3 randomized controlled trials examining olHDF versus conventional HD.

CONTRAST Study

The Convective Transport Study randomly assigned 714 patients to either olHDF or low flux HD. There was no difference between the groups in the primary outcome of all-cause mortality after a 3 year follow-up. However, in post-hoc analyses, receiving high dose olHDF (>22L of convective volume per session) was associated with a lower all-cause mortality compared to low flux HD (HR 0.62).

Turkish olHDF Study

This study randomized 782 patients to olHDF or high flux HD. The composite endpoint of all-cause mortality and nonfatal cardiovascular event rate was not different between the groups after a 2 year follow-up. However, again in a post-hoc analysis, a higher delivered dose of convective clearance (>17.4L, the median clearance) was associated with a lower risk of overall (RR 0.54) and cardiovascular mortality (RR 0.29).

Spanish olHDF Study

The latest study set out to deliver a high dose of replacement fluid and they succeeded (median convective volumes approximately 23L). They assigned 906 patients to either continue their current modality (mostly high flux HD) or switch to olHDF. The primary outcome of all-cause mortality occurred 30% less frequently in the olHDF group (p=0.01) after approximately 2 years.

Verdict: My previous experience with olHDF involved using it in an ad-hoc basis for patients with uremic symptoms despite ‘adequate’ KT/V urea or in patients with long dialysis vintage (extrapolating results from the HEMO study as high flux HD is a form of low dose HDF). Many European Nephrologists have presumed outcomes would be better but with very little data to back that up. We now have 3 RCTs suggesting a relationship between high dose olHDF and improved mortality. In our dialysis patients with such high mortality and with few interventions proven to impact this over decades, these results should be appreciated by the Nephrology community. It is at least time to reconsider the barriers to its use.

Posted by Paul Phelan