Monday, September 10, 2012

A Quest for a Pot of Gold

In the quest for better solute clearance, two divergent paths were taken on each side of the Atlantic. The US nephrology community has concentrated more on low weight molecules. The European counterpart has focused on both low and middle weight molecules.
The European endeavor has led to the evolution of the on-line hemodiafiltration (HDF), combining HF and HD. A water-permeable filter allows middle molecule removal by convection. Dialysate then supplements low molecular weight solute removal by diffusion. Production of the replacement fluid from dialysate in the circuit (thus called “on-line”) cuts the cost.
Since Fresenius’ Online Plus™ came out in 1998, on-line HDF has gained popularity in Europe and other continents. In the US? Not so much, but we may see it more as it was just cleared by FDA for the market this April.
The idea of middle molecule removal sounds physiological. But is there really any advantage?
It has been suggested that the on-line HDF may reduce intra-dialytic hypotension, improve nutritional status, and decrease ESA (erythropoiesis stimulating agent) requirement. But what about the hard end points (all-cause mortality and cardiovascular outcomes)?
In the recent CONTRAST study, 700 patients in the Netherlands, Canada, and Norway were randomized to on-line HDF or low-flux HD. The surprise? There was no CONTRAST between the two groups… The CONSOLATION was a minimal survival benefit among those who received top-quartile convective volume.
Did this disappoint the nephrology community? Yes, to some extent. In a recent CJASN editorial, Dr. Kuhlman from Germany pointed out  that in Europe the advantages of on-line HDF over conventional HD have been “somehow taken for granted”.
Did this put an end to on-line HDF? The answer is no. A couple of more European studies are on their way, so is the research to solve technical challenges. This is a never ending journey, even if it may end up with the quest for a pot of gold at the end of the rainbow.

Posted by Tomoki Tsukahara

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