Slide 1

On behalf of myself, Alejandro Martin-Malo and Luciano Pedrini and the entire guideline group chaired by Professor Vanholder and also the contributors from the ERA membership I’ll present a selection from the dialysis strategies guidelines.

Slide 2

We start off by making a recommendation on the time and frequency of dialysis. I don’t think it’s too controversial. We are recommending that patients are treated at least 3 times a week and the total weekly dialysis duration should be at least 12 hours. That means if you are doing daily dialysis, the sessions have to be at least 2 hours 6 times a week.
We make a little provision that if you want to start the patients on dialysis early with a considerable renal function, it maybe appropriate to reduce the dialysis time taking renal function into account.
But we’re not to prescriptive about how that’s achieved.
We’d also like to recommend that we consider increasing treatment time under certain conditions where there is some evidence that longer treatment might be beneficial which are listed here.

Slide 3

I have to say that our approach is a little different to the recently published KDOQI update published last year. KDOQI are recommending 3 times a week as we do minimal but they allow down to 3 hours per session.

Slide 4

We rather stand by our recommendation. There has been no adequate randomised controlled trial to settle the issue so there’s a lack of hard evidence. This is the DOPPS study showing mortality gradually increasing as you reduce dialysis time through 4 hours down towards 3 hours. The prescription of dialysis time is, of course, a practical issue and in Europe our commonly prescribed treatments are 4 hours, so it’s no problem for us to achieve at least that. That maybe different in the United States.

Slide 5

Going to convection and flux, there is a considerable amount of evidence that suggests that high flux membranes might be beneficial but nothing clearly proving the point in a randomised controlled trial and even the HEMO Study didn’t show this but there maybe some results of a study DENOMSAN, which will be presented this afternoon, the NPO study which might settle the issue. We were also recommending haemodiafiltration to maximise the large and middle molecule clearance achievable by high flux dialysis.

Slide 6

Our approach is very similar to KDOQI and they say that you should use high flux dialysers unless you can’t guarantee the water quality. KDOQI say you shouldn’t really use cellulosic dialysers anymore.

Slide 7

Again, from the DOPPS study there wasn’t really much difference in outcome between low flux and high flux but when you move to high efficiency dialysis, you do get a significant reduction in mortality corrected for comorbidity and other factors. This reduction only occurs once you have achieved a certain minimum volume of exchange just putting a small volume makes a proportionally less difference. This is why our guidelines are recommending the highest possible exchange volumes when you do haemodiafiltration.

Slide 8

Moving on to the methodology of dialysis adequacy dose measurement we say that it should be measured at least  monthly, this is opinion based on current practice. We are recommending that we use a method that’s comparable to formal urea kinetic modelling using pre- and post-dialysis blood samples and the Gotch method described in the literature, taking ultrafiltration, urea generation and the post-dialysis rebound into account. That doesn’t mean that you have to make these measurements every time you do an adequacy measurement you just have to know how your method that you use in your unit compares to this gold standard. When reporting your results externally to registries and so on, you should convert it into a value equal to what you would obtain by using this method. You can take renal function into account so long as you measure it frequently enough to avoid overestimation as GFR falls and we’re recommending using the same frequency as recommended in the PD guidelines and that’s at least every 2 months unless you’re certain that the renal function is very stable.
For 3 times weekly dialysis we should be using equilibrated Kt/V and this takes the post-dialysis rebound into account and evens out the differences that you get when using different lengths of dialysis. I’ll go into that a little more later on.
Of course, if you’re not doing 3 times a week dialysis, then Kt/V is not really appropriate and we should use more sophisticated methods that take renal function into account including equivalent renal clearance, standard Kt/V or the solute removal index.

Slide 9

The minimal adequate dose we say that we should prescribe a target equilibrated Kt/V of 1.2 but we could an consider increasing it in females and those with high comorbidity. We are not, on the basis of the evidence, saying that there must be a definite minimal level that you can’t go below although the KDOQI guidelines have set that. With other schedules other than 3 times a week we should have at least a SRI of 2 or an equivalent renal clearance of 12 ml/min.

Slide 10

Comparing with the KDOQI guidelines we say prescribe 1.2-1.4. KDOQI say you should prescribe 1.4, so they’re actually saying that you need a higher level and they’re mandating a minimum of 1.2 but that single pool equivalent to just over a Kt/V of 1 equilibrated which is their a minimum. They say that you can include renal function but only if it’s more than 2 ml/min of urea clearance.

Slide 11

It’s probably worth focusing on this difference between the prescribed target level and the minimal adequate level. If you consider that your aiming for a particular target Kt/V, for example, aiming for 1.2, because of a natural error in the measurements and also the variation between patients due to factors you can’t control like access problems, blood flow and so on, then there will be a scatter of results and the mean will be somewhere near what you’re aiming at.

Slide 12

One way to improve your compliance with the standard, you don’t aim at the standard the minimum level, you aim somewhat higher.

Slide 13

And you can improve your compliance further by improving your accuracy of aim and reducing the standard deviation, so in addition to aiming higher.

Slide 14

The blue points here are the distribution obtained from the HEMO study standard-dose group which is now considered optimum. The HEMO study wasn’t able to show any benefit for systematically prescribing or delivering a higher dose. The standard-dose have formed this distribution with almost all of the patients eventually achieving a Kt/V of more than 1 but the average just over 1.1.
The KDOQI guidelines are mandating a minimum of 1.6 which would fail most of the, or half of the standard dose groups, so they’re saying that we really should aim higher than achieved in the HEMO study standard-dose. They’re saying you should aim at 1.4 single pool which is just over 1.3 equilibrated. The European guidelines are not setting a minimal level we’re just saying we should aim at 1.2 which would achieve a similar distribution to that achieved in the HEMO study standard-dose group. We didn’t think we could go beyond that on the evidence but they’re will obviously be much more discussion about this controversy and hopefully more studies.

Slide 15

Another difference between our standard and others is how we take the rebound into account. This is a 4-hour dialysis with the urea falling to the end of dialysis and rebounding. If you perform the same treatment in half the time, you may achieve the same Kt/V, both of these curves have the same single pool Kt/V but the short dialysis is clearly inferior as there is a larger rebound and this is reflected in the eKt/V which will give a lower value for this although the single pool Kt/V would be the same for both treatments and we thought it was important to include that at least when we’re using our data to compare with other sets of data and for research purposes or for registry.

Slide 16

The next point is how to quantify dialysis that’s more frequent or less frequent than 3 times a week. The 3 methods solute removal index, standard Kt/V and equivalent urea clearance are very, very similar in approach and in fact, the main difference is that the solute removal index relates to the peak urea concentration and the stdKt/V is the mean of the pre-dialysis peaks. That sounds like a very small difference but in certain situations, it can be significant.

The EKR uses a time average concentration rather than any pre-dialysis concentrations.

Slide 17

This is a typical 3 times a week dialysis with the urea rising and falling with the dialysis cycles. The actual peak which the SRI would use would be 40 here, the mean of the 3 peaks is 34, so the stdKt/V would be 2 and the SRI would be slightly lower because of the higher peak at 1.8.

Slide 18

If you performed all 3 dialyses in the consecutive days of the week, for example Monday, Tuesday and Wednesday, you get a much higher peak at the end of the week as you would expect. But the mean of the 3 peaks remains exactly the same, so that the stdKt/V would remain exactly the same and the SRI would be much less reflecting the higher peak.

Slide 19

In an extreme example if you perform all 3 dialyses on the same day, you get a very high peak obviously, a very low SRI but your std Kt/V would be the same and I would consider this as a limitation to using the stdKt/V.

Slide 20

I’m saying a little bit now about dialysis schedule and middle molecule clearance for example β 2 microglobulin. Here we have the fall of β 2 microglobulin in a standard high flux dialysis. There’s a significant rebound after dialysis which should be taken into account and note that we’re getting peak levels about half the levels that you get with low flux dialysis which would normally be around 40. By increasing the clearance rate adding haemodiafiltration you can get the post-dialysis urea down quite significantly. There’s a bigger rebound and you get the peaks down a little bit further but it’s only when you move to very long treatments for example, this 8 hour treatment for example, nocturnal, 3 times a week dialysis with haemodiafiltration that you get a further significant reduction in β 2 microglobulin but clearly we’re reaching the limits of what we can achieve with 3 times a week and even 8 hourly haemodiafiltration is probably not practical.

Slide 21

But when we move to 6 times a week, this is 3 times a week haemodiafiltration, we’re able to push further and further the β2 levels and in your extreme example with 8-hourly daily haemodiafiltration we’re approaching the normal, at least the average level over the week is approaching what you would expect normally.

Slide 22

Another slide from the DOPPS study. When we’re using short treatments 3 times a week there was very little difference in the outcome from different levels of Kt/V going from 1.2 -1.6. But the situation is completely different if you’re using longer treatment times. It is now possible to demonstrate quite large significant differences in outcome with increasing Kt/V coupled with longer treatment times and we expect the same to be true with more frequent dialysis.

Slide 23

So, in conclusion there is a broad agreement between the European best practice guidelines and KDOQI. We have a tendency to recommend increased treatment times and frequency, at least 4 hours 3 times a week in Europe. There’s a tendency to recommend high flux dialysis and additionally haemodiafiltration in Europe, this is not recommended in the States. Dose methods are to include frequency.

Slide 24

The further work needed is we need to look a lot more, focus a lot more on middle molecule clearance, how we define toxicity, whether it depends on the peak concentration or the TAC and defining an adequate terminology for targets and acceptable range minimal adequate and so on. How prescriptive should we be? We’ve been criticised for not telling everybody exactly how they should do it, how to calculate, how to sample and standardisation, how we should communicate with registries, the QUEST initiative and so on. Thank you.

Slide 25

Chairman: Thank you James are there any questions? I think everybody is running out to the next session. Anyway thank you very much to the audience and for everybody who attended this meeting. Thank you also to the speakers for their excellent presentations. Good afternoon.