Slide 1

Dear Mr Chairman, dear Ladies and Gentlemen, as we all know, AKI necessitating renal replacement therapy is a common problem in the critical patient.

Slide 2

As you all know, we have a variety of different treatment opportunities, so we have to choose which treatment should be used for the AKI patient or in other words what is the best treatment we could apply to the patients today?
First of all, we could go for continuous renal replacement therapies but then we will also have to choose whether it is beneficial to use CVVH, CVVHD, CVVHDF or even high volume or very high volume CVVH. To make things even more complicated we also can choose to go for intermittent procedures like intermittent hemodialysis or sustained low efficiency dialysis called SLED.

Slide 3

So let’s start with the continuous procedures. A basic and often raised question is should we use CVVH or CVVHD or in other words convection or diffusion? So this is a nice paper published by Ricci and co-workers, this is a prospective cohort study with a cross-over design and 15 patients suffering AKI. The final end points of this study have been filter run time and the clearance of small and middle molecules. All patients were treated with a treatment dose of 35 ml/h/kg and the results are shown on the left side. As you can see the treatment time and the clearance rates for creatinine and urea and as you see CVVH and CVVHD are comparable in human control and they also state that CVVH and CVVHD are comparable for the removal of small and even middle molecular weight solutes.

Slide 4

The next interesting but not surprising effect in this study has been that filter run time is significantly longer using CVVHD. That’s because there’s a lesser hemoconcentration effect during CVVHD and this is probably the cause for longer filter patency.

Slide 5

As we have seen, CVVH and CVVHD are comparable provided the same treatment dose is delivered to the patient. What treatment dose should be delivered to the patient? You all know this landmark trial by Ronco, as was already presented and Ronco treated patients either with 20, 35 or 45 ml/h/kg filtration rate. So the major result of this study was that patients receiving less than 35 ml/h/kg filtration rate suffered the highest mortality rate. So by today it’s widely accepted that patients should be treated with at least 35 ml/h/kg.

Slide 6

These results have recently been confirmed by Saudan and co-workers. Saudan and co-workers compared CVVH with a filtration rate of only 25 ml/h/kg to CVVHDF. In CVVHDF a dialysis dose of 18 ml/h/kg was added to CVVH.
What was the major result of this trial?
From our point of view it’s not the fact that a higher treatment dose is better than a lower one. This was already shown by Ronco and co-workers. From our point view it’s the fact that adding a dialysis dose to CVVH improves survival and that means that the treatment dose is more important than the CRRT modality.

Slide 7

So what about high volume or very high volume hemofiltration?
To make a long story short for the moment high volume and very high volume hemofiltration remains an interesting but experimental renal replacement procedure and should be reserved to clinical trials.

Slide 8

Now, I’ll come to a very emotional and very complex debate. Since the first description of continuous arteriovenous hemofiltration in 1977 CRRT has gained wide acceptance in the treatment of critical patients. However up to now clinicians are still missing a well designed prospective randomised trial to answer the question whether or not CRRT is associated with an increased survival compared to intermittent hemodialysis.

Slide 9

An important trial on this regard is from Vinsonneau published in the Lancet 2006 in a multicentre randomised trial 360 patients were included and 184 received intermittent hemodialysis and 176 CVVHDF. The final end point of this study was 60 days survival rate and patients were allowed to switch --- in both treatment arms if clinically necessary.

Slide 10

Let’s have a quick overview of some treatment modalities of this study. Intermittent hemodialysis was performed every second day with an average duration of 5.2 hours. Blood flow was 280ml/min and dialysate flow was 500 ml/min. Ultrafiltration rate 2200 L/day. Continuous venovenous hemodiafiltration was applied with a treatment dose of around 30 ml/hour/kg therefore it was below the recommendations by Ronco. The explanation for that is quite simple because this study was designed in 1988, so before the recommendations were made by Ronco.

Slide 11

This is the major result of this trial and as you can see, there’s no difference in the mortality rate at 60 days or 20 days and there’s even no difference in the mortality rate at day 90 so the authors stated that all patients could be treated with intermittent or severe hemodialysis or CVVHDF.

Slide 12

The authors also stated that intermittent hemodialysis was well tolerated by critically ill patients but this remains controversial because the authors used an increased sodium content of the dialysate which was 150 mmol/L and as you all know a high sodium content stabilizes blood pressure but also induces thirst in the conscious patient. Secondly the temperature of the dialysate fluid was reduced to 35°C and a low dialysate temperature leads to peripheral vasoconstriction and also stabilises blood pressure but also induces chills and discomfort if the patient is not sedated.

Slide 13

So maybe daily treatment is superior to alternated treatment and we have evidence that this is a fact. This was an investigation of Schiffl and colleagues and he found that daily treatment with intermittent hemodialysis was associated with an increased survival compared to alternated treatment and he argues that the increased Kt/V, the increased dialysis dose is most crucial in this regard. Some may argue that the delivered dialysis dose in the every second day treatment group was lower than recommended.

Slide 14

Slow extended daily dialysis has been become very popular in recent years. Slow extended daily dialysis called SLEDD is an intermittent dialysis procedure with a prolonged treatment time of 6-12 or even 18 hours per day. Therefore, we can reduce blood flow rates and dialysate flow rates markedly compared to standard limited procedures.

Slide 15

SLEDD is well tolerated hemodynamically as was shown by Kilstein and co-workers. The authors compared CVVH and SLEDD and found no difference in the mean arterial pressure, the heart rate, the cardiac output and the systemic vascular resistance.

Slide 16

When we prolong treatment time, it is also of interest if time is fundamental for the quality of dialysis independently of the applied treatment dose. This was investigated by Elott and co-workers. They used a Genius system with 90 L of dialysate. So the treatment dose was similar in all patients and we can see that by increasing the treatment time from 4 to 6 to 8 hours the solute removal is increased.
We have seen in the work of Vinsonneau and co-workers that there was no mortality difference in patients that received either intermittent dialysis and CRRT. But maybe the treatment modality does affect renal outcome.

Slide 17

So this is a study by Bell and co-workers published in 2007. This is a multicentre retrospective study and they found that also here the hospital mortality was similar between CRRT and intermittent hemodialysis but the incidence of ESRD was much higher in the treatment group treated with intermittent hemodialysis compared to CRRT and they even found that patients suffering ESRD after intermittent hemodialysis had a much higher mortality rate compared to patients suffering ESRD after CRRT. Otherwise there was no difference in mortality rate in patients which did not develop ESRD.

Slide 18

So what is the conclusion of the data presented up to now? From our point of view the modality of renal replacement therapy either CRRT or intermittent renal replacement therapy should be considered as complementary in the treatment of patients suffering acute renal failure and the treatment choice should be based on the patients’ conditions and on the treatment options available. If we perform intermittent hemodialysis, it should be done on a daily basis for a prolonged time period as with SLEDD.

Slide 19

Finally, let’s see if there’s a role for hybrid treatment strategies in septic patients suffering multi organ dysfunction combining both CRRT and septic mediator elimination.

Slide 20

Polymyxin was found in pre-clinical and small clinical trials to eliminate endotoxin which is an important toxic trigger. So Vincent and co-workers performed a multicentre prospective randomised trial and found no difference in the endotoxin elimination or interleukin reduction.

Slide 21

Patients showed an improved cardiovascular hemodynamic status but unfortunately, there was no progression in organ function and there was also no benefit in the 28 day survival and the length of ICU stay.

Slide 22

As a new treatment modality, there’s the use of high cut-off hemofilters. High cut-off filters are designed with an increased pore size of around 10 nm and therefore, allow to eliminate middle molecules including septic mediators.

Slide 23

In this pilot trial by Morgera and co-workers the high cut-off hemofilter but not the conventional hemofilter was able to remove significant amounts of IL-6, thereby lowering the plasma IL-6 levels by using CRRT.

Slide 24

Shown by Haase and co-workers recently even by intermittent dialysis we are able to eliminate significant more IL-6 with a high cut-off hemofilter compared to standard hemofilters.

Slide 25

So what is the role for hybrid treatment strategies? We would say that apart from first pilot studies there is no striking evidence that any hybrid treatment strategy has a beneficial effect on the outcome of AKI patients suffering from septic MODS. Although promising, these procedures should be restricted to trials.

Slide 26

Thank you very much.

Slide 27

Chairman: Thank you very much Doctor Schneider for this very interesting and very elegant overview and I think a quite unbiased presentation although sometimes there was some slip of the words like tricks and so on but nevertheless very well balanced. Are there any questions or remarks from the audience?

Question: Thanks so much for your presentation. However, I have an objection. When we talk about CRRT and today I think you have missed one point and that’s peritoneal dialysis. Some people in may laugh at that. If you think about the New England Journal, the Vietnamese paper of 2002 comparing PD to hemofiltration, the PD done in that study was a stone age PD. Last month in Kidney International there was a randomised controlled trial with 120 patients comparing high volume APD with daily hemodialysis and the results are the same as you get those Vinsonneau published in Lancet and in the same KI issue there is work from Brazil and in the same KI issue there is a retrospective work from Denmark on PD used in paediatric patients for a long time. So I think it’s important you had a very nice presentation but biased because PD should be put into these therapeutic armamentaria to treat patients with acute renal failure.

Chairman: I think this is quite correct.

Dr Schneider: Thank you very much for this comment, in fact we prefer to use CRRT instead of peritoneal dialysis. It is shown that PD can be safely used in patients with heart failure for example. In our nephrology department we prefer CRRT because it can be immediately used in  opposition to PD.

Question: I agree but if you read this paper, then I see that you can use high volume APD even for high catabolic patients and APD as CRRT is continuous renal replacement therapy.

Chairman: Can you comment because you will speak about ..?

Chairman: I have my personal idea about that. I think that the fact that actually there is no clear evidence that one technique is superior to another in terms of survival it’s not that bad. I think that you can read the other way round and since the local expertise and the impossibility, don’t forget we must not forget that we are talking about very complicated techniques that not every centre is able or has the possibility to perform. So the fact of having a relative equivalence of techniques to my eyes is not a problem in the sense that the local centre can use one technique and taking into consideration local expertise and local possibilities. This is not something to neglect in my opinion.

Chairman: And with that regard I would like to make a kind of vote in the audience. Who’s using CRRT mainly in their patients in the ICU? How many of those are using a dose above 35 ml/min as recommended because there’s a huge logistic and financial..? So it’s a minority. That’s one of the problems of CRRT I think indeed as José indicated in a lot of countries it’s just not affordable.

Dr Schneider: Already shown in the best study that a minority of patients treated with 35 ml/h/kg, most of the patients only received 20 ml/h/kg.

Chairman: I have a second remark as we still have some time about the superflux. Don’t you fear that in an ICU and it relates a bit to the same in an ICU environment where water treatment might not be optimal at least in most of the ICUs because it’s not in the same way installed or used or maintained as in a chronic hemodialysis unit that there might be some problems with the quality, the purity of your dialysate and if you’re using superflux membranes that there might be extra additional inflammation already in these inflamed patients?

Dr Schneider: We’re using high flux hemofilters and there’s no, as the Best study did not show differences in the material of the high flux hemofilters you couldn´t say one is superior to the other one. So if you use biocompatible membranes, all hemofilters should be comparable in my opinion.

Chairman: But when you look to the quality of your dialysate that you use in the water treatment systems, might there not be a problem? Or is this not an issue?

Dr Schneider: Sorry I didn’t understand the question.

Chairman: So if you’re using high flux or superflux membranes in an ICU environment and you’re using a normal regular dialyser, you need a water treatment system. If you don’t maintain that properly and most of the time it means that you use it properly and regularly, there might be a problem with your water quality which might induce extra inflammation.

Dr Schneider: In our department we’re using bicarbonate solutions company made so quality is not an issue.

Chairman: Not online that’s what you mean. So thank you very much for this well-balanced and very nice presentation.