Slide 1

Thank you very much Mr Chairman. Rather than going into a boring list of old guidelines because these nutrition guidelines were very long, we have 45 pages printed in the NDT supplement, I would like to focus a little bit more on protein energy metabolism and requirements.

Slide 2

What we should still know is that malnutrition is still present in haemodialysis patients and you can see from this recent survey 2006 that the mean albumin level in the French population is 36.3 g/L and as you know, the minimum level of albumin is 40 which indicates that almost 70% of dialysis patients have still albumin problems and mostly malnutrition.

Slide 3

So by addressing this difficult topic we drafted 6 guidelines and I would like to start by the protein requirements.

Slide 4

And we slightly decreased the amount of recommended protein intake to 1.1 g, formerly it was 1.2 g/kg/day. This is based on recalls on intake and if you estimate this intake by the output, the nPCR or nPNA, the requested level should be greater than 1.0 and the difference between these two numbers corresponds to the unmeasured nitrogen losses. So we got these levels because most of the previous nitrogen balances were performed on a very few number of patients. At least 30 patients maximum did give this 1.2 g formerly used. And since 2000 we got a number of epidemiological studies increasing this data and allowing to not only use nitrogen balance but more epidemiological data.

Slide 5

The requirement of a patient is like a Gaussian curve. The protein requirement in a non-dialysis patient is 0.5 g/kg per day as a mean level but for a safety reason we always recommend to give more with standard deviation in addition to cover 97.5% of the population, that is we increase artificially the requirements of the patient and this is an explanation to why some patients may be well in balance even though they don’t take the 1.1 or 1.2 g that you recommend. This has been shown in many epidemiological studies.

Slide 6

So if you take this study, for example, based on 129 haemodialysis patients and they made a CT scan of the leg you can see here these patients have the same bone size and this patient were eating less than 0.7 g and he has a very low muscle mass and this patient was eating more than 1.3 g and he has a very different muscle mass. So by looking at this data on this patient with nPNA and they were able to measure lean body mass, subcutaneous and visceral fat mass and you can compute these levels of body composition, muscle, fat and you see that either in men or in women when you reach this level of 0.9-1.1 g, you don’t have anymore improvement after that.

Slide 7

This is also confirmed by this study in more than 30.000 patients from the – cohort in the States and you can see that mortality based on nPCR and nPNA here on the two different levels 0.9-1, 1.0-1.1 here as a reference level there is no mortality here but if you go down this level here the mortality of the patient increased. So basically it turns out that these levels which are not nitrogen balanced are safe to the patients.

Slide 8

The second important point is energy requirements. We kind of stopped this 35 kcal/kg/day, we rather give a range for 30-40 kcal/kg/day based on physical activity and I think this is extremely important.

First we have a persistent inadequacy between recommended intakes and current practice. I don’t know one nephrologist reaching 35 in all these patients and everybody complains it’s not possible. In fact, if you look at the energy requirements, there is a basal metabolic rate which is called resting energy expenditure it’s when you lie on a bed for 24 hours, nobody does that but this is possible.

Slide 9

This can be estimated by different formulas, Harris and Benedict, indirect calorimetry and these values are the same in chronic kidney disease as in volunteers, there is no difference here. However, you increment this basal metabolic rate by an activity factor because you’re moving every day and this activity factor is usually 20% or more than the resting energy expenditure and then you get to your daily energy expenditure. The mean activity factor is 40%, so you don’t increase your basal rate by more than 40%. If you are an active adult, healthy. So if you make just these small calculations for a woman, 75 years old you get this resting 1100 kcal then you get the theoretical activity factor, you find 32 kcal. But she has arthritis, she is old and under dialysis she doesn’t move, you know that and for sure she doesn’t have more than 20% of activity. Then you get this 28 kcal.

Slide 10

So, I think this is important when recommending intake to a patient to get an idea of his physical activity.

Slide 11

We have now the possibility to measure physical activity. An energy expenditure can be measured by very complicated things but here as you I can show you as an example in an adult volunteer which is supposed to be healthy and over 3 days the mean energy expenditure is 2000 kcal on week days of regular work and so if you divide by the weight you find 28.5 kcal. So it is possible that the energy expenditure we already recommended may have been too high because of the reduction in physical activity in everybody including you and me.

Slide 12

What about treatment of malnutrition regarding protein and energy?

Slide 13

First, we have to remember that aminoacids are a very important part of the protein synthesis that everybody breaks 250 g of protein which is 1.5 kg of muscle, everyday we break this muscle. So aminoacids are very important in regulating this equilibrium.

Slide 14

If you look at what happens during one haemodialysis session, this is a plasma aminoacid profile on 10 patients, you see that there is a sharp, a very acute drop in plasma aminoacids, 30% from the baseline and this is the only situation in life in disease.

Slide 15

There is no other single disease where your aminoacids can drop as fast in the body. So then this drop in aminoacids blocks the protein synthesis in the muscle. There is ample data to confirm that if you don’t have aminoacids, you block your protein synthesis.

Slide 16

But what happens then? Because these patients were fasted, the plasma aminoacids should have continued to drop until the end of the session. What happens is that there is a plateau here after 1 hour and because these patients were not fed, this plateau can only come from the muscle catabolism which will try to correct this profound aminoacid drop.

Slide 17

There is a second reason with this protein catabolism occurring during the dialysis session. What happens if you feed the patients during the session? This is a nice study showing that if you give yoghurt enriched with aminoacids and lipids for every 30 minutes during the session of dialysis with a total of 45 g of protein and 1100 low calories you can see that you can correct this abnormality here. This is fasting, the haemodialysis you have the drop in aminoacids from control, you see the same drop I just showed you but if you feed the patient, you correct this abnormality.

Slide 18

So this is an oral supplement. Of course, if you make the nitrogen balance, you have a negative nitrogen balance during fasting and a very high positive nitrogen balance during the dialysis, if you feed the patients.

Slide 19

Is this the same pattern given IV as IDPN intradialytic parenteral nutrition? You can see the exact same pattern without infusion, decrease in aminoacids with infusion, correction up to normal from these aminoacids. Again the same positive effect on nitrogen balance.

Slide 20

So what are the long-term effects of supplement in malnourished haemodialysis patients?

Slide 21

With the oral supplements we have a meta-analysis which is as you know a good level of evidence although the number of patients is not very big it’s only 400 patients and you can see that looking at serum albumin the overall effect showed that giving nutritional supplements, an oral nutritional supplement did increase serum albumin in these patients and the main increase was 4 g/L when these patients took oral supplements. It’s important to recall that every 1 g of increment in serum albumin is associated with a 5% in reduction of mortality.

Slide 22

So the guideline rates of nutritional supplements should be prescribed, if the counselling does not achieve an increase in nutrient intake to the minimum level recommended. Products specifically formulated for dialysis patients should be prescribed in preference to standard supplements for non-renal patients for abuse reasons of volume and electrolyte overload. Enteral tube should be used also if the oral supplement did not succeed to improve the nutritional status.

Slide 23

What about intravenous supplements?

Slide 24

We just had this large Fine study published showing that in a randomised fashion that should be a good level of evidence, these malnourished haemodialysis patients were given either oral supplements or oral supplement plus a supplement of intravenous nutrition for 1 year and they were followed for 2 years.

Slide 25

So the mean intake with oral supplements was 5 kcal/kg/day and 0.4 g protein/kg. The mean intake from the IV supplement 3 times a week so when normalised by day was 6 kcal/day and 0.3 g of aminoacids per day and they were standard nutritional supplements.

Slide 26

So what we observed was a dramatic response with an increase in albumin quite rapid, 3 months sustainable time in both groups and the exact same pattern from serum albumin. You can see in addition that there was no difference between the group receiving oral only or the group receiving both oral or IDPN.

Slide 27

Interestingly, if you look at mortality, what we observed that if the patient became anabolic within 3 months which is the pre-albumin increased by 30 mg/L, the mortality of this given patient was reduced by 50%. This is an important finding that if you re-nourish the patient and if the patient responds to this nutrition, he will clearly reduce his mortality.

Slide 28

So the guideline for IV supplements read when intensive dietary support, oral supplement and enteral have failed, a course of parenteral nutrition is recommended. Intradialytic parenteral nutrition, IDPN is recommended only if spontaneous nutrient intake is greater than 20 kcal and 0.8 g protein /kg/day. This is very important because as you saw, the amount provided by IDPN is reduced, it is not very big so you cannot hope to re-nourish a patient if he doesn’t eat enough besides IDPN, otherwise you should prescribe a total parenteral nutrition.

Slide 29

So, I’ll briefly address these two guidelines here. We also developed a number of recommendations and diagnosis and follow up of nutritional status. We also developed vitamin and --- sediment but this was not a guideline because of poor level of evidence, it was only recommendations for vitamin and choice elements and we also had the metabolic acidosis guideline which did not --- differ from the previous published in 2000. Again, I would like to mention that besides the 400 new publications we have studied we still lack good evidence data and we still lack randomised studies and the level of these guidelines is still quite poor. Thank you very much.

Slide 30

Chairman: Thank you Denis for this excellent summary. Are there any questions?  I just would like to make one remark that you mentioned this positive effect on nutritional balance of feeding during dialysis but that the haemodynamic instability guidelines discourage feeding during dialysis because of risk of hypotension.

Dr Fouque: I know but we have to protect each field I think. I’m pro nutrition.

Chairman: So thank you very much.