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Thank you and thank you to the organisers and the scientific committee for this kind invitation.

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When we deal with artificial nutrition in critically ill patients with acute renal failure, patients in the ICU, we have to face many problems. First of all, dysmetabolism of critical illness is made worse by the acute loss of kidney homeostatic function. Moreover, nutritional approach is made difficult by the complexity of the syndrome itself and by the need of renal replacement therapy.

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Unfortunately, we have no high quality scientific evidence on this topic; in other words, there are no randomised controlled trials on the topic. So clinical practice, our clinical practice in this field, must be based on expert opinion.

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Most of the information I will give during my talk is taken from the recently published Guidelines of the European Society for Enteral Nutrition in Adult Renal Failure; Clinical Nutrition 2006. From the same guidelines for Parenteral Nutrition that are going to be published in the next months again, in Clinical Nutrition.

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On this basis in my talk I will go in depth into three topics; epidemiological aspects and prognostic value of malnutrition and artificial nutrition in acute renal failure patients. Nutrient needs in these patients and a very important concept, the integration between artificial nutrition and renal replacement therapy

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If we stratify patients with acute renal failure on the basis of their nutritional status evaluated by using simple tools such as, for example, the SGA method, we can see that malnutrition is a frequent finding among these patients and about 35% of these patients can be classified as severely malnourished.

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But why is malnutrition so frequently observed in acute renal failure patients? There are many factors, many reasons and many mechanisms. A very important aspect is that dysmetabolism of critical illness in these patients is exacerbated by the acute loss of kidney homeostatic function. In other words, very important mechanisms such as oxidative stress, insulin resistance and many deranged metabolic pathways not only act in terms of propagation and maintenance of the acute kidney injury syndrome but probably, they are also able to contribute in a very important way to the altered balance between degradation and synthesis of proteins, so we have catabolism and malnutrition.

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We have to pay attention to other factors, for example, the fact that even treatment can worsen nutritional status in these patients. For example, renal replacement therapy in these patients is associated with a loss of aminoacids and proteins. 10-15 g of aminoacids per day. 5-10 g per day of proteins and there are modalities of renal replacement therapy that are associated with increased losses such as for example, continuous therapies.

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But malnutrition in these patients is not only a problem of high prevalence, malnutrition has a very important independent negative prognostic value. So, the presence of malnutrition in particular of severe malnutrition, is associated with an increased mortality risk as compared to patients with acute renal failure with the same severity of illness but normal nutritional status.

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On the other hand, artificial nutrition is likely to be beneficial in these patients. Again, there are no randomised controlled trials on this topic and we have to rely on observational studies, on large databases of patients like this study, for example, from Austria. In this observational study the authors were able to demonstrate that probably artificial nutrition, especially under the form of enteral nutrition, is beneficial in these patients.

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This is another study in which a positive nitrogen balance was demonstrated to be directly associated with a positive hospital outcome and there was again, a statistically significant advantage of artificial nutrition, as enteral nutrition, on patient outcome.

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So, what are the aims or what should be the aims of nutritional support in patients with acute renal failure? First of all, preventing malnutrition, preserverating lean body mass, avoiding further metabolic derangements, avoiding fluid and electrolyte derangements, supporting immune function, decreasing inflammation and oxidative stress. Finally, reducing, if it’s possible mortality.

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But when we have decided to start artificial nutrition in these patients, what protein and energy intakes?

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There are some basic numbers we need to start, numbers on catabolism and numbers on energy expenditure. What are the numbers on catabolism? Measured protein catabolic rates in these patients are about 1.5-2 g of proteins/kg/day. If we look at the literature data, numbers are in this order of values.

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What about energy expenditure? If we measure energy expenditure in these patients, we obtain numbers between 25-30 Kcal/kg/day. There is no difference between patients with acute renal failure or without acute renal failure, if we take into account critically ill ventilated patients.

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With these numbers what is the best compromise in terms of combination of energy intake and protein intake in terms of positive effects on nitrogen balance in these patients? The magic numbers are again 25-30 Kcal/kg/day and 1.5-2 g of proteins/kg/day and the calorie/nitrogen ratio should be about 100. Again, this is an observational study not a randomised controlled trial.

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We were able to confirm indirectly this observation in a small crossover study on a group of patients with acute renal failure, critically ill patients with acute renal failure who were each receiving an isonitrogenous diet. Patients were receiving about 1.5 g/kg/day of proteins. If you change the amount of energy, 30-40 Kcal, there was no important effect on nitrogen balance, nitrogen balance was the same.

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But there is another side of the coin, patients receiving more calories had more positive fluid balance, increased insulin need and higher glucose levels.

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We know very well and, I think that Doctor Ikizler will spend his talk especially on this topic, that high glucose levels in these patients, like in other critically ill patients, are associated with an increased risk of death.

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But what are the qualitative aspects of protein and energy intake in these patients? Proteins are to be given as essential and non-essential aminoacids. Energy should be given 2/3 as glucose, not more than 5 g/kg/day and 1/3 as lipids. If you do parenteral nutrition, you have to use lipid emulsions; LCTs or MCT/LCTs, medium chain plus long chain or long chain triglycerides at 1.2 g/kg/day of lipid emulsion. The emulsion should be infused in 24 hours.

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If you pay attention to these very simple rules, there are no problems in terms of serum triglyceride levels in these patients. In other words, serum triglyceride levels before and after at the end of parenteral nutrition with lipid emulsions are not different.

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What about the modality of nutritional support in these patients? Enteral nutrition should be the preferred modality of nutritional support in these patients. Enteral nutrition is safe in patients with acute renal failure and we were able to demonstrate that there were no clinically relevant increases in complications. A combination of enteral and parenteral nutrition is often needed, mainly to reach the targeted intake of proteins.

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Now, I would like to stress a very important concept, the key role of the integration between artificial nutrition and renal replacement therapy in these patients. These patients, critically ill patients with acute renal failure need daily renal replacement therapy under the form of haemodialysis, daily haemodialysis or daily haemofiltration, daily prolonged intermittent treatments such as RRT or SLED or CRRT. This kind of RRT allows a better nutrition.

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This is an example in patients receiving renal replacement therapy as SLED. We were able to obtain the targeted amount of energy and protein intakes, about 100% of this calculated need 30 Kcal/kg/day and 0.25 g/kg/day of nitrogen in these patients who were receiving daily SLED.

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In summary, malnutrition is frequent in patients with acute renal failure and represents an independent predictor of mortality and morbidity. At the present time there is no definitive demonstration from randomised controlled trials concerning the positive effects of artificial nutrition on prognosis in these patients. However, artificial nutrition should be considered a key component of the complex therapeutic strategy in these patients. Energy at 25-30 Kcal/kg/day and protein at 1.5-2 g/kg/day should be provided in these patients, patients with acute renal failure on renal replacement therapy obviously. Enteral nutrition should be the preferred modality for nutritional support and we are able to reach a more adequate nutritional support with daily renal replacement therapy. Thank you.

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Chairman: Thank you Doctor Fiaccadori. Questions from the audience? Two questions. Meanwhile I have a curiosity for you. You mentioned that in these patients -- the oxidative stress is increased. Are there experiences addressing this particular aspect of malnutrition in these critically ill patients?

Dr. Fiaccadori: I have no personal experience about this topic and in my knowledge there are no studies available up to now correlating malnutrition and oxidative stress in these patients. There are no studies aimed at evaluating the possible positive effects of nutritional support on oxidative stress in these patients, especially malnourished patients.

Question: Excuse me, I’m just asking, when we increase the protein intake from 1 g/kg/day – 2 g/kg/day, are we going to switch the protein catabolic status into a protein anabolic status? If not, why do we resort to this especially because if we increase the protein intake in this way, we might increase the need of dialysis for patients who can recover without need of renal replacement therapy whatsoever?

Dr. Fiaccadori: My talk was focused on patients on renal replacement therapy, more critically ill patients, not on patients on conservative therapy. There are patients with acute renal failure that can be treated with conservative therapy. These patients not very often need a full nutritional support. The first question, there is a sort of fixed catabolism in these patients and this catabolism has been quantified in 1.5-2 g/kg/day of protein. So, if you don’t give the patient this amount of protein, they are at very increased risk of lean body mass loss. So, you have to give this amount of proteins and you have to adjust the need of renal replacement therapy. The most important thing is nutrition, then we have to adapt and to choose the right dose of dialysis, haemofiltration or SLED whatever modality treatment you want.

Question: Do we have a prospective trial showing that this modality is better than a lower protein intake regarding morbidity and mortality?

Dr. Fiaccadori: There are some data and I have just shown some data about higher protein intake and more positive nitrogen balance but these are observational studies, not randomised controlled trials.

Question: Question. – the role of glutamine, we know that it is important in sepsis in the ICU. What is the role in septic acute renal failure?

Dr. Fiaccadori: Again, unfortunately there are no data about this topic. If you want you can supplement nutrition in these patients with glutamine like in other critically ill patients. You have to take into consideration the fact that if you infuse glutamine and the patient is receiving a high efficient treatment, there is the risk to lose a significant amount of glutamine. There are some data about losses of glutamine during continuous treatment and I think that a lot of glutamine is lost also during SLED.

Question: What would energy levels in hypercatabolic patients be ? Would you recommend higher energy levels more than 30Kcal/kg/day or across the border regardless of the degree of catabolism? Do you recommend the same degree of energy intake?

Dr. Fiaccadori: Yes, I think that 30 Kcal is the maximum. There are some observational data, the paper of Macias published in JPEN 1996 that demonstrates that probably if you increase energy intake in these patients to more than 40 Kcal/kg/day, you increase catabolism. The mechanisms is not well know but for example, too many calories could increase catecholaminenergic tone or the adrenergic tone of the individual, for example. So you have a negative effect, if you increase energy more than 40 Kcal.

Question: Even in hypercatabolic patients?

Dr. Fiaccadori: In my opinion even in hypercatabolic patients 30 Kcal is the maximum.

Question: Another question.

Question: There’s a trend not to use higher and higher doses of CRRT the 35 specular in septic patients even higher with high volume. So what would you recommend? How much protein would you give those types of patents undergoing high volume therapies, let’s say 45 cc specular higher?

Dr. Fiaccadori: You can calculate that with these treatments your patients probably are losing about the equivalent of 0.3 g/kg/day at least, as aminoacids and proteins. So you have to increase the supplementation, if you are using these treatments, very high efficiency treatments. So, 1.5 g of protein plus 0.3 for the treatment.

Question: Enrico congratulations for the excellent talk. My question is about the protein loss throughout the dialysis session. How important is the choice of the membrane or do you think that it is indifferent the different kinds of membrane? High permeability, low permeability.

Dr. Fiaccadori: The trend is to use in these patients treatments with high volumes, high efficiency and treatments with high flux membranes. So, if you choose a high flux membrane and the treatment lasts 24 hours, you have to take into account that proteins and aminoacids and for example, glutamine could be lost in very important amounts.

Question: Ok thank you very much Doctor Fiaccadori.