Slide 1

Ok thank you very much ladies and gentlemen, dear colleagues. First I’d like to thank the organisers of the EDTA, Professors Lameire and Alvestrand for inviting me to come and speak today on behalf of the European Association of Rehabilitation in CKD. My topic today is rehabilitation and exercise training in patients with CKD and diabetes. Well the truth be known there’s not a lot of work actually done in patients with CKD and diabetes on exercise training but I’m going to try and give you a small overview of some aspects. 

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To start with survival, we’ve heard about survival in the first talk of diabetes, diabetic patients on renal replacement therapy that the 5-year survival is very, very poor and here we can see several factors affecting survival. I think obviously we know that albumin is a very important factor in survival and that malnourishment, malnutrition actually increases mortality by 66%. I think very interesting to see is the fact that inactivity is also a very dangerous risk factor in this group of patients and that they’re naturally very inactive.

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During the course of CKD patients’ maximal exercise capacity decreases so that by the time they’ve actually reached dialysis they usually have 40-50% of the expected norm and so they’ve lost a lot of functional capacity and exercise capacity.

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If we look at the prevalence of CKD, this is a study from Hallan and Norway but it’s quite similar throughout Europe, the other studies from the UK and Spain and so on showing similar prevalences. We see that we don’t even have CKD5 which is our dialysis population but we see that already in CKD 3, 4.5% of the population has some sort of renal failure and a large proportion of these patients out there are patients with vascular disease and type 2 diabetes.

Slide 5

Recently Foley showed that similarly looking early in the course of development of CKD sarcopenia percent of sarcopenia or muscle atrophy increased really early on, so that patients in CKD3, 60% of them actually had some sort of muscle atrophy once again showing that this is an early effect and we do know that a lot of those patients do have vascular causes for their renal failure but also type 2 diabetes.

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So, what are the factors actually affecting loss of muscle in CKD? We have interaction between whole body protein and a pool of free aminoacids. We also have protein intake which is often decreased due to increasing anorexia which can come in CKD4 in this group of patients.
We also have effects of aminoacid oxidation with increased acidosis, this is a very important factor and protein synthesis is decreased in patients with CKD and due to changed aminoacid metabolism. GH/IGF resistance, low protein intake and inactivity. But we also have a higher level of protein degradation and that’s mainly driven through the acidosis cortisol route through the ubiquity proteasome pathway and also this whole group of patients whether diabetic or not do have an increased incidence of IGF resistance. Hemodialysis fuels protein degradation as do the higher degrees of inflammation and cytokines in these patients.

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This is a study form the UK from Leicester showing the effects of acidosis on protein metabolism in patients with CKD and what we see here is just the pure effect of acidosis on protein metabolism degradation and the effects of a protein reduced diet and acidosis. These are CKD 3-4 patients. Then when the acidosis was corrected with sodium bicarbonate, there was a significant decrease in protein degradation and in fact, the decrease is quite marked because this decrease basically is equivalent to about 1 kg of muscle a month and that’s quite a strong effect of acidosis on muscle. 

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We can also see the effects of hemodialysis on protein metabolism. The hemodialysis in itself is a catabolic stimulus and results in a decrease or deficit between protein synthesis and protein degradation during dialysis but also after dialysis it continues for some time.

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One can look at insulin resistance in relationship to body mass and this is a recent study by Lee and basically what they’ve shown is in non-obese and obese patients that the higher the level of body fat is compared to lean body mass and this is in non-diabetic hemodialysis patients, the higher the insulin resistance. So that patients with CKD on hemodialysis have a higher level of insulin resistance even if they’re non-diabetic.

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Similarly, this shows the effects of advanced CKD on muscle metabolism in relationship to insulin resistance in hemodialysis patients.

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Here we see that although there’s a positive correlation between insulin resistance and protein synthesis and insulin resistance and protein breakdown, actually there’s a higher loss of protein as insulin resistance decreases. So the insulin resistance in this group of patients does somehow fuel protein breakdown. Although this study shows the effects of protein metabolism in hemodialysis patients with and without diabetes and you can see that the non-diabetics patients seem to maintain a reasonable balance in this study by Pupim while the diabetic patients have a continuous outflow or breakdown of muscle protein.

Slide 13

So is there anything one can do about that? There are lots of things we can do about that and my subject is exercise, exercise we do know from other studies and others in non-uremic patients and also in non-diabetic uremic patients is a very positive, has positive effects on protein metabolism and this is a study on intradialytic nutrition in hemodialysis patients showing that those patients who exercised had a better balance of protein uptake compared to those who didn’t exercise during the dialysis session.

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This is a very early experimental study in 5-6 nephrectomised rats showing the positive effect of exercise. Now these rats actually swam for about 5-6 hours and I think it’s difficult to get our patients to do that, so it’s an experimental situation but we do see these are sedentary controls, exercise controls, sedentary uremic, and exercise uremic and basically what we see is that we have a lower net protein degradation in the exercising rats compared to the non-exercising rats.

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So exercise training in this group of patients could be a good option and it’s definitely not a dangerous option. Often when we think of exercise training, we think that our patients should start running, I don’t know, 5-10 miles, well they can’t do that. Especially in the diabetic dialysis patients we have to adjust exercise to their actual functional status and ability and as you can see from these authentic pictures, exercise can mean very reasonable levels of exertion for this group of patients while they’re actually in their dialysis beds.

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There have been quite a few studies now that say that exercise training is just on the brink of moving from research experimental showing that it’s actually possible into becoming part of clinical practice. We’re not quite there yet but we’re on the brink of that with enough studies in pre-dialysis and dialysis patients to show that it is effective and efficient in increasing muscular strength.

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But it also can increase body muscle protein as this slide from Castaneda’s research shows where these are in pre-dialysis CKD 4 patients where she showed that the increase in muscle strength increased total body potassium which is quite a sensitive marker for total body mass.

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So what does exercise training do for insulin resistance and glucose disappearance rate? Well, there are not many modern studies but this is one of the first studies from the US showing that long-term, this is 12 months of relatively high intensive exercise training, did have a positive effect on glucose disappearance rate and insulin affinity apart from that it also seems to have positive effects on inflammation, cytokines as shown by Castaneda.

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This was resistance training, this is aerobic training.

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So regular exercise training in CKD patients has a whole slew of positive effects apart from increasing quality of life and giving patients a feeling that they can actually do something themselves.

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Whenever you start there’s always a possibility to actually increase the maximal exercise capacity. Better to start early but never too late to do it. When one’s prescribing exercise training as a physician and in conjunction with a physiotherapist to exercise physiologist, it’s important to set the goal because we do have patients who have very varying degrees of functional capacity and functional status.

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We have to individualise the goal.

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And find out what do these patients actually need to do, is it to be able to work? Manage their home? Care for themselves? Just to carry on living at home, go shopping or have social activities? There’s nothing more satisfying than enabling somebody to carry on working but there’s also something very satisfying in being able to enable, as I’ve just recently experienced an 89 year old man who was basically bed ridden and needed a wheel chair to move now thanks to cycling during hemodialysis he’s actually able to walk 150 m and it enables him to be at home with his wife at least once a week which is very positive for him.

Slide 24

So I’d just like to conclude.

Slide 25

And would like you to start prescribing exercise as medicine and pushing exercise into clinical practice because it’s a positive thing for our patients.

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Thank you.