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1 1 di 18 Assessment of fluid status in PD patients Raymond T. Krediet, Amsterdam, Netherlands Chairs:Walther H. Boer, Utrecht, The Netherlands F. Fevzi Ersoy, Antalya, Turkey Prof. Raymond T. Krediet DDivision of Nephrology Academic Medical Center University of Amsterdam Amsterdam, Netherlands slide 1 slide 2

2 2 di 18 This slide shows the house on the three canals. This is one of the canals, that s another and behind there s another one. The fact that you have a house here on the meeting point of three canals just illustrates the importance of fluid management. slide 3 So, how is volume status maintained in PD patients? Well, first of all, of course, you have intake, fluid intake much influenced by the intake of sodium. Fluid goes out by either residual renal function, which decreases during follow-up and of course, during peritoneal ultrafiltration, and removal of sodium and that is a mechanism that also decreases in time in some patients. That means that especially long-term patients could be hypervolemic. Of course, they may have hypertension, overhydration, and left ventricular hypertrophy. Therefore, assessment of food status is an important one. slide 4

3 3 di 18 What about assessments? It s more difficult in peritoneal dialysis than in haemodialysis because in haemodialysis it is easy to dehydrate your patients every dialysis treatment. So the question there is, are PD patients fluid overloaded? If you want to answer that, you could just look first at hypertension and presence of LVH. slide 5 Well, if you look at hypertension, it s there in about one third of the patients but also one third together has a normal or a high normal blood pressure. So not every patient has hypertension and therefore, there s one third also here with severe hypertension. slide 6

4 4 di 18 This study from Japan also shows the effect of hydration status on blood pressure and that s especially systolic blood pressure. So, patients with severe overhydration had a higher systolic blood pressure than the other ones and also you could see it on the chest-ray when you looked at the cardiothoracic ratio and they also have a higher ANP, atrial natriuretic peptide and I ll come back to that later. slide 7 LVH, well, that is present in something like 80% of peritoneal dialysis patients at least in this one study that already dates from I guess it s somewhat better at the moment and the possibility of icodextrin and so on. slide 8

5 5 di 18 So, how do we assess volume status in individual PD patients? First of all, of course, there s clinical assessment, which is very important, and then you have emission techniques like chest x-ray, you can look at the diameter of the inferior vena cava but that is a rather specialised technique. There are biochemical parameters that might be helpful in some situations, you can use bioimpedance. I ll discuss all of these whilst I m with you. slide 9 First of all, the biochemical parameters, I think serum albumin and natriuretic peptides are some to have a closer look at. slide 10

6 6 di 18 Serum albumin is often called --- to be a marker of nutritional status, it s not, it s a very poor marker of nutritional status. Patients who die from anorexia nervosa have a normal serum albumin. So it only says something about nutritional status when there s also inflammation. It s a marker of the severity of comorbidity, it s decreased in inflammatory disorders but what is very much important is that it is decreased in overhydration. That is something. slide 11 Here is an old study from the United Kingdom by Doctor Jones. In that study, he divided his patients according to serum albumin. So there was a group with levels consistently below 36 and another group was above 37. When he compared them, he saw that body weight was a bit higher but not significantly. CRP, no difference at all but the extracellular fluid volume assessed by BIA was clearly higher here in these patients. Here it s expressed as percentage of lean body mass and it was also markedly increased in these patients when it was related to total body water. These figures are extremely high figures; more than 50-60% of extracellular volume relative to total body water is a very high value. slide 12

7 7 di 18 You see it over here again, this is the group with low serum albumin, this is the group with normal serum albumin. Here you see when the extracellular volume was expressed related to body weight, actual body weight, here it is expressed relative to lean body mass and here it s expressed as percentage of total body water. You see if you do that, you get extremely high failures, much higher than for instance, when you relate it to lean body mass. slide 13 Then I go on with the natriuretic peptides. The first one discovered was ANP. It s secreted by the heart cells in the atrium and at about the same time BNP, b type natriuretic peptide came up secreted by cells from the heart ventricles. One of the things to remember is that both have a minor terminal part, which has a longer plasma half-life than the original hormones. The original hormones have rather shorter half-life and that means when you measure them, results can be very much variable depending on the acute situations because these amino peptides have a much longer half-life. They reflect the hydration status or heart status, which is more important than the original hormones do. slide 14

8 8 di 18 What do we know? They are increased during peritonitis. It is important to realise that they are only useful in the episodes of heart disease. Data in PD patients are limited but I ll show what there is. slide 15 This is an old study comparing CAPD with haemodialysis before and after haemodialysis and CAPD, although it is higher than controls does rather well over here, especially when you compare it to haemodialysis, which would suggest that not all PD patients are overhydrated. slide 16

9 9 di 18 More recently, doctor Rutter from Rotterdam did an analysis in the NECOSAD population in the Netherlands. So what he took was the population 6 months after the start of dialysis. Those were 68 PD patients. This was the residual GFR of that group of patients. Both and all patients had markedly elevated levels of ANP, the end terminal part over here and total BNP also the same. But you can also see that the ranges are enormous. slide 17 Then he divided them into the group above the median and the group below the median value. Here in this Kaplan-Meier curve you see what happens for ANP and here for BNP. So in both situations you see that the survival of these patients was lower when ANP or BNP were higher. So it s a marker of mortality. slide 18

10 10 di 18 That was even more clear when hazards ratio were calculated for e-anp and BNP. If you look at those hazards ratios, these are unadjusted ones and these are adjusted ones, you see that the relative risk of both ANP and BNP for death are about 10-fold increased, so an enormous excess risk factor for dying. slide 19 Somewhat more about the b-type natriuretic peptide. I ve already said it s a pro-hormone; it s cleaved into an active part and into an inactive molecule. The N-BNP or (NT)-pro-B-natriuretic peptide and that is the one that is normally mostly used in studies because of its relative stability. So, it reflects what happens in some lower term. Longer half-life as I said but there s one thing that you have to keep in mind and that is that BNP and N-BNP is removed by glomerular filtration because of its molecular weight. Therefore, you find in all patients with renal failure higher concentrations than in normals. So the maximum value for normals is about 200 picog/ml but in PD patients normal values are above 1500 and that s not because they re all overhydrated but that is because the removal of N-BNP is worse because of the presence of renal failure. slide 20

11 11 di 18 These are some data from my own group, not in PD patients here but in pre-dialysis patients. These patients were divided according to tertiles of BNP. So the lowest tertiles, the mid and the highest tertile. If you make a comparison between these tertiles and you focus on the highest BNP tertile, you see that indeed these patients had a somewhat serum albumin, that they have somewhat lower measured GFR and that they had fantastic values of (NT)-pro-B-natriuretic peptide. How is that in dialysis? slide 21 Here you see that the effect of heart failure was present, so these patients had no heart failure assessed by ultrasound of the heart. These patients were in heart failure also assessed as by ultrasound of the heart and you see that the values are a bit higher over there but there s still an enormous overlap. slide 22

12 12 di 18 A study in PD patients has been published by the group in Hong Kong by Doctor Angela Wong. She divided her patients into those with no congestion and with congestion and also here marked differences present in pro-bnp and otherwise also systolic blood pressure was higher. Diastolic doesn t matter and also here serum albumin was a bit lower. So confirming all the other results that I ve shown you. slide 23 Those patients in the Hong Kong study, the patients with highest quartile of BNP had the worst survival. The ones with the lowest value had the best survival. So increased BNP is an important indicator of risk of dying. slide 24

13 13 di 18 This study from Canada examined BNP with some other parameters and the first three are overall derived from BIA studies. I ll come back to that in a moment but also serum albumin was related to (NT)-pro-B-natriuretic peptide. slide 25 Before really starting at BIA, things just to remind you what you measure with this BIA. What you measure is total body water, which of course, has an intercellular and an extracellular component. total body water includes lean body mass but lean body mass is a bit larger because also proteins are also included in that. slide 26

14 14 di 18 The old method was the single frequency method but that assumes a fixed relationship between extracellular and intercellular water so making it difficult to interpret the extracellular volume. Multi-frequency is better and it says it enables to distinguish between inter and extracellular fluid resistance but the way that it is done in the programme that --- has only been investigated in patients with normal renal function and we have no separate investigations done on these ratios in patients with ESRD. It might very well be that the permeability to water and the division of total body water and extracellular water is different in them. Segmental BIA has no clear advantage. slide 27 So what do you measure if you do BIA? When you compare it with other measurements of fluid transport. Well, the reference methods are deuterium oxide for total body water and the bromide space for extracellular body water. BIA measures the resistance that is mostly important for the fluid parameter. As I said, the ratio between extracellular volume and total body water is based on data obtained in normal. For instance, you have to realise that total body water does not influence the serum albumin but the excess of volume will influence it. slide 28

15 15 di 18 So the relationship between albumin and extracellular volume over total body water ratio are different and haemodialysis compared to peritoneal dialysis patients. So, in PD patients this ratio, this is the most severe group, is more dependent on albumin than in the haemodialysis situation. slide 29 This shows you some comparisons with the gold standard. This is for total body water, this is BIA and this is deuterium. You would say that there is a nice relationship if you just look at the correlation but when you do a Bland and Altman analysis as is shown over here where you look at the difference between the two methods, you see that the ranges are enormous from more than plus 10 l to something like minus 6 l for total body water. slide 30

16 16 di 18 So an enormous range and that is also what you see for extracellular volume. So this is BIA and this is sodium bromide space, a nice relationship but if you do the Bland and Altman analysis, again a very wide range. slide 31 Does that mean that we cannot use it? Well, not exactly, because there is a wide variability among patients as you see for the results you obtain with BIA but it is likely that differences are the constant when you use it for follow-up of individual patients. That has been done in this study where the effects of icodextrin were assessed. So a randomised controlled trial. This is the group that remained on glucose, this is the group who got icodextrin, this is dry weight, which in PD terms means after drainage and you see that that goes up in the glucose group and goes down a bit in the icodextrin group, so suggesting less overhydration. If you look at total body water with deuterium oxide, you see the same but also when you do BIA measurements for total body water extracellular fluid, you see the same time course. So all these methods used have more or less the same shape meaning that icodextrin use reduces the total body water extracellular volume. slide 32

17 17 di 18 So Mr Chairman, ladies and gentlemen in conclusion I think that assessment of hydration status is important because many PD patients are hypertensive and overhydrated but it s many, certainly not all of them and besides clinical assessment which is still the cornerstone natriuretic peptides in BIA perhaps sometimes albumin may prove additional information, but they all have their limitations. If you look at BIA, the value of BIA is probably not in a single follow-up situation in patients but it may be useful during follow-up. slide 33 I thank you for your attention. slide 34

18 18 di 18 Chairman: Thank you very much I think there s time for one or two brief questions. Any questions from the audience? For practical purposes, have you come up with cut-off values for one of the natriuretic peptides or BIA measurements to help you in clinical practice? Prof. Krediet: No, I think they have still not been established. I said more than 1500 for BNP in PD patients as a kind of upper value of normal but it has not been established yet properly. Chairman: But clinical practice has helped you to decide to breakdown dry weight or don t you use it in clinical practice? Prof.Krediet: Well, if they are , it s evident of course that there must either be very severe heart failure or severe overhydration. If you want to distinguish between them of course, you can do echocardiography to look at myocardial function and things like that. But I think in a situation where a patient has no overt heart failure also by echocardiography then NT-BNP is probably very valuable for assessment of hydration status. Again, what is evident for all these things that there is no single reference method. So if you are in doubt of whether your patients are overhydrated or not, first of all you should look at them and after that look at additional parameters but keep in mind that they are just an addition to clinical judgement. It can be very helpful in a certain situation but certainly not in all situations. Chairman: Thank you very much.

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