CENTRAL AND EASTERN EUROPE: THE CHALLENGE OF AN EX­PANDING RENAL POPULATION WITH AN EVOLVING DISEASE PATTERN

Adrian Covic, Iasi, Romania

Chair: Adrian Covic, Iasi, Romania

Netar P. Mallick, Manchester

Prof Adrian Covic Full Professor of Nephrology Dialysis and Renal Transplantation Unit “C. I. Parhon” University Hospital Iasi, Romania

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Slide 1

Thank you Mr Chairman.

Slide 2

I will start by asking more philosophical and also some political questions. In fact what is East and what is Western Europe? You all are aware, in fact, that these days we have really a clash of civilisations.

Slide 3

While we are asking this question because should we, the ERA-EDTA, the registry systematically address for the first time the issue of a comprehensive comparison between West and East? There are important differences and I’m going to discuss with you outcomes, dialysis practice and also factors influencing dialysis.

Slide 4

What are the differences between West and Eastern Europe amongst factors that might influence dialysis? Let me take you through a very rapid overview of the general population.

Slide 5

Of course, the survival in the general population is different, as you can see, there is a higher expectation of life in Western Europe.

Slide 6

So there is a larger proportion of old patients and you’ve seen that, older patients arriving to dialysis and that might be part of the explanation why we have an increase in the incidence and prevalence of old dialysis patients in the West. But also let’s not forget that we have some differences.

Slide 7

There are some genetic variations in Europe. We can look at this in two ways by simply looking, as you can see, on your left hand side the blood type distribution but also if we look into a more sophisticated way looking at the synthetic variables summarising allele frequency in 120 protein loci.

Slide 8

So there is a difference, as you can see, between Eastern and Western Europe.

Slide 9

There is also a difference in terms of GDP and more.

Slide 10

So when we look at the GDP per capita and in purchasing power standards. So, in fact, the difference is from 1-2, from 1-3 and we are all aware of that.

Slide 11

In fact, this translates to a huge difference in total health expenditure as a percentage of GDP.

Slide 12

This is important because we’ll have a difference in the total number of practicing physicians. If you look at the West, you have a relatively homogeneous and high number of practicing physicians. Whilst if you look at Central and Eastern Europe, you can see a relatively inhomogeneous and lower number of practicing physicians.

Slide 13

Fortunately, for the old let’s say communist times, the social and education difference is not so high between Eastern and Western Europe. In fact, if we look, there seems to be a little bit more of a social and education prevalence in Eastern Europe.

Slide 14

There are some important social and alimentary habits between the two regions. If we look, for example, at the fruit and vegetable consumptions and it’s not only between the East and West but also between the South and North of Europe.

Slide 15

Also if we look at the wine consumption, there is a difference and of course, the good wines from Italy and France probably are the explanations why these two excellent teams made it to the final of the World Championship.

Slide 16

To me, in fact, the most important differences are related to the religions and to the history of Europe because the history of Europe actually made a formidable impact on what we are today and also I think on some of the comorbidities in the general population and I’m just going to present one of them which is relevant to our population.

Slide 17

Look at the hepatitis B and the hepatitis C prevalence in those two areas and you can see clearly that in Central and Eastern Europe, for example, in Romania, in Russia but also in some of the other countries there is an important and you might argue that HBV and HCV are somehow endemic in these two regions.

Slide 18

Now, I’m going to move to the dialysis. Are there any important differences in East and Western Europe? For sure when I started dialysis I was working on this kind of machines. And this was not too long ago. Probably when Francesco started dialysis he was working on these types of machines. So you can already see some of the differences. But let’s go into more detail.

Slide 19

First of all there is a difference in the incidence of the renal replacement therapy per million population. There is a huge increase in the incidences, as you’ve heard from the previous speaker, in Western European countries. There is somehow a difference between different areas in Eastern Europe but over all the message is clear, there is a smaller incidence.

Slide 20

This is somehow related to the GDP and I’ve eluded the GDP because in this very nice graph you can see that there is a relationship when we go to a global perspective between GDP, between income and between the number of incident and prevalent dialysis and renal replacement therapy population.

Slide 21

But the Eastern Europe is really catching up very, very fast. Romania, for example, I’m using Romania as a very good example and I’m going to come back to that, it’s now well known for its huge increase in facilities. This is the Cinderella story, in fact, and we’ve published this recently in NDT and you can see there are impressive amounts of increase. These rates, you can see these rates of increase nowhere in the World, I mean we’re talking about rates of increase of more than 100% from the previous year. I can assure you we’ve looked at our data, those rates of increase are similar year by year and similar rates of increase are in the other Eastern European countries.

Slide 22

Somehow the population and the distribution of the different renal replacement therapy modalities is different. You can see Eastern Europe and in Eastern Europe still dialysis is mainly, the hemodialysis is the major modality. It’s somehow similar to Japan whilst in Western Europe and particularly, in the Northern countries nowadays transplantation has become the major, the main thrust to treat our end-stage renal disease patients.

Slide 23

I’m now going in the final part of my presentation to try to sum up some very new and exciting data because, in fact, when I received this subject and as I said I conceived this subject with my friend Francesco Locatelli and my friend Carmine Zoccali, we didn’t know what was going to be available and there are no available data, there is no DOPPS for Eastern Europe, there is no DOPPS for Europe. So what I did for you is, in fact, I’ve shopped around and I’m going to present you data from the only or the largest dedicated database which is the Fresenius Medical Care database. It’s a huge and impressive database. I’m going to refer to some of the registry data, which I’ve taken from Kitty Jager. I’m going to reverse to some of the excellent industry studies recently presented here. I have some data from the National Societies and as a case study I’m going to present some data from our own National Registry and I’m going to rap this up.

Slide 24

Now what about the Fresenius Medical Care Network? As you can see first of all, the increase in renal replacement in hemodialysis is much faster again in Eastern Europe compared to Western Europe.

Slide 25

There is, of course, a difference and by the way this is a huge database as you can see, it’s more than 20,000 patients and it’s an extremely well designed and well collected database.

Slide 26

These are the demographic differences from this database and age is, of course, higher in Western Europe but mind you age in dialysis is not so low in Eastern Europe, it’s still 63 as you can see. There are some differences in gender, there are some differences in weight and we’ve heard the importance of obesity and as you can see, surprisingly obesity is much more prevalent in Eastern Europe but that was the case for the general population.

Slide 27

So then if we look to the ERA-EDTA Registry data, not the systematic data but the best data we have there is some difference in terms of mean age at the start of dialysis.

Slide 28

And this is the Romanian data showing you two things. First of all, is that you have really an equal amount of patients which are really very young still, which are middle-aged but also a significant group, as you can see in yellow, of about 1/3 and again rapidly increase of really old patients. So we are really catching up this is the epidemiological transition. The area of residence. That’s another important issue because you won’t find the same distribution of urban dialysis centre treating urban patients. It’s more the rural patients, which have to travel quite a lot to the centres, or you have to really to implement peritoneal dialysis similar to countries like Mexico.

Slide 29

Now if we pull together all the data from the Fresenius Medical Care, from the ORAMA and Francesco presented that and from the COSMOS, you can see that the proportion of diabetes is, of course, higher in Western Europe.

Slide 30

So to summarise this demographic data there are clear differences in East versus Western Europe and this is the data from where I gathered and I can have a profile for you, the Eastern European patients are younger, there are less diabetics not more diabetics, it’s a heavier patient from rural areas with a less higher education and possibly more alcohol consumption and more HBV, HCV prevalence.

Slide 31

What about the dialysis complications? I’m going to maintain the same pattern of presentation and I’m going to refer to the major end-stage renal disease complications, first anaemia.

Slide 32

This is data from ORAMA and ORAMA, which is the Optimal Renal Anaemia Management Assessment and we’ve been involved in that, data are presented throughout this conference, is looking at the treatment of anaemia across centres and across countries.

Slide 33

It’s a prospective study assessing adherence to the European Best Practice Guidelines and their impact on the patient outcomes, as you can see there, is well balanced. Western Europe is represented by 20 centres, Germany and Italy. Eastern Europe is represented by 27 centres from many countries and there is a fair amount of patients.

Slide 34

The first conclusion is that, as you can see, there is a difference of about 1 g in haemoglobin between Western and Eastern Europe. It’s a fairly similar level in Western Europe and there are important variations in Eastern Europe. But in fact, ORAMA and that’s very well presented in the abstract and I urge you to visit the posters with the data, in fact, what happens in Eastern Europe is that patients are stabilised at a lower haemoglobin level. In fact, the proportion of patients with stable 10-12 g/dL of Hb is similar in the East and in the West. So it’s a question really of resources, it’s a question of allocating the resources not of non-adherence to the guidelines. It’s really stabilising the patients to a lower level and in the light of the new data regarding the upper limit I’m wondering who in the end is going to win this game.

Slide 35

These are the main conclusions from ORAMA. So the mean Hb was significantly lower in the East. The mean Hb in the Fresenius Medical Care Network was 11.5. The adherence to the European Best Practice Guidelines was non-satisfactory in both regions, particularly in Eastern Europe and at least one Hb measurement, baseline or prior to the study, was outside of the guidelines more in the East as you can see almost ubiquitous more than in the West. However, the proportion of patients, which was stable was similar in the two countries.

Slide 36

This data from a study, it’s a prospective study, it’s a survival study which we have initiated and Hb values for Romania at renal replacement therapy initiation is 8.8. So it’s fairly low, as you can see and mind you this is in patients, which are EPO naïve.

Slide 37

What is now the mineral and bone metabolism? Again data from the Fresenius Medical Care Network. There is clearly a difference between Eastern and Western Europe. It’s the level of PTH, is lower in Eastern Europe. The level of phosphates is a little bit higher as is the level of calcium.

Slide 38

I have the privilege also to show you some data, which has been presented in more detail here by Professor Cannata and also in some of the posters. He lent me this slide. This is a very nice prospective multicentre observational and non-interventional cohort. It’s a web-based database. It’s a 3-year study. There are many countries from both regions. It has many ambitious objectives.

Slide 39

I just want to point out one of those, the primary objective. One of those is to investigate the K/DOQI target achievements in a representative sample of European dialysis patients by type of dialysis, by type of centre, small or large, a university centre, non-university centre, private, non-private, time on dialysis to look at prevalent early patients or prevalent patients which have a longer dialysis and amongst new dialysis subjects.

Slide 40

This is a very nice study. It will also look at mortality.

Slide 41

And overall cardiovascular hospitalisation in relation to this achievement of DOQI guidelines

Slide 42

and we have some baseline data.

Slide 43

And again as you can see there is a picture, which is familiar to us. First of all, is that there is a difference between West and East.

Slide 44

There is a favour in the West but the difference is not important and in fact, if we look at when all the targets, the guidelines are achieved, we are only talking of about 5-10%.

Slide 45

However, the importance of this study is great because in the DOPPS, as you can see, it’s about 5%. So either the DOPPS didn’t catch the entire picture of Europe, which is probable, or we are having an improvement in our nephrological practice.

Slide 46

What about the data from the prospective Romanian Renal Registry? As you can see the serum calcium is not as high but the serum phosphate is really high. So this is really a problem for the incident patients. Yes there is this tendency of a very low PTH and of adynamic bone disease and I’ve discussed with colleagues from Macedonia from other parts in the Balkan regions in Eastern Europe and that’s the impression, that there’s a lot of adynamic bone disease. However, because of the age and because of the lower prevalence of diabetes there is not an important prevalence of aortic calcification and we looked at those. The majority, they don’t have in fact aortic calcification.

Slide 47

Now I’m going to try to demolish a myth. The myth is that when we try to publish papers is that well there are differences because, of course, the Eastern European patients are younger and they have less comorbidities. Well please look at this kind of data. This is again from a very good database, the Fresenius Medical Care database where every item you can imagine is recorded and is recorded repeatedly. Look at the prevalence of the congestive coronary heart disease. Also the prevalence of the heart failure, severe liver disease, pulmonary disease and so on. In fact, if anything, it’s equal or in fact, more in the Eastern part of Europe.

Slide 48

This is confirmed by the Romanian Renal Registry. Again these are incident patients and look please at the coronary artery disease at the initiation of dialysis. The chronic heart failure, the prevalence of arrhythmia and so on. So it’s a lot of cardiovascular morbidity, a lot of hepatic disease, hepatic infection, comorbidity. So, it’s a lot of comorbidity out there.

Slide 49

Now, again to try to demolish this myth I’ve compared, for example, this Romanian data in black just to be more powerful to the Western countries. As you can see, it’s at least equal and in some instances ischemic heart disease is higher than in the Western countries.

Slide 50

However, for some reason or another the survival, the number of deaths is really low, in fact it is customary to see in Eastern European countries gross mortality of between 5-12%. It’s 5% in my centre and this is repeatedly shown and we’re now going to provide prospective data on that.

Slide 51

So I’m going to conclude with the following, that Europe is not homogeneous. There are significant differences in genetics, in demographics, in history, in the social structure. So we have to do studies Eastern versus Western Europe. The renal replacement therapy is lower, the incidence and the prevalence in Eastern Europe. However, there is an impressive increase in Eastern Europe and I bet that in 5 years time we’re going to really discuss similar levels. The Eastern Europe population is younger, more diabetics, heavier, more from rural areas, less higher education, more alcohol consumption.

Slide 52

The adherence to some of the EBPG is non-satisfactory, particularly in Eastern Europe. However, patients are stabilised at a lower level and at least there is a similar comorbidity profile. In fact, it’s slightly higher in Eastern Europe and there is an excellent, despite this, an excellent survival in Eastern Europe.

Slide 53

I have to again to stress that the team behind this is the ERA-EDTA Registry. It’s Daniele Marcelli from the FMC Network. It’s Professor Mircescu, my colleague from the Renal Romanian Registry. It’s Jorge Cannata from the COSMOS. It’s the ORAMA team and it’s many presidents from the societies in Eastern Europe, which I thank very much. Thank you.