Slide 1

Mr Chairman, Ladies and Gentlemen. So, it’s really a pleasure to share this afternoon session about the DOPPS. I was the one of the starting physicians from France with --- in this I would say very exciting study which is known as the Framingham study from dialysis now. Of course, as a physician and dialysis doctors everyday we have to implement new guidelines and so define and implement guidelines, but this is the – we get the information from the guidelines and the results of the guidelines particularly in this presentation since we are not looking at the cross-sectional analysis but we will have sort of pictures for 3 waves of the DOPPS meaning that we will have the complete movie from the starting point until 2008.

Slide 2

So the trend and of course, we’ll look at the first aspects which are demographics and comorbid conditions.

Slide 3

But mainly comorbid trend in age and particularly on diuretics just to show that there are 3 periods, 80, 98 up to 2007 now just to show that the age according to the different countries and world, in all countries there’s an increase of age and it’s about 4-5 years more in new and prevalent patients on dialysis. This is a first country that was enrolled and this is the second part of the country enrolled from Belgium, Australia and New Zealand but in all countries it’s the same trend, increase of age.

Slide 4

But also interestingly is diabetes and this is a major concern for the comorbid conditions as you can see, on the left you get all the countries with the first wave of the DOPPS. Of course, you see that the US is always at the top about 56-58% of diabetic patients but even in the European countries and in Japan you can see that there is an increase, a trend to increase in all countries. In Europe it’s about 28% as compared to the US. But again, looking at Canada, Australia and Sweden and Belgium it’s also increasing. So there is a trend of increasing of the age and this particularly comorbid condition, diabetes.

Slide 5

So you know that EBPG concerning the guidelines particularly for dialysis dose, haemoglobin concentration, phosphorous and all the calcium phosphate and PTA disorders. This is just to remember the guidelines you get the numbers and the target values in mg/dL and mmol/L. So we will see how we comply with these guidelines.

Slide 6

So the first is dialysis dose and treatment. Interestingly, if you look at the Kt/V which is over 1.2 in Europe as you can see, most of the countries increased the dialysis dose. Germany was not really interested at the beginning but now they have about 80% and a group of patients with more than 1.2 per session. You see other countries are moving up forward and most I would say between 80-90% of the countries get a Kt/V of 1.2.

Slide 7

The same trend was a new country with some exceptions for Belgium which is on the bottom part but an increase of the dialysis dose was given in all countries.

Slide 8

Does it impact on the mortality? Of course, if you take as a reference this value 1.2-1.4, you can see that of course, less than 1.2 the increase in mortality was 24% but if you increase the dialysis dose and if you maintain 1.4-1.6, which was not confirmed by the – study but DOPPS has a completely different approach, you can see that you can reduce by 10 and 20% literally if you get more than 1.6 of Kt/V. So dialysis dose is increasing, it will improve the mortality or the survival of our patients.

Slide 9

The second aspect which is also a lesson from the DOPPS is the treatment time. This is just to show that most of the countries increased the treatment time during these 3 wave periods except some countries France is literally the same and Japan is the same but you can see from Germany and from Spain, US most of the countries increased the treatment time and we can consider that they increased by about 10-15 minutes. No change from Australia, Belgium except Canada which was about the same. But you see most of the countries are doing now literally 4 hours 3 times a week as a minimum.

Slide 10

This is also interesting since it has a very strong impact on the mortality. This is just looking at all-cause mortality according to the treatment time. If you take as reference 4 hours 3 times a week as a session, of course, if you reduce by 30 minutes, you increase mortality by 19%. If you reduce by 1 hour and 30 minutes, you increase the mortality to 34%. You will see that increasing the time on the next line will reduce the mortality in the patient.

Slide 11

This is also coming from the DOPPS, different continents, from Europe, the US and Japan. It is very interesting to see that relative risk of death is declining with the time on dialysis. If you move from 4 hours to 4 and a half hours, you can see that you reduce mortality including in Japan where there is a very mortality. So you can see the ratio by 30 minutes you can reduce by 16% the mortality of your patients and in Japan, it’s about 6% in Europe and 7% in US. So meaning that increasing the time of dialysis reduces mortality in your patients.

Slide 12

That’s also very interesting since if you combine treatment time versus dialysis dose, the survival of the patient is independently increased. If you provide a very high dose of treatment to your patient, you see that increasing the time is also a way of reducing the mortality risk in your patients. So time is very important and it works independently from the dialysis dose in your patients.

Slide 13

So as a summary, just a percent of patients with a Kt/V of 1.2 is increased in our countries except I would say Canada.
Mean treatment time tends to increase in many countries except France, Japan, U.K. and Canada but as you see, most of the countries have 4 hours 3 times a week.
Longer treatment time and higher Kt/V or higher dose is independently predictive of lower mortality. Of course there is some evidence of synergistic interaction between these two parameters; treatment time and dialysis dose.

Slide 14

So what about anaemia?

Slide 15

Anaemia is also very interesting since you see that all the countries increased the haemoglobin level over the 3 waves and particularly this is very interesting from Japan, you move from 10 g/dL literally to 11 g/dL but all the countries except Germany which is stable at about 11.6, most of the countries moved forward and also in the new countries except Sweden that was on a very high level of more than 12. g/dL they come on the group of 11.6 or 11.8.

Slide 16

So most of the countries increased the anaemia and increased the concentration of haemoglobin. Also the use of erythropoietin and this is a percentage of countries using the erythropoietin as you can see, most is virtually 90% in all the countries without significant changes over the 2 or 3 waves, so 90% of the patients received erythropoietin.

Slide 17

What about iron? This is IV iron, very small countries are at risk, not small countries but small percentages of patients receiving 1/3 in Japan but you can see that in most countries about 2/3 of the patients received iron by IV in Europe mainly and it’s the same for the US which is not 2/3 but ¾.

Slide 18

So in terms of anaemia management haemoglobin levels increased in all our countries except in Germany and in Sweden and a percent of patients receiving erythropoietin increased or did not change between the two phases, it’s 90%. A percentage of patients receiving IV iron decreased or did not change in the main countries but again 2/3 of patients received iron by the IV route.

Slide 19

What about this last mineral metabolism indicators?

Slide 20

Phosphorous, calcium and PTH? This is a serum phosphorous according to the country and you see the yellow line is a perfect target and you see that if you look across the countries, I would say 40% of the patients are in the target meaning that a very small percentage about 10-15% are lower in concentration but still they are according to the country, about 40-60% of the patients who get high phosphorous concentrations.

Slide 21

But there are some small changes. If you see, for example, France or Spain you have some small changes proving that there are some beneficial effects of doing guidelines since a percentage of patients with high phosphorous is reduced.

Slide 22

It’s the same for the calcium. Calcium is about 50% in the normal target or on the target.

Slide 23

A percentage of patients over the target is between 30-70% according to the country. A very small percentage less than 10% in this lower range of the calcium.

Slide 24

So now if you look at the PTH and this is interesting to look at the PTH concentrations, as you can see the percentage of patients between 150-300 μg/L is also increased according to the country except for some countries for the UK.

Slide 25

But most of the countries improved the percentage of patients and we can see or can say today that about 1/3 of the patients are on the target for the PTH and it’s about the same for the new countries.

Slide 26

Now, looking for this change over time. This is a yellow line, a yellow region which is 150-300 you see it’s a small percentage, 1/3. A large percentage, a large proportion of patients which is around 50% are on the lower concentration of PTH, a very small percentage 20-30% higher concentration of PTH. So most of the patients are exposed to hyperparathyroidism now as compared to what we knew 15 years ago.

Slide 27

The trend in vitamin D prescription also there are large differences. This is a block of Europe, Japan and US according to the different waves, if you go from Europe, no significant change. You see that about 40% received the vitamin E as iron by the oral route which is not the case in the US, most of the patients are receiving the vitamin D by the IV route. So no significant change over time except from the US where they are receiving the vitamin D by the IV which is not the case in Europe and in Japan.

Slide 28

Phosphate binders also, you see that calcium-based phosphate binders are declining over time from 95-65% so a reduction of 30%. Aluminium or magnesium is very low and sevelamer or the new one, sevelamer, lanthanum is increasing from 0-34%.

Slide 29

So there is a decline of the use of calcium-based phosphate binders and an increase of the new substances without calcium.

Slide 30

Parathyroidectomy, so prevalence of parathyroidectomy is interesting to see according to the different periods and particularly, if you look at the different countries, parathyroidectomy is quite frequent I would say in France for example, very unusual in the US. But if you see the European side, you are maintaining parathyroidectomy. It is the same in Australia and New Zealand which is not the case in US and in Italy so a completely different. approach in terms of parathyroidectomy. On the baseline phosphorous and mortality since we know that hyperphosphoremia is very deleterious.

Slide 31

It’s very interesting to see the distribution of the patients and you can see that this is the distribution – the values which is a target of phosphorous about 50% of the patients. If you look now at the impact of the relative risk of mortality, you see that all-cause mortality is increased and this ratio is about  0.5-6 mg/dL, you see the threshold and there is a linear increase of the mortality but it’s more impressive on the cardiac meaning that all-cause is impacted by hyperphosphoremia but more impressive on the cardiac and you can see that the mortality is clearly increased by 2.5 after a very high value which is more than 2 mmol for the European. No significant impact on non-cardiac I would say risk. So phosphorous is deleterious clearly for the cardiovascular events.

Slide 32

For calcium all-cause mortality is not really impressive. It increases after about 10 mg/dL, it increases also linearly and also it impacts on cardiovascular events and no significant impact on the non-cardiac causes.

Slide 33

So in summary on this aspect, general increase in the percent of patients within the guidelines for serum phosphorous, calcium and PTH but a wide variability between the countries.
Increased use of vitamin D, we remember that IV was used in the US but vitamin D is used by the oral route in Europe and Japan.
Increased use of phosphate binders in Europe and in Japan but a decrease in the US. These are non-calcium based phosphate binders.
Elevated serum phosphorous and calcium is associated with an increased risk of mortality and particularly related to cardiovascular events.

Slide 34

Just to conclude I would say that treatment time and percentage of patients within the guidelines in terms of dialysis dose increases in most countries.
Longer treatment time and higher dose are synergistic to lower the mortality in the patients and this is a nice trend that we observed in the DOPPS.
Haemoglobin levels and percentage of patients receiving erythropoietin is increased in most countries, more than 90%.
Percentage of patients within the guidelines for the phosphorous, calcium and PTH increase but as I said, a very wide variability according to the country and of course, you have to remember that serum phosphorous is really the killer for the dialysis patient more than the calcium and this is really associated with an increased risk of cardiovascular mortality events. Thank you for your attention.