ERA-EDTA Registry Office, St Thomas' Hospital, London SE1 7EH, UK
Correspondence and offprint requests to: Prof. F. Berthoux, Service de Nephrologie, Hôpital Nord, F-42055 Saint-Etienne Cedex 2, France.
Abstract
Background. The new Centre Questionnaire, mainly based on the collection of epidemiological data, was launched in 1996 and the overall response rate of centres for the 15 countries constituting the European Union (EU) reached 82.2% (66100%) for 1995.
Results. We could derive the following information for a general population of 372.6 million. In 1995, the incidence of new end-stage renal failure (ESRF) patients (Ni/P) was 120 p.m.p. (per million population) with a clear north to south/west gradient (69 in Ireland, 131 in Italy and 163 in Germany). The incidence of ESRF deaths (No/P) was 67 p.m.p. (from 35 in Ireland to 89 in Germany). The net increase of patients was therefore 53 p.m.p. (from 13 in Greece to 74 in Germany). The point prevalence of treated ESRF patients (Ns/P) alive on 31 December 1995 was 644 p.m.p. (from 444 in Finland to 773 in Italy). The mean increase in the stock of ESRF patients was +8.2% (4.6 to 13.0) as a linear rate and +0.085 as a fractional rate (exponential). The first treatment of new patients (Ni) was haemodialysis (HD; 81%), peritoneal dialysis (PD; 18%) and pre-emptive renal transplantation (Tx; 1%). The latest treatment for patients still alive was HD (58.5%), PD (9%) or functional Tx (32.5%). The number of Tx was 30 p.m.p. (from 14 in Greece to 45 in Spain). The death rate was 10.4% for all those with ESRF, with 14.4% for those dialysed and 2.2% for transplanted patients. In 1995, 6.5% of dialysed patients received a graft and 4.0% of transplant patients returned to dialysis. The linear expansion rate of the dialysis pool and the transplant pool was respectively 8.3% and 7.9%.
Conclusions. This data shows considerable disparities among countries of the EU which merit further evaluation. Also this analysis by the ERA Registry provides data of value for health and economic purposes.
Introduction
End-stage renal failure (ESRF) unfortunately remains the end result of many renal diseases, despite much progress both in diagnosis and management. It is frustrating that despite four decades of effort, nephrologists are still unable to effectively prevent the progression of most renal diseases towards chronic renal failure (CRF) and thereafter ESRF.
Since 1958, it has been possible to carry out long term haemodialysis (HD) initially on a highly selected group of patients but thereafter on a much more widespread basis, the frequency being related mainly to the political and economic conditions of the different countries. The first renal transplant (Tx) was performed in 1954, but its more widespread adoption began with the use of cadaver organs in 1959 and the introduction of the first immunosuppressive drug, azathroprine, in 1962. The introduction of long term peritoneal dialysis (PD) occurred later and the widespread adoption of this technique began with the development of continuous ambulatory peritoneal dialysis (CAPD).
Thus, we now have three techniques to treat ESRF: HD, PD and Tx. Unfortunately, the use of these techniques continues to be limited by the economic resources of the different countries which in turn are linked to the gross national product (GNP) and the health policies of these countries.
The nephrological community is committed to make all these techniques available for every patient with ESRF whose quality of life can be improved by their use. However, even in the more wealthy countries there are financial constraints on the use of renal replacement therapy (RRT) with the risk of suitable patients failing to receive treatment.
In this paper, we present the 1995 epidemiological data on patients treated for ESRF in Europe by all available modalities of treatment. The information is not complete for all countries, which limits the validity and value of the data. However, for the European Union (EU), formerly called the European Economic Community (EEC), the data is now much more complete and we have therefore focused on the EU countries in this analysis. The EU currently comprises 15 countries: Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, The Netherlands, Portugal, Spain, Sweden and United Kingdom (UK).
Material and methods
The European Dialysis and Transplant Association (EDTA) Registry was created three decades ago for the purpose of evaluating ESRF and its treatment. In the last decade, several factors contributed to a decrease in the performance of this registry. These included an increase in the number of dialysis and transplant centres, an increase in the number of patients on treatment, lack of specific support for filling in patient questionnaires, failure of adaptation to the progress of computer science, and lack of regular feedback of data. At the same time, the association extended its activity to general nephrology and became the European Renal Association (ERA) and the registry became the ERA Registry. As a result of the poor response rate to the Patient Questionnaires (PQ), the ERA Registry was completely reorganized [13]. In addition, a new Centre Questionnaire (CQ) was launched to collect epidemiological data on a yearly basis, starting from the year 1995. The analysis by country of the results of the 1995 CQ is presented in this manuscript.
This CQ was sent to all dialysis and transplant centres known to the registry, either directly or through regional or national registries. The following questions were asked: number of new patients starting their first RRT in the year; modality of first RRT; number of ESRF patients dying during the year with modality of RRT at time of death; number of ESRF patients alive on 31 December and the modality of treatment; number of dialysed patients receiving a renal Tx during the year; number of transplanted patients returning to dialysis during the year.
Adjustment of data according to response rate
The general population surveyed by the centres was, in general, greatly overestimated by them. In the case of 100% response rate (RR), the general population of the country was taken as that for mid-1995. All these populations were obtained from 1995 World Population Data Sheet (Population Reference Bureau Inc, Washington DC, USA).
Until now, the ERA Registry has only published reported treated ESRF and due to the low response rate, the numbers published have been a considerable underestimate. For this analysis, we decided to publish only data for countries with a response rate of at least 60%, which was arbitrarily chosen and which in the future will be increased to 75% or higher. In order to estimate the true numbers for countries with RR between 60% and 99%, we extrapolated the reported numbers to a 100% RR. In this calculation, we have assumed that the populations surveyed in the different centres (big, medium, small) were homogeneous within a country but, of course, we cannot be certain that this is so. However, we have shown that the size of the centres (i.e. number of patients) was independent of the response rates in the reports to our registry. The accuracy of these estimates was directly correlated to the RR: fair between 60% and 74%; good between 75% and 89%; excellent between 90% and 99%; and perfect for 100%.
Epidemiology of treated ESRF in 1995
The analysis was done according to a single-compartment model [46] as previously published (Figure 1).
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From these numbers, we derived:
Epidemiology of treated ESRF in 1995 by dialysis (D) or Tx
The analysis was done according to a bi-compartmental model [46] as previously described (Figure 2).
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From these numbers, we produced:
The characteristics of the Tx compartment were as follows:
From these numbers, we produced:
Epidemiology of treated ESRF by HD or PD
For new patients, the first RRT was HD(NiHD) or PD(NiPD) or pre-emptive Tx(NiTx) with Ni=NiHD+ NiPD+NiTx and NiD=NiHD+NiPD.
For patients dying during the year, the last RRT was HD(NoHD) or PD(NoPD) or Tx (NoTx) with No=NoHD+NoPD + NoTx and NoD=NoHD+NoPD.
For living ESRF patients, the RRT on 31 December was HD(NsHD) or PD (NsPD) or Tx(NsTx) with Ns=NsHD+NsPD+NsTx and NsD=NsHD+NsPD.
Grouping of European countries
We have analysed the 15 countries constituting the EU (ex-EEC). The numbers obtained for each country were added up and the total numbers were considered as for a unique entity, with secondary calculations of the different characteristics of this entity.
Results
Epidemiology of ESRF in the EU for 1995
The results are given in Table I. The general population surveyed was 372.6 millions (column 3). The overall response rate was 84.3% for the general population covered e.g. 314.1 M (column 2).
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The mean point prevalence of treated ESRF was 644 p.m.p. ranging from 444 in Finland to 773 in Italy (column 9). The mean net expansion of the ESRF pool was 53 p.m.p. with values ranging from 13 in Greece to 80 in Luxembourg (column 10).
The flow rate of new ESRF patients represented 18.6% of the total pool with values from 10.8% in Ireland to 25.1% in Luxembourg (column 11). The death rate among treated ESRF patients was 10.4% ranging from 5.4% in Ireland to 12.6% in denmark (column 12). The ESRF pool linear expansion rate was 8.2% with values from 4.6% in Finland to 13.0% in Luxembourg (column 13). The ESRF pool fractional expansion rate was 0.085 with range from 0.023 in Greece to 0.139 in Luxembourg (column 14).
Epidemiology of treated ESRF by dialysis (any modalities) in the EU for 1995
The results are given in Table II.
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The mean dialysis death rate, KoD=NoD/NsD was 14.4% ranging from 10.8% in Portugal to 23.5% in Finland and expressed as a % of the D pool.
The number of patients alive and treated by dialysis (any modalities) was 161 883 on 31 December 1995. The mean point prevalence was 434 p.m.p. with values ranging from 137 in Ireland to 618 in Italy.
The mean percentage of dialysis patients undergoing a renal transplant during the year, KDTx, was 6.5% ranging from 2.8% in Greece to 23.3% in Ireland. Failure of transplantation with return to dialysis, KTxD, accounted for 1.9% of the D pool with values ranging from 0.6% in Portugal to 8.6% in Ireland.
The mean linear expansion rate of the D pool KD, was 8.3% ranging from 0.8% in Greece to 16.0% in Luxembourg.
The total number of patients on dialysis at 31 December 1995 (NsD) represented 67.5% of all ESRF patients with values from 21.4% in Ireland to 90.6% in Portugal.
The different utilization of dialysis treatment modalities in the EU during 1995: HD vs PD
The results are given in Table III and Table IV
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At the time of death of ESRF patients during 1995, the treatment modality was HD in 75.3% (ranging from 59.9% in UK to 93.3% in Luxembourg), PD in 17.8% (from 0% in Luxembourg to 29.0% in Greece) and Tx in 6.9% (ranging from 0.6% in Greece to 17.2% in Finland; No=NoHD+NoPD+NoTx).
For living patients, the treatment on 31 December 1995 was HD in 58.5% (ranging from 13.4% in Ireland to 89.0% in Portugal), PD in 9.0% (ranging from 1.6% in Portugal to 21.1% in UK) and a functioning Tx in 32.5% (ranging from 9.4% in Portugal to 78.6% in Ireland).
The mean death rate was 13.4% for HD (ranging from 9.6% in Greece to 29.8% in Ireland) as compared to 20.7% for PD (ranging from 6.9% in Ireland to 39.7% in Greece). However, these death rates cannot be interpreted without correction for age and the length of time on treatment.
Epidemiology of treated ESRF by Tx in the EU for 1995
The results are given in Table V.
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The mean death rate, KoTx, was 2.2% with values from 0.5% in Greece to 8.8% in Portugal. However allowance needs to be made for age and duration of time since Tx.
The number of failures with return to dialysis during 1995, NTxD, was 3140 giving a failure rate, KTxD of 4.0% with values from 0.8% in Belgium to 6.1% in Austria and Portugal.
The mean point prevalence of ESRF treated by Tx was 209 p.m.p. with a range from 57 in Portugal to 503 in Ireland. On 31 December 1995, the mean percentage of ESRF patients alive with a functioning Tx was 32.5% with values ranging from 9.4% in Portugal to 61.8% in Finland and 78.6% in Ireland.
The mean linear expansion rate of the Tx pool, KTx, was 7.9% with values from 4.1% in denmark to 50.7% in Portugal.
Discussion
Epidemiological data
In this analysis, we have studied a population of 372.6 million inhabitants with an overall response rate of 82.2%. This RR was fair for three countries (France, Portugal, Spain); good for four countries (Germany, Ireland, Sweden, UK); excellent for three countries (Austria, Greece, Italy) and perfect for five countries (Belgium, Denmark, Finland, Luxembourg, Netherlands) with national registries [7,8].
For the first time, our registry, in collaboration with national registries has been able to publish fairly complete data on the epidemiology of ESRF and its treatment by HD, PD and Tx with an estimate of all treated patients and not only reported patients. This is the start of an annual production of new epidemiological data, but we hope to be faster in the future.
Content of the data
This large set of data shows many variations between countries which have a fairly similar economic background. Thus at least some of the differences may not be due to strategic differences in health programmes but to different epidemiological characteristics. Such disparities may also exist within the countries and in the future, the national registries will be able to further study these regional differences. At the level of our registry, it will be our task to clarify and explain the differences between countries and this will only be possible by closer cooperation and exchange of information with the national registries. For these reasons, we are encouraging the development of both national and regional registries.
An example of the differences between countries is the incidence of ESRF which is 120 p.m.p. for whole EU. However, there is clearly a north to south/west gradient with countries belonging to northern Europe such as Denmark, Finland, Ireland, Sweden and the UK having the lowest values (from 68 to 99) while the countries of southern Europe (Italy, Portugal, Spain) exhibiting higher values (from 121 to 131) and those of western Europe (Belgium, France, Luxembourg, Netherlands) having intermediate values (from 82 to 155) except for Germany (163). One can only speculate whether these differences are due to the age distribution of the population (9) or other factors and further studies are required to address these issues. One of the limitation of the CQ, is the absence of information on gender and age of the patients (for new patients, a/o dead patients, a/o treated alive patients) which does not permit the adjustements of basic epidemiological information (incidence, prevalence, etc.) and further comparisons between countries.
Treatment of ESRF in 1995
The data also show variations among countries in the use of available modalities of treatment, which could be explained by different economic policies. Nevertheless, the different cultures and the different medical approaches could also be important explanations. These different points also need to be addressed by specific studies. For example, PD is well accepted as first line treatment in northern Europe with up to 30% of patients receiving this treatment in Denmark, Finland, Sweden and UK. This is in contrast to Germany (10%), Spain (13%), Belgium (6%) and Austria (8%).
Along the same lines, renal Tx is more widely used in Northern Europe and a few countries achieve more than 50% of all ESRF patients with a functioning graft e.g. Ireland with 78.6%, Finland (61.8%), UK (51.9%), Sweden (52.7%) and The Netherlands (50.1%). The economic savings resulting from the widespread use of Tx in these countries is potentially considerable.
Modelling of ESRF epidemiology and treatment
In this paper, we have presented simple data with analysis according to compartment modelling [5]. For simplicity, we have used the linear rates, but for future prediction we should use the constant fractional rates (exponential analysis). We have so far restricted the presentation to K expon, KD expon and KTx expon.
Other predictive methods have been proposed and published [1013] and the reality is probably far more complex than suggested by the different models proposed. In the future, much more sophisticated techniques such as the neural networks (so called artificial intelligence) will be used which will integrate all the changes observed over time and use them for future predictions. These predictions will assume increasing importance in the calculation of health care needs and their cost.
Comparison with other world registries
We have been able to compare 1995 data from USA, Japan, Canada and the EU. The 1995 incidence of new treated ESRF patients is much higher in the USA with 262 p.m.p. and Japan (210), but lower in Canada (104) as compared to 120 in the EU. This is not explained by the ageing of the population and we need to consider specific ESRF causes (such as vascular renal diseases and diabetic nephropathy in the USA), specific environmental factors or specific strategies of ESRF treatment (clearly patients seem to be treated much earlier in the USA). All these points and others need to be addressed by specific international epidemiological studies.
The 1995 incidence of ESRF death is also the highest in the USA with 191 p.m.p. while it is 115 in Japan and 64 in Canada, as compared to 67 in the EU.
The 1995 point prevalence of treated patients is the highest in Japan with 1230 p.m.p. while it is 1013 in the USA, 613 in Canada and 644 in the EU. The figure for Japan is the result of a very high incidence of new patients combined with a low mortality rate (9.3%).
All these data are shown in Table VI. It is interesting to note that the ESRF linear expansion rate is very similar in all countries (from 6.6 to 8.2%).
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We have presented in this analysis an accurate estimate of the 1995 epidemiology of ESRF in the 15 countries constituting our current EU.
Comparisons inside and outside Europe clearly raise many interesting questions to be solved in the future by multinational epidemiological studies.
In the future the ERA Registry will seek to work in closer collaboration with the national and regional registries within Europe and also with the other international registries.
Notes
* The national co-ordinators and/or directors of national registries participating in this study are listed below: H. J. Stummvoll and R. Kramar for Austria; F. Collart for French-speaking Belgium; M. de Broe for Flemish-speaking Belgium; H. Lokkegaard for Denmark; C. Grönhagen-Riska and S. Stenman for Finland; C. Jacobs for France; H. J. Schober-Halstenberg and U. Frei for Germany; V. Hadjiconstantinou for Greece; G. Colasanti for Italy; F. de Charro for Netherlands; J. Pinto dos Santos for Portugal; F. Garcia-Lopez and N. R. Robles for Spain; J. Ahlmen and S. Schon for Sweden and T. G. Feest for UK.
References