## Abstract

Background. This study compared the prevalence of co-morbidity in patients starting renal replacement therapy (RRT) between European countries and further examined how co-morbidity affects access to transplantation.

Methods. In this ERA-EDTA registry special study, 17907 patients from Austria, Catalonia (Spain), Lombardy (Italy), Norway, and the UK (England/Wales) were included (1994–2001). Co-morbidity was recorded at the start of RRT.

Results. The prevalence of co-morbidity was: diabetes mellitus (DM) (primary renal disease and co-morbidity) 28%, ischaemic heart disease (IHD) 23%, peripheral vascular disease (PVD) 24%, cerebrovascular disease (CVD) 14% and malignancy 11%. With exception of malignancy, the prevalence of co-morbidity was highest in Austria, but differences were small among other countries. With exception of DM, males suffered more often from co-morbidity than females. In general, the percentage of haemodialysis was higher in patients with co-morbidity, but treatment modality differed substantially between countries. Using a Cox regression with adjustment for demographics, country, year of start and other co-morbidities, the presence of each of the co-morbid conditions made it less likely [RR; 95%CI] to receive a transplant within 4 years: DM [0.79; 0.70–0.88], IHD [0.59; 0.50–0.70], PVD [0.57; 0.49–0.67], CVD [0.49; 0.39–0.61], and malignancy [0.32; 0.24–0.42]. The age, gender and year of start adjusted relative risk [95%CI] to receive a renal transplant within 4 years ranged from 0.23 [0.19–0.27] for Lombardy (Italy) to 3.86 [3.36–4.45] for Norway (Austria = reference). These international differences existed for patients with and without co-morbidity.

Conclusions. The prevalence of co-morbidity was highest in Austria but differences were small among other countries. The access to a renal graft was most affected by the presence of malignancy and least affected by the presence of DM. International differences in access to transplantation were only partly due to co-morbid variability.

## Introduction

Co-morbidity affects the prognosis of patients with end-stage renal disease (ESRD). Several studies have shown the negative effect of co-morbid conditions on survival and quality of life [1–6]. In addition, a number of American studies have shown that the presence of co-morbidity reduced access to renal transplantation [7,8].

Knowledge on co-morbid variability is thus considered to be important. Many studies have reported the prevalence of coexisting diseases in dialysis patients in the United States (US) [3–5,7,8], and recently, the I-DOPPS study has reported co-morbidity of haemodialysis patients in a number of European countries [4,9], and compared this with that of Japanese and US patients [4]. Within Europe, some studies and renal registries have reported co-morbidity data in their own region or country [10–12]. However, little is known about differences in co-morbid conditions among European countries. We therefore started a study with national and regional renal registries in Europe that include co-morbidity in their data collection.

This paper focuses on the comparison of co-morbidity in patients starting renal replacement therapy (RRT), including haemodialysis (HD), peritoneal dialysis (PD), and transplantation, in different parts of Europe. In addition, it describes how these co-morbid conditions affect access to renal transplantation within those countries.

## Methods

### Population

The ERA-EDTA Registry routine data collection does not include data on co-morbidity. Therefore, we asked the 15 national and/or regional registries sending individual patient data including survival data to the ERA-EDTA Registry at the time of the study, whether they also collected data on co-morbid conditions at the start of RRT. Four of them collected co-morbidity data for a sufficiently long period to study the effect of co-morbidity on access to renal transplantation, including the Austrian Dialysis and Transplant Registry (OEDTR) (1998–2001), Catalan Renal Registry (Registre de Malalts Renals de Catalunya (RMRC) Catalonia, Spain) (1995–2001), Norwegian Renal Registry (1999–2001), and the UK Renal Registry (UK, England/Wales) (1999–2001). To increase geographical spread across Europe, we asked the well-established Italian Registry from Lombardy (Registro Lombardo Dialisi e Trapianto) to participate, which they did (1994–1997). Patients older than 18 years of age at the start of RRT were included.

### Co-morbid conditions

Data collection on co-morbidity was performed by a doctor or a high-skilled nurse. Appendix 1 shows the classification of each of the following co-morbid conditions for each participating registry: diabetes mellitus (both as a renal disease and as a co-morbidity in addition to another renal disease), heart failure, ischaemic heart disease, peripheral vascular disease, cerebrovascular disease, malignancy, liver disease and lung disease. Some registries gave definitions or more detailed descriptions of diagnostic criteria for each co-morbidity. In all cases, the co-morbid conditions were indicated as being present or absent in the medical history at the start of RRT. Sometimes they were further specified by providing subcategories of the disease involved. In all registries, it was possible to distinguish between ‘no co-morbidity’ or ‘missing data on co-morbidity’, with the exception of Norway. In this latter country, all patients without co-morbidity data were considered to have no co-morbidity. The few patients in Catalonia (Spain) (n = 12) and Lombardy (Italy) (n = 189) without any co-morbidity data were excluded from the study.

We compared the classification of the co-morbid conditions, to see whether international comparison of co-morbid conditions was hampered by differences in definitions. The classification of liver and lung disease differed substantially with respect to the included categories. Moreover, data on heart failure were not registered in the UK (England/Wales) and Austria did not collect data on lung diseases in the study period. Further analyses were therefore only performed for co-morbid conditions, which were comparable between the European countries, including diabetes mellitus, ischaemic heart disease, peripheral vascular disease, cerebrovascular disease and malignancy.

### Data analyses

The prevalence of each co-morbid condition was studied in relation to country, age group, gender, diabetic status, and treatment modality. As patients may have diabetes mellitus on top of another renal disease, diabetes mellitus included both diabetes as renal disease and as a co-morbidity, unless noted explicitly. The prevalence of co-morbid conditions was analysed for treatment modality at day 91 after the start of RRT, as some patients receive haemodialysis for a short period, while preparations are made for peritoneal dialysis. Adjustments were performed for age and gender where appropriate, using the distribution of age and gender of all patients of the co-morbidity study. Differences between countries and gender were analysed using ANOVA for continuous variables, and Chi-square test for categorical variables. It should be noted, however, that the vast majority of the differences were statistically significant as a result of the large sample size, and therefore, P-values were not presented.

Multivariate Cox proportional hazards regression, with adjustment for age, gender, country and year of start of RRT was used to examine the association between the presence of co-morbid conditions and the time to a first kidney transplant within 4 years after the start of RRT. In addition, we compared the chance of receiving such a transplant between countries. Because of the relatively small number of patients with co-morbid conditions who received kidney transplants, the association between specific co-morbid conditions and time for the first transplant could only be determined for all countries together. Follow-up time was censored at death, recovery of renal function, and loss of follow-up. In addition, it was censored when patients were still alive and on dialysis after 4 years or, when this was earlier, at the end of the observation period. To examine the association between the presence of co-morbidity and the time to the first living or cadaver donor transplantation separately, follow-up time was additionally censored for a cadaver or living donor transplantation, respectively. Although receiving a transplantation is a positive event, results of Cox regression analyses are, as usual, presented as relative ‘risks’. All analyses were performed using SAS 8.0.

## Results

### Population

Table 1 presents the baseline characteristics of the patients by country. For all countries together, 17907 patients were eligible for the analyses. The mean age was 62 years, 39% were female and 20% had diabetes as renal disease. The mean age varied between 60 years in the UK (England/Wales) and 64 years in Catalonia (Spain). Furthermore, in Austria the percentage of diabetes mellitus as renal disease was twice as high as in the other countries.

Table 1.

Baseline characteristics of RRT patients by national or regional registry

All countries Austria Catalonia, Spain Lombardy, Italy Norway UK, England/Wales
Number of patients 17907 3859 5932 4292 1204 2620
Incidence of RRT in 2000 (pmp)$– 128.6 145.1 126# 89.1 89 Age at start RRT Median (years) 65.4 64.3 67.4 64.8 64.5 63.5 Mean (years) 62.2 62.1 63.7 61.7 61.4 60.3 65+ (%) 51.1 48.4 56.4 49.3 49.1 46.8 75+ (%) 20.4 19.0 23.8 17.6 22.3 18.4 Female (%) 38.8 40.6 38.0 39.6 34.5 38.7 Primary renal disease (%) Glomerulonephritis 16.8 13.9 14.8 21.6 20.6 16.6 Interstitial nephritis 11.3 9.8 11.5 11.8 11.1 12.1 Cystic kidney disease 7.5 6.2 8.3 7.8 7.0 7.6 Hypertension/renal vascular disease 17.5 16.5 17.5 17.9 27.1 13.7 Diabetes mellitus 20.4 33.0 19.5 14.3 14.6 16.7 Other multisystem disease 6.2 5.1 4.7 6.2 10.7 8.9 Other congenital and hereditary kidney disease 20.4 15.6 23.8 20.4 9.0 24.6 All countries Austria Catalonia, Spain Lombardy, Italy Norway UK, England/Wales Number of patients 17907 3859 5932 4292 1204 2620 Incidence of RRT in 2000 (pmp)$ – 128.6 145.1 126# 89.1 89
Age at start RRT
Median (years) 65.4 64.3 67.4 64.8 64.5 63.5
Mean (years) 62.2 62.1 63.7 61.7 61.4 60.3
65+ (%) 51.1 48.4 56.4 49.3 49.1 46.8
75+ (%) 20.4 19.0 23.8 17.6 22.3 18.4
Female (%) 38.8 40.6 38.0 39.6 34.5 38.7
Primary renal disease (%)
Glomerulonephritis 16.8 13.9 14.8 21.6 20.6 16.6
Interstitial nephritis 11.3 9.8 11.5 11.8 11.1 12.1
Cystic kidney disease 7.5 6.2 8.3 7.8 7.0 7.6
Hypertension/renal vascular disease 17.5 16.5 17.5 17.9 27.1 13.7
Diabetes mellitus 20.4 33.0 19.5 14.3 14.6 16.7
Other multisystem disease 6.2 5.1 4.7 6.2 10.7 8.9
Other congenital and hereditary kidney disease 20.4 15.6 23.8 20.4 9.0 24.6

\$pmp = per million population; #incidence of RRT pmp in 1996 as this year is in the middle of the inclusion period 1994–1997.

### Prevalence of co-morbid conditions

#### By age group and gender

Figure 1 illustrates that the prevalence of diabetes mellitus was higher in males in the age group 45–64 years, whereas in the other age groups the percentage was higher in females. This gender difference was due to the prevalence of diabetes as renal disease and not due to the prevalence of diabetes as co-morbidity. The prevalence of ischaemic heart disease was higher in males than in females across all age categories. Also, the prevalence of peripheral vascular disease, cerebrovascular disease and malignancy was higher in males than in females in the higher age categories (above the age of 45 years for the first two co-morbidities and above 65 years for the latter one). Furthermore, as expected, the prevalence of co-morbidity increased with age. The distribution of co-morbidity over age groups and gender was similar across countries.

Fig. 1.

Prevalence of co-morbid conditions in RRT patients, by gender and age group. DM, diabetes mellitus (primary renal disease or co-morbidity); IHD, ischaemic heart disease; PVD, peripheral vascular disease; CVD, cerebrovascular disease; MAL, malignancy.

Fig. 1.

Prevalence of co-morbid conditions in RRT patients, by gender and age group. DM, diabetes mellitus (primary renal disease or co-morbidity); IHD, ischaemic heart disease; PVD, peripheral vascular disease; CVD, cerebrovascular disease; MAL, malignancy.

#### By country and diabetic status

Table 2 shows the prevalence of co-morbidity by country and diabetic status. As expected, diabetics had a higher prevalence of ischaemic heart disease, peripheral vascular disease, and cerebrovascular disease than non-diabetics. With the exception of malignancy, the prevalence of all co-morbid conditions was highest in Austria, both in diabetics and non-diabetics. In both groups, Norway ranked second and the UK (England/Wales) ranked third in the prevalence of ischaemic heart disease. In Catalonia (Spain) the prevalence of peripheral vascular disease was remarkably high in diabetics. Otherwise, the differences in co-morbidity between countries were relatively small.

Table 2.

Prevalence of co-morbidity (%), by diabetic status and by country, unadjusted and adjusted for age and gender

All countries Austria

Catalonia, Spain

Lombardy, Italy

Norway

UK, England/ Wales

All
Diabetes mellitus (PRD and co-morbidity) 27.8 40.6 39.5 27.5 27.2 20.8 20.8 22.8 22.8 23.6 23.7
Diabetes mellitus (PRD) 20.4 33.0 32.0 19.5 19.6 14.3 14.1 14.6 14.2 16.7 16.5
Diabetes mellitus (co-morbidity) 7.5 7.6 7.6 8.1 7.7 6.6 6.7 8.6 8.6 7.1 7.3
Ischaemic heart disease 23.4 31.5 31.4 20.0 19.1 18.3 18.6 26.3 26.9 25.8 26.8
Peripheral vascular disease 23.7 36.6 36.2 27.1 26.1 14.8 15.0 19.1 19.3 13.7 14.3
Cerebrovascular disease 14.4 24.9 25.0 11.7 11.1 10.6 10.9 11.1 11.6 12.7 13.4
Malignancy 10.9 11.2 11.3 8.7 8.3 12.6 12.7 13.9 14.4 11.1 11.6
With diabetes mellitus
Ischaemic heart disease 36.4 44.3 43.3 34.7 33.1 26.4 25.6 35.4 39.6 35.6 38.1
Peripheral vascular disease 42.7 54.9 54.4 49.8 48.9 27.8 27.5 21.2 22.3 23.9 23.9
Cerebrovascular disease 22.0 34.2 33.6 17.2 16.3 15.3 15.3 12.8 14.9 17.5 18.4
Malignancy 7.7 8.3 8.4 7.1 6.7 8.6 8.5 7.7 9.5 6.4 7.2
Without diabetes mellitus
Ischaemic heart disease 18.3 22.8 23.7 14.5 13.8 16.2 16.5 23.7 23.1 22.6 22.8
Peripheral vascular disease 16.4 24.1 25.0 18.5 17.6 11.4 11.7 18.4 17.9 10.3 10.5
Cerebrovascular disease 11.4 18.7 19.5 9.6 9.1 9.4 9.6 10.7 10.6 10.7 10.9
Malignancy 12.1 13.1 13.4 9.3 8.9 13.7 13.8 15.7 15.5 12.5 12.8
All countries Austria

Catalonia, Spain

Lombardy, Italy

Norway

UK, England/ Wales

All
Diabetes mellitus (PRD and co-morbidity) 27.8 40.6 39.5 27.5 27.2 20.8 20.8 22.8 22.8 23.6 23.7
Diabetes mellitus (PRD) 20.4 33.0 32.0 19.5 19.6 14.3 14.1 14.6 14.2 16.7 16.5
Diabetes mellitus (co-morbidity) 7.5 7.6 7.6 8.1 7.7 6.6 6.7 8.6 8.6 7.1 7.3
Ischaemic heart disease 23.4 31.5 31.4 20.0 19.1 18.3 18.6 26.3 26.9 25.8 26.8
Peripheral vascular disease 23.7 36.6 36.2 27.1 26.1 14.8 15.0 19.1 19.3 13.7 14.3
Cerebrovascular disease 14.4 24.9 25.0 11.7 11.1 10.6 10.9 11.1 11.6 12.7 13.4
Malignancy 10.9 11.2 11.3 8.7 8.3 12.6 12.7 13.9 14.4 11.1 11.6
With diabetes mellitus
Ischaemic heart disease 36.4 44.3 43.3 34.7 33.1 26.4 25.6 35.4 39.6 35.6 38.1
Peripheral vascular disease 42.7 54.9 54.4 49.8 48.9 27.8 27.5 21.2 22.3 23.9 23.9
Cerebrovascular disease 22.0 34.2 33.6 17.2 16.3 15.3 15.3 12.8 14.9 17.5 18.4
Malignancy 7.7 8.3 8.4 7.1 6.7 8.6 8.5 7.7 9.5 6.4 7.2
Without diabetes mellitus
Ischaemic heart disease 18.3 22.8 23.7 14.5 13.8 16.2 16.5 23.7 23.1 22.6 22.8
Peripheral vascular disease 16.4 24.1 25.0 18.5 17.6 11.4 11.7 18.4 17.9 10.3 10.5
Cerebrovascular disease 11.4 18.7 19.5 9.6 9.1 9.4 9.6 10.7 10.6 10.7 10.9
Malignancy 12.1 13.1 13.4 9.3 8.9 13.7 13.8 15.7 15.5 12.5 12.8

The prevalence of co-morbid conditions was also examined separately for diabetes as renal disease and diabetes as co-morbidity. The prevalence of peripheral vascular disease was higher (with exception of Norway) in patients with diabetes as renal disease compared to patients with diabetes as a co-morbidity, whereas prevalence of malignancy was lower.

#### By treatment modality and country

Table 3 shows that there were important international differences in treatment modality at day 91. In both patients with and without co-morbid conditions, the percentage of patients living on a functioning graft was much higher in Norway and the percentage of patients starting on peritoneal dialysis was much higher in Lombardy (Italy) and the UK (England/Wales) than in other countries. In general, patients with a co-morbidity were more often treated with haemodialysis and less often with peritoneal dialysis or living on a functioning graft compared to patients without co-morbid conditions, but the type of co-morbidity did not affect treatment modality choice.

Table 3.

Percentage of patients on haemodialysis, peritoneal dialysis and renal transplantation at day 91 after the start of RRT, by co-morbidity

All countries

Austria

Catalonia, Spain

Lombardy, Italy

Norway

UK, England/Wales

HD PD TX HD PD TX HD PD TX HD PD TX HD PD TX HD PD TX
All patients 78.8 18.8 2.4 89.0 9.4 1.7 90.6 8.1 1.2 66.0 31.3 2.7 71.4 16.4 12.3 62.4 36.3 1.4
No co-morbid condition 75.4 20.6 3.9 84.0 12.9 3.1 89.3 8.5 2.2 65.4 30.8 3.8 64.8 17.1 18.5 57.7 39.8 2.5
Co-morbid condition (≥1) 81.7 17.0 1.3 91.5 7.5 1.0 91.9 7.8 0.4 66.6 32.0 1.4 75.9 16.3 7.7 67.1 32.5 0.5
Co-morbid condition (≥2) 85.3 14.4 0.3 94.7 5.1 0.2 92.7 7.3 67.6 32.2 0.2 83.0 14.3 2.8 66.3 33.4 0.3
All countries

Austria

Catalonia, Spain

Lombardy, Italy

Norway

UK, England/Wales

HD PD TX HD PD TX HD PD TX HD PD TX HD PD TX HD PD TX
All patients 78.8 18.8 2.4 89.0 9.4 1.7 90.6 8.1 1.2 66.0 31.3 2.7 71.4 16.4 12.3 62.4 36.3 1.4
No co-morbid condition 75.4 20.6 3.9 84.0 12.9 3.1 89.3 8.5 2.2 65.4 30.8 3.8 64.8 17.1 18.5 57.7 39.8 2.5
Co-morbid condition (≥1) 81.7 17.0 1.3 91.5 7.5 1.0 91.9 7.8 0.4 66.6 32.0 1.4 75.9 16.3 7.7 67.1 32.5 0.5
Co-morbid condition (≥2) 85.3 14.4 0.3 94.7 5.1 0.2 92.7 7.3 67.6 32.2 0.2 83.0 14.3 2.8 66.3 33.4 0.3

Overall, 57.2% of the haemodialysis patients, 50.4% of those on peritoneal dialysis and 28.4% of the patients living on a functioning graft had at least one co-morbidity at the start of RRT. In Lombardy (Italy) there was more similarity between patients selected for the two dialysis modalities: 50.5% of the haemodialysis patients and 50.6% of those on peritoneal dialysis had at least one co-morbid condition.

Overall, 6.3% of the patients with a co-morbidity and 24.3% of the patients without a co-morbidity received a transplant within 4 years. Using a Cox regression model with adjustment for age, gender, country and year of start of RRT, the relative risk (95%CI) to receive a renal allograft within 4 years after the start of RRT was 0.50 (0.45–0.55) for patients with at least one co-morbid condition compared to patients without co-existing diseases.

The presence of each of the co-morbid conditions made receiving a transplant within 4 years after the start of RRT less likely, also after adjustment for age, gender, country, year of start and the other co-morbid conditions (Table 4). A patient's chance of receiving a transplant was least affected by the presence of diabetes mellitus (RR = 0.79; 95%CI: 0.70–0.88), and most affected by the presence of a malignancy (RR = 0.33; 95%CI: 0.25–0.43), compared to patients without those co-morbidities. Adjusted for the other factors, females (RR = 0.95; 95%CI: 0.87–1.00) and older persons (RR = 0.94; 95%CI: 0.94–0.95 per year) were less likely to receive an allograft within 4 years.

Table 4.

Relative risk of receiving a first transplant within four years after the start of RRT, by co-morbidity

Relative risk (95%CI)

Unadjusted Adjusted for age, gender, country, year of start, and other co-morbid diseases
Diabetes mellitus (PRD and co-morbidity) 0.68 (0.61–0.76) 0.79 (0.70–0.88)
Ischaemic heart disease 0.36 (0.31–0.42) 0.59 (0.50–0.70)
Peripheral vascular disease 0.43 (0.37–0.51) 0.57 (0.49–0.67)
Cerebrovascular disease 0.33 (0.26–0.41) 0.49 (0.39–0.61)
Malignancy 0.19 (0.14–0.25) 0.33 (0.25–0.43)
Relative risk (95%CI)

Unadjusted Adjusted for age, gender, country, year of start, and other co-morbid diseases
Diabetes mellitus (PRD and co-morbidity) 0.68 (0.61–0.76) 0.79 (0.70–0.88)
Ischaemic heart disease 0.36 (0.31–0.42) 0.59 (0.50–0.70)
Peripheral vascular disease 0.43 (0.37–0.51) 0.57 (0.49–0.67)
Cerebrovascular disease 0.33 (0.26–0.41) 0.49 (0.39–0.61)
Malignancy 0.19 (0.14–0.25) 0.33 (0.25–0.43)

Univariate and multivariate Cox proportional hazard regression was performed. Patients with a co-morbidity were compared to patients without that specific co-morbidity.

Table 5 illustrates that patients in Lombardy (Italy) were least likely to receive a first transplant within 4 years, whereas patients living in Norway were by far most likely to receive an allograft, both in patients with and without co-morbidity. Compared to Austria, the adjusted relative risk (95%CI) of receiving a cadaver donor transplant was higher in Catalonia (Spain) (RR = 1.18; 95%CI: 1.03–1.34) and Norway (RR = 2.40: 95%CI: 2.00–2.87) and lower in Lombardy (Italy) (RR = 0.24; 95%CI: 0.20–0.29) and the UK (England/Wales) (RR = 0.43; 95%CI: 0.35–0.53). In the case of a living donor transplant, the chance of receiving an allograft was much higher in Norway (RR = 10.3; 95%CI: 7.71–13.8) and lower in Catalonia (Spain) (RR = 0.15; 95%CI: 0.09–0.25), Lombardy (Italy) (RR = 0.18; 95%CI: 0.10–0.31), and the UK (England/Wales) (RR = 0.40; 95%CI: 0.24–0.66). These patterns were similar for patients with and without co-morbid conditions. Furthermore, patients who received peritoneal dialysis as their first therapy had a significantly higher chance of receiving a first renal transplant within 4 years than patients on haemodialysis both in Austria (RR = 1.46; 95%CI: 1.10–1.93) and Norway (RR = 1.67; 95%CI: 1.23–2.25), after adjustment for age, gender, and year of start. This chance was not significantly different in Catalonia (Spain) (RR = 0.94; 95%CI: 0.76–1.15), Lombardy (Italy) (RR = 1.01; 95%CI: 0.77–1.33), or the UK (England/Wales) (RR = 1.43; 95%CI: 0.99–2.05). These results were the same when the analysis was repeated for dialysis modality at day 91 after the start of RRT. Similar results were found when we repeated the analysis for the end points transplantation within 2 years and transplantation within 3 years.

Table 5.

Relative risk of receiving a first transplant within four years after the start of RRT, by country and by co-morbid status

Observation period Relative risk (95%CI)

All patients Patients without co-morbidity Patients with co-morbidity
Austria 1998–2001
Catalonia, Spain 1995–2001 1.02 (0.90–1.15) 1.12 (0.96–1.30) 0.66 (0.52–0.84)
Lombardy, Italy 1994–1997 0.23 (0.19–0.27) 0.26 (0.21–0.32) 0.12 (0.08–0.17)
Norway 1999–2001 3.86 (3.36–4.45) 4.10 (3.43–4.91) 3.19 (2.51–4.04)
UK (England/Wales) 1999–2001 0.43 (0.35–0.52) 0.46 (0.37–0.58) 0.33 (0.23–0.49)
Observation period Relative risk (95%CI)

All patients Patients without co-morbidity Patients with co-morbidity
Austria 1998–2001
Catalonia, Spain 1995–2001 1.02 (0.90–1.15) 1.12 (0.96–1.30) 0.66 (0.52–0.84)
Lombardy, Italy 1994–1997 0.23 (0.19–0.27) 0.26 (0.21–0.32) 0.12 (0.08–0.17)
Norway 1999–2001 3.86 (3.36–4.45) 4.10 (3.43–4.91) 3.19 (2.51–4.04)
UK (England/Wales) 1999–2001 0.43 (0.35–0.52) 0.46 (0.37–0.58) 0.33 (0.23–0.49)

Multivariate Cox proportional hazard regression was performed, adjusted for age, gender and year of start.

An explanation for the international differences in relative risks of receiving a transplant may relate to the availability of kidney donors on the one hand and the number of dialysis patients on the other. Therefore, we presented these data by country in Table 6. The number of transplants was highest in Catalonia (Spain), whereas this region ranked second with respect to the prevalence of dialysis patients.

Table 6.

Availability of kidney donors and the number of dialysis patients per million population (pmp), by country

Austria Catalonia, Spain Lombardy, Italy Norway UK, England/Wales
Number of transplants performed in 2001
All kidney donors 48.0 63.2 26.1 46.6 29.8
Living kidney donors 5.8 2.1 1.6 19.0 6.1
Cadaver kidney donors 42.2 61.1 24.5 27.6 23.7
Prevalence of dialysis patients on December 31, 2000 369.7 558.4 614.6 142.3 260.0
Austria Catalonia, Spain Lombardy, Italy Norway UK, England/Wales
Number of transplants performed in 2001
All kidney donors 48.0 63.2 26.1 46.6 29.8
Living kidney donors 5.8 2.1 1.6 19.0 6.1
Cadaver kidney donors 42.2 61.1 24.5 27.6 23.7
Prevalence of dialysis patients on December 31, 2000 369.7 558.4 614.6 142.3 260.0

Number of transplants performed in 1997.

Number of dialysis patients on December 31, 1996.

## Discussion

The current study on the comparison of the prevalence of co-morbidity within Europe extends the Euro-DOPPS study by including all patients starting RRT and by including some other countries. Furthermore, this is the first European study that examined how co-morbidity affects access to renal transplantation.

The overall prevalence of co-morbid conditions in our study is similar to that reported by the Euro-DOPPS study which showed a prevalence of 22.4% for diabetes mellitus, 26.3% for ischaemic heart disease, and 19.9% for peripheral vascular disease in incident haemodialysis patients [9], and a prevalence of 13.7% for cerebrovascular disease and 9.0% for malignancy in prevalent haemodialysis patients [4]. In addition, our study showed that males starting RRT suffered more often from ischaemic heart disease, peripheral vascular disease, cerebrovascular disease and malignancy than females, especially in the higher age groups. With the exception of malignancy, these gender differences are also found in the general population [13]. Although the prevalence of diabetes was lower in elderly males than in elderly females starting RRT, it should be noted that the absolute number of RRT patients with diabetes as ESRD is higher in males [14], simply because there are more men starting RRT. Furthermore, the higher prevalence of peripheral vascular disease in patients with diabetes as the cause of renal failure compared to patients with diabetes as co-morbidity, might be due to the longer duration of diabetes in the first group.

The prevalence of ischaemic heart disease, peripheral vascular disease and cerebrovascular disease was much higher in Austria compared to the other countries, which may, to a large extent, be explained by the high prevalence of diabetes in Austria. We cannot, however, rule out that the diagnosis of a specific co-morbid condition varied in the different countries, as a detailed description of diagnostic criteria for each co-morbidity was often lacking. The Euro-DOPPS study showed a much higher prevalence of different co-morbid conditions in German haemodialysis compared to France, Italy, Spain, and the UK: diabetes (39.1%), coronary artery disease (41.8%), and peripheral vascular disease (26.1%) [9]. This suggests a large similarity between the RRT populations of Austria and Germany. Additionally, both in the current study and the Euro-DOPPS study, the prevalence of co-morbidity was relatively low in Italy. The prevalence of co-morbidity in Norway might be underestimated, as in this country patients without any co-morbidity data were considered to have no co-morbidity. As a consequence, the relative risk of receiving a renal transplant for a Norwegian patient, the highest across all countries, might even be underestimated.

We confirmed other studies which showed that, in most countries, sicker patients are selected for haemodialysis [15,16]. In Lombardy (Italy) however, this seems not to be the case. Such differences in modality selection, whether it concerns transplantation or peritoneal dialysis, may affect outcome comparisons in studies restricted to one treatment modality such as the DOPPS study, even when adjusted for co-morbidity.

In this European study, co-morbidity affects access to renal transplantation to a similar extent as in the United States, where McCauley et al. [8] reported a 63% (95%CI: 35–79%) reduced access. In agreement with our study, Gaylin et al. [7] found a lower chance of receiving a transplant for patients with diabetes as cause of renal failure (RR = 0.72; P = 0.01), coronary heart disease (RR = 0.70; P = 0.03) and peripheral vascular disease (RR = 0.68; P = 0.04) in the United States compared to patients without these specific co-morbid conditions. Their data also suggested that the presence of cerebrovascular accident and the presence of malignancy reduced access to transplantation, but these associations did not reach statistical significance, which may be due to the much smaller sample size of that study. In the current study, the access to renal transplantation was least affected by the presence of diabetes. Wolfe et al. [17] have shown that the reduced access of diabetes patients is mainly due to a lower chance of being wait-listed and not as much to a reduced chance after wait-listing. In contrast, Oniscu et al. [18] found that diabetes both reduced access to the waiting list and the chance to receive an allograft while on the waiting list. Unfortunately, our data did not include the study of waiting list referral per se.

In conclusion, among the countries studied, the prevalence of co-morbidity was highest in Austria but differences were small among other countries. This study confirms that co-morbidity affects access to renal transplantation. In addition, it shows that the access to a renal transplant was least affected by the presence of diabetes and most affected by the presence of a malignancy. International differences in access to transplantation were primarily due to differences in the availability of donor kidneys in relation to the number of dialysis patients, and could hardly be explained by co-morbid variability.

## Appendix 1. Classification of co-morbid conditions used by renal registries

Classification of co-morbidity Definition or more detailed description of the classification of co-morbidity
Diabetes mellitus
Austria Diabetes mellitus type I Insulin needed within a year after diagnosis
Diabetes mellitus type II Age at start of diabetes mellitus >40 years, treatment with oral antidiabetics or diet possible for a longer period of time
Secondary diabetes mellitus Caused by other conditions (pancreatic diseases, hormonal imbalance, drug or chemically induced, insulin receptor abnormality, genetic syndrome)
Unspecified diabetes mellitus Note: Transitory steroid-induced diabetes mellitus should not be classified as diabetes mellitus
Catalonia (Spain) Diabetes mellitus type I
Diabetes mellitus type II
Secondary or unspecified diabetes mellitus
Lombardy (Italy) Diabetes mellitus type I
Diabetes mellitus type II
Secondary or unspecified diabetes mellitus
Norway Diabetes mellitus type I Insulin-dependent from debut (not secondary)
Diabetes mellitus type II
Secondary diabetes mellitus
Unspecified diabetes mellitus
UK (England/Wales) Diabetes mellitus Including diet-controlled and drug-induced diabetes mellitus
Heart failure
Austria Congestive heart failure
Catalonia (Spain) ICD-9-CM* code 425, 428
425:Cardiomyopathy;
428:Heart failure
Lombardy (Italy) Heart failure
Norway Heart failure If a patient has both ischaemic heart disease and heart failure at the start of RRT, only ischaemic heart disease has been registered
UK (England/Wales) –
Ischaemic heart disease
Austria Coronary heart disease Documented by angiography, stress echo, thallium scintigraphy etc.
Myocardial infarction
Angina pectoris
Catalonia (Spain) ICD-9-CM* code 410-414
410:Acute myocardial infarction;
411:Other forms of sub-acute ischaemic heart disease;
412:Old myocardial infarction;
413:Angina pectoris;
414:Other forms of chronic ischaemic heart disease
Lombardy (Italy) Coronary heart disease
Myocardial infarction
Angina pectoris
Norway Myocardial infarction
Angina pectoris
UK (England/Wales) CABG or coronary angioplasty
Myocardial infarction Diagnosed by ST segment evaluation, Q waves in relevant leads, enzyme rise >2x upper limit of normal (or rise in creatinine kinase-MB above local reference range)
Angina pectoris History of chest pain on exercise with or without ECG changes, exercise tolerance test, radionucleotide imaging or angiography
Peripheral vascular disease
Austria Peripheral vascular disease Included aortic aneurysm, diffuse vascular calcifications, documented vascular stenosis
Catalonia (Spain) ICD-9-CM* code 440–441, 443
440:Atherosclerosis;
441:Aortic aneurysm and dissection;
443:Other peripheral vascular disease
Lombardy (Italy) Peripheral vascular disease
Norway Peripheral vascular disease Including all arteries (except carotid/cerebrovascular and coronary). Should include both symptomatic disease and affection necessitating pre-transplant intervention
UK (England/Wales) Claudication Current claudication based on a history, with or without Doppler or angiographic evidence
Angioplasty, stenting vascular graft (non-coronary) Includes vascular grafts (e.g. aortic bifurcation grafts) and renal artery stents
Amputation for peripheral vascular disease
Cerebrovascular disease
Austria Cerebrovascular disease
Catalonia (Spain) ICD-9-CM* code 430–438, 342
430:Subarachnoid haemorrhage;
431:Intracerebral haemorrhage;
432:Other and unspecified intracranial haemorrhage;
433:Occlusion and stenosis of precerebral arteries; 434:Occlusion of cerebral arteries;
435:Transient cerebral ischaemia;
436:Acute but ill-defined cerebrovascular disease;
437:Other and ill-defined cerebrovascular disease;
438:Late effects of cerebrovascular disease;
342:Hemiplegia and hemiparesis
Lombardy (Italy) Cerebrovascular disease
Norway Cerebrovascular disease
UK (England/Wales) Cerebrovascular disease Any history of strokes (whatever cause) and including transient ischaemic attacks caused by carotid disease
Malignancy
Austria Malignancy Solid tumour and other malignancies, including basal cell carcinoma
Catalonia (Spain) ICD-9-CM* code 140–208, 230–239 Including basal cell carcinoma
Lombardy (Italy) Malignancy Including basal cell carcinoma
Norway Malignancy Including basal cell carcinoma
UK (England/Wales) Malignancy Any history of malignancy (even if curative) e.g. removal of melanoma, excluding basal cell carcinoma
Liver disease
Austria Alcohol liver disease
Viral liver disease
Catalonia (Spain) ICD-9-CM* code 571
571:Chronic liver disease and cirrhosis
Lombardy (Italy) Alcoholic or viral cirrhosis
Cirrhosis linked to viral infection (hepatitis B or C)
Norway Liver disease
UK (England/Wales) Liver disease Persistent enzyme evidence of hepatic dysfunction or biopsy evidence or hepatitis B antigen- or hepatitis C antigen (polymerase chain reaction) positive serology
Lung disease
Austria –
Catalonia (Spain) ICD-9-CM* code 491–496
491:Chronic bronchitis;
492:Emphysema;
493:Asthma;
494:Bronchiectasis;
495:Extrinsic allergic alveolitis;
496:Chronic airway obstruction (not elsewhere classified)
Lombardy (Italy) Chronic respiratory disease
Norway Lung disease
UK (England/Wales) Chronic obstructive pulmonary disease (COPD) A slowly progressive airways disorder characterized by obstruction of the expiratory airflow, which does not change markedly over several months, may be accompanied by airway hyper-reactivity and may be partially reversible
Classification of co-morbidity Definition or more detailed description of the classification of co-morbidity
Diabetes mellitus
Austria Diabetes mellitus type I Insulin needed within a year after diagnosis
Diabetes mellitus type II Age at start of diabetes mellitus >40 years, treatment with oral antidiabetics or diet possible for a longer period of time
Secondary diabetes mellitus Caused by other conditions (pancreatic diseases, hormonal imbalance, drug or chemically induced, insulin receptor abnormality, genetic syndrome)
Unspecified diabetes mellitus Note: Transitory steroid-induced diabetes mellitus should not be classified as diabetes mellitus
Catalonia (Spain) Diabetes mellitus type I
Diabetes mellitus type II
Secondary or unspecified diabetes mellitus
Lombardy (Italy) Diabetes mellitus type I
Diabetes mellitus type II
Secondary or unspecified diabetes mellitus
Norway Diabetes mellitus type I Insulin-dependent from debut (not secondary)
Diabetes mellitus type II
Secondary diabetes mellitus
Unspecified diabetes mellitus
UK (England/Wales) Diabetes mellitus Including diet-controlled and drug-induced diabetes mellitus
Heart failure
Austria Congestive heart failure
Catalonia (Spain) ICD-9-CM* code 425, 428
425:Cardiomyopathy;
428:Heart failure
Lombardy (Italy) Heart failure
Norway Heart failure If a patient has both ischaemic heart disease and heart failure at the start of RRT, only ischaemic heart disease has been registered
UK (England/Wales) –
Ischaemic heart disease
Austria Coronary heart disease Documented by angiography, stress echo, thallium scintigraphy etc.
Myocardial infarction
Angina pectoris
Catalonia (Spain) ICD-9-CM* code 410-414
410:Acute myocardial infarction;
411:Other forms of sub-acute ischaemic heart disease;
412:Old myocardial infarction;
413:Angina pectoris;
414:Other forms of chronic ischaemic heart disease
Lombardy (Italy) Coronary heart disease
Myocardial infarction
Angina pectoris
Norway Myocardial infarction
Angina pectoris
UK (England/Wales) CABG or coronary angioplasty
Myocardial infarction Diagnosed by ST segment evaluation, Q waves in relevant leads, enzyme rise >2x upper limit of normal (or rise in creatinine kinase-MB above local reference range)
Angina pectoris History of chest pain on exercise with or without ECG changes, exercise tolerance test, radionucleotide imaging or angiography
Peripheral vascular disease
Austria Peripheral vascular disease Included aortic aneurysm, diffuse vascular calcifications, documented vascular stenosis
Catalonia (Spain) ICD-9-CM* code 440–441, 443
440:Atherosclerosis;
441:Aortic aneurysm and dissection;
443:Other peripheral vascular disease
Lombardy (Italy) Peripheral vascular disease
Norway Peripheral vascular disease Including all arteries (except carotid/cerebrovascular and coronary). Should include both symptomatic disease and affection necessitating pre-transplant intervention
UK (England/Wales) Claudication Current claudication based on a history, with or without Doppler or angiographic evidence
Angioplasty, stenting vascular graft (non-coronary) Includes vascular grafts (e.g. aortic bifurcation grafts) and renal artery stents
Amputation for peripheral vascular disease
Cerebrovascular disease
Austria Cerebrovascular disease
Catalonia (Spain) ICD-9-CM* code 430–438, 342
430:Subarachnoid haemorrhage;
431:Intracerebral haemorrhage;
432:Other and unspecified intracranial haemorrhage;
433:Occlusion and stenosis of precerebral arteries; 434:Occlusion of cerebral arteries;
435:Transient cerebral ischaemia;
436:Acute but ill-defined cerebrovascular disease;
437:Other and ill-defined cerebrovascular disease;
438:Late effects of cerebrovascular disease;
342:Hemiplegia and hemiparesis
Lombardy (Italy) Cerebrovascular disease
Norway Cerebrovascular disease
UK (England/Wales) Cerebrovascular disease Any history of strokes (whatever cause) and including transient ischaemic attacks caused by carotid disease
Malignancy
Austria Malignancy Solid tumour and other malignancies, including basal cell carcinoma
Catalonia (Spain) ICD-9-CM* code 140–208, 230–239 Including basal cell carcinoma
Lombardy (Italy) Malignancy Including basal cell carcinoma
Norway Malignancy Including basal cell carcinoma
UK (England/Wales) Malignancy Any history of malignancy (even if curative) e.g. removal of melanoma, excluding basal cell carcinoma
Liver disease
Austria Alcohol liver disease
Viral liver disease
Catalonia (Spain) ICD-9-CM* code 571
571:Chronic liver disease and cirrhosis
Lombardy (Italy) Alcoholic or viral cirrhosis
Cirrhosis linked to viral infection (hepatitis B or C)
Norway Liver disease
UK (England/Wales) Liver disease Persistent enzyme evidence of hepatic dysfunction or biopsy evidence or hepatitis B antigen- or hepatitis C antigen (polymerase chain reaction) positive serology
Lung disease
Austria –
Catalonia (Spain) ICD-9-CM* code 491–496
491:Chronic bronchitis;
492:Emphysema;
493:Asthma;
494:Bronchiectasis;
495:Extrinsic allergic alveolitis;
496:Chronic airway obstruction (not elsewhere classified)
Lombardy (Italy) Chronic respiratory disease
Norway Lung disease
UK (England/Wales) Chronic obstructive pulmonary disease (COPD) A slowly progressive airways disorder characterized by obstruction of the expiratory airflow, which does not change markedly over several months, may be accompanied by airway hyper-reactivity and may be partially reversible

*United States National Center for Health Statistics. Annotated International Classification of Diseases, Ninth Revision, Clinical Modification. Ann Arbor: Edwards Brothers, Inc., 1987.

We would like to thank the patients and staff of all the dialysis and transplant units who have contributed data via their national and regional renal registries. We would also like to thank Dr H.K. Stumvoll (Austrian Dialysis and Transplant Registry (OEDTR)); Dr M. Clèries (Catalan Transplant Organization (OCATT)), Dr T. Feest (the UK Renal Registry), and the ERA-EDTA Registry committee members and staff members for their advice in the analysis and drafting of the paper. The ERA-EDTA Registry is funded by the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA). The following companies have committed funds in the form of unrestricted educational grants to assist the ERA-EDTA in the financial support of the Registry: Amgen, Baxter, Fresenius Medical Care, Gambro, Hoffmann-La Roche, Hospal, Ortho-Biotech and Shire.

Conflict of interest statement. None declared.

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## Author notes

1ERA–EDTA Registry, Academic Medical Center, University of Amsterdam, Department of Medical Informatics, Amsterdam, 2Leiden University Medical Centre, Department of Clinical Epidemiology, Leiden, The Netherlands, 3The UK Renal Registry, Southmead Hospital, Bristol, UK, 4Registro Lombardo Dialisi e Trapianto, “Ospedale UBOLDO”, Cernusco S/N, Milano, Italy, 5Austrian Dialysis and Transplant Registry (OEDTR), General Hospital of Wels, Wels, Austria, 6Norwegian Renal Registry, Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway and 7Catalan Renal Registry (RMRC), Catalan Transplant Organisation, Catalan Health Service, Autonomous Government of Catalonia, Barcelona