EUGLOREH project
THE STATUS OF HEALTH IN THE EUROPEAN UNION:
TOWARDS A HEALTHIER EUROPE

FULL REPORT

PART II - HEALTH CONDITIONS

5. HEALTH IMPACTS OF NON COMMUNICABLE DISEASES AND RELATED TIME-TRENDS

5.7. Chronic kidney disease and end stage renal disease

5.7.3. Data description and analysis

Links:  Standard Highlighted

Link to concordances are always highlighted on mouse hover

5.7.3. Data description and analysis

 

Incidence

 

Children and adolescents

 

CKD in the pre-ESRD phases in childhood and adolescence in the above mentioned population-based registry in Italy (Italkid) have shown an incidence rate of CKD (defined as a GFR <75 ml/min per 1.74 m2) of 12.1 cases per million of the age-related population (pmarp) (Ardissino et al., 2004). In the Swedish study (considering children and adolescents in the 6 months-16 years range) the corresponding figure was 7.7 cases /year pmarp (<30 ml/min per 1.74 m2 ) (Esbjorner et al, 1997). In 2005 the incidence rate of RRT for ESRD in children aged 0-14 was 7.1 patients pmarp (Table 5.7.3).

 

Adults

 

CKD incidence in adults has been studied very little (Obrador et al, 2002) and is marred with difficulties (Winkelmayer et al, 2005). No data has been published in Europe. In the Atherosclerosis Risk in Communities (ARIC) Study in the USA, a study which enrolled individuals 45-64 years old, the incidence rate of 3-5 CKD was 7.8 per 1000 patients x years (Kurella et al, 2005). Similarly scarce are the data concerning changes in CKD over time, whilst the correlation with changes in the incidence of ESRD are mainly based on NHANES surveys and on a survey made in Norway. In the USA, the incidence of ESRD appears to be increasing faster than that observed for CKD (Hsu et al, 2004). Indeed, 9 new cases of ESRD developed in 1983 for every 1000 prevalent patients with CKD in 1978. By comparison, 16 cases of ESRD had developed in 1996 for every 1000 patients with CKD in 1991. A similar finding in terms of the relative stability of CKD versus a marked increase in ESRD was noticed in a second study that examined NHANES data (Coresh et al,2005).

 

In Europe similar data are available only in Norway. Prevalence of 1-5 CKD in Norway was 10.2% which is similar to the current prevalence in the USA (11%). This contrasts with ESRD incidence rates which are three times higher in the United States compared to Norway. In a recent comparative study (Hallan et al, 2006a) the relative risk for progression from CKD stages 3 or 4 to ESRD in US white patients compared to Norwegian patients was 2.5. This was only modestly modified by adjustment for age, gender, and diabetes. Age and GFR at the beginning of dialysis were similar, hypertension and cardiovascular mortality in the populations were comparable, but US white patients were referred later to a nephrologist and had higher prevalence of obesity and diabetes.

 

In 2005 the incidence rates of RRT for ESRD ranged from 57 patients pmp in Estonia to 205 patients pmp in Portugal (Table 5.7.4 and Table 5.7.5). Just like prevalence, the incidence rate of RRT for ESRD in 2005 steeply increased with age and was higher in males than in females (Table 5.7.3). Whereas incidence rates in Canada (160 pmp in 2005) are similar to those in Europe, incidence rates in US whites (286 pmp in 2005) (U.S. Renal Data System, USRDS, 2007) are 1.5-3 times as high as in Europe. This is partly due to a higher US incidence rate of diabetic ESRD.

 

Table 5.7.3. Incidence of RRT over the 1992-2005 period per age group, gender and cause of renal failure.

 

Table 5.7.4. Incidence of RRT over the 1992-2005 period per country

 

Table 5.7.5. Incidence of RRT over the 2000-2005 period per country.

 

Trends over time

 

There is no information on the trends of the CKD incidence rate in children/adolescents or adults.

In the 1992-2005 period the incidence rate of RRT increased by more than 50% (Table 5.7.3). This was primarily due to the incidence rate in patients over 65 years of age which had more than doubled. Whereas the incidence of RRT for diabetic and hypertensive ESRD became twice as high, the incidence of RRT for ESRD due to glomerulonephritis/ glomerulosclerosis remained stable.

Although there are considerable differences in absolute incidence rates of RRT for ESRD across countries, there was a consistent increase in incidence rates in virtually all Member States at least until 2002. This was mainly driven by an increase in the incidence rates of RRT for diabetic and hypertensive ESRD (Stengel et al, 2003; van Dijk et al, 2005) After 2002, the incidence rates have tended to stabilize. The stabilization, or even decrease in some causes of ESRD, have prompted some investigators to suggest that treatment strategies for the prevention of ESRD have finally started to bear fruit (Gansevoort et al, 2004; Stewart et al, 2006). The increasing incidence rates together with improvements in survival of RRT patients (Jager and van Dijk 2007) resulted in a concomitant increase in the prevalence of RRT over the past decades that is posing a still increasing economic burden on Member States.

 

Socioeconomic variation in incidence

 

As for prevalence the incidence rate of RRT was higher in socially deprived areas of the UK than it was in other areas (UK Renal Registry, 2003).

 

Prevalence

 

For the 27 EU Member countries, national surveys on the prevalence of CKD among adults are available for 12 countries. The data for the United Kingdom (UK) and Ireland and part of the Italian data were based on information derived from general practitioners data-bases. Data from other countries are based on population samples representative of the general population of those countries.

 

There is still a paucity of data on CKD. Data in Europe have been gathered both by using medical databases (Ireland, England, Italy) or population surveys. Data from medical databases overestimate the prevalence of diseases and this is apparent also in the data collected in this review. Indeed the prevalence of stages 3-5 CKD was 1.3 to 1.5 times higher in medical databases in Ireland, England and Italy than in population based studies in Belgium, Netherlands, Spain, Italy, Iceland, Norway. The prevalence of stage 3-5 CKD appears reasonably similar across EU countries and more frequent in females than in males. The higher prevalence on CKD in females, which flies in the face of ESRD statistics where men are disproportionally affected (Table 5.7.7), may depend on the fact that the GFR, as estimated by the MDRD equation (Levey et al, 1999), is lower in females than in males. Furthermore, the performance of this equation in people with normal or mildly impaired GFR may be sub-optimal (Lin et al, 2003).

 

Children and adolescents

 

Information on CKD in the pre-ESRD phases for children and adolescents is very limited (Warady and Chadha, 2007; Ardissino et al 2003). Data in a population-based registry in Italy including all people <20 years reported a prevalence of CKD (defined as a GFR <75 ml/min per 1.74 m2) of 74.7 cases pmarp (Ardissino et al, 2003). In a survey in Sweden in a more restricted age-range (6 months-16 years) and applying a lower GFR cut-off for defining CKD (<30 ml/min per 1.74 m2 ), the corresponding figure was 21 cases pmarp (Esbjorner et al, 1997).

 

The prevalence of ESRD undergoing RRT in children (<20 years) in Europe is about 60 cases pmarp (Van der Heijden et al, 2004). In 2005 the prevalence of RRT in the 0-14 years age group was 43 per million of age related population (Table 5.7.7).

 

Adults

 

The prevalence of CKD by stages (as defined in Tables 5.7..1 and 5.7..2) in The Netherlands (De Zeeuw et al, 2005) and in Spain (Garcia-Lopez and Epirce, 2007) is shown in Figure 5.7.2.

 

Figure 5.7.2. Prevalence of chronic kidney disease per stage in two EU Countries

 

Prevalence of stages 3-5 CKD - i.e. the stages showing a higher risk for CV complications and for evolution to ESRD (Go et al, 2004) - in population-based studies ranges from 3.57% (Norway) (Hallan et al, 2006) to 7.2% (Germany) (Meisinger et al, 2006) in males and from 6.2% (Italy) (Cirillo et al, 2006) to 10.2% (Iceland) (Viktorsdottir et al, 2005) in females (Figure 5.7.3), while higher figures are reported in medical databases (Stevens et al, 2007). Stage 3-5 CKD prevalence was either similar in males and females (Germany, Italy) or higher in females (Belgium (Van Biesen et al, 2007) , England (Stevens et al, 2007), Iceland (Viktorsdottir et al, 2005), Norway (Hallan et al, 2006; Hallan et al, 2006). In all countries where this information was available the prevalence of stage 3-5 CKD increased with age (Figure 5.7.4).

 

Figure 5.7.3. Prevalence of stages 3-5 of chronic kidney disease in selected EUGLOREH countries.

 

Figure 5.7.4. Sex and age specific prevalence of stages 3-5 of chronic kidney disease by age and sex.

 

In 2005 the crude prevalence of RRT for ESRD varied from 321 patients pmp in Romania to 1057 patients pmp in Germany (Tables 5.7.6 A and B). It increased with age and was more than 50% higher in males compared to females (Table 5.7.7). Prevalence of RRT in Europeans is lower than that in US whites (1209 pmp) and in Canadians (1003 pmp) (U.S. Renal Data System, USRDS ,2007).

 

Table 5.7.6A. Prevalence of RRT over the period 1992-2005 by country.

 

Table 5.7.6B. Prevalence of RRT over the period 2000-2005 by country.

 

Table 5.7.7. Prevalence of RRT over the period 1992-2005 by age group, gender and cause of renal failure.

 

Trends over time

 

There is still very scarce information on time-trends of CKD. The most solid source of information remain periodic surveys made in the USA (NHANES III and NHANES IV performed between 1988-1994 and between 1999-2004 respectively). In those surveys, the prevalence of stage 1-5 CKD rose from 14.5% (NHANES III) to 16.8% (NHANES IV) (Tonelli et al, 2006; Zoccali and DeJong, 2007), while the prevalence of stages 3-5 remained almost unmodified at about 6%. None of these data are available in European countries.

In Europe over the period 1992-2005 (Table 5.7.7) the overall adjusted prevalence of RRT for ESRD increased from 480 to 807 patients per million population (pmp). This was due to a 40% increase in the 15-64 age group and a more than 130% increase in the 65+ age group. In the 0-14 age group, however, the prevalence remained stable throughout the period.

 

Mortality

 

A recent meta-analysis has shown that the risk of mortality in CKD rises exponentially with decreasing GFR (USRDS 2007 ). Mortality in ESRD patients is very high. Five-year mortality rates in incident RRT patients are 52% in all patients, and 21%, 32% and 72% for patients aged 0-14, 15-64 and over 65 years of age respectively (Table 5.7.8). Five-year mortality in patients on dialysis is almost five times as high as that after kidney transplantation: 60% and 13%, respectively.

Mortality on RRT is lower in Europe compared to the US (Sixth Annual Report UK Renal Registry, 2003; Warady and Chadha, 2007; ERA-EDTA Registry, 2005). Also within Europe there are considerable differences in patient survival (van Dijk et al, 2007). International studies to investigate the reasons for different outcomes in haemodialysis patients are in progress (Young et al, 2000).

 

Table 5.7.8. 90-day, one-, two- and five-year mortality rates in incident RRT patients per age group, gender and cause of renal failure.

 

Trends over time

 

Previous analyses have shown that compared to patients starting dialysis in the cohort 1980-1984, dialysis patients in the more recent cohorts had a 6% (cohort 1990-1994) and 12% (cohort 1995-1999) lower risk of death. The mortality risk reduction in transplant recipients was much higher: 32% and 56%, respectively (Van Dijk et al, 2001).

 

In conclusion, as previously emphasised, there is still a paucity of data on CKD. Data in Europe have been gathered both by using medical databases (Ireland, England, Italy) or population surveys. Data from medical databases overestimate the prevalence of diseases and this was apparent also in the data collected in this review. Indeed, the prevalence of stage 3-5 CKD was 1.3 to 1.5 times higher in medical databases in Ireland, England and Italy than in population based studies in Belgium, Netherlands, Spain, Italy, Iceland, Norway. The prevalence of stage 3-5 CKD appears reasonably similar across EU countries and more frequent in females than in males. The higher prevalence on CKD in females, which flies in the face of ESRD statistics where men are disproportionally affected (Table 5.7.7), may depend on the fact that the GFR, as estimated by the MDRD equation (Levey et al, 1999), is lower in females than in males. Furthermore, the performance of this equation in people with normal or mildly impaired GFR may be sub-optimal (Lin et al, 2003).

 

Although there are considerable differences in absolute incidence rates of RRT for ESRD across countries, there was a consistent increase in incidence rates in virtually all Member States at least until 2002. This was mainly driven by an increase in the incidence rates of RRT for diabetic and hypertensive ESRD (Stengel et al, 2003; van Dijk et al, 2005) After 2002 the incidence rates have tended to stabilize. The stabilization, or even decrease in some causes of ESRD, have prompted some investigators to suggest that treatment strategies for the prevention of ESRD have finally started to bear fruit (Gansevoort et al, 2004; Stewart et al, 2006). The increasing incidence rates together with improvements in survival of RRT patients (Jager and van Dijk 2007) resulted in a concomitant increase in the prevalence of RRT over the past decades that is posing a still increasing economic burden on Member States.

 

Mortality in ESRD patients is still very high. Although the better survival of transplant recipients is, at least in part, due to selection bias, the survival of RRT patients could be considerably improved at reduced costs by increasing organ donation rates.