Anneke Kramer

An update on renal replacement therapy in Europe: ERA–EDTA Registry data from 1997 to 2006

BACKGROUND Recent studies have indicated a stabilization in the incidence rates of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in a number of European countries. The aim of this study was to provide an update on the incidence, prevalence and outcomes of RRT in Europe over the past decade. METHODS Nineteen European national or regional renal registries with registry data from 1997 to 2006 participated in the study. Incidence and prevalence trends were analysed with Poisson and Joinpoint regression. Cox regression methods were used to examine patient survival. RESULTS The total adjusted incidence rate of RRT for ESRD increased from 109.9 per million population (pmp) in 1997 to 119.7 pmp in 2000, i.e. an average annual percentage change (AAPC) of 2.9% (95% CI 2.1-3.8%). Thereafter, the incidence increased at a much lower rate to 125.4 pmp in 2006 [AAPC 0.6% (95% CI 0.3-0.8%)]. This change in the trend of the incidence of RRT was largely due to a stabilization in the incidence rates of RRT for females aged 65-74 years, males aged 75-84 years and patients receiving RRT for ESRD due to hypertension/renal vascular disease. The overall adjusted prevalence in Europe continued to increase linearly at 2.7% per year. Between the periods 1997-2001 and 2002-2006, the risk of death decreased for all treatment modalities, with the most substantial improvement in patients starting peritoneal dialysis [19% (95% CI 15-22%)] and in patients receiving a kidney transplant [17% (95% CI 11-23%)]. CONCLUSION This European study shows that the annual rise of the overall incidence rate of RRT for ESRD has diminished and that in several age groups the incidence rates have now stabilized. The survival of dialysis patients and kidney transplant recipients has continued to improve.

Renal replacement therapy in Europe: a summary of the 2012 ERA-EDTA Registry Annual Report

Background This article summarizes the 2012 European Renal Association—European Dialysis and Transplant Association Registry Annual Report (available at www.era-edta-reg.org) with a specific focus on older patients (defined as ≥65 years). Methods Data provided by 45 national or regional renal registries in 30 countries in Europe and bordering the Mediterranean Sea were used. Individual patient level data were received from 31 renal registries, whereas 14 renal registries contributed data in an aggregated form. The incidence, prevalence and survival probabilities of patients with end-stage renal disease (ESRD) receiving renal replacement therapy (RRT) and renal transplantation rates for 2012 are presented. Results In 2012, the overall unadjusted incidence rate of patients with ESRD receiving RRT was 109.6 per million population (pmp) (n = 69 035), ranging from 219.9 pmp in Portugal to 24.2 pmp in Montenegro. The proportion of incident patients ≥75 years varied from 15 to 44% between countries. The overall unadjusted prevalence on 31 December 2012 was 716.7 pmp (n = 451 270), ranging from 1670.2 pmp in Portugal to 146.7 pmp in the Ukraine. The proportion of prevalent patients ≥75 years varied from 11 to 32% between countries. The overall renal transplantation rate in 2012 was 28.3 pmp (n = 15 673), with the highest rate seen in the Spanish region of Catalonia. The proportion of patients ≥65 years receiving a transplant ranged from 0 to 35%. Five-year adjusted survival for all RRT patients was 59.7% (95% confidence interval, CI: 59.3–60.0) which fell to 39.3% (95% CI: 38.7–39.9) in patients 65–74 years and 21.3% (95% CI: 20.8–21.9) in patients ≥75 years.

Renal replacement therapy for autosomal dominant polycystic kidney disease (ADPKD) in Europe: prevalence and survival-an analysis of data from the ERA-EDTA Registry.

BACKGROUND Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common renal disease requiring renal replacement therapy (RRT). Still, there are few epidemiological data on the prevalence of, and survival on RRT for ADPKD. METHODS This study used data from the ERA-EDTA Registry on RRT prevalence and survival on RRT in 12 European countries with 208 million inhabitants. We studied four 5-year periods (1991-2010). Survival analysis was performed by the Kaplan-Meier method and by Cox proportional hazards regression. RESULTS From the first to the last study period, the prevalence of RRT for ADPKD increased from 56.8 to 91.1 per million population (pmp). The percentage of prevalent RRT patients with ADPKD remained fairly stable at 9.8%. Two-year survival of ADPKD patients on RRT (adjusted for age, sex and country) increased significantly from 89.0 to 92.8%, and was higher than for non-ADPKD subjects. Improved survival was noted for all RRT modalities: haemodialysis [adjusted hazard ratio for mortality during the last versus first time period 0.75 (95% confidence interval 0.61-0.91), peritoneal dialysis 0.55 (0.38-0.80) and transplantation 0.52 (0.32-0.74)]. Cardiovascular mortality as a proportion of total mortality on RRT decreased more in ADPKD patients (from 53 to 29%), than in non-ADPKD patients (from 44 to 35%). Of note, the incidence rate of RRT for ADPKD remained relatively stable at 7.6 versus 8.3 pmp from the first to the last study period, which will be discussed in detail in a separate study. CONCLUSIONS In ADPKD patients on RRT, survival has improved markedly, especially due to a decrease in cardiovascular mortality. This has led to a considerable increase in the number of ADPKD patients being treated with RRT.

Global variation in renal replacement therapy for end-stage renal disease

BACKGROUND Incidence rates of renal replacement therapy (RRT) for end-stage renal disease vary considerably worldwide. This study examines the independent association between the general population, health care system and renal service characteristics and RRT incidence rates. METHODS RRT incidence data (2003-2005) were obtained from renal registries; general population age and health and macroeconomic indices were collected from secondary sources. Renal service organization and resource data were obtained through interviews and questionnaires. Linear regression models were built to establish the factors independently associated with RRT incidence, stratified by the Human Development Index where required. False discovery rate (FDR) correction was adjusted for multiple testing. RESULTS Across the 46 countries (population 1.25 billion), RRT incidence rates ranged from 12 to 455 (median 130) per million population. Gross domestic product (GDP) per capita [incidence rate ratio (IRR): 1.02 per

The changing trends and outcomes in renal replacement therapy: data from the ERA-EDTA Registry

1000 increase, P(FDR) = 0.047], percentage of GDP spent on health care (IRR: 1.11 per % increase, P(FDR) = 0.006) and dialysis facility reimbursement rate relative to GDP (IRR: 0.76 per GDP per capita-sized increase in reimbursement rate, P(FDR) = 0.007) were independently associated with RRT incidence. In more developed countries, the private for-profit share of haemodialysis facilities was also associated with higher incidence (IRR: 1.009 per % increase, P(FDR) = 0.003). CONCLUSIONS Macroeconomic and renal service factors are more often associated with RRT incidence rates than measured demographic or general population health status factors.

Chronic kidney disease and end-stage renal disease—a review produced to contribute to the report ‘the status of health in the European union: towards a healthier Europe’

BACKGROUND This study examines the time trends in incidence, prevalence, patient and kidney allograft survival and causes of death (COD) in patients receiving renal replacement therapy (RRT) in Europe. METHODS Eighteen national or regional renal registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry between 1998 and 2011 were included. Incidence and prevalence time trends between 2001 and 2011 were studied with Joinpoint and Poisson regression. Patient and kidney allograft survival and COD between 1998 and 2011 were analysed using Kaplan-Meier and competing risk methods and Cox regression. RESULTS From 2001 to 2008, the adjusted incidence of RRT rose by 1.1% (95% CI: 0.6, 1.7) annually to 131 per million population (pmp). During 2008-2011, the adjusted incidence fell by 2.2% (95% CI: -4.2, -0.2) annually to 125 pmp. This decline occurred predominantly in patients aged 45-64 years, 65-74 years and in the primary renal diseases diabetes mellitus type 1 and 2, renovascular disease and glomerulonephritis. Between 2001 and 2011, the overall adjusted prevalence increased from 724 to 1032 pmp (+3.3% annually, 95% CI: 2.8, 3.8). The adjusted 5-year patient survival on RRT improved between 1998-2002 and 2003-2007 [adjusted hazard ratio (HRa) 0.85, 95% CI: 0.84, 0.86]. Comparing these time periods, the risk of cardiovascular deaths fell by 25% (HRa 0.75, 95% CI: 0.74, 0.77). However the risk of malignant death rose by 9% (HRa 1.09, 95% CI: 1.03, 1.16) in patients ≥65 years. CONCLUSION This European study shows a declining RRT incidence, particularly in patients aged 45-64 years, 65-74 years and secondary to diabetic nephropathy. Encouragingly, the adjusted RRT patient survival continues to improve. The risk of cardiovascular death has decreased, though the risk of death from malignancy has increased in the older population.

Analysis of data from the ERA-EDTA Registry indicates that conventional treatments for chronic kidney disease do not reduce the need for renal replacement therapy in autosomal dominant polycystic kidney disease

The Report on the Status of Health in the European Union (EUGLOREH) is a project aimed at describing health problems in member states of the European Community. This project is an effort of more than 170 European experts and the collaboration of the health authorities or institutions from all EU Member States, major intergovernmental, International and European Organizations and Agencies. In this report, for the first time special emphasis is given to chronic diseases. Chronic kidney disease (CKD) is increasingly recognized as a major public health problem. However, with some notable exceptions, until now this disease has received scarce attention both at European level and at member states level. In 2007, the ERA-EDTA Registry was invited to contribute to EUGLOREH. The Registry made a major effort to gather published and unpublished information on the epidemiology of CKD and ESRD and to provide a comprehensive overview on CKD and ESRD in European countries. The review was completed in early 2008 and included into the final EUGLOREH published in the WEB as of 20 March 2009.

Epidemiology of CKD in Europe: an uncertain scenario

Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage kidney failure, but is often identified early and therefore amenable to timely treatment. Interventions known to postpone the need for renal replacement therapy (RRT) in non-ADPKD patients have also been tested in ADPKD patients, but with inconclusive results. To help resolve this we determined changes in RRT incidence rates as an indicator for increasing effective renoprotection over time in ADPKD. We analyzed data from the European Renal Association-European Dialyses and Transplant Association Registry on 315,444 patients starting RRT in 12 European countries between 1991 and 2010, grouped into four 5-year periods. Of them, 20,596 were due to ADPKD. Between the first and last period the mean age at onset of RRT increased from 56.6 to 58.0 years. The age- and gender-adjusted incidence rate of RRT for ADPKD increased slightly over the four periods from 7.6 to 8.3 per million population. No change over time was found in the incidence of RRT for ADPKD up to age 50, whereas in recent time periods the incidence in patients above the age of 70 clearly increased. Among countries there was a significant positive association between RRT take-on rates for non-ADPKD kidney disease and ADPKD. Thus, the increased age at onset of RRT is most likely due to an increased access for elderly ADPKD patients or lower competing risk prior to the start of RRT rather than the consequence of effective emerging renoprotective treatments for ADPKD.

Renal replacement therapy in Europe: a summary of the 2013 ERA-EDTA Registry Annual Report with a focus on diabetes mellitus

In the large, diachronic scenario of systemic epidemiology, chronic kidney disease (CKD) is a component of a new epidemic of diseases that, over the twentieth century, replaced malnutrition and infection as leading causes of mortality in the population [1]. Neoplasia, cardiovascular and respiratory diseases and diabetes are ascending the priority rank in the global-health agenda. These diseases reduce life expectancy and engender disability in all population strata including the poorest segment of the population, a stratum still considered to be mainly hit by infectious diseases. Public health interventions calibrated to the level of challenge that these diseases impose are now considered as a great opportunity of averting death and adverse clinical outcomes in developed as well as in developing countries. In 2005, the World Health Organization (WHO) emphasized that chronic diseases are a global priority [2]. It was calculated that, if governments are able to put in place public health policies that produce a 2% yearly reduction in mortality rates for chronic diseases, an achievable goal, 36 million deaths would be prevented worldwide between 2005 and 2015 [3]. The WHO department of Measurement and Health Information estimates that almost 80% of life-years that could be gained by such policies would come from deaths averted in people aged under 70 years [3], i.e. from the most active population strata. Even more than a health priority, the goal of reducing mortality rates by chronic diseases is an economic priority because it could save about 10% of the loss in income due to death and disability which amounts to

Exploring the Association between Macroeconomic Indicators and Dialysis Mortality

8 billion in the developing countries only [4]. Limitation of two major environmental risk factors, salt intake and smoking, and the use of cardiovascular drugs in high-risk patients are of proven cost effectiveness not only in high-income but also in lowand middle-income countries [5]. Appropriate health policies could be very effective, and measures adopted over the last three decades in Poland and Finland are an instructive demonstration of how much can be achieved with simple, well-targeted interventions. In the early 1990s, the Polish government reduced subsidies on animal fats. Polyunsaturated oils such as soya bean and rapeseed oil substituted saturated animal fat in the diet of Polish people, and as a consequence coronary heart disease mortality dropped by more than 25% between 1991 and 2002, a dramatic effect which could not be explained by increased fruit consumption or decreased smoking [6]. The educational campaigns and public policies adopted in Finland in the 1970s [7] represent a paradigmatic example of how much can be achieved in terms of population health by the adoption of a well-articulated intervention plan. In most western countries, the epidemic of cardiovascular disease, diabetes and neoplasia is receiving increasing attention by the public and policymakers. Yet, the CKD epidemic remains largely a ‘silent’ epidemic. The nephrology community is making a worldwide-extended, major effort for raising the status of CKD among chronic diseases, and the World Kidney Day has now become the icon of such a tantalizing effort [8]. Yet, the yields of these efforts have still to materialize. The face-to-face comparison with diabetes is a case in proof. Diabetes and CKD have a similar prevalence in the general population, and part of the clinical outcomes of diabetes are accounted for by CKD triggered by this disease. Promoting prevention programmes focussing on diabetes is legitimately considered as a major public health goal in most western countries, and this disease is, in various European countries, included among priority research themes for funding. In contrast, most health authorities literally ignore CKD prevention. The improving Kidney Outcome Global Initiative (KDIGO) poses surveillance of CKD by periodic surveys or by specific registries as a means for monitoring the epidemic at country level [9]. Prevention of end-stage renal disease (ESRD) was set as a specific goal of ‘Healthy people 2010’, a health-promotion and disease-prevention initiative which was started in the USA in 1979 [10]. However, until very recently, official documents released by the European Community or by the majority of European Community governments did not even mention CKD as an issue of public health concern. A 2007 report on health in Italy [11], one of the largest European countries, released by the national institute of statistic (ISTAT) did not even include CKD among chronic diseases, and similar ignorance of the problem is traceable in contemporary documents prepared by high-level agencies of other countries.