Confounding effect of comorbidity in survival studies in patients on renal replacement therapy.

BACKGROUND: After taking other confounding factors into account, the impact of comorbidity on mortality was investigated when comparing mortality between five European countries, dialysis modalities and renal disease groups. METHODS: The study included 15 571 incident patients on renal replacement therapy (RRT) from five national or regional registries participating in the European Renal Association-European Dialysis and Transplant Association Registry that collect comorbidity data. The presence of diabetes mellitus, ischaemic heart disease, peripheral vascular disease, cerebrovascular disease and malignancy was recorded at the start of RRT. RESULTS: The comorbidities were each independently associated with mortality, with hazard ratios (HRs) ranging from 1.40 (95% CI: 1.30-1.51) for peripheral vascular disease to 1.65 (95% CI: 1.48-1.83) for diabetes. Age, gender, primary renal disease, modality and country together explained 14.4% of the variance in mortality; the comorbidities explained an additional 1.9%. In the comparison of renal vascular disease with glomerulonephritis, the crude HR of 2.40 (95% CI: 2.12-2.72) changed to 1.24 (95% CI: 1.09-1.41) after adjustment for age, gender, primary renal disease, treatment modality and country and to 1.06 (95% CI: 0.93-1.22) after further adjustment for the comorbidities. For the comparison between countries and other patient groups, the change in the survival estimate after adjustment for comorbidity was less. CONCLUSION: Comorbidity is an important predictor for mortality. However, after adjustment for age, gender, primary renal disease, treatment modality and country, when comparing outcomes between patient groups the influence of comorbidity may be less important than expected.

The enigma of hypertensive ESRD: observations on incidence and trends in 18 European, Canadian, and Asian-Pacific populations, 1998 to 2002.

BACKGROUND: Despite improved treatment of hypertension and decreasing rates of stroke and coronary heart disease, the reported incidence of hypertensive end-stage renal disease (ESRD) increased during the 1990s. However, bias, particularly from variations in acceptance into ESRD treatment (ascertainment) and diagnosis (classification), has been a major source of error when comparing ESRD incidences or estimating trends. METHODS: Age-standardized rates were calculated in persons aged 30 to 44, 45 to 64, and 65 to 74 years for 15 countries or regions (separately for the Europid and non-Europid populations of Canada, Australia, and New Zealand), and temporal trends were estimated by means of Poisson regression. For 10 countries or regions, population-based estimates of mean systolic blood pressures and prevalences of hypertension were extracted from published sources. RESULTS: Hypertensive ESRD, comprising ESRD attributed to essential hypertension or renal artery occlusion, was least common in Finland, non-Aboriginal Australians, and non-Polynesian New Zealanders; intermediate in most European and Canadian populations; and most common in Aboriginal Australians and New Zealand Maori and Pacific Island people. Rates correlated with the incidence of all other nondiabetic ESRD, but not with diabetic ESRD or community rates of hypertension. Between 1998 and 2002, hypertensive ESRD did not increase in Northwestern Europe or non-Aboriginal Canadians, although it did so in Australia. CONCLUSION: Despite the likelihood of classification bias, the probability remains of significant variation in incidence of hypertensive ESRD within the group of Europid populations. These between-population differences are not explained by community rates of hypertension or ascertainment bias.

The ERA-EDTA cohort study--comparison of methods to predict survival on renal replacement therapy.

BACKGROUND: Accurate prediction of patient survival from the time of starting renal replacement therapy (RRT) is desirable, but previously published predictive models have low accuracy. We have attempted to overcome limitations of previous studies by conducting an ambidirectional inception cohort study in patients on RRT from centres throughout Europe. A conventional multivariate regression (MVR) model, a self-learning rule-based model (RBM) and a simple co-morbidity score [the Charlson score modified for renal disease (MCS)] were compared. METHODS: In 1996, all 3640 dialysis centres registered with the ERA-EDTA were invited to identify all patients on RRT for end-stage renal failure (ESRF) who died during the 28 days of February 1997 (training cohort) and all patients who started RRT in the same period (validation cohort). Fifty-four clinical and laboratory variables from the time of starting RRT were collected in both cohorts using a two-page questionnaire. The data from the training cohort were given to statisticians at the Amsterdam Academic Medical Centre to create the MVR model and to engineers in Strathclyde University to create the RBM. They were then given the baseline data from patients in the validation cohort to predict how long each patient would survive. Follow-up questionnaires were sent to the centre of each patient in the validation cohort to determine actual survival. RESULTS: A total of 2310 patients from 793 centres in 37 countries in the ERA-EDTA area were used to construct and validate the models. For predicting 1-year survival, the RBM had the highest positive predictive value (PPV) (84.2%), the MVR model had the highest negative predictive value (NPV) (47%) and the RBM had the highest likelihood ratio (1.59). For predicting 5-year survival, the MCS had the highest PPV (79.4%), the RBM had the highest NPV (74.3%) and the MCS had the highest likelihood ratio (7.0). The proportion of explained variance in survival for MCS, MVR and RBM was 14.6, 12.9 and 3.95%, respectively. CONCLUSION: Using the ambidirectional inception cohort design of this ERA-EDTA Registry survey, we have been able to create and validate two novel instruments to predict survival in patients starting RRT and compare them with a simple scoring model. The models tended to predict 5-year survival with more accuracy than 1-year survival. Examples of potential applications include informing clinical decision making about the likely benefit of starting RRT and listing for transplantation, adjusting for baseline risk in comparative studies and identifying specific risk groups to participate in clinical trials.

Prevalence of co-morbidity in different European RRT populations and its effect on access to renal transplantation.

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.

Renal replacement therapy for diabetic end-stage renal disease: data from 10 registries in Europe (1991-2000).

BACKGROUND: There is concern about the rising prevalence of type 2 diabetes mellitus and of the resultant nephropathy. This study uses data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry to provide information on the epidemiology and outcome of renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetic nephropathy (DN). METHODS: Data from the following 10 registries: Austria, French-speaking Belgium, Denmark, Finland, Greece, Norway, Scotland (UK), Catalonia (Spain), Sweden, and The Netherlands were combined. Average annual changes (%) were estimated by Poisson regression. Analyses of mortality were performed by Cox regression. RESULTS: An increase in patients with type 2 DN entering RRT has been observed (+11.9% annually, P < 0.05), while large differences in RRT incidence in this disease continue to exist between countries in Europe. There was a reduction in mortality during the first 2 years on dialysis therapy among patients with type 2 DN (AHR 0.96, 95%CI 0.94-0.97 annually). The mortality among transplant recipients decreased for both type 1 DN and nondiabetic ESRD (non DN) within the 1995-1998 cohort (type 1 DN: AHR 0.49, 95% CI 0.35-0.68; non DN: AHR 0.79, 95% CI 0.69-0.90) compared to the 1991-1994 cohort. CONCLUSION: This report has shown that during the last decade there has been a marked increase in the incidence of RRT for type 2 DN. Survival analysis showed that over the period 1991-1999 the mortality rates of all dialysis patients and of type 1 diabetic and nondiabetic renal transplant recipients have fallen.

Renal replacement therapy in children: data from 12 registries in Europe.

In June 2000 the ERA-EDTA Registry office moved to Amsterdam and started collecting core data on renal replacement therapy (RRT) entirely through national and regional registries. This paper reports the pediatric data from 12 registries. The analysis comprised 3,184 patients aged less than 20 years and starting RRT between 1980 and the end of 2000. The incidence of RRT rose from 7.1 per million of age-related population (pmarp) in the 1980-1984 cohort to 9.9 pmarp in the 1985-1989 cohort, and remained stable thereafter. The prevalence increased from 22.9 pmarp in 1980 to 62.1 in 2000. Hemodialysis was the commonest form of treatment at the start of dialysis, but peritoneal dialysis gained popularity during the late 1980s. Pre-emptive transplantation accounted for 18% of the first treatment modality in the 1995-2000 cohort. The relative risk of death of patients starting dialysis in the period 1995-2000 was reduced by 36% [adjusted hazard ratio (AHR) 0.64 [95% confidence interval (CI) 0.41-1.00] and that of those receiving a first allograft by 42% [AHR 0.58 (95% CI 0.34-1.00)], compared with patients in the period 1980-1984. The prevalence of RRT in children has continued to rise, while its incidence has been stable for about 15 years. Patient survival has improved in both dialysis patients and transplant recipients. The development of this pediatric registry will form the basis for more-detailed and focused studies in the future.

Trends in the incidence of renal replacement therapy for end-stage renal disease in Europe, 1990-1999.

BACKGROUND: The epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) varies considerably worldwide, but we have lacked reliable quantitative estimates of trends in the incidence by age, sex and cause in Europe over the last decade. METHODS: We analysed data from nine countries participating in the ERA-EDTA registry: Austria, Belgium, Denmark, Finland, Greece, The Netherlands, Norway, Spain and UK (Scotland). Adjusted incidence rates for age and sex were studied for 2 year periods between 1990 and 1999. Average annual changes (%) were estimated by Poisson regression. RESULTS: The adjusted incidence rate of RRT increased from 79.4 per million population (pmp) (range: 58.4-101.0) in 1990-1991 to 117.1 pmp (91.6-144.8) in 1998-1999, i.e. 4.8% (3.1-6.4%) each year. This increase did not flatten out at the end of the decade, except in The Netherlands, and was greater in men than women, 5.2 vs 4.0%/year. In most countries, the incidence rate remained stable for those younger than 45 years; it rose by 2.2%/year on average in the 45-64 year age group and by 7.0% among those 65-74 years; it tripled over the decade in those 75 years or older, and by 1998-1999 it ranged from 140.9 to 540.4 pmp between countries. The incidence of ESRD due to diabetes, hypertension and renal vascular disease nearly doubled over 10 years; in 1998-1999, it varied between countries from 10.2 to 39.3 pmp for diabetes, from 5.8 to 21.0 for hypertension, and from 1.0 to 15.5 for renal vascular disease. CONCLUSION: RRT incidence continues to rise but at various rates in the European countries studied, tending to widen the gap between them. This mainly results from enlarging differences in incidence in the elderly and, to a lesser extent, in that due to diabetes, hypertension and renal vascular disease.