Epidemiology of end-stage renal disease in the Ile-de-France area: a prospective study in 1998
Paul Jungers,1,
Gabriel Choukroun1,
Christophe Robino1,
Ziad A. Massy2,
Pierre Taupin3,
Mathilde Labrunie2,
Nguyen-Khoa Man2 and
Paul Landais3
1 Department of Nephrology,
2 INSERM U 507 and
3 Department of Biostatistics, Necker Hospital, Paris, France
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Abstract
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Background. The objective of this study was to determine the incidence and prevalence of end-stage renal disease (ESRD) requiring maintenance dialysis in the Ile-de-France district (Paris area), and the characteristics of patients at start of dialysis.
Methods. This is a prospective epidemiological study with the cooperation of all dialysis facilities of the Ile-de-France district (population 10.7 million inhabitants as of March 1999). All consecutive ESRD patients who started dialysis from January 1 to December 31 1998, with demographic and clinical characteristics, and of the total number of patients on dialysis with their distribution according to dialysis modality were recorded.
Results. The total number of ESRD patients in 1998 was 1155, including 29 (2.5%) children aged
17 years and 86 (7.4%) returns to dialysis following kidney graft failure. Incidence of first-dialysed patients was 100 per million population (p.m.p.) and overall incidence, including returns from transplantation, was 108 p.m.p. The mean age of first-dialysed adult patients was 59.8±16.8 years, with 21.6% aged
75 years. Patients with vascular renal disease were 22.5% and those with diabetic nephropathy 20.6%. As a whole, 36.5% of patients were referred to the nephrologist
6 months before start of dialysis, including 32.2% referred
1 month before starting. Prevalence of cardiovascular disease was nearly twice as high in patients referred <6 months of starting dialysis than in those who benefited from effective nephrological care for >3 years in the predialysis period. By multivariate analysis, this difference persisted after adjustment for age and other confounding covariates. The total number of patients on maintenance dialysis increased from 417 to 433 p.m.p. (a yearly 3.8% increase) from the beginning to the end of 1998.
Conclusion. This recent epidemiological study in a large French urban area indicates an annual incidence of 100 new ESRD patients p.m.p., with a high proportion of older, vascular and diabetic patients. Overall incidence, including returns from transplantation, reached 108 p.m.p. Cardiovascular disease was significantly less frequent in patients who received nephrological care for
3 years prior to start of dialysis than in late referred patients, underlining the benefits of early nephrological management of renal patients.
Keywords: ESRD; France; Ile-de-France; incidence of ESRD; prevalence of dialysis patients; renal replacement therapy requirements
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Introduction
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The incidence of patients requiring maintenance dialysis therapy is relentlessly growing throughout the world, due to the increasing number of older patients with diabetic nephropathy and vascular renal disease reaching end-stage renal disease (ESRD), in parallel with the continuous ageing of the general population [1]. The mean increment in the number of new patients with ESRD accepted for renal replacement therapy (RRT) was estimated at 5% per year over the last 4 years in the USA [1] and 6.5% over the last 5 years in Japan [2]. Data from European countries also indicate an increase in both incidence and prevalence of dialysis-treated ESRD patients in the order of 4% per year as a mean [3].
Because the epidemiology of renal disease varies greatly among countries, proper knowledge of the annual incidence of new patients reaching ESRD, and of patients returning to dialysis following kidney graft failure, is needed to establish accurate predictions for the logistics of dialysis therapy. According to the reports of the European Dialysis and Transplant Association European Renal Association (EDTAERA), the total number of new ESRD patients accepted for RRT in France during 1991 was 4350, an incidence of 77.1 patients per million population (p.m.p.) [4]. This was close to the incidence of 75.8 new ESRD patients p.m.p. registered during the year 1993 in the Rhône-Alps area in France [6], and to the 81.2% estimation gained from a prospective epidemiological inquiry conducted in the Ile-de-France district in 19911992 to evaluate the age- and gender-related incidence of chronic renal failure (CRF) [5].
Because the latter figure was an indirect estimation of the incidence of ESRD in the Ile-de-France district, and because an increase in the incidence of patients with ESRD was to be expected over the recent years, a prospective study was undertaken to evaluate the incidence of ESRD in the Ile-de-France area during a 1 year period (1998). The aim of the study was to accurately determine the annual incidence of ESRD (including returns to dialysis after kidney graft failure), the demographic and clinical characteristics of patients at start of maintenance dialysis and the pattern of nephrological referral. We also analysed the prevalence of cardiovascular comorbidity with respect to the duration of effective pre-dialysis nephrological care. The prevalence of dialysis-treated patients and the distribution of modes of dialysis (in-centre versus out-centre) were determined, and their variation was evaluated by reference to data gained from a governmental inquiry in January 1995 [7].
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Subjects and methods
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The study was prospective and was conducted under the auspices of the French Society of Nephrology. All 91 nephrology units and dialysis facilities of the Ile-de-France district volunteered to participate, namely Nephrology units of university hospitals and general hospitals, in-centre haemodialysis units, self-care dialysis units, units caring for peritoneal dialysis and the regional association for home dialysis patients.
All consecutive patients with irreversible renal failure who were accepted on a programme of maintenance dialysis from January 1 to December 31, 1998, were included in the study. Patients with acute, reversible renal failure were excluded from the study, but patients returning to dialysis following kidney graft failure were included.
Data were collected using a questionnaire form filled out by the staff of the various dialysis units, after the patients effectively had started RRT. The following data were recorded at the time of starting dialysis: age, gender, geographical localization, body weight and height, occupational status (working, disabled or retired), causal renal disease, presence of diabetes mellitus or other comorbidity. Comorbid conditions recorded were congestive heart failure (Class III and IV of NYHA), history of myocardial infarction (or coronary revascularization procedure, or angiographic evidence of coronary stenosis), peripheral vascular disease, history of cerebral infarction, chronic lung disease, severe liver disease and past or present malignancy. Also recorded were serum creatinine and albumin levels before first dialysis, duration of predialysis nephrological care, mode of dialysis, either haemodialysis (HD) or peritoneal dialysis (PD), presence of a previously created functional vascular access or need for temporary central vein catheterization.
In addition, the total number of patients receiving HD or PD in each unit, with the distribution between centre-HD, self-care HD, home HD and PD was recorded at the beginning of January 1998, and again at the beginning of January 1999, in order to determine the prevalence of dialysis-treated patients and its evolution over this 1 year period.
Data were analysed using the SAS® software package and are presented as mean±SD. Incidence and prevalence of patients are given as number p.m.p. The Student's t test, ANOVA or the MannWhitney test, when required, were used to compare means between independent groups. The Pearson
2 test was used to compare qualitative variables. Multiple logistic regression analysis was used to evaluate the influence of predialysis nephrological care duration on the prevalence of cardiovascular disease at start of dialysis. Covariates who were found to correlate on single regression analysis were included in the adjusted model (age, gender, diabetes). Risks were expressed as odds ratios fitted with 95% confidence intervals (CI). Values of P<0.05 were assumed to be significant.
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Results
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Overall incidence of ESRD
A total of 1155 patients with ESRD due to chronic or irreversible acute renal failure were accepted on maintenance dialysis therapy during the year 1998, including 29 children aged
17 years (2.5%) and 86 patients (7.4%) returning to dialysis following kidney graft failure. The total population of the Ile-de-France district, as of the French National Census in March 1999, was 10 695 300 inhabitants. The number of new (first-dialysis) ESRD patients was 1069, an incidence of 100 p.m.p./year, and the total number of ESRD patients requiring RRT was 1155, an overall incidence of 108 p.m.p./year.
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Epidemiology of ESRD in the Ile-de-France district
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Analysis of the demographic and clinical characteristics of incident patients was restricted to the 1040 adult (
18 years of age) first-dialysis patients. They were 642 males (61.7%) and 398 females (38.3%), a sex-ratio of 1.61, 95% of the patients were Caucasian. The mean age of patients at start of dialysis was 59.8±16.8 years, slightly lower in men (58.9±16.6) than in women (61.2±17.1 years, P=0.04). Distribution of patients with respect to age at start of dialysis is given in Figure 1
. ESRD patients aged 1859 years accounted for 45.3%, and patients aged
60 years for 54.7%, including 21.6% aged
75 years. Incidence of new adult patients, expressed per million population in the various age groups, is given in Table 1
. Incidence of ERSD was about twice higher in males than in females in all age groups. The overall incidence of ESRD was 14 p.m.p. (95% CI 919) in patients aged <18 years, 79 p.m.p. (7287) in the age range 1859 years and 212 p.m.p. (195230) in patients aged
60 years. Incidence of ERSD was about six times higher in males aged
75 years than in those aged 1839 years, and four times higher in females.
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Table 1. Age-related annual incidence of new ESRD patients in the Ile-de-France region expressed as number p.m.p. in the corresponding age groups (95% CI) in 1998
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Distribution of patients with respect to primary renal disease is given in Table 2
. Vascular renal disease (angionephrosclerosis) was present in 22.5% of patients, (15.3% of them with demonstrated renal artery stenosis), and diabetic nephropathy in 20.6% (72% of whom had type 2 diabetes mellitus). Altogether, vascular renal disease and diabetic nephropathy accounted for 43.1% of diagnoses. The mean age of these patients was significantly higher than in the other types of renal diseases, but the mean age of patients with hypertensive nephrosclerosis or with renal artery stenosis was similar (70.9±12.8 and 72.4±9.4 years, respectively).
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Nephrological referral pattern and comorbidity
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Complete data as to the duration of predialysis nephrological care and preparation for dialysis were obtained in 977 patients. Patients who were referred to the nephrologist at least 6 months before start of dialysis comprised 63.5%, whereas 36.5% were referred <6 months before start of dialysis, including 4.5% who were referred within 15 months and 32.2% who were referred <30 days before first dialysis (Table 3
). Of the latter, most were referred in emergency conditions and had to start haemodialysis within 24 h of hospitalization. Thus, central vein catherization was used as first vascular access in 32% of cases. The remaining were first dialysed on arterioveinous fistula. Duration of hospital stay was significantly higher in patients referred <30 days of first dialysis (median 28 days) than in those who received nephrological care for
6 months (median 3 days). The mean age of patients did not differ whether they had been referred <6 months or
6 months before start of dialysis (59.6±18.1 vs 59.7±16.1 years, NS).
Comorbid conditions present at start of RRT are indicated in Table 4
. Cardiovascular complications were predominant. At least one major cardiovascular complication (previous myocardial or cerebral infarction, congestive heart failure and/or peripheral vascular disease) was present in 32.7% of patients (Table 4
). However, prevalence of these cardiovascular complications was significantly lower in the 405 patients followed for at least 3 years (25.4%) than in the 358 who were referred <6 months before first dialysis (40.3%) and in the 214 who received nephrological care for 0.53 years (33.5%, overall
2 P<0.001) (Figure 2
). Univariate regression analysis showed an increased risk of cardiovascular disease with age, gender, diabetes and duration of predialysis nephrological care. By multiple logistic regression analysis, after adjustment on age, gender, presence or absence of diabetes and type of nephropathy, the duration of predialysis nephrological care still remained an independent factor predicting the risk of cardiovascular disease at ESRD, with an odds ratio of 1.7 (CI 1.22.4, P=0.002) for patients referred <3 years, compared with patients followed for at least 3 years prior to start of dialysis (Table 5
).

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Fig. 2. Proportion of patients with cardiovascular complications at start of dialysis with respect to the duration of predialysis nephrological care.
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Laboratory parameters
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Mean serum creatinine value at start of dialysis was 811±298 µmol/l, and was higher in late referral patients (933±383 µmol/l) than in those who received nephrological care for at least 6 months (755± 229 µmol/l, P<0.0001). Mean estimated creatinine clearance at start of dialysis was 8.0±2.7 ml/min/1.73 m2 in the whole group, and was lower in late than in early referral patients (7.2±2.5 vs 8.5±2.7 ml/min/1.73 m2, P<0.001). Serum albumin was significantly lower in late referral patients than in those who received nephrological care for at least 6 months (Table 6
).
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Table 6. Mean serum creatinine, estimated creatinine clearance (Ccr) and serum albumin level at start of dialysis with respect to predialysis nephrological care duration
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Mode of dialysis
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The initial mode of dialysis was centre-haemodialysis in 68.3% of patients and out-centre dialysis in 31.7%, in the form of self-care haemodialysis (18.5%), home haemodialysis (1.7%) or peritoneal dialysis (11.6%). Out-centre dialysis was adopted in a significantly lower proportion of patients referred <6 months before ESRD than in those who received nephrological care for at least 6 months (21.8 vs 37.5%, P<0.01) (Table 7
).
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Table 7. Modes of dialysis (in-centre vs out-centre) according to the duration of predialysis nephrological care (%)
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Variation of the prevalence of dialysis patients in the Ile-de-France district
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From January 1998 to January 1999, the total number of patients on maintenance dialysis in the Ile-de-France district rose from 4463 (417 p.m.p.) to 4632 (433 p.m.p.), an increase of 3.8% over 1 year. The total number of patients on dialysis in the Ile-de-France district in January 1995, known from a previous inquiry of the Direction Régionale des Affaires Sanitaires et Sociales d'Ile-de-France (DRASSIF) [7] was 4018. Thus, the average increase in prevalence over the 4 year period 19951999 was 3.8% per year.
The distribution of ESRD patients according to the mode of dialysis from 1995 to 1999 is given in Table 8
. The number of centre-HD patients increased only slightly (by 5%), whereas the number of patients treated with self-care HD rose markedly (by 60%), as did the number of patients treated with peritoneal dialysis (by 50%). In contrast, the number of home-HD patients declined by 14% during this time. Overall, the proportion of out-centre treated patients rose from 26.3% in January 1995 to 32.9% in January 1999.
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Table 8. Variation of the prevalence of dialysis-treated patients according to the mode of dialysis in the Ile-de-France district from 1995 to 1999
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Discussion
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This epidemiological study provides the first prospective evaluation of the annual incidence of ESRD patients in the Ile-de-France district, a large French urban area, the total population of which is nearly 11 million inhabitants as established by the most recent national census (March 1999). This population is as large as the whole population of countries such as Belgium, Switzerland or Sweden. Because all nephrology and dialysis centre units of the Ile-de-France district participated, data provided by this study with respect to the annual incidence of ESRD patients requiring maintenance dialysis are expected to be exhaustive. In addition, this study provides updated information on the demographic characteristics comorbidity, referral pattern and mode of dialysis of ESRD patients in the Ile-de-France district.
The overall annual incidence of 100 new ESRD patients p.m.p./year in 1998 in our study is close to the incidence of 114 p.m.p./year reported in Spain in 1997 [8]. The latest preliminary data from the EDTAERA Registry report bearing on the year 1995 [3] (limited to countries with response rates >80%), indicate an overall annual incidence of RRT in 11 European countries of 131 p.m.p., but with marked regional variations, as higher values were registered in Italy (133 p.m.p.) and in Germany (163 p.m.p.) than in other European countries (from 69 p.m.p. in Ireland to 116 p.m.p. in Belgium). In any case, the incidence of ESRD was clearly lower in the Ile-de-France area and in other European countries than in Japan (160 p.m.p. in 1996) [2] and in the USA (218 p.m.p. in 1997 in white population) [1].
Diabetic nephropathy and vascular renal disease accounted, respectively, for 20.6 and 22.5% of our incident patients in 1998. In Spain, diabetic nephropathy and vascular renal disease accounted for 19 and 15%, respectively, of incident cases in 1996 [8], whereas in the USA these diseases are more frequently observed in dialysed patients, since they represent 44.5 and 26.6%, respectively, of incident patients in 1997 [1].
In our study, the incidence of ESRD was nearly twice as high in males than in females, and this was observed at every age. Such a preponderance of male ESRD patients is also observed in other countries [13,8,9]. However, a salient observation is the considerable increase in the incidence of ESRD with age, as the overall incidence rose from 55 p.m.p in patients aged 1839 years to 258 p.m.p in those aged
75 years. The increase was especially apparent in males, with an incidence of ESRD peaking at 441 p.m.p in men aged
75 years compared to 69 p.m.p in men aged 1839. A marked increase in the frequency of ESRD with age has similarly been observed in the USA [1], where the incidence of ESRD in 1997 was 109 p.m.p. in the age range 2044 years, compared with 1292 p.m.p. in the population
75 years of age. Increase in the incidence of first-dialysis adult patients from 1992 to 1998 in the Ile-de France area was 23%, or 4% per year as a mean, a lower rate than that observed in the USA or in Japan. During the 4 year period from January 1995 to January 1999, the total prevalence of dialysis patients rose from 375 to 433 p.m.p. The mean increase in rate was 3.8% per year, markedly less than that observed in the USA during the same period, but very similar to the 3.8% annual increase in prevalence observed in Germany between 1995 and 1996 [9].
The number of centre-HD treated patients remained quite stable in the Ile-de-France district, whereas the absolute number and the proportion of patients treated with out-centre modalities markedly increased to reach 32.9% at the end of 1998. Similarly, in the Lyon's area, the proportion of out-centre-treated haemodialysis patients was 35.6% in 1993 [6]. This reflects the result of a voluntary policy in France aimed at encouraging out-centre techniques in order to provide better autonomy to patients and to reduce the costs of dialysis.
Despite repeated publications in the early 1990s alerting the medical community to the deleterious effects of late referral of renal patients [1012], the proportion of late referral ESRD patients was still high in 1998 in the Ile-de-France area, as 36% of patients were referred <6 months before first dialysis. At least two thirds of late referrals were unjustified, as nearly all patients benefited health insurance coverage and asymptomatic or acute renal failure presentation was observed in only 10% of patients. A high proportion of unjustified late referral of ESRD patients is still observed in all countries, with figures varying from 25 to 45% [1315].
Most of our late referral patients had to start dialysis in emergency conditions within 2448 h of referral through central vein catherization in the absence of a previously created vascular access. The length of hospitalization was considerably higher (median 28 days) than in patients who received nephrological care for at least 6 months, in whom initial hospitalization lasted only 3 days on average. In addition to the overcost resulting from a longer hospital stay, late referral patients were less likely to start RRT with peritoneal dialysis or with self-care or home haemodialysis than did patients who benefited from longer nephrological care.
In parallel with the increasing age of ESRD patients, the proportion of patients with significant morbidity at the start of RRT, especially cardiovascular comorbidity, was high in our series. A similarly high prevalence of cardiovascular risk factors at the time of starting RRT has also been reported in other countries, and cardiovascular comorbidity has been shown to be significantly associated with mortality on dialysis [1618]. Of note, the prevalence of cardiovascular disease was found to be higher in patients who received nephrological care for <6 months, or even for 0.53 years, than in patients who benefited from nephrological care for at least 3 years prior to ESRD. This difference does not reflect an older age of late referred patients because the mean age of patients did not differ with respect to the timing of referral. This observation rather suggests that a longer duration of effective nephrological management is associated with a lower incidence of cardiovascular complications in uraemic patients, probably due to a better control of hypertension, anaemia, left ventricular hypertrophy, dyslipidemia, secondary hyperparathyroidism, hyperhomocysteinaemia, and other remediable factors of uraemic toxicity [19,20].
In conclusion, this prospective epidemiological study in a large French urban region provides evidence that the number of both incident and prevalent ESRD patients requiring maintenance dialysis increased by nearly 4% per year over the recent years in our country. Despite all efforts to improve early nephrological referral of renal patients, the proportion of late referrals remains excessive. However, our study provides evidence that a longer duration of predialysis nephrological care is associated with a significantly lower prevalence of cardiovascular comorbidity at start of RRT. Such results strongly argue to encourage early nephrological management of patients with chronic renal failure.
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Acknowledgments
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We gratefully thank all of our colleagues who voluntarily participated in this study. We thank Mrs Catherine Dupont for dedicated assistance in the registration of patients data and preparation of the manuscript.
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Notes
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Correspondence and offprint requests to: Prof. Paul Jungers, Département de Néphrologie, Hôpital Necker, 149, rue de Sèvres, F-75743 Paris Cedex 15, France. 
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Received for publication: 19. 1.00
Revision received 4. 7.00.