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NDT Advance Access originally published online on November 21, 2008
Nephrology Dialysis Transplantation 2009 24(2):578-588; doi:10.1093/ndt/gfn464
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© The Author [2008].
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Baseline characteristics of an incident haemodialysis population in Spain: results from ANSWER—a multicentre, prospective, observational cohort study

Rafael Pérez-García1, Alejandro Martín-Malo2, Joan Fort3, Xavier Cuevas4, Fina Lladós5, Javier Lozano5, Fernando García6 and on behalf of all Investigators from the ANSWER study

1 Servicio de Nefrologia, Hospital Gregorio Marañón, Madrid 2 Servicio de Nefrologia, Hospital Reina Sofia, Cordoba 3 Servicio de Nefrologia, Hospital Vall d’Hebron 4 Servicio de Nefrologia, Hospital Consorci Sanitari de Terrassa 5 Amgen S.A., Barcelona 6 Unidad de Epidemiología Clinica, Hospital Puerta de Hierro, Madrid, Spain

Correspondence and offprint requests to: Rafael Pérez-García, Servicio de Nefrología, Hospital Gregorio Marañón, C/Doctor Esquerdo, 46-28007 Madrid, Spain. Tel: +34-915-86-80-47; Fax: +34-915-86-83-18; E-mail: rperezgarcia{at}senefro.org



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. The ANSWER study aims to identify risk factors leading to increased cardiovascular morbidity and mortality in a Spanish incident haemodialysis population. This paper summarizes the baseline characteristics of this population.

Methods. A prospective, observational, one-cohort study, including all consecutive incident haemodialysis patients from 147 Spanish nephrology services, was conducted. Patients were enrolled between October 2003 and September 2004. Sociodemographic, clinical, laboratory and health care characteristics were collected.

Results. Baseline characteristics are described for 2341 incident haemodialysis patients [mean (SD) age 65.2 (14.5) years, 63% males]. The main cause of renal failure was diabetic nephropathy (26%). The majority of patients (57%) had a Karnofsky score of 80–100 and 27% were followed up by a nephrologist for ≤6 months. In total, 86% of the patients had hypertension, 43% had dyslipidaemia and 44% had a history of cardiovascular disease. Initial vascular access was obtained via a temporary catheter in 30% of patients, via a permanent catheter in 16% and via an arteriovenous fistula in 54%. Albumin levels were <3.5 g/dl in 43% of patients. Immediately prior to the onset of haemodialysis, the mean (SD) glomerular filtration rate (GFR) was 7.6 (2.8) ml/min/1.73 m2, and only 6.7% of the patients were within the K/DOQI guidelines for all four bone mineral markers. In addition, a high proportion of patients had anaemia markers outside the EBPG guidelines (haemoglobin <11 g/dl, 59%, ferritin <100 or >500 ng/ml, 41% and saturated transferrin <20 or >40%, 50%) despite previous treatment with erythropoiesis-stimulating agents in 41% of cases.

Conclusions. There is excessive use of temporary catheters and a high prevalence of uraemia-related cardiovascular risk factors among incident haemodialysis patients in Spain. The poor control of hypertension, anaemia, malnutrition and mineral metabolism and late referral to a nephrologist indicate the need for improving the therapeutic management of patients before the onset of haemodialysis.

Keywords: cardiovascular; haemodialysis; malnutrition; risk factors; vascular access



   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 References
 
Haemodialysis has become an increasingly safe and well-tolerated therapy for patients with end-stage renal disease (ESRD). Nevertheless, life expectancy of dialysis patients remains significantly shorter than that of the general population with similar demographics [1]. There is also a high incidence of cardiovascular morbidity and mortality in this population [2,3]. Large, prospective, observational studies, including the Dialysis Outcomes and Practice Patterns Study (DOPPS) [4], and the United States Renal Data System Dialysis Morbidity and Mortality Wave 2 study [5,6] have provided important insights into the characteristics and likely prognosis of haemodialysis patients. A number of prospective epidemiological studies from several European countries have also described the incident haemodialysis population [7–15], which can help to assess the influence of a multitude of risk factors on the increased mortality among these patients. In this regard, the ANSWER study is currently underway in a large incident haemodialysis population in Spain.

The primary objective of the ANSWER study is to determine and quantify the risk factors influencing cardiovascular morbidity and mortality in incident haemodialysis patients in Spain. In addition, the study also aims to provide information on the baseline characteristics of the incident haemodialysis population; in this paper, we report these data and make comparisons with other incident and prevalent populations reported in the literature.



   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 References
 
ANSWER is a multicentre, prospective, observational cohort study in incident haemodialysis patients all over Spain. Most dialysis facilities from Spain (n = 235) were invited to participate in the study, of which 147 (62.5%) centres agreed to participate. The local ethics committees approved the study and all patients enrolled in the study provided informed consent.

Patients
All incident haemodialysis patients (i.e. patients starting chronic haemodialysis treatment, who had received haemodialysis for ≤30 days) aged ≥18 years were eligible for inclusion in the study. Patients were excluded if they had undergone renal replacement therapy previously, were already receiving haemodialysis (≥30 days) or peritoneal dialysis, or had received a kidney transplant.

Following initiation of the study at each site in October 2003, patients were consecutively enrolled as they started haemodialysis treatment. Enrolment was stratified by region according to the incidence of haemodialysis in a reference population [16], in order to obtain a sample in which all Spanish regions would be represented in the same proportion as in the target population.

Patient assessments
Sociodemographic, clinical, laboratory (maximum 30 days before start of haemodialysis) and health care (concomitant drug therapy and haemodialysis characteristics) variables were recorded at baseline (within first 30 days of haemodialysis) and assessed at regular intervals during the study period, with all the study patients followed up for at least 2 years.

Variables recorded at baseline included waist measurement, smoking status (active smoker, non-smoker, ex-smoker), alcohol consumption (grams of alcohol [17]), employment status and education. The clinical variables assessed included history of renal failure and various comorbidities: diabetes, dyslipidaemia [cholesterol >220 mg/dl or low-density cholesterol (LDL-C) >100 mg/dl or treatment with statins], hypertension [systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg or treatment with antihypertensives], parathyroidectomy, malnutrition (physician's subjective assessment) and cardiovascular disease (heart failure, left ventricular hypertrophy, cardiac arrhythmia, ischaemic heart disease, cerebrovascular disease, peripheral vascular disease and any other diseases of the circulatory system). The Charlson age-comorbidity index [18,19], performance status [Karnofsky score (KS)] and health-related quality of life (QoL) assessed with the Medical Outcome Survey Short Form 36 (SF-36) questionnaire [20], previously validated for the Spanish population [21], were also recorded.

Parameters describing the patients’ initial haemodialysis experience (first month after starting) were also obtained. Dialysis intolerance was defined as hypotension recorded at >50% of dialyses performed during the past month. The urea reduction ratio (URR) and Kt/V were calculated for each patient according to a standard formula (second-generation Daugirdas formula for eKt/V [22]). Glomerular filtration rate (GFR) was estimated according to the MDRD equation [23].

Bone mineral markers [intact parathyroid hormone (iPTH), phosphorus, total calcium and calcium–phosphorus product (Ca x P)] were assessed according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) target ranges [24]. Anaemia markers (haemoglobin, haematocrit, ferritin and saturated transferrin) were assessed according to the European Best Practice Guidelines (EBPG) [25].

Statistical analysis
Summary statistics were calculated for continuous and categorical endpoints. Differences between subgroups were assessed using chi-square tests for categorical variables and Student's t-test or the Mann–Whitney U-test for continuous variables (according to normality). The Bonferroni method [26] was applied for adjusting the significance level in these analyses. Differences were considered significant at P < 0.00022 (0.05/228). Differences between means and odds ratios with respect to the reference subgroup, together with their 95% confidence interval, are displayed only for the variables with significant results. The calculations were performed using SPSS® 14.0.



   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 References
 
Sociodemographic characteristics and aetiology of kidney disease
A total of 2406 incident patients undergoing dialysis were enrolled from 147 hospital nephrology services and associated haemodialysis centres throughout Spain between 1 October 2003 and 30 September 2004. Sixty-five patients were excluded from analysis, as they did not meet the inclusion criteria. The resulting sample, 2341 patients, accounts for ~58% of the total incident patients during the study period (according to the 2003 and 2004 estimates of the incidence of haemodialysis in Spain of the National Registry [27,28]).

Table 1 summarizes the patient demographics and baseline characteristics. Most patients were elderly (29% over 75 years), male (63%) and overweight [59% had body mass index (BMI) >25 kg/m2]. The education level was low (38% had no primary education). The most common reason for renal failure was diabetic nephropathy (26%), and 27% of patients had been followed up by a nephrologist for <6 months prior to the onset of haemodialysis (24% in the subgroup with diabetic nephropathy and 26% in the subgroup with vascular nephropathy). The prevalence of hepatitis C virus positive patients was 5.4%.


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  		Table 1 Baseline sociodemographic, clinical and haemodialysis characteristics of the study population

 
Comorbidities, functional status, medications and quality of life
Comorbidities were common, particularly hypertension (86%), with almost all hypertensive patients being non-controlled (89% with SPB ≥140 mmHg or DBP ≥90 mmHg), despite most of them receiving antihypertensive treatment (80%). There was also a high frequency of previous cardiovascular disease (44%) and dyslipidaemia (43%) (Table 1). The prevalence of diabetes mellitus was 10% higher than that of diabetic nephropathy. Approximately 1 in 10 patients had developed a tumour.

As expected, the use of concomitant medications reflects the comorbidities in this population (Table 2). Half of the patients were treated with iron supplements either before (47%) or after (53%) the initiation of haemodialysis. Most patients were receiving or were starting treatment with erythropoiesis-stimulating agents (ESA, 80%) and phosphate binders (71%). Of the patients on ESAs, 52% were treated prior to dialysis initiation (62% in the subgroup with >6 months of predialysis nephrological care versus 38% in the ≤6 months group, P < 0.0001) and 48% began ESA treatment at the time of dialysis initiation. The use of beta-blockers was lower than expected in view of the comorbidities (24% of total sample, 16% as antihypertensive treatment and 8% as cardiovascular therapy).


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  		Table 2 Use of concomitant medications at haemodialysis initiation

 
The presence of comorbidities [mean of Charlson Index of 6.2 (SD 2.4)] resulted in a severely decreased quality of life when compared with the general Spanish population (Table 1). Over half of the patients (57%) had a Karnofsky score between 80 and 100. Younger patients had a better functional status [mean KS of 82 (SD 14) for patients <65 years] than the older patients [71 (16) for patients ≥65 years, P < 0.0005].

Blood chemistry
Table 3 summarizes the patients’ baseline blood chemistry values. A high proportion of diabetic patients had uncontrolled glycaemia (48% >126 mg/dl, 34% with HbA1c >7%), whereas LDL-C was mostly within the normal range and high-density lipoprotein (HDL)-cholesterol was below the normal range in one-third of cases. The nutritional status of the patients was quite poor (43% had albumin levels <3.5 g/dl) and the inflammation status was highly variable (SD 6.2 mg/dl for the C-reactive protein). The mean GFR prior to dialysis onset was 7.6 (SD 2.8) ml/min/1.73 m2 and the mean 24-h diuresis was 1602 (SD 920) ml.


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  		Table 3 Blood chemistry at baseline

 
Anaemia and mineral metabolism
A large proportion of patients were outside the EBPG targets for haematological parameters related to the management of anaemia (haemoglobin <11 g/dl in 59%). Ferritin and saturated transferrin levels were decreased in 31% and 39% of patients, respectively. Most patients were also outside the K/DOQI guideline target ranges for bone mineral markers (Table 4). Overall, only 6.7% of the patients were within the four K/DOQI target ranges at the same time. The population means were also outside the K/DOQI guideline target ranges for iPTH and phosphorus, but not for total albumin-adjusted calcium or Ca x P, probably due to the large percentage of patients with low total calcium levels.


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  		Table 4 Haematological and bone mineral markers parameters at baseline

 
Baseline haemodialysis characteristics
Baseline haemodialysis variables are detailed in Table 1. The majority of patients received three haemodialysis sessions per week with a mean of 3.6 h of dialysis per session. Similar proportions of patients had high-flux or low-flux membranes and similar proportions received low-molecular-weight or standard heparin. Vascular access in patients at the start of haemodialysis was achieved by using either catheter (46%) or arteriovenous fistula (AVF) (52%) and in a small proportion of patients using polytetrafluoroethylene AVF (2%).

Characteristics of the patients with initial vascular access via a catheter
The patients with initial vascular access via a permanent catheter were older and had worse nutritional status, more comorbidities (higher Charlson index) and worse residual renal function (lower 24-h diuresis) than patients with a temporary catheter or an AVF (Table 5). The subgroup with temporary catheters was characterized by greater use of low-molecular-weight heparin and a higher degree of anaemia, hypocalcaemia and hyperphosphataemia (Table 5).


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  		Table 5 Differences in clinical and sociodemographic characteristics of incident haemodialysis patients grouped by the type of initial vascular access (only those variables with significant differences with respect to AV fistula patients are displayed)

 
Characteristics of patients with late referral to the nephrologist
In the subgroup analyses, patients who were referred to the nephrologist <6 months before the start of dialysis had worse functional and nutritional status, a lower degree of dyslipidaemia and hypertension (and more recently diagnosed) and worse residual renal function (higher creatinine and lower 24-h diuresis) than patients who referred >12 months ago (Table 6). As expected, systemic aetiologies (e.g. myeloma and vasculitis) were also related to the late referral to the nephrologist. Anaemia, hyperferritinaemia and uncontrolled mineral metabolism (hypocalcaemia and hyperphosphataemia) were much more frequently observed in the late referral group. Vascular access was obtained via an AVF in only 25% of patients who were referred late compared with 52–64% in the other subgroups.


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  		Table 6 Differences in clinical and sociodemographic characteristics of incident haemodialysis patients grouped by duration of predialysis nephrological care (only those variables with significant differences with respect to >12 months patients are displayed)

 
Characteristics of patients with previous ischaemic cardiovascular disease
The presence of previous ischaemic cardiovascular disease in the incident dialysis population was related to all the classic cardiovascular risk factors in the general population (advanced age, male gender, former or current smoker, diabetes mellitus, history of dyslipidaemia or hypertension) except obesity (Table 7). It is notable that despite a higher percentage of dyslipidaemia and lower HDL-C levels, the mean total cholesterol was lower in the patients with previous cardiovascular disease. This inverse relationship was not due to the greater use of statins in the cardiovascular group (42% versus 58% in the non-cardiovascular groups). Table 7 also shows greater catheter use, worse residual renal function and nutritional status, and a lower degree of hyperphosphataemia in this subgroup of patients.


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  		Table 7 Differences in clinical and sociodemographic characteristics of incident haemodialysis patients grouped by the presence of previous ischaemic cardiovascular disease (only those variables with significant differences are displayed)

 


   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
References
 
ANSWER is the first large, prospective, observational study of incident haemodialysis patients in Spain, which will help to clarify, together with other recent ongoing studies in Europe (the Netherlands [7,8], France [10–12], Italy [13,14] and Sweden [15]) and North America (CHOICE [29], Wave-2 USRDS [30–32]), the risk factors associated with cardiovascular morbidity and mortality in these patients. The ANSWER study enrolled all consecutive incident haemodialysis patients, whereas most other haemodialysis studies have excluded patients who did not survive the first 3 months [7,14,29,31] or have included ‘prevalent’ patients (DOPPS [33], MAR [34]). Studies of ‘incident’ populations are needed to verify the previously described associations for ‘prevalent’ populations, because those studies suffered from the bias of not enrolling patients with higher cardiovascular risk, that is, those who die in the first months after dialysis onset.

The sociodemographic characteristics of our cohort are similar to those reported for other European incident populations. The mean age and percentage of patients older than 65 or 75 years in our sample are similar to those reported in other European countries [8–10,14]) and the USA [35].

About a quarter of the patients developed renal failure due to diabetic nephropathy. This figure is similar to that reported in other European studies [12,13,16,36–38]. The prevalence of vascular nephropathy in the present study is also similar to that reported in other Spanish and Italian studies [13,16], but it seems slightly lower than the prevalence reported from the Netherlands [8] or France [9,10,12]. Our results support the findings of López Revuelta and colleagues [16] that the aetiology of chronic kidney disease in European incident haemodialysis populations is different from the aetiology among the incident population in the USA, where diabetes and hypertension account for >70% of cases, compared with <50% in Europe.

Due to the high mean age of the study population and significant prevalence of comorbidities, the functional status was moderately affected, consistent with findings of previous Spanish studies in the incident haemodialysis population [38]. Interestingly, the functional status in our patients is better than that of incident patients in the UK of similar mean age [39,40], but is similar to that of American patients, who were an average of 10 years younger [41]. The gender distribution in both the UK and US samples was different from ours (more males in the UK and US samples), but the worse functional status of the UK sample may be related to the higher proportion of unplanned initiation of haemodialysis in that population (44–47%) [39,40]. The QoL results revealed severely affected physical and mental health, similar to previous reports of Spanish incident haemodialysis patients [42,43].

Regarding the use of catheter as first vascular access, we found fewer shunts than reported in the DOPPS study for Spain. This may be attributed to the differences among recruiting facilities [44,45]. The fact that there are many more facilities participating in the ANSWER study (147 compared with 20 in the DOPPS) probably provides a more confident estimate of the real situation of vascular access in Spain. Furthermore, our results are in agreement with previous studies in Spain, in which between 46% and 51% of incident patients were found not to have permanent AVF access [46,47], and this proportion has remained stable during the past few years [48].

Although a minimum nephrological follow-up of 6 months prior to haemodialysis onset is recommended, late referral has been reported for about a quarter of Spanish incident patients, similar to previous findings from other European countries [9,49,50]. The high proportion of catheter use in the late referral group, also described in DOPPS [51], highlights the need for early referral as far as possible. A shorter time of nephrologist follow-up has been associated with higher mortality in haemodialysis patients independent of catheter vascular access [52], indicating the presence of other negative factors in these patients. The worse clinical status at the onset of haemodialysis in the late referral subgroup may contribute to this phenomenon [53,54].

With respect to kidney function at haemodialysis onset in our patients, the GFR was lower in our patients compared with reports from previous studies in Spain and other European countries [49,50,55], and 8 in 10 patients were below the limit of 10 ml/min recommended by the K/DOQI guidelines [56]. These data suggest a delayed onset of haemodialysis in our settings. Initiation of haemodialysis above this limit may prolong survival according to the NECOSAD study [57]. Other haemodialysis quality indicators, such as the low initial eKt/V, also suggest inadequate haemodialysis onset although almost half the patients are using high-flux membranes.

About 10% of the population had history of neoplasia. This figure is a bit higher than that reported for the Spanish DOPPS cohort (6%), but agrees with the 9% of the EURO-DOPPS [36] prevalent patients and also with the 11% reported for the incident French population [10] (although that study considered only active neoplasia).

The antecedents of cardiovascular disease in our sample were, as expected, very common. The prevalence of ischaemic heart disease was similar to that in Italy, France and Sweden [11,14,15,58], but lower than that in the UK, Germany and the USA [58,35]. The prevalence of peripheral vascular disease was similar to that in Sweden and the USA [14,35], but lower than the prevalence in France, Germany, Italy and the UK [9,11,58]. The prevalence of heart failure was similar to that in France, Germany and Italy [9,58], but lower than the prevalence in the UK and the USA [58,35]. Finally, the prevalence of cerebrovascular disease was a little higher than or similar to that in Italy, France, Sweden and the USA [9,11,13,15,35]. The differences in these prevalences must be viewed with caution, as they may be related to different disease definitions or methods of collection.

With regard to the prevalence of classic cardiovascular risk factors, the majority of patients had uncontrolled hypertension, despite almost all patients receiving antihypertensive treatment. Diabetes affected one-third of our patients, similar to other European studies [12,15], and far from one-half in the USA [59,35]. Glycaemic control was poor, and 1 in 5 patients were obese. Both the proportion of obese patients and the mean BMI were highly consistent with the findings from almost all previously described incident European and North American populations [7,15,32,35,50,59]. However, malnutrition was less prevalent in our sample than in the Netherlands or Sweden [7,15]. This discordance is probably due to an underestimation of malnutrition by Spanish physicians, as one-third of our patients had low albumin levels. The high prevalence of other emergent cardiovascular risk factors (hyperhomocysteinaemia, hyperfibrinogenaemia and elevated lipoprotein (a)) in our sample with respect to the general Spanish population [60] agrees with previous results in maintenance [61] and incident [10] haemodialysis patients. Since this is a cross-sectional analysis, the causal relationship between all these findings and cardiovascular status cannot be verified. Future data will produce more reliable results regarding the predictive value of the collected variables.

Anaemia-related target ranges, which are strongly predictive of reduced mortality in chronic kidney disease [2,6], were achieved by a relatively low percentage of patients. Despite almost 1 in 2 patients receiving ESAs prior to haemodialysis onset, >50% were anaemic, and more than one-third had iron deficiency, which suggests incorrect ESA administration and insufficient correction of iron stores. Less than 1 in 10 patients were within the K/DOQI targets for all four bone and mineral metabolism parameters, iPTH being the most uncontrolled. These findings correlate with those from the NECOSAD study [7]. Data from prevalent populations indicate that the degree of control of bone mineral disease is not better after the onset of haemodialysis [62]. Studies of the recently available therapies (calcimimetics, calcium-free P-chelating agents or new vitamin D analogues) may help to resolve this issue in the near future.

With regard to the classic cardiovascular risk factors, the expected associations with previous smoking, dyslipidaemia, hypertension and diabetes were observed in patients with a history of cardiovascular disease. However, the cholesterol levels were lower in the group with cardiovascular disease, which could be related to the worse nutritional status in those patients.

This cohort study has some limitations. The non-random (but consecutive) patient selection may have resulted in some selection bias. However, the extended inclusion period and the fact that the final sample represents more than half of all incident Spanish patients during this period [27,28] support the validity of the recruited cohort. In addition, as enrolment at each site was stratified according to the incidence of haemodialysis in a reference population, the 2341 patients in the study were considered to be representative of the target population in Spain.

For the purposes of international comparisons, our study confirms that there are important differences in the prevalence of cardiovascular and mortality risk factors, especially with respect to North American populations. Spain has an extremely high rate of renal transplantation (47% of patients on renal replacement therapy in 2004 [28] versus 29% in the USA [63]). This should be taken into account when comparing the prospective cardiovascular morbidity and mortality results in the future.

In summary, the ANSWER study provides valuable new data, thus adding to our knowledge of the characteristics of incident haemodialysis patients in Spain and Europe. Most patients present at an advanced age and have hypertension, diabetes and previous cardiovascular disease. Their functional status is moderately affected, considering the high mean age. Our results also show that in the Spanish setting, haemodialysis is started too late and that patients are also referred too late to the nephrologist (late referral for 1 in 4 patients with diabetic and vascular nephropathy). Also, not enough effort was made to place a permanent AVF before haemodialysis onset in patients referred >6 months ago, and such efforts must be specially made in older and diabetic patients.

This study has also revealed an extremely high prevalence of emergent and uraemia-related cardiovascular risk factors and poor glycaemic control, low HDL-C, hypertension, anaemia, malnutrition, hypo- and hyperparathyroidism, hyperphosphataemia and hypo- and hypercalcaemia. These results reflect the need for improving the therapeutic management of incident dialysis patients before the onset of haemodialysis.



   Acknowledgments
 
This study was supported in part by a grant from Amgen, S.A., Spain. Writing assistance was supported by Amgen. The authors wish to thank all participating investigators of the ANSWER study: P. Abrigar; J. Aguilera; M.J. Aladrén; M. Alcalá; R. Alegre; M.A. Aliaga; J. Almirall; R. Alonso; R. Alvarez; R. Amador; M.L. Amoedo; B. Andrés; P. Angelet; A. Antolín; M. Arambarri; M.D. Arenas; A. Argoitia; M. Arranz; A. Arraque; G. Arribas; J. Arrieta; M.J. Arroyo; J. Arteaga; B. Aurrekoetxea; B. Avilés; Y. Aznar; F. Barbosa; G. Barril; M.A. Basterrechea; M. Belart; S. Beltran; G. Bernal; A. Bernat; M.E. Besada; A. Betriu; M.M. Biechy; A. Blanco; A. Blasco; L. Bolaños; B. Bonilla; A. Bordils; A. Botella; J.J. Bravo; M.T. Calderón; J. Calls; J. Calpe; C. Calvar; J.A. Calviño; E. Calvo; G. Camacho; A. Cardoso; P. Caro; M.A. Carretón; A. Cases; I. Castellano; E. Castellote; R. Causadias; M. Ceballos; J. Cebollada; S. Cerezo; M.C. Cid; M.T. Compte; J. Contreras; A. Covarsi; L. Craver; A. Crespo; J.M. Cruzado; A. Cubas; X. Cuevas; M. Cuxart; A.I. Díaz; C. Díaz; H. Díaz; J. Diego; M.L. Domínguez; C.A. Donapetry; V. Durán; S. Fabado; M.A. Fenollosa; E. Fernández; E.J. Fernández; J. Fernández; J.E. Fernández; M.A. Fernández; M.D. Fernández; N. Fontseré; J. Fort; A. Fraile; P. Fraile; R. Franquelo; E. Gago; M.J. Galán; A. Gallego; A. Gámez; C. Gámez; A. García; C. García; C.M. García; F. García; I. García; J. García; J.A. García; J.B. García; M. García; M.J. García; M.M. García; M.T. García; O. García; R. García; S.A. García; Z. García; E. Garrigós; R. Gauna; J.M. Gil; M.T. Gil; I. Gimeno; J.D. Giráldez; J.R. Gómez; M.A. Gonzalez; A. González; B. González; F.J. González; F.M. González; J. González; M. Goñi; R. Gota; M.C. Gracia; I. Granado; M. Granda; J. Grande; J.M. Graña; E. Gruss; I. Guerrero; C.S. Guervós; M.D. Güimil; A. Guzmán; M. Heral; M. Heras; J. Hernández; M.T. Hernández; J.A. Herrero; J.C. Herrero; C.J. Hornos; I. Iribar; J.M. Irrizu; M. Jiménez; P.J. Labrador; M. Lago; I. Lampreabe; B. León; R. Llópez; A. Llopis; J.M. Logroño; D. López; E. López; F. López; J. López; J.L. López; M. López; M.O. López; T. López; I. Lorenzo; J. Lorenzo; V. Lorenzo; M.A. Macia; L. Marcas; J. Marco; N. Marigliano; A. Marín; B. Martín; F. Martín; G. Martín; J. Martín; P. Martín; A. Martinez; P. Martínez; C. Massanet; M. Matas; P. Mateos; P. Mateos; J.M. Mauri; M.L. Medina; J.L. Miguel; I. Millán; E. Miranda; J. Mòdol; I. Moina; P. Molina; J. Montenegro; C. Montoyo; B. Moragrega; M.V. Moreno; R. Moreno; R. Mouzo; M.L. Muñiz; A.B. Muñoz; C. Muñoz; J.M. Muñoz; S. Muray; J. Naranjo; M. Naranjo; M. Navarro; M.J. Navarro; R. Novillos; J. Núñez; P. Oleo; J. Olivares; J.Á. Oliver; R. Ordoñez; M. Ortega; M.D. Ortí; J.M. Osorio; A. Otero; A. Palma; J.M. Pastor; J. Payán; B. Pazos; A. Pérez; C. Pérez; M.A. Pérez; R. Pérez; A. Peris; M. Picazo; M. Pifarré; M.D. Pino; V.C. Piñera; J.L. Pizarro; M. Pons; J.M. Portoles; M.M. Pousa; C. Pozo; M.C. Prados; M.D. Prados; M. Prieto; J. Prim; B. Ramos; C. Ramos; I. Ramos; N. Ramos; A. Rifà; B. Rincón; E.A. Rivas; R. Roca; A. Rodríguez; J.R. Rodríguez; M.I. Rodríguez; M.L. Rodríguez; P. Rodríguez; J. Romero; E. Rubio; A. Ruiz; A.M. Ruiz; J. Ruiz; J.E. Ruiz; P. Ruiz; R. Ruiz; C. Sánchez; E. Sánchez; F. Sánchez; I. Sánchez; M. Sánchez; M.C. Sánchez; M.D. Sánchez; O. Sánchez; P. Sánchez; D. Sánchez-Guisande; J. Sancho; R. Sans; C. Santamaría; F. Sastre; M. Serra; M. Serra; A. Serrano; M. Sevilla; T. Sierra; G. Silgado; J. Sobrado; A. Soldevila; J.M. Soler; S. Tallón; A. Tato; A. Toledo; F. Tornero; I. Torregrosa; G. Torres; J. Usón; J. Valdés; A. Valera; V. Valverde; M. Vera; F. Vidaur; J. Viladoms and M.T. Villaverde.

Conflict of interest statement. Fina Lladós and Javier Lozano are employees of AMGEN Inc. There is no other conflict of interest.



   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

  1. Pozzoni P, Del Vecchio L, Pontoriero G, et al. Long-term outcome in hemodialysis: morbidity and mortality. J Nephrol (2004) 17:S87–S95.[CrossRef][Web of Science][Medline]
  2. Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol (1998) 9(Suppl_12):16–23.[CrossRef]
  3. Hegarty J, Foley RN. Anaemia, renal insufficiency and cardiovascular outcome. Nephrol Dial Transplant (2001) 16(Suppl 1):102–104.[Abstract/Free Full Text]
  4. Goodkin DA, Mapes DL, Held PJ. The dialysis outcomes and practice patterns study (DOPPS): how can we improve the care of hemodialysis patients? Semin Dial (2001) 14:157–159.[CrossRef][Web of Science][Medline]
  5. Trespalacios FC, Taylor AJ, Agodoa LY, et al. Incident acute coronary syndromes in chronic dialysis patients in the United States. Kidney Int (2002) 62:1799–1805.[CrossRef][Web of Science][Medline]
  6. Stack AG, Bloembergen WE. Prevalence and clinical correlates of coronary artery disease among new dialysis patients in the United States: a cross-sectional study. J Am Soc Nephrol (2001) 12:1516–1523.[Abstract/Free Full Text]
  7. Merkus MP, Jager KJ, Dekker FW, et alThe NECOSAD Study Group. Predictors of poor outcome in chronic dialysis patients: the Netherlands Cooperative Study on the Adequacy of Dialysis. Am J Kidney Dis (2000) 35:69–79.[Web of Science][Medline]
  8. Noordzij M, Korevaar JC, Bos WJ, et al. Mineral metabolism and cardiovascular morbidity and mortality risk: peritoneal dialysis patients compared with haemodialysis patients. Nephrol Dial Transplant (2006) 21:2513–2520.[Abstract/Free Full Text]
  9. Jungers P, Choukroun G, Robino C, et al. Epidemiology of end-stage renal disease in the Ile-de-France area: a prospective study in 1998. Nephrol Dial Transplant (2000) 15:2000–2006.[Abstract/Free Full Text]
  10. Pernod G, Bosson JL, Golshayan D, et al. The Diamant Alpin Dialysis Cohort Study: clinico-biological characteristics and cardiovascular genetic risk profile of incident patients. J Nephrol (2004) 17:66–75.[CrossRef][Web of Science][Medline]
  11. Pernod G, Bosson JL, Golshayan D, et al. Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort. Kidney Int (2006) 69:1424–1430.[Web of Science][Medline]
  12. Villar E, Remontet L, Labeeuw M, et al. Effect of age, gender, and diabetes on excess death in end-stage renal failure. J Am Soc Nephrol (2007) 18:2125–2134.[Abstract/Free Full Text]
  13. Di Benedetto A, Marcelli D, D’Andrea A, et al. Risk factors and underlying cardiovascular diseases in incident ESRD patients. J Nephrol (2005) 18:592–598.[Web of Science][Medline]
  14. Locatelli F, Marcelli D, Conte F, et al. Survival and development of cardiovascular disease by modality of treatment in patients with end-stage renal disease. J Am Soc Nephrol (2001) 12:2411–2417.[Abstract/Free Full Text]
  15. Honda H, Qureshi AR, Heimbürger O, et al. Serum albumin, C-reactive protein, interleukin 6, and fetuin a as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. Am J Kidney Dis (2006) 47:139–148.[CrossRef][Web of Science][Medline]
  16. López Revuelta K, Saracho R, García López F, et al. Informe de diálisis y trasplante año 2001 de la Sociedad Española de Nefrología y Registros Autonómicos. Nefrología (2004) 24:21–33.[Medline]
  17. Altisent R, Córdoba R, Martin JM. Criterios operativos para le prevención del alcoholismo. Med Clin (Barc) (1992) 99:584–588.[Medline]
  18. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis (1987) 40:373–383.[CrossRef][Web of Science][Medline]
  19. Charlson M, Szatrowski TP, Peterson J, et al. Validation of a combined comorbidity index. J Clin Epidemiol (1994) 47:1245–1251.[CrossRef][Web of Science][Medline]
  20. Ware J, Snow KK, Kosinski M, et al. SF-36 Health Survey: Manual and Interpretation Guide (1993) Boston, MA: The Health Institute, New England Medical Center.
  21. Alonso J, Prieto L, Antó JM. La versión española del SF-36 Health Survey (Cuestionario de Salud SF-36): un instrumento para la medida de los resultados clínicos. Med Clin (Barc) (1995) 104:771–776.[Medline]
  22. Daugirdas JT. Simplified equations for monitoring Kt/V, PCRn, eKt/V, and ePCRn. Adv Ren Replace Ther (1995) 2:295–304.[Medline]
  23. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration equation from serum creatinine: a new prediction equation. Ann Intern Med (1999) 130:461–470.[Abstract/Free Full Text]
  24. National Kidney Foundation (NKF) K/DOQI Guidelines. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis (2003) 42:S7–S201.[CrossRef][Web of Science]
  25. Locatelli F, Aljama P, Bárány P, et al. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant (2004) 19(Suppl 2):ii1–ii47.[Free Full Text]
  26. Bland JM, Altman DG. Multiple significance tests: the Bonferroni method. BMJ (1995) 310:170.[Free Full Text]
  27. Sociedad Española deNefrología-Grupo deRegistros deEnfermos Renales. Informe de Diálisis y Trasplante, 2003; SEN 2004.
  28. Sociedad Española deNefrología-Grupo deRegistros deEnfermos Renales. Informe de Diálisis y Trasplante, 2004; SEN 2005.
  29. Miskulin DC, Meyer KB, Athienites NV, et al. Comorbidity and other factors associated with modality selection in incident dialysis patients: the CHOICE Study. Choices for Healthy Outcomes in Caring for End-Stage Renal Disease. Am J Kidney Dis (2002) 39:324–336.[Web of Science][Medline]
  30. Ishani A, Collins AJ, Herzog CA, et al. Septicemia, access and cardiovascular disease in dialysis patients: the USRDS Wave 2 study. Kidney Int (2005) 68:311–318.[CrossRef][Web of Science][Medline]
  31. Li Z, Lacson E Jr, Lowrie EG, et al. The epidemiology of systolic blood pressure and death risk in hemodialysis patients. Am J Kidney Dis (2006) 48:606–615.[CrossRef][Web of Science][Medline]
  32. Wolf M, Shah A, Gutierrez O, et al. Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int (2007) 72:1004–1013.[CrossRef][Web of Science][Medline]
  33. Rayner HC, Pisoni RL, Bommer J, et al. Mortality and hospitalization in haemodialysis patients in five European countries: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant (2004) 19:108–120.[Abstract/Free Full Text]
  34. Portolés J, López-Gómez JM, Aljama P. Riesgo cardiovascular en hemodiálisis en España: prevalencia, pautas de actuación y objetivos (estudio MAR). Nefrologia (2005) 25:297–306.[Web of Science][Medline]
  35. United States Renal Data System. (2006) 2006 Annual Data Report. National Institutes of Health, National Institute of Diabetes & Digestive & Kidney Diseases, Division of Kidney, Urologic, & Hematologic Diseases.
  36. Cruz PM, Piera L, Bragg-Gresham JL, et al. Results of the international hemodialysis study DOPPS in Spain and Europe. Nefrologia (2003) 23:437–443.[Web of Science][Medline]
  37. Hecking E, Bragg-Gresham JL, Rayner HC, et al. Haemodialysis prescription, adherence and nutritional indicators in five European countries: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant (2004) 19:100–107.[Abstract/Free Full Text]
  38. Valdés C, García-Mendoza M, Rebollo P, et al. Mental health at the third month of haemodialysis as a predictor of short-term survival. Nephrol Dial Transplant (2006) 21:3223–3230.[Abstract/Free Full Text]
  39. McKane W, Chandna SM, Tattersall JE, et al. Identical decline of residual renal function in high-flux biocompatible hemodialysis and CAPD. Kidney Int (2002) 61:256–265.[CrossRef][Web of Science][Medline]
  40. Chandna SM, Schulz J, Lawrence C, et al. Is there a rationale for rationing chronic dialysis? A hospital based cohort study of factors affecting survival and morbidity. BMJ (1999) 318:217–223.[Abstract/Free Full Text]
  41. Kimmel PL, Peterson RA, Weihs KL, et al. Psychologic functioning, quality of life, and behavioral compliance in patients beginning hemodialysis. J Am Soc Nephrol (1996) 7:2152–2159.[Abstract]
  42. Sanz Guajardo D, Orte L, Gómez-Campderá F, et alINESIR Group. Calidad de vida en los pacientes con insuficiencia renal cronica. Influencia de la intervencion precoz del nefrologo y de la consulta predialisis. Nefrologia (2006) 26(Suppl 3):56–65.[Web of Science][Medline]
  43. López Revuelta K, García López FJ, de Alvaro Moreno F, et al. Perceived mental health at the start of dialysis as a predictor of morbidity and mortality in patients with end-stage renal disease (CALVIDIA Study). Nephrol Dial Transplant (2004) 19:2347–2353.[Abstract/Free Full Text]
  44. Pisoni RL, Young EW, Dykstra DM, et al. Vascular access use in Europe and the United States: results from the DOPPS. Kidney Int (2002) 61:305–316.[CrossRef][Web of Science][Medline]
  45. Rodríguez Hernández JA, López Pedret J, Piera L. El acceso vascular en España: análisis de su distribución, morbilidad y sistemas de monitorización. Nefrologia (2001) 21:45–51.[Medline]
  46. Rodríguez JA, Armadans L, Ferrer E, et al. The function of permanent vascular access. Nephrol Dial Transplant (2000) 15:402–408.[Abstract/Free Full Text]
  47. Rodríguez JA, López J, Piera L. El acceso vascular en España: análisis de su distribución, morbilidad y sistemas de monitorización. Nefrología (2001) 21:45–51.[Medline]
  48. RMRC: Informe Estadistic 2000. (2001) Servei Català de la Salut. Departament de Sanitat i Seguretat Social. Barcelona.
  49. Valderrábano F, Hörl WH, Macdougall IC, et al. PRE-dialysis survey on anaemia management. Nephrol Dial Transplant (2003) 18:89–100.[Abstract/Free Full Text]
  50. Gómez-Campderá FJ, Orte L, Aguilar MD, et alINESIR Group. Situación clínica del paciente en el momento de iniciar diálisis. Estudio INESIR. Nefrologia (2006) 26(Suppl 3):12–18.[Medline]
  51. Rayner HC, Besarab A, Brown WW, et al. Vascular access results from the Dialysis Outcomes and Practice Patterns Study (DOPPS): performance against Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines. Am J Kidney Dis (2004a) 44(Suppl 2):S22–S26.[CrossRef][Web of Science]
  52. Lorenzo V, Martn M, Rufino M, et al. Predialysis nephrologic care and a functioning arteriovenous fistula at entry are associated with better survival in incident hemodialysis patients: an observational cohort study. Am J Kidney Dis (2004) 43:999–1007.[CrossRef][Web of Science][Medline]
  53. Ifudu O, Dawood M, Homel P, et al. Excess morbidity in patients starting uremia therapy without prior care by a nephrologist. Am J Kidney Dis (1996) 28:841–845.[Web of Science][Medline]
  54. Roubicek C, Brunet P, Huiart L, et al. Timing of nephrology referral: influence on mortality and morbidity. Am J Kidney Dis (2000) 36:35–41.[CrossRef][Web of Science][Medline]
  55. Castellano I, Gallego S, Labrador PJ, et al. Comienzo de tratamiento renal sustitutivo en la provincia de Caceres. Nefrologia (2006) 26:379–381.[Web of Science][Medline]
  56. National Kidney Foundation. NKF-K/DOQI Clinical Practice Guidelines for Hemodialysis Adequacy: update 2000. Am J Kidney Dis (2001) 37(Suppl 1):S7–S64.[Web of Science][Medline]
  57. Korevaar JC, Jansen MA, Dekker FW, et alNetherlands Cooperative Study on the Adequacy of Dialysis Study Group. When to initiate dialysis: effect of proposed US guidelines on survival. Lancet (2001) 358:1046–1050.[CrossRef][Web of Science][Medline]
  58. Locatelli F, Pisoni RL, Combe C, et al. Anaemia in haemodialysis patients of five European countries: association with morbidity and mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant (2004) 19:121–132.[Abstract/Free Full Text]
  59. Longenecker JC, Coresh J, Powe NR, et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: the CHOICE Study. J Am Soc Nephrol (2002) 13:1918–1927.[Abstract/Free Full Text]
  60. Manresa JM, Zamora A, Tomás M, et al. Relationship of classical and non-classical risk factors with genetic variants relevant to coronary heart disease. Eur J Cardiovasc Prev Rehabil (2006) 13:738–744.[CrossRef][Medline]
  61. Bostom AG, Shemin D, Verhoef P, et al. Elevated fasting total plasma homocysteine levels and cardiovascular disease outcomes in maintenance dialysis patients. A prospective study. Arterioscler Thromb Vasc Biol (1997) 17:2554–2558.[Abstract/Free Full Text]
  62. Young EW, Akiba T, Albert JM, et al. Magnitude and impact of abnormal mineral metabolism in hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis (2004) 44(Suppl 2):34–38.[CrossRef][Medline]
  63. Foley RN, Collins AJ. End-stage renal disease in the United States: an update from the United States Renal Data System. J Am Soc Nephrol (2007) 18:2644–2648.[Abstract/Free Full Text]
Received for publication: 21.12.07
Accepted in revised form: 22. 7.08


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