Naarden, Netherlands
Naarden, Netherlands

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Bos W.J.W.,St Antonius Hospital | Van Manen J.G.,University of Twente | Boeschoten E.W.,Hans Mak Institute | Dekker F.W.,Leiden University
Journal of Hypertension | Year: 2010

Background: SBP is a potent predictor of mortality. However, in hemodialysis populations, the relation between SBP and mortality is a matter of debate. In hemodialysis patients, low SBP rather than high SBP has been related to mortality. It has been suggested that this inverse relationship is 'normalized' in dialysis patients with a low mortality risk and that short-term and long-term effects of SBP might differ. Design: We analyzed the relationship of mortality and SBP in 1111 incident hemodialysis patients participating in the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) cohort. Long-term and short-term effects were studied in patients with (n = 452) and without (n = 659) cardiovascular comorbidity. Results: Maximal follow-up was 7.5 years; 477 patients died. Two-year mortality rate was 44 and 20% in the groups with and without cardiovascular comorbidity, respectively. Both in the whole group and in both subpopulations, low SBP was associated with an increased mortality. The increased mortality risk associated with low SBP was especially observed as a short-term effect (6 months). In neither group did we observe a significant long-term effect between SBP and mortality. Conclusion: Our data do not support the hypothesis that the inverse relation between SBP and mortality is 'normalized' in a dialysis population with a low absolute mortality risk. Neither do our data support the hypothesis that elevated SBP increases mortality risk in the long-term. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Ocak G.,Leiden University | Rotmans J.I.,Leiden University | Vossen C.Y.,Leiden University | Vossen C.Y.,University Utrecht | And 4 more authors.
BMC Nephrology | Year: 2013

Background: There are only a few risk factors known for primary patency loss in patients with an arteriovenous graft or fistula. Furthermore, a limited number of studies have investigated the association between arteriovenous access modality and primary patency loss and mortality. The aim of this study was to investigate risk factors for patency loss and to investigate the association between graft versus fistula use and outcomes (patency loss and mortality). Methods. We prospectively followed 919 incident hemodialysis patients and calculated hazard ratios (HRs) for putative risk factors of primary patency loss using Cox regression. Furthermore, HRs were calculated to study the association between graft versus fistula use and two-year primary patency loss and two-year mortality. Results: Cardiovascular disease, prior catheter use, lowest tertile of albumin, highest tertile of hsCRP, and lowest tertile of fetuin-A were associated with primary patency loss in both patients with grafts and fistulas. Increased age, female sex, and diabetes mellitus were only associated with primary patency loss in patients with a fistula. We did not observe an association between primary patency loss and BMI, residual GFR, levels of calcium, phosphorus, and total cholesterol. Furthermore, graft use as compared with fistula use was associated with an 1.4-fold (95% CI 1.0-1.9) increased risk of primary patency loss and with an 1.5-fold(95% CI 1.0-2.2) increased mortality risk. Conclusion: Cardiovascular disease, prior catheter use, albumin, hsCRP, and fetuin-A are risk factors for patency loss. Graft use as compared with fistula use was associated with an increased risk of patency loss and mortality. © 2013 Ocak et al.; licensee BioMed Central Ltd.


Van Diepen M.,Leiden University | Schroijen M.A.,Leiden University | Dekkers O.M.,Leiden University | Rotmans J.I.,Leiden University | And 2 more authors.
PLoS ONE | Year: 2014

Background: While some prediction models have been developed for diabetic populations, prediction rules for mortality in diabetic dialysis patients are still lacking. Therefore, the objective of this study was to identify predictors for 1-year mortality in diabetic dialysis patients and use these results to develop a prediction model. Methods: Data were used from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a multicenter, prospective cohort study in which incident patients with end stage renal disease (ESRD) were monitored until transplantation or death. For the present analysis, patients with DM at baseline were included. A prediction algorithm for 1- year all-cause mortality was developed through multivariate logistic regression. Candidate predictors were selected based on literature and clinical expertise. The final model was constructed through backward selection. The model's predictive performance, measured by calibration and discrimination, was assessed and internally validated through bootstrapping. Results: A total of 394 patients were available for statistical analysis; 82 (21%) patients died within one year after baseline (3 months after starting dialysis therapy). The final prediction model contained seven predictors; age, smoking, history of macrovascular complications, duration of diabetes mellitus, Karnofsky scale, serum albumin and hemoglobin level. Predictive performance was good, as shown by the c-statistic of 0.810. Internal validation showed a slightly lower, but still adequate performance. Sensitivity analyses showed stability of results. Conclusions: A prediction model containing seven predictors has been identified in order to predict 1-year mortality for diabetic incident dialysis patients. Predictive performance of the model was good. Before implementing the model in clinical practice, for example for counseling patients regarding their prognosis, external validation is necessary. © 2014 van Diepen et al.


De Jager D.J.,Leiden University | Voormolen N.,Leiden University | Dekker F.W.,Leiden University | Boeschoten E.W.,Hans Mak Institute | Grootendorst D.C.,Leiden University
Nephrology Dialysis Transplantation | Year: 2011

Objective. The objective of the study was to estimate the association between time of referral and survival during dialysis in diabetics and patients aged < 70 years.Design, setting and subjects. This study was a prospective follow-up study in 1438 incident dialysis patients (19962004, 62% male, 60 ± 15 years) in The Netherlands.Main outcome measures. Referral (time between first pre-dialysis visit to a nephrologist and dialysis initiation) was classified as: late (< 3 months), early (312 months) or very early (< 12 months). All-cause mortality risk within the first year of dialysis was calculated [HR (95% confidence interval, CI), adjusted for age, sex and primary kidney disease (PKD)]. Additive interaction between time of referral and diabetes mellitus (adjusted for age and sex) or age (adjusted for sex and PKD) was assessed by synergy index [S (95% CI)].Results. Thirty-two percent were late referred, 12% early and 56% very early; 21% had diabetes; and 30% were < 70 years. Early and late referrals were associated with increased mortality compared with very early referral [HRadjearly: 1.5 (1.0, 2.4), late: 1.8 (1.3, 2.5)]. A similar trend was observed in diabetics and non-diabetics. However, no interaction between time of referral and diabetes was present [Slate 0.8 (0.4, 1.9), Searly 1.2 (0.4, 3.6)]. Likewise, in patients aged < 70 and < 70 years, time of referral was associated with increased mortality, without interaction [Slate 0.9 (0.4, 1.8), Searly 0.8 (0.3, 2.0)].Conclusion. Late referral is associated with increased mortality in the first year of dialysis. Diabetes or high age does not have an additional worsening effect, implying that timely referral is important in future dialysis patients irrespective of diabetes or high age. © The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.2011Oxford University Press. © The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.


Jansen D.L.,Netherlands Institute for Health Services Research | Rijken M.,Netherlands Institute for Health Services Research | Heijmans M.,Netherlands Institute for Health Services Research | Boeschoten E.W.,Hans Mak Institute
Psychology and Health | Year: 2010

Compared to healthy people, end-stage renal disease (ESRD) patients participate less in paid jobs and social activities. This study explored the perceived autonomy, state self-esteem and labour participation in ESRD patients on dialysis, and the role illness and treatment perceptions play in these concepts. Patients completed questionnaires at home or in the dialysis centre (N = 166). Data were analysed using bivariate and multivariate analyses. Labour participation among dialysis patients was low, the average autonomy levels were only moderate, and the average self-esteem level was rather high. On the whole, positive illness and treatment perceptions were associated with higher autonomy and self-esteem, but not with labour participation. Multiple regression analyses demonstrated that illness and treatment perceptions explained 18 to 27% of the variance in autonomy and self-esteem. Perceptions of personal control, less impact of the illness and treatment, and less concern were important predictors. Our results indicate that dialysis patients' beliefs about their illness and treatment play an important role in their perceived autonomy and self-esteem. Stimulating positive (realistic) beliefs and altering maladaptive beliefs might contribute to a greater sense of autonomy and self-esteem, and to social participation in general. Interventions focusing on these beliefs may assist patients to adjust to ESRD. © 2010 Taylor & Francis.


Drechsler C.,Leiden University | Drechsler C.,University of Würzburg | Verduijn M.,Leiden University | Pilz S.,Medical University of Graz | And 6 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2011

Background and objectives Serum alkaline phosphatase (AP) is associated with vascular calcification and mortality in hemodialysis patients, but AP derives from various tissues of origin. The aim of this study was to assess the effect of bone-specific AP (BAP) on morbidity and mortality in dialysis patients. Design, setting, participants, & measurements From a prospective cohort study of incident dialysis patients in The Netherlands, all patients with measured BAP at 12 months after the start of dialysis (baseline) were included in the analysis (n = 800; mean age, 59 ± 15 years; mean BAP = 18 ± 13 U/L). By Cox regression analyses, we assessed the impact of BAP levels on short-term mortality (6 months) and longer-term mortality (4-year follow-up). Results High levels of BAP strongly affected short-term mortality. After adjustment for confounders, patients in the highest BAP tertile had a 5.7-fold increased risk of death within 6 months compared with patients in the lowest tertile. The effect applied to both cardiovascular and noncardiovascular mortality. Furthermore, high levels of BAP were associated with increased cardiovascular mortality in the longer term. In comparison with total AP, the effect sizes related to clinical outcomes were much higher for BAP. Conclusions High levels of BAP were strongly associated with short-term mortality in dialysis patients, pointing out the important impact of bone turnover. Longitudinal assessments of BAP may be useful for the treatment monitoring in clinical practice in dialysis patients. © 2011 by the American Society of Nephrology.


Hoogeveen E.K.,Robert Bosch GmbH | Halbesma N.,Leiden University | Rothman K.J.,Rti International | Stijnen T.,Leiden University | And 4 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2012

Background and objectives Many studies show that obesity in dialysis patients is not strongly associated with mortality but not whether this modest association is constant over age. This study investigated the extent to which the relation of body mass index (BMI) and mortality differs between younger and older dialysis patients. Design, setting, participants, & measurements Adult dialysis patients were prospectively followed from their first dialysis treatment for 7 years or until death or transplantation. Patients were stratified by age (<65 or ≥65 years) and baseline BMI (<20, 20-24 [reference], 25-29, and ≥30 kg/m 2). Results The study sample included 984 patients younger than 65 years and 765 patients 65 years or older; cumulative survival proportions at end of follow-up were 50% and 16%. Age-standardized mortality rate was 1.7 times higher in obese younger patients than those with normal BMI, corresponding to an excess rate of 5.2 deaths/100 patient-years. Mortality rates were almost equal between obese older patients and those with normal BMI. Excess rates of younger and older patients with low compared with normal BMI were 8.7 and 1.1 deaths/100 patient-years. After adjustment for age, sex, smoking, comorbidity, and treatment modality, hazard ratios by increasing BMI were 2.00,1,0.95, and 1.57 for younger patients and 1.07,1, 0.88, and 0.91 for older patients, implying that obesity is a 1.7-fold (95% confidence interval, 1.1- to 2.9-fold) stronger risk factor in younger than older patients. Conclusions In contrast to older dialysis patients, younger patients with low or very high BMI had a substantially elevated risk for death. © 2012 by the American Society of Nephrology.


Kolesnyk I.,University of Amsterdam | Noordzij M.,University of Amsterdam | Dekker F.W.,Leiden University | Boeschoten E.W.,Hans Mak Institute | Krediet R.T.,University of Amsterdam
Peritoneal Dialysis International | Year: 2011

Background: Many studies have shown the renoprotective effect of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) in patients with chronic kidney disease stages I-IV. Two randomized controlled trials (RCTs) showed a positive effect of AII inhibitors on residual glomerular filtration rate (rGFR) in peritoneal dialysis (PD) patients. However, these studies were small and were performed in a highly selected group of PD patients. Our aim was to confirm the above findings in a larger number of prospectively followed PD patients. Methods: First we analyzed the time course of decline of rGFR in 452 incident PD patients that were not anuric at the start of dialysis and that had structured follow-up data, with measurements at 3, 6, 12, 18, 24, 30, and 36 months after the start of dialysis. Changes in rGFR over time were analyzed with a linear mixed model for repeated measures. In addition, Cox regression models were used to estimate the risk of developing anuria. In a second approach, we aimed to repeat the above analyses in a selected group of patients that theoretically could have been randomized and therefore resembled the population studied in the 2 mentioned RCTs. In this group the follow-up was restricted to 1 year. Results: 201 patients were treated with ACEi/ARBs and 251 did not take these drugs at the start of PD. More patients from the treated group had diabetes and used more antihypertensive medications. The time course of decline of rGFR was not different between the 2 groups over the 3 years of PD treatment (p = 0.52). Less than 25% of patients from each group became anuric and there was no difference in time to development of complete anuria between the treated and untreated groups. In the second approach, 130 patients were included: 37 were treated with ACEi/ARBs and 93 were not. Again, no difference was found between the 2 groups with respect to the rate of decline of rGFR and time of anuria development. Conclusion: Our findings are not in line with the results of previous RCTs. The biggest limitation of observational studies is the inability to avoid confounding by indication. However, a RCT in such a setting also does not give a reliable answer. Given all the benefits of ACEi/ARBs, the medications should not be withheld from PD patients. However, their renoprotective effects may often be overruled by other factors influencing the time course of rGFR. © 2011 International Society for Peritoneal Dialysis.


Michels W.M.,University of Amsterdam | Michels W.M.,Leiden University | Verduijn M.,Leiden University | Grootendorst D.C.,Leiden University | And 4 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2011

Background and objectives: We compared the decline of RRF in patients starting dialysis on APD with those starting on CAPD, because a faster decline on APD has been suggested. Design, setting, participants, & measurements: NECOSAD patients starting dialysis on APD or CAPD with RRF at baseline were included and followed for 3 years. Residual GFR (rGFR) was the mean of urea and creatinine clearances. Differences in yearly decline of rGFR were estimated in analyses with linear repeated measures models, whereas the risk of complete loss of RRF was estimated by calculating hazard ratios (HRs) for APD compared with CAPD. As-treated (AT) and intention-to-treat (ITT) designs were used. All of the analyses were adjusted for age, gender, comorbidity, and primary kidney disease and stratified according to follow-up and mean baseline GFR. Results: The 505 CAPD and 78 APD patients had no major baseline differences. No differences were found in the analyses on yearly decline of rGFR. APD patients did have a higher risk of losing RRF in the first year (ITT crude HR 2.43 [confidence interval 95%, 1.48 to 4.00], adjusted 2.66 [1.60 to 4.44]; AT crude 1.89 [1.04 to 3.45], adjusted 2.15 [1.16 to 3.98]). The higher risk of losing all RRF was most pronounced in patients with the highest rGFR at baseline (ITT; crude 3.91 [1.54 to 9.94], adjusted 1.85 to 14.17). Conclusions: The risk of losing RRF is higher for patients starting dialysis on APD compared with those starting on CAPD, especially in the first year. Copyright © 2011 by the American Society of Nephrology.


Schroijen M.A.,Leiden University | Dekkers O.M.,Leiden University | Grootendorst D.C.,Leiden University | Noordzij M.,Academic Medical Center Amsterdam | And 4 more authors.
BMC Nephrology | Year: 2011

Background: On dialysis, survival among patients with diabetes mellitus is inferior to survival of non-diabetic patients. We hypothesized that patients with diabetes as primary renal disease have worse survival compared to patients with diabetes as a co-morbid condition and aimed to compare all-cause mortality between these patient groups. Methods. Data were collected from the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a multicenter, prospective cohort study in which new patients with end stage renal disease (ESRD) were monitored until transplantation or death. Patients with diabetes as primary cause of ESRD were compared with patients with diabetes as co-morbid condition and both of these patient groups were compared to patients without diabetes. Analysis was performed using Kaplan-Meier and Cox regression. Results: Fifteen % of the patients had diabetic nephropathy as primary renal disease (N = 281); 6% had diabetes as co-morbid condition (N = 107) and 79% had no diabetes (N = 1465). During follow-up 42% of patients (N = 787) died. Compared to non-diabetic patients, mortality risk was increased for both patients with diabetes as primary renal disease HR: 1.9 (95% CI 1.6, 2.3) and for patients with diabetes as co-morbid condition HR: 1.7 (95% CI 1.3, 2.2). Mortality was not significantly higher in patients with diabetes as primary renal disease compared to patients with diabetes as co-morbid condition (HR 1.06; 95% CI 0.79, 1.43). Conclusions: This study in patients with ESRD showed no survival difference between patients with diabetes as primary renal disease and patients with diabetes as a co-morbid condition. Both conditions were associated with increased mortality risk compared to non-diabetic patients. © 2011 Schroijen et al; licensee BioMed Central Ltd.

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