Marion Verduijn

Leiden University Medical Centre, Leyden, South Holland, Netherlands

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Publications (35)139.82 Total impact

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    ABSTRACT: The protein C pathway plays an important role in the maintenance of endothelial barrier function and in the inflammatory and coagulant processes that are characteristic of patients on dialysis. We investigated whether common single nucleotide variants (SNV) in genes encoding protein C pathway components were associated with all-cause 5 years mortality risk in dialysis patients. Single nucleotides variants in the factor V gene (F5 rs6025; factor V Leiden), the thrombomodulin gene (THBD rs1042580), the protein C gene (PROC rs1799808 and 1799809) and the endothelial protein C receptor gene (PROCR rs867186, rs2069951, and rs2069952) were genotyped in 1070 dialysis patients from the NEtherlands COoperative Study on the Adequacy of Dialysis (NECOSAD) cohort) and in 1243 dialysis patients from the German 4D cohort. Factor V Leiden was associated with a 1.5-fold (95% CI 1.1-1.9) increased 5-year all-cause mortality risk and carriers of the AG/GG genotypes of the PROC rs1799809 had a 1.2-fold (95% CI 1.0-1.4) increased 5-year all-cause mortality risk. The other SNVs in THBD, PROC, and PROCR were not associated with 5-years mortality. Our study suggests that factor V Leiden and PROC rs1799809 contributes to an increased mortality risk in dialysis patients.
    Full-text · Article · May 2014 · PLoS ONE
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    ABSTRACT: Factors explaining the association between impaired kidney function and venous thrombosis have not been identified so far. The aim of our study was to determine whether the association between impaired kidney function and venous thrombosis can be explained by the concurrent presence of genetic or acquired venous thrombosis risk factors. The glomerular filtration rate was estimated (eGFR) in 2473 venous thrombosis patients and 2936 controls from a population-based case-control study. Kidney function was grouped into 6 categories based on percentiles of the eGFR in the controls (>50th percentile [reference], 10th-50th percentile, 5th-10th percentile, 2.5th-5th percentile, 1st-2.5th percentile, and <1st percentile). Several hemostatic factors showed a procoagulant shift with decreasing kidney function in controls, most notably factor VIII and von Willebrand factor (VWF). As compared with eGFR> 50th percentile, factor VIII levels (adjusted mean difference of 60 IU/dl for the <1st eGFR percentile category) and VWF levels (adjusted mean difference of 60 IU/dl for the <1st eGFR percentile category) increased with each percentile category. The ORs for venous thrombosis similarly increased across the categories from 1.1 (95%CI,0.9-1.3) for the 10th-50th percentile to 3.7 (95%CI,2.4-5.7) for the <1st percentile category. Adjustment for factor VIII or von Willebrand factor attenuated these ORs indicating an effect of eGFR on thrombosis through these factors. Adjustments for other risk factors for venous thrombosis did not affect the ORs. Impaired kidney function affects venous thrombosis risk via concurrently raised factor VIII and von Willebrand factor levels.
    Preview · Article · Nov 2013 · Circulation
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    ABSTRACT: 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.
    Full-text · Article · Apr 2013 · BMC Nephrology
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    ABSTRACT: Although an association between venous thrombosis and chronic kidney disease has recently been established, it is unknown which patients with chronic kidney disease are most likely to benefit from thromboprophylaxis. The aim of this study was to assess the association between venous thrombosis and chronic kidney disease in combination with arterial thrombosis, malignancy, surgery and thrombophilia to identify high-risk groups as a basis for personalized prevention. This study included 2473 consecutive patients with first venous thrombosis and 2936 controls from a case–control study (the MEGA study). Moderately decreased kidney function (eGFR 30–60 mL min−1) was associated with a 2.5-fold (95% CI, 1.9–3.4) increased risk and severely decreased kidney function (eGFR < 30 mL min−1) was associated with a 5.5-fold (95% CI 1.8–16.7) increased risk of venous thrombosis, compared with those with normal kidney function (eGFR > 90 mL min−1). The risk of venous thrombosis was additionally increased for moderately and severely reduced kidney function in combination with arterial thrombosis (odds ratio, 4.9; 95% CI, 2.2–10.9), malignancy (5.8; 95% CI, 2.8–12.1), surgery (14.0; 95%, CI 5.0–39.4), immobilization (17.1; 95% CI, 6.8–43.0) or thrombophilia (odds ratios, 4.3–9.5), with particularly high risks when three or more risk factors were present (odds ratio, 56.3; 95% CI, 7.6–419.3). Decreased kidney function is associated with an increased risk of venous thrombosis. The risk increased substantially in the presence of one or more other risk factors for thrombosis.
    No preview · Article · Feb 2013 · Journal of Thrombosis and Haemostasis
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    ABSTRACT: Background: The risk of venous thrombosis associated with major illnesses is not well known, and neither is the risk associated with the combined effect of immobilization and thrombophilia. The aim of this study was to assess the effect on the development of venous thrombosis of several major illnesses in combination with immobilization, body mass index, and thrombophilia, to identify high-risk groups that may provide a basis for personalized prevention. Methods: This study included 4311 consecutive patients with a first episode of venous thrombosis, and 5768 controls from a case-control study (MEGA study). We calculated odds ratios (ORs) for venous thrombosis for patients with a self-reported history of major illnesses. Results: Venous thrombosis risk was increased for all investigated major illnesses: liver disease, OR 1.7 (95% confidence interval [CI]1.0-2.9); kidney disease, OR 3.7 (95% CI 2.3-5.9); rheumatoid arthritis, OR 1.5 (95% CI 1.2-1.9); multiple sclerosis, OR 2.4 (95% CI 1.3-4.3); heart failure, OR 1.7 (95% CI 1.2-2.3); hemorrhagic stroke, OR 4.9 (95% CI 2.4-9.9); arterial thrombosis, OR 1.5 (95% CI 1.2-1.8); and the presence of any of the above major illnesses, OR 1.7 (95% CI 1.5-1.9). Combinations of major illnesses with immobilization and increased factor VIII (OR 79.9; 95% CI 33.2-192.2), increased FIX (OR 35.3; 95% CI 14.2-87.8), increased von Willebrand factor (OR 88.0; 95% CI 33.9-228.3), FV Leiden (OR 84.2; 95% CI 19.5-363.6), and blood group non-O (OR 53.1; 95% CI 30.9-91.4) were associated with increased venous thrombosis risks. Conclusions: All of the major illnesses reported here were associated with an increased risk of venous thrombosis. These risks were most pronounced at the time of immobilization or in the presence of thrombophilia.
    Full-text · Article · Oct 2012 · Journal of Thrombosis and Haemostasis
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    ABSTRACT: Objective: Depressive symptoms seem to pose a risk factor for mortality among patients on dialysis. It is currently unknown whether the association is only short-lived and whether associations over time depend on specific causes of mortality. Methods: In a prospective nationwide cohort study, 1528 patients with end-stage renal disease starting on dialysis completed the Mental Health Inventory. Patients were observed up to 5 years or until the end of follow-up in April 2011. Cox regression analyses were used to calculate associations between depressive symptoms and short-term (0-6 months), medium-term (6-24 months), or long-term (24-60 months) cardiovascular and noncardiovascular mortality. Results: The adjusted hazard ratio (HR) was 1.43 (95% confidence interval [CI] = 1.08-1.88) for cardiovascular mortality and 2.07 (95% CI = 1.62-2.64) for noncardiovascular mortality. Depressive symptoms posed a strong risk factor for noncardiovascular mortality at the short term (HR = 2.82, 95% CI = 1.58-5.05), medium term (HR = 2.08, 95% CI = 1.40-3.09), and long term (HR = 1.84, 95% CI = 1.26-2.69), whereas the association between depressive symptoms and cardiovascular mortality was not observed during the first 6 months of follow-up (HR = 1.03, 95% CI = 0.49-2.15). Conclusions: Depressive symptoms at the start of dialysis therapy are associated with short-, medium-, and long-term mortality. The cause-specific mortality risk over time may help clinicians to understand multifactorial causes of the association between depressive symptoms and survival.
    No preview · Article · Oct 2012 · Psychosomatic Medicine
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    ABSTRACT: See also Zoccali C, Mallamaci F. Pulmonary embolism in chronic kidney disease: a lethal, overlooked and research orphan disease. This issue, pp 2481–3. Summary. Background: It is has been suggested that dialysis patients have lower mortality rates for pulmonary embolism than the general population, because of platelet dysfunction and bleeding tendency. However, there is limited information whether dialysis is indeed associated with a decreased mortality risk from pulmonary embolism. Objective: The aim of our study was to evaluate whether mortality rate ratios for pulmonary embolism were lower than for myocardial infarction and stroke in dialysis patients compared with the general population. Methods: Cardiovascular causes of death for 130 439 incident dialysis patients registered in the ERA-EDTA Registry were compared with the cardiovascular causes of death for the European general population. Results: The age- and sex-standardized mortality rate (SMR) from pulmonary embolism was 12.2 (95% CI 10.2–14.6) times higher in dialysis patients than in the general population. The SMRs in dialysis patients compared with the general population were 11.0 (95% CI 10.6–11.4) for myocardial infarction, 8.4 (95% CI 8.0–8.8) for stroke, and 8.3 (95% CI 8.0–8.5) for other cardiovascular diseases. In dialysis patients, primary kidney disease due to diabetes was associated with an increased mortality risk due to pulmonary embolism (HR 1.9; 95% CI 1.0–3.8), myocardial infarction (HR 4.1; 95% CI 3.4–4.9), stroke (HR 3.5; 95% CI 2.8–4.4), and other cardiovascular causes of death (HR 3.4; 95% CI 2.9–3.9) compared with patients with polycystic kidney disease. Conclusions: Dialysis patients were found to have an unexpected highly increased mortality rate for pulmonary embolism and increased mortality rates for myocardial infarction and stroke.
    Full-text · Article · Sep 2012 · Journal of Thrombosis and Haemostasis
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    ABSTRACT: Functional variants in the IL6 gene, in particular the -174G/C polymorphism (rs1800795), affect the mortality risk in dialysis patients. Peritoneal dialysis (PD) patients harbouring the C allele of the -174G/C polymorphism of IL6 showed faster peritoneal transport. The aim of this study was to investigate this IL6 variant as risk factor for mortality and technique failure in a large cohort of Caucasian PD patients. A Dutch multicentre cohort of 398 incident PD patients (NECOSAD) was analysed. Survival analysis was performed for death and technique failure with a maximum follow-up of 5 years. A combined PD cohort from Amsterdam (Academic Medical Center, N = 71) and Brussels (Université catholique de Louvain Medical School, N = 102) was used for independent replication. In NECOSAD, 105 patients died on dialysis [incidence rate 10.3/100 person-years (py)], and 138 patients experienced technique failure (16.2/100 py), with peritonitis as important cause. Patients with the C/C genotype had a 71% increased mortality risk compared to patients with the G/G genotype (95% confidence interval 0.98-2.98); this effect was mainly a long-term effect: a 2.7-fold increased mortality risk was found in patients having survived 2 years since the start on dialysis, and a 1.7-fold increased risk for the combined end point (mortality or technique failure). In the combined replication cohort, no increased risks were found in patients with the C/C genotype. The C/C genotype of the -174G/C polymorphism was associated with an increased mortality risk in 398 Dutch incident PD patients. The existence of substantial differences between the two academic replication cohorts and the discovery cohort from NECOSAD and the limited power of these cohorts prevented an independent replication of the NECOSAD findings.
    No preview · Article · May 2012 · Nephrology Dialysis Transplantation
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    ABSTRACT: Background and OBJECTIVES: In automated peritoneal dialysis (APD), a patient's peritoneal membrane is more intensively exposed to fresh dialysate than it is in continuous ambulatory peritoneal dialysis (CAPD). Our aim was to study, in incident peritoneal dialysis (PD) patients, the influence of APD-compared with that of CAPD-on peritoneal transport over 4 years.Design, Setting, Participants, and Measurements: Patients were included if at least 2 annual standard permeability analyses (SPAs) performed with 3.86% glucose were available while the patient was using the same modality with which they had started PD (APD or CAPD). Patients were followed until their first modality switch. Differences in the pattern of SPA outcomes over time were tested using repeated-measures models adjusted for age, sex, comorbidity, primary kidney disease, and year of PD start. RESULTS: The 59 CAPD patients enrolled were older than the 47 APD patients enrolled (mean age: 58 ± 14 years vs 49 ± 14 years; p < 0.01), and they had started PD earlier (mean start year: 2000 vs 2002). Over time, no differences in solute (p > 0.19) or fluid transport (p > 0.13) were observed. Similarly, free water transport (p = 0.43) and small-pore transport (p = 0.31) were not different between the modalities. Over time, patients on APD showed a faster decline in effective lymphatic absorption rate (ELAR: p = 0.02) and in transcapillary ultrafiltration (TCUF: p = 0.07, adjusted p = 0.05). Further adjustment did not change the results. CONCLUSIONS: Compared with patients starting on CAPD, those starting on APD experienced a faster decline in ELAR and TCUF. Other transport parameters were not different over time between the groups.
    No preview · Article · Apr 2012
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    Cristian Spitoni · Marion Verduijn · Hein Putter
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    ABSTRACT: In this paper we discuss estimation of transition probabilities for semi-Markov multi-state models. Non-parametric and semi-parametric estimators of the transition probabilities for a large class of models (forward going models) are proposed. Large sample theory is derived using the functional delta method and the use of resampling is proposed to derive confidence bands for the transition probabilities. The last part of the paper concerns the presentation of the main ideas of the R implementation of the proposed estimators, and data from a renal replacement study are used to illustrate the behavior of the estimators proposed.
    Preview · Article · Jan 2012 · The International Journal of Biostatistics
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    ABSTRACT: Whether the risk of both venous and arterial thrombosis is increased in dialysis patients as compared to the general population is unknown. In addition, it is unknown which subgroups are at highest risk. Furthermore, it is unknown whether having a history of venous thrombosis or arterial thrombosis prior to dialysis treatment increases mortality risk. A total of 455 dialysis patients were followed for objectively verified symptomatic thrombotic events between January 1997 and June 2009. The incidence rates in dialysis patients as compared to the general population was 5.6-fold (95% CI 3.1-8.9) increased for venous thrombosis, 11.9-fold (95% CI 9.3-14.9) increased for myocardial infarction, and 8.4-fold (95% CI 5.7-11.5) increased for ischaemic stroke. The combination of haemodialysis, lowest tertile of albumin, history of venous thrombosis, and malignancy was associated with subsequent venous thrombosis. Increased age, renal vascular disease, diabetes, high cholesterol levels, history of venous thrombosis, and history of arterial thrombosis were associated with subsequent arterial thrombosis. The all-cause mortality risk was 1.9-fold (95% CI 1.1-3.3) increased for patients with a history of venous thrombosis and 1.9-fold (95% CI 1.4-2.6) increased for patients with a history of arterial thrombosis. A potential limitation of this study was that in some risk categories associations with venous thrombosis did not reach statistical significance due to small numbers. In conclusion, dialysis patients have clearly elevated risks of venous thrombosis and arterial thrombosis and occurrence of venous thrombosis or arterial thrombosis prior to the start of dialysis is associated with an increased mortality risk.
    No preview · Article · Dec 2011 · Thrombosis and Haemostasis
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    ABSTRACT: Ethnic minority patients on dialysis are reported to have better survival rates relative to Caucasians. The reasons for this finding are not fully understood and European studies are scarce. This study examined whether ethnic differences in survival could be explained by patient characteristics, including psychosocial factors. We analysed data of the Netherlands Cooperative Study on the Adequacy of Dialysis study, an observational prospective cohort study of patients who started dialysis between 1997 and 2007 in the Netherlands. Ethnicity was classified as Caucasian, Black or Asian, assessed by local nurses. Data collected at the start of dialysis treatment included demographic, clinical and psychosocial characteristics. Psychosocial characteristics included data on health-related quality of life (HRQoL), mental health status and general health perception. Cox proportional hazards analysis was used to explore ethnic survival differences. One thousand seven hundred and ninety-one patients were Caucasian, 45 Black and 108 Asian. The ethnic groups differed significantly in age, residual glomerular filtration rate, diabetes mellitus, erythropoietin use, plasma calcium, parathormone and creatinine, marital status and general health perception. No ethnic differences were found in HRQoL and mental health status. Crude hazard ratios (HRs) for mortality for Caucasians compared to Blacks and Asians were 3.1 [95% confidence interval (CI) 1.6-5.9] and 1.1 (95% CI 0.9-1.5), respectively. After adjustment for a range of potential explanatory variables, including psychosocial factors, the HRs were 2.5 (95% CI 1.2-4.9) compared with Blacks and 1.2 (95% CI 0.9-1.6) compared with Asians. Although patient numbers were rather small, this study demonstrates, with 95% confidence, better survival for Black compared to Caucasian dialysis patients and equal survival for Asian compared to Caucasian dialysis patients in the Netherlands. This could not be explained by patient characteristics, including psychosocial factors.
    No preview · Article · Nov 2011 · Nephrology Dialysis Transplantation
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    Marion Verduijn · Kitty J Jager · Carmine Zoccali · Friedo W Dekker
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    ABSTRACT: Genetic association studies are a means to investigate the causal role of genes in diseases in order to unravel pathways involved in the etiology of disease. There are two types of genetic association studies: hypothesis-driven studies, i.e. candidate gene studies, targeting genes with a known or presumed role in pathways or diseases of interest, and non-hypothesis-driven studies, i.e. genome-wide association studies, aiming for the discovery of new genetic associations. This educational article is an introduction to genetic association studies for nephrologists and researchers in the domain of kidney disease.
    Full-text · Article · Aug 2011 · Nephron Clinical Practice
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    ABSTRACT: Catheter use has been associated with an increased mortality risk in haemodialysis patients. However, differences in the all-cause and cause-specific mortality risk between catheter use and arteriovenous access use in young and elderly haemodialysis patients have not yet been investigated. In this prospective cohort study of 1109 incident haemodialysis patients from 38 centres in the Netherlands, hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated for 2-year all-cause, infection-related and cardiovascular mortality in patients with a catheter as compared to patients with an arteriovenous access stratified for age (< 65 years and ≥ 65 years). Of the 1109 patients, 919 had an arteriovenous access and 190 had a catheter. The mortality rate was 76 per 1000 person-years in young patients with an arteriovenous access, 129 per 1000 person-years in young patients with a catheter, 222 per 1000 person-years in elderly patients with an arteriovenous access and 427 per 1000 person-years in elderly patients with a catheter. The adjusted HR was 3.15 (95% CI: 2.09-4.75) for elderly patients with a catheter as compared to young patients with an arteriovenous access. The adjusted HRs in elderly patients with a catheter as compared to elderly patients with an arteriovenous access were 1.54 (95% CI: 1.13-2.12) for all-cause mortality, 1.60 (95%: CI 0.62-4.19) for infection-related mortality and 1.67 (95% CI: 1.04-2.68) for cardiovascular mortality. Especially, elderly haemodialysis patients with a catheter have an increased all-cause, infection-related and cardiovascular mortality risk as compared to patients with an arteriovenous access.
    Full-text · Article · Jul 2011 · Nephrology Dialysis Transplantation
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    ABSTRACT: Randomized clinical trials are expensive and time consuming. Therefore, strategies are needed to prioritise tracks for drug development. Genetic association studies may provide such a strategy by considering the differences between genotypes as a proxy for a natural, lifelong, randomized at conception, clinical trial. Previously an association with better survival was found in dialysis patients with systemic inflammation carrying a deletion variant of the CC-chemokine receptor 5 (CCR5). We hypothesized that in an analogous manner, pharmacological CCR5 blockade could protect against inflammation-driven mortality and estimated if such a treatment would be cost-effective. A genetic screen and treat strategy was modelled using a decision-analytic Markov model, in which patients were screened for the CCR5 deletion 32 polymorphism and those with the wild type and systemic inflammation were treated with pharmacological CCR5 blockers. Kidney transplantation and mortality rates were calculated using patient level data. Extensive sensitivity analyses were performed. The cost-effectiveness of the genetic screen and treat strategy was &OV0556;18 557 per life year gained and &OV0556;21 896 per quality-adjusted life years gained. Concordance between the genetic association and pharmacological effectiveness was a main driver of cost-effectiveness. Sensitivity analyses showed that even a modest effectiveness of pharmacological CCR5 blockade would result in a treatment strategy that is good value for money. Pharmacological blockade of the CCR5 receptor in inflamed dialysis patients can be incorporated in a potentially cost-effective screen and treat programme. These findings provide formal rationale for clinical studies. This study illustrates the potential of genetic association studies for drug development, as a source of Mendelian randomized evidence from an observational setting.
    Full-text · Article · Jul 2011 · Pharmacogenetics and Genomics
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    ABSTRACT: Although women have a survival advantage in the general population, women on dialysis have similar mortality to men. We hypothesized that this paired mortality risk during dialysis may be explained by a relative excess of cardiovascular-related mortality in women. We compared 5-year age-stratified cardiovascular and noncardiovascular mortality rates, relative risks, and hazard ratios in a European cohort of incident adult dialysis patients (European Renal Association-European Dialysis and Transplant Association [ERA-EDTA] Registry) with the European general population (Eurostat). Cause of death was recorded by ERA-EDTA codes in dialysis patients and by International Statistical Classification of Diseases codes in the general population. Overall, sex did not have a predictive effect on outcome in dialysis. Stratification into age categories and causes of death showed greater noncardiovascular mortality in young women (<45 years). In other age categories (45 to 55 and >55 years), women presented lower cardiovascular mortality. This cardiovascular benefit was, however, smaller than in the general population. Stratification by diabetic nephropathy showed that diabetic women in all age categories remained at increased mortality risk compared with men, an effect mainly attributed to the noncardiovascular component. Mortality rates and causes of death in men and women on dialysis vary with age. Increased noncardiovascular mortality may explain the loss of the survival advantage of women on dialysis. Both young and diabetic women starting dialysis are at a higher mortality risk than equal men.
    Full-text · Article · Jul 2011 · Clinical Journal of the American Society of Nephrology

  • No preview · Article · Jun 2011 · CKJ: Clinical Kidney Journal
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    ABSTRACT: INTRODUCTION AND AIMS: Higher residential altitude has been associated with greater erythropoietin response and longer survival in ESRD patients. It has been hypothesized that persistent activation of hypoxia-inducible factors (HIF) at higher altitude may explain these associations. Animal models have shown that inactivation of prolyl-hydroxylases - regulators of HIF - suppresses mammary gland proliferation in vitro, with similar findings in lung, brain, and hematopoietic cancer lines. Thus, HIF activation may also affect cancer incidence in vivo. No studies have evaluated the association between altitude and cancer incidence. METHODS: We studied incident ESRD patients (1996-2006) who had no diagnosis of cancer prior to initiation of chronic dialysis. We required 2 medical claims with a cancer diagnosis (except for non-melanoma skin cancer) to define incident cancer. We also used previously validated algorithms to ascertain six specific malignancies: breast, lung, gastric, and colorectal cancer, leukemia and lymphoma. Patients were stratified by residential altitude (<250 ft./76 m.; 250-1999 ft./76-609 m., 2000-3999 ft./610-1218 m., 4000-5999 ft./1219-1828 m., ≥6000 ft./1829 m.). Cox regression was used to study the univariate and adjusted (for demographics, comorbidities, laboratories) associations among residential altitude and these incident cancer outcomes. RESULTS: The Medical Evidence Report forms of 928965 incident ESRD patients indicated no diagnosis of cancer and 118878 (12.8%) patients were found to have any cancer during follow up. Univariate analyses revealed a monotonic decrease in cancer incidence with higher altitude (p<0.001), which was only slightly attenuated after full adjustment. Compared with patients residing near sea level (<250 ft.), the adjusted relative risks of cancer decreased by 5% (95% CI: 3-6%), 9% (4-13%), 13% (8-19%), and 14% (1-24%) among patients living at 250-1999, 2000-3999, 4000-5999, and ≥6000 ft., respectively (see metric conversion above). Using only the six validated cancer algorithms above, the associations were even more pronounced. CONCLUSIONS: Higher residential altitude among ESRD patients was associated with lower cancer incidence despite adjustment for a large number of factors. While causality cannot be inferred from our study, our findings corroborate in vitro studies showing reduced cancer cell growth with prolyl-hydroxylase inhibition.
    No preview · Article · Jun 2011 · CKJ: Clinical Kidney Journal
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    ABSTRACT: 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. 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). 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. 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.
    No preview · Article · May 2011 · Clinical Journal of the American Society of Nephrology
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    Full-text · Article · May 2011