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.

BackgroundThere 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).MethodsWe 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.ResultsCardiovascular 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.ConclusionCardiovascular 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.

The association between chronic kidney disease and bleeding is unknown. We followed 10 347 subjects at high cardiovascular risk for bleeding events. Chronic kidney disease was associated with a 1.5‐fold increased bleeding risk. Especially albuminuria rather than decreased kidney function was associated with bleeding events. Summary BackgroundThere are indications that patients with chronic kidney disease have an increased bleeding risk. ObjectivesTo investigate the association between chronic kidney disease and bleeding in patients at high cardiovascular risk. MethodsWe included 10 347 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2015 for an outpatient visit with classic risk factors for arterial disease or with symptomatic arterial disease (Second Manifestation of Arterial disease [SMART] cohort). Patients were staged according to the KDIGO guidelines, on the basis of estimated glomerular filtration rate (eGFR) and albuminuria, and were followed for the occurrence of major hemorrhagic events until March 2015. Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding were calculated with Cox proportional hazards analyses. ResultsThe incidence rate for bleeding in subjects with chronic kidney disease was 8.0 per 1000 person‐years and that for subjects without chronic kidney disease was 3.5 per 1000 person‐years. Patients with chronic kidney disease (n = 2443) had a 1.5‐fold (95% CI 1.2–1.9) increased risk of bleeding as compared with subjects without chronic kidney disease (n = 7904) after adjustment. Subjects with an eGFR of < 45 mL min−1 1.73 m–2 with albuminuria had a 3.5‐fold (95% CI 2.3–5.3) increased bleeding risk, whereas an eGFR of < 45 mL min−1 1.73 m–2 without albuminuria was not associated with an increased bleeding risk (HR 1.3, 95% CI 0.7–2.5). ConclusionChronic kidney disease is a risk factor for bleeding in patients with classic risk factors for arterial disease or with symptomatic arterial disease, especially in the presence of albuminuria.

To cite this article: Ocak G, Vossen CY, Verduijn M, Dekker FW, Rosendaal FR, Cannegieter SC, Lijfering WM. Risk of venous thrombosis in patients with major illnesses: results from the MEGA study. J Thromb Haemost 2013; 11: 116-23.Summary. 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; increased FIX (OR 35.3;, 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.

To cite this article: Ocak G, Verduijn M, Vossen CY, Lijfering WM, Dekker FW, Rosendaal FR, Gansevoort RT, Mahmoodi BK. Chronic kidney disease stages 1-3 increase the risk of venous thrombosis. J Thromb Haemost 2010; 8: 2428-35.Summary Background: End-stage renal disease has been associated with venous thrombosis (VT). However, the risk of VT in the early stages of chronic kidney disease (CKD) has not yet been investigated. The aim of this study was to investigate whether CKD patients with stage 1-3 disease are at increased risk of VT. Methods: Eight thousand four hundred and ninety-five subjects were included in a prospective cohort study, in which renal function and albuminuria were assessed, starting in 1997-1998, and were followed for the occurrence of VT until 1 June 2007. CKD patients were staged according to the Kidney Disease Outcomes Quality Initiative guidelines, on the basis of 24-h urine albumin excretion and estimated glomerular filtration rates. Objectively verified symptomatic VT was considered to be the endpoint. Results: Of the 8495 subjects, 243 had CKD stage 1, 856 CKD stage 2, and 491 CKD stage 3. During a median follow-up period of 9.2 years, 128 individuals developed VT. The hazard ratios (HRs) for CKD stages 1, 2 and 3 were, respectively, 2.2 [95% confidence interval (CI) 0.9-5.1], 1.9 (95% CI 1.1-3.1) and 1.6 (95% CI 0.9-2.8) relative to those without CKD after adjustment for age, sex, body mass index, hypertension, diabetes, malignancy, and high-sensitivity C-reactive protein. ) had an adjusted HR of 3.0, and subjects with CKD stage 3 without albuminuria had an adjusted HR of 1.0. Conclusions: CKD stages 1 and 2, and CKD stage 3 in the presence of albuminuria, are risk factors for VT. The risk of VT is more related to albuminuria than to impaired glomerular filtration rate.

Background— 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. Methods and Results— 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 [reference], 10th–50th, 5th–10th, 2.5th–5th, 1st–2.5th, and <1st percentile). Several hemostatic factors showed a procoagulant shift with decreasing kidney function in controls, most notably factor VIII and von Willebrand factor. Compared with eGFR >50th percentile, factor VIII levels (adjusted mean difference, 60 IU/dL for the <1st eGFR percentile category) and von Willebrand factor levels (adjusted mean difference, 60 IU/dL for the <1st eGFR percentile category) increased with each percentile category. The odds ratios for venous thrombosis similarly increased across the categories from 1.1 (95% confidence interval, 0.9–1.3) for the 10th to 50th percentile to 3.7 (95% confidence interval, 2.4–5.7) for the <1st percentile category. Adjustment for factor VIII or von Willebrand factor attenuated these odds ratios, indicating an effect of eGFR on thrombosis through these factors. Adjustments for other risk factors for venous thrombosis did not affect the odds ratios. Conclusion— Impaired kidney function affects venous thrombosis risk via concurrently raised factor VIII and von Willebrand factor levels.

BackgroundConcerns are present on the limited value of renal function alone in defining the optimal moment to start dialysis. Disease-related symptoms and health-related quality of life (HRQOL) may have additional clinical value in defining this moment, but little is known about how these parameters change during pre-dialysis care. The aims of our study were to describe the course of symptoms and HRQOL during pre-dialysis care and to investigate their association with poor health outcomes.MethodsIn the prospective PREPARE-2 cohort, incident patients starting specialized pre-dialysis care were included when referred to one of the 25 participating Dutch outpatient clinics (2004–2011). In the present analysis, 436 patients with data available on symptoms and HRQOL were included. Clinical data, symptoms (revised illness perception questionnaire), and HRQOL (short form-36 questionnaire; physical and mental summary score) were collected every 6-month interval. A time-dependent Cox proportional hazard model was used to associate symptoms and HRQOL with the combined poor health outcome (i.e. starting dialysis, receiving a kidney transplant, and death).ResultsAll symptoms increased, especially fatigue and loss of strength, and both the physical and mental summary score decreased over time, with the most pronounced change during the last 6–12 months of follow-up. Furthermore, each additional symptom (adjusted HR 1.04 (95% CI, 1.00–1.09)) and each 3-point lower physical and mental summary score (adjusted HR 1.04 (1.02–1.06) and 1.04 (1.02–1.06) respectively) were associated with a higher risk of reaching the combined poor health outcome within the subsequent 6 months.ConclusionsThe number of symptoms increased and both the physical and mental HRQOL score decreased during pre-dialysis care and these changes were associated with starting dialysis, receiving a kidney transplant, and death. These results may indicate that symptoms and HRQOL are good markers for the medical condition and disease stage of pre-dialysis patients.

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.