Gurbey Ocak

Haemodialysis catheters increase mortality as compared to arteriovenous accesses especially in elderly patients

BACKGROUND 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. METHODS 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). RESULTS 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. CONCLUSIONS 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.

Risk of venous thrombosis in patients with major illnesses: results from the MEGA study.

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; 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.

Mortality due to pulmonary embolism, myocardial infarction, and stroke among incident dialysis patients.

See also Zoccali C, Mallamaci F. Pulmonary embolism in chronic kidney disease: a lethal, overlooked and research orphan disease. This issue, pp 2481–3.

Role of Hemostatic Factors on the Risk of Venous Thrombosis in People With Impaired Kidney Function

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.

Risk of venous thrombosis in patients with chronic kidney disease: identification of high‐risk groups

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.

Type of arteriovenous vascular access and association with patency and mortality

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 EQUAL study: a European study in chronic kidney disease stage 4 patients

The timing of the start of dialysis in elderly patients is driven by the desire to optimize the quantity and quality of life. Limited data exist on how the level of renal function, and uraemic signs and symptoms can be used to determine when dialysis should be initiated in elderly patients. EQUAL, an international prospective cohort study, aims to address these issues. To this end, it will enroll 3500 patients >65 years of age with CKD of various aetiologies under the care of nephrologists. These patients will be followed until death, discharge from the nephrology clinic to primary care or until the end of the observation period after 4 years of follow-up. At the time of enrollment, patients must have an estimated glomerular filtration rate (eGFR) of 20 mL/min/1.73 m(2) or lower, but should not yet be on dialysis. Standardized data collection will include demographics, lifestyle, comorbidities, uraemic signs and symptoms, nutritional status, medication and routine blood and urine biochemistry. It will also comprise quality of life data, information on decision making including patients preferences and patients satisfaction.

Venous and arterial thrombosis in dialysis patients

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.

Candidate Gene Analysis of Arteriovenous Fistula Failure in Hemodialysis Patients

BACKGROUND AND OBJECTIVES Arteriovenous fistula (AVF) failure remains an important cause of morbidity in hemodialysis patients. The exact underlying mechanisms responsible for AVF failure are unknown but processes like proliferation, inflammation, vascular remodeling, and thrombosis are thought to be involved. The current objective was to investigate the association between AVF failure and single nucleotide polymorphisms (SNPs) in genes related to these pathophysiologic processes in a large population of incident hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A total of 479 incident hemodialysis patients were included between January 1997 and April 2004. Follow-up lasted 2 years or until AVF failure, defined as surgery, percutaneous endovascular intervention, or abandonment of the vascular access. Forty-three SNPs in 26 genes, related to proliferation, inflammation, endothelial function, vascular remodeling, coagulation, and calcium/phosphate metabolism, were genotyped. Relations were analyzed using Cox regression analysis. RESULTS In total, 207 (43.2%) patients developed AVF failure. After adjustment, two SNPs were significantly associated with an increased risk of AVF failure. The hazard ratio (95% confidence interval) of LRP1 rs1466535 was 1.75 (1.15 to 2.66) and patients with factor V Leiden had a hazard ratio of 2.54 (1.41 to 4.56) to develop AVF failure. The other SNPs were not associated with AVF failure. CONCLUSIONS In this large cohort of hemodialysis patients, only 2 of the 43 candidate SNPs were associated with an increased risk of AVF failure. Whether other factors, like local hemodynamic circumstances, are more important or other SNPs play a role in AVF failure remains to be elucidated.

Course of Symptoms and Health-Related Quality of Life during Specialized Pre-Dialysis Care

Background Concerns 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. Methods In 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). Results All 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. Conclusions The 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.