Mortality due to bleeding, myocardial infarction and stroke in dialysis patients.

Essentials Mortality due to bleeding vs. arterial thrombosis in dialysis patients is unknown. We compared death causes of 201 918 dialysis patients with the general population. Dialysis was associated with increased mortality risks of bleeding and arterial thrombosis. Clinicians should be aware of the increased bleeding and thrombosis risks. SUMMARY: Background Dialysis has been associated with both bleeding and thrombotic events. However, there is limited information on bleeding as a cause of death versus arterial thrombosis as a cause of death. Objectives To investigate the occurrence of bleeding, myocardial infarction and stroke as causes of death in the dialysis population as compared with the general population. Methods We included 201 918 patients from 11 countries providing data to the ERA-EDTA Registry who started dialysis treatment between 1994 and 2011, and followed them for 3 years. Age-standardized and sex-standardized mortality rate ratios for bleeding, myocardial infarction and stroke as causes of death were calculated in dialysis patients as compared with the European general population. Associations between potential risk factors and these causes of death in dialysis patients were investigated by calculating hazard ratios (HRs) with 95% confidence intervals (CIs) by the use of Cox proportional-hazards regression. Results As compared with the general population, the age-standardized and sex-standardized mortality rate ratios in dialysis patients were 12.8 (95% CI 11.9-13.7) for bleeding as a cause of death (6.2 per 1000 person-years among dialysis patients versus 0.3 per 1000 person-years in the general population), 13.4 (95% CI 13.0-13.9) for myocardial infarction (22.5 versus 0.9 per 1000 person-years), and 12.4 (95% CI 11.9-12.9) for stroke (14.3 versus 0.7 per 1000 person-years). Conclusion Dialysis patients have highly increased risks of death caused by bleeding and arterial thrombosis as compared with the general population. Clinicians should be aware of the increased mortality risks caused by these conditions.

Chronic kidney disease and bleeding risk in patients at high cardiovascular risk: a cohort study.

Essentials 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: Background There are indications that patients with chronic kidney disease have an increased bleeding risk. Objectives To investigate the association between chronic kidney disease and bleeding in patients at high cardiovascular risk. Methods We 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. Results The 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). Conclusion Chronic 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.

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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: This study included 2473 consecutive patients with first venous thrombosis and 2936 controls from a case-control study (the MEGA study). RESULTS: 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). CONCLUSION: 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.

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

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.

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.

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.

Hepatocyte antigen expression in subtypes of intestinal metaplasia of the stomach.

OBJECTIVE: Recently, hepatocyte antigen (Hep) was introduced as a sensitive and reliable marker of intestinal metaplasia (IM). However, the distribution of Hep expression in subtypes of IM was not described. METHODS: We examined the expression of Hep in 58 cases of chronic gastritis associated with IM by immunohistochemical staining. Cases were classified as: 19 of IM Type I (complete) cases, 16 cases of IM Type II (incomplete) and 23 cases of IM Type III (incomplete). The distribution of Hep expression was classified into four groups according to the intensity of Hep expressing metaplastic cells: negative, low, moderate and high. We also compared expression of Hep with that of MUC-1, MUC-2 and MUC-5AC. RESULTS: Hep expression showed granular cytoplasmic staining and was specifically identified in columnar cells, but not in goblet cells. There was no significant difference between Hep expression and subtypes of IM (p > 0.005). However the difference between the distribution of Hep expression among three subtypes of IM was significant (p < 0.001). No relationship was observed among the expression of Hep, MUC-1, MUC-2 and MUC-5AC. CONCLUSION: Results of the present study revealed that the distribution of Hep expression is high in the majority of the complete type (Type I) IM cases, moderate in the majority of the incomplete Type II IM cases and low in all of the incomplete Type III IM cases and suggest that besides its role as a sensitive marker in IM, the evaluation of the distribution of Hep expression might be useful in the classification of IM.

Chronic kidney disease stages 1-3 increase the risk of venous thrombosis.

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. Subjects with CKD stage 3 and albuminuria (≥ 30 mg d(-1)) 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.