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Cardiovascular disease is associated with increased fracture risk in the general population. Few data exist on the association between cardiovascular health and incident fracture risk in patients with advanced CKD, a high-risk population for fractures. We aimed to assess the link between fracture risk and cardiovascular health in a prospective cohort of 210 patients with CKD stage G4-5. Incident fractures were recorded during a prospective follow-up of 5 years. Laboratory parameters, abdominal aortic calcification score, echocardiography, ultrasound assessment of brachial artery flow-mediated dilatation and carotid intima-media thickness, and maximal stress ergometry were obtained at baseline. A total of 51 fractures were observed in 40 (19%) patients during follow-up. In separate multivariable Cox proportional hazards models adjusted for age, gender, and baseline eGFR, TnT (HR 1.007, CI 95% 1.003-1.010, p < 0.001) and ProBNP (HR 1.000, CI 95% 1.000-1.000, p = 0.017) were associated with incident fractures and the association persisted after adjusting for coronary artery disease (CAD). The patients unable to perform the ergometry test had a higher risk of incident fractures compared to others (36.1% vs 15.5%, p = 0.009). A cardiovascular composite risk score summarizing TnT, ProBNP, and ergometry data was independently associated with incident fractures in a multivariable Cox model (HR 1.373, CI 95% 1.180-1.599, p < 0.001). Patients with the lowest score were observed with no fractures, while patients with the highest score were observed with a fracture risk of 40.5% during follow-up. Risk of incident fractures is associated with biomarkers of cardiovascular health and a composite cardiovascular risk score in patients with advanced CKD.
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BACKGROUND AND AIMS: Abdominal aortic calcification (AAC) is common in chronic kidney disease (CKD) patients and associated with increased mortality. Comparative data on the AAC score progression in CKD patients transitioning from conservative treatment to different modalities of renal replacement therapy (RRT) are lacking and were examined. METHODS: 150 study patients underwent lateral lumbar radiograph to study AAC in the beginning of the study before commencing RRT (AAC1) and at 3 years of follow-up (AAC2). We examined the associations between repeated laboratory tests taken every 3 months, echocardiographic and clinical variables and AAC increment per year (ΔAAC), and the association between ΔAAC and outcomes during follow-up. RESULTS: At the time of AAC2 measurement, 39 patients were on hemodialysis, 39 on peritoneal dialysis, 39 had a transplant, and 33 were on conservative treatment. Median AAC1 was 4.8 (0.5-9.0) and median AAC2 8.0 (1.5-12.0) (p < 0.0001). ΔAAC was similar across the treatment groups (p = 0.19). ΔAAC was independently associated with mean left ventricular mass index (LVMI) (log LVMI: ß = 0.97, p = 0.02) and mean phosphorus through follow-up (log phosphorus: ß = 1.19, p = 0.02) in the multivariable model. Time to transplantation was associated with ΔAAC in transplant recipients (per month on the waiting list: ß = 0.04, p = 0.001). ΔAAC was associated with mortality (HR 1.427, 95% confidence interval 1.044-1.950, p = 0.03). CONCLUSION: AAC progresses rapidly in patients with CKD, and ΔAAC is similar across the CKD treatment groups including transplant recipients. The increment rate is associated with mortality and in transplant recipients with the time on the transplant waiting list.
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Falência Renal Crônica/complicações , Calcificação Vascular/patologia , Idoso , Aorta Abdominal/patologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Diálise Renal , Fatores de Risco , Calcificação Vascular/diagnóstico , Calcificação Vascular/etiologiaRESUMO
INTRODUCTION: Chronic kidney disease (CKD) is associated with impaired maximal exercise capacity (MEC). However, data are scarce on the development of MEC in CKD stage 4-5 patients transitioning to renal replacement therapy (RRT). METHODS: We explored the change in MEC measured in watts (Wlast4) with 2 consecutive maximal bicycle stress ergometry tests in 122 CKD stage 4-5 patients transitioning to dialysis and transplantation in an observational follow-up study. RESULTS: Mean age was 58.9 ± 13.9 years and 43 (35.2%) were female. Mean time between the baseline and follow-up ergometry tests was 1,012 ± 327 days and 29 (23.8%) patients had not initiated RRT, 50 (41.0%) were undergoing dialysis, and 43 (35.2%) had received a kidney transplant at the time of the follow-up ergometry test. The mean Wlast4 was 91 ± 37 W and 84 ± 37 W for the baseline and follow-up ergometry tests, respectively (p < 0.001). The mean Wlast4 declined between the baseline and follow-up ergometry tests in patients not requiring RRT (p = 0.001) and transplant recipients (p = 0.005), but not in dialysis patients (p = 0.478). There were no differences in the ratio of Wlast4 of the follow-up to the baseline ergometry tests (∆Wlast4) between patients on different treatment modalities at the time of the follow-up test (p = 0.097). Mean capillary blood bicarbonate was significantly associated with ∆Wlast4 after adjusting for age and treatment modality in the multivariate linear regression analysis (ß = 0.226, p = 0.012). CONCLUSION: MEC declined or remained poor in advanced CKD patients transitioning to RRT or continuing conservative care in this observational study. Mean capillary blood bicarbonate was independently associated with the development of MEC.
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Tolerância ao Exercício , Insuficiência Renal Crônica/terapia , Terapia de Substituição Renal , Idoso , Seguimentos , Humanos , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Diálise Renal , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologiaRESUMO
BACKGROUND: Development of vascular calcification is accelerated in patients with end-stage renal disease. In addition to traditional risk factors of cardiovascular disease (CVD) abnormal bone and mineral metabolism together with many other factors contribute to the excess cardiovascular burden in patients on dialysis. Aortic calcification score and coronary calcification score are predictive of CVD and mortality. The aim of this study was to evaluate the possible relationship between arterial calcification and bone metabolism. METHODS: Thirty two patients on dialysis were included. All patients underwent a bone biopsy to assess bone histomorphometry and a 18F-NaF PET scan. Fluoride activity was measured in the lumbar spine (L1 - L4) and at the anterior iliac crest. Arterial calcification scores were assessed by computerized tomography for quantification of coronary artery calcification score and lateral lumbar radiography for aortic calcification score. RESULTS: This study group showed high prevalence of arterial calcification and 59% had verified CVD. Both CAC and AAC were significantly higher in patients with verified CVD. Only 22% had low turnover bone disease. There was a weak association between fluoride activity, which reflects bone turnover, measured in the lumbar spine, and CAC and between PTH and CAC. There was also a weak association between erosion surfaces and AAC. No significant association was found between calcification score and any other parameter measured. CONCLUSIONS: The results in this study highlight the complexity, when evaluating the link between bone remodeling and vascular calcification in patients with multiple comorbidities and extensive atherosclerosis. Several studies suggest an impact of bone turnover on development of arterial calcification and there is some evidence of reduced progression of vascular calcification with improvement in bone status. The present study indicates an association between vascular calcification and bone turnover, even though many parameters of bone turnover failed to show significance. In the presence of multiple other factors contributing to the development of calcification, the impact of bone remodeling might be diminished. TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov protocol registration and result system, ID is NCT02967042 . Date of registration is 17/11/2016.
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Densidade Óssea/fisiologia , Osso e Ossos/metabolismo , Falência Renal Crônica/fisiopatologia , Minerais/metabolismo , Calcificação Vascular/fisiopatologia , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças da Aorta/fisiopatologia , Remodelação Óssea/fisiologia , Doença da Artéria Coronariana/fisiopatologia , Feminino , Fluordesoxiglucose F18 , Humanos , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Diálise RenalRESUMO
Bone biopsy is the gold standard for characterization of renal osteodystrophy (ROD). However, the classification of the subtypes of ROD based on histomorphometric parameters is not unambiguous and the range of normal values for turnover differ in different publications. 18F-Sodium Fluoride positron emission tomography (18F-NaF PET) is a dynamic imaging technique that measures turnover. 18F-NaF PET has previously been shown to correlate with histomorphometric parameters. In this cross-sectional study, 26 patients on dialysis underwent a 18F-NaF PET and a bone biopsy. Bone turnover-based classification was assessed using Malluche's historical reference values for normal bone turnover. In unified turnover-mineralization-volume (TMV)-based classification, the whole histopathological picture was evaluated and the range for normal turnover was set accordingly. Fluoride activity was measured in the lumbar spine (L1-L4) and at the anterior iliac crest. On the basis of turnover-based classification of ROD, 12% had high turnover and 61% had low turnover bone disease. On the basis of unified TMV-based classification of ROD, 42% had high turnover/hyperparathyroid bone disease and 23% had low turnover/adynamic bone disease. When using unified TMV-based classification of ROD, 18F-NaF PET had an AUC of 0.86 to discriminate hyperparathyroid bone disease from other types of ROD and an AUC of 0.87, for discriminating adynamic bone disease. There was a disproportion between turnover-based classification and unified TMV-based classification. More research is needed to establish normal range of bone turnover in patients with CKD and to establish the role of PET imaging in ROD.
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Distúrbio Mineral e Ósseo na Doença Renal Crônica , Fluoreto de Sódio , Remodelação Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico por imagem , Estudos Transversais , Fluoretos , Humanos , Tomografia por Emissão de PósitronsRESUMO
INTRODUCTION: Patients with CKD have an impaired health-related quality of life (QoL). Most studies have been conducted on dialysis patients, and less is known about QoL and its determinants in predialysis patients. We studied the association between QoL and comorbidities, cardiac biomarkers, echocardiography, and mortality in patients with CKD stage 4-5 not on dialysis. METHODS: A total of 140 patients enrolled in the Chronic Arterial Disease, Quality of Life and Mortality in Chronic Kidney Injury (CADKID) study filled the Kidney Disease Quality of Life Short Form (KDQOL-SF) at the beginning of the study. Echocardiography and biochemical parameters were obtained at baseline. Patients were followed up for at least 2 years or until death. RESULTS: The median age was 66 years, and 51 (36%) patients were female. The median estimated glomerular filtration rate was 13 mL/min per 1.73 m2. Obesity, diabetes, atrial fibrillation, and congestive heart failure were associated with lower QoL scores in multiple KDQOL-SF domains. Cardiac biomarkers, troponin T (p = 0.02), N-terminal pro-B-type natriuretic peptide (p = 0.006), and the echocardiographic parameter of cardiac systolic function left ventricular global longitudinal strain (p = 0.02) were significant predictors of lower physical component summary (PCS) score in multivariable regression models after controlling for age, BMI, and diabetes. A low PCS score predicted mortality in a multivariable Cox proportional hazards model [HR 0.96 (95% CI 0.92-0.99), p = 0.03]. QoL was not associated with kidney disease progression. CONCLUSION: Impaired QoL in CKD stage 4-5 patients not on dialysis is associated with cardiac biomarker levels, echocardiographic indices, and mortality.
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Qualidade de Vida , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Idoso , Ecocardiografia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Troponina T/sangueRESUMO
BACKGROUND: Cardiac biomarkers Troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (proBNP) and abdominal aortic calcification score (AAC) are associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). The effects of cardiac biomarkers and AAC on maximal exercise capacity in CKD are unknown and were studied. METHODS: One hundred seventy-four CKD 4-5 patients not on maintenance dialysis underwent maximal bicycle ergometry stress testing, lateral lumbar radiograph to study AAC, echocardiography and biochemical assessments. RESULTS: The subjects with proportional maximal ergometry workload (WMAX%) less than 50% of the expected values had higher TnT, proBNP, AAC, left ventricular end-diastolic diameter, left ventricular mass index, E/e' and pulse pressure, and lower global longitudinal strain compared to the better performing patients. TnT (ß = - 0.09, p = 0.02), AAC (ß = - 1.67, p < 0.0001) and diabetes (ß = - 11.7, p < 0.0001) remained significantly associated with WMAX% in the multivariable model. Maximal ergometry workload (in Watts) was similarly associated with TnT and AAC in addition to age, male gender, hemoglobin and diastolic blood pressure in a respective multivariate model. AAC and TnT showed fair predictive power for WMAX% less than 50% of the expected value with AUCs of 0.70 and 0.75, respectively. CONCLUSIONS: TnT and AAC are independently associated with maximal ergometry stress test workload in patients with advanced CKD. TRIAL REGISTRATION: http://www.ClinicalTrials.gov NCT04223726.
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Aorta Abdominal , Teste de Esforço , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Troponina T/sangue , Calcificação Vascular/sangue , Calcificação Vascular/fisiopatologia , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Índice de Gravidade de Doença , Calcificação Vascular/complicaçõesRESUMO
BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).
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Aspirina/uso terapêutico , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/efeitos adversos , Aterosclerose/complicações , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Método Duplo-Cego , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Rivaroxabana/efeitos adversos , Prevenção Secundária/métodosRESUMO
BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528). CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.
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Anticoagulantes/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Úlcera Péptica/prevenção & controle , Inibidores da Bomba de Prótons/administração & dosagem , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/epidemiologia , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.
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Aspirina/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Rivaroxabana/administração & dosagem , Idoso , Aspirina/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Método Duplo-Cego , Esquema de Medicação , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/microbiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/efeitos adversos , Doença Arterial Periférica/diagnóstico , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Patients with advanced chronic kidney disease (CKD stage 4-5) have an increased risk of death. To study the determinants of all-cause mortality, we recruited 210 consecutive CKD stage 4-5 patients not on dialysis to the prospective Chronic Arterial Disease, quality of life and mortality in chronic KIDney injury (CADKID) study. METHODS: One hundred seventy-four patients underwent maximal bicycle ergometry stress testing and lateral lumbar radiography to study abdominal aortic calcification score and echocardiography. Carotid and femoral artery intima-media thickness and elasticity and brachial artery flow-mediated dilatation were measured in 156 patients. RESULTS: The duration of follow-up was 42 ± 17 months (range 134-2,217 days). The mean age was 61 ± 14 years, and the estimated glomerular filtration rate was 12 (11-15) mL/min/1.73 m2. Thirty-six (21%) patients died during follow-up (time to death 835 ± 372 days). Seventy-five and 21 patients had diabetes and coronary artery disease, respectively, and all but one had hypertension. In the respective multivariate proportional hazards models adjusted for age, sex, and coronary artery disease, the significant determinants of mortality were troponin T, N-terminal pro-B-type natriuretic peptide, maximal ergometry performance, abdominal aortic calcification score, E/e' ratio, and albumin. CONCLUSION: Stress ergometry performance, abdominal aortic calcification score, E/e' of echocardiography, and plasma cardiac biomarkers and albumin predict mortality in advanced CKD.
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Doença da Artéria Coronariana/epidemiologia , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/mortalidade , Calcificação Vascular/epidemiologia , Idoso , Biomarcadores/sangue , Espessura Intima-Media Carotídea , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Ecocardiografia , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Troponina T/sangue , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico , Calcificação Vascular/etiologiaRESUMO
BACKGROUND: The prevalence of left atrial enlargement (LAE) and fragmented QRS (fQRS) diagnosed using ECG criteria in patients with severe chronic kidney disease (CKD) is unknown. Furthermore, there is limited data on predicting new-onset atrial fibrillation (AF) with LAE or fQRS in this patient group. METHODS: We enrolled 165 consecutive non-dialysis patients with CKD stage 4-5 without prior AF diagnosis between 2013 and 2017 in a prospective follow-up cohort study. LAE was defined as total P-wave duration ≥120 ms in lead II ± > 1 biphasic P-waves in leads II, III or aVF; or duration of terminal negative portion of P-wave > 40 ms or depth of terminal negative portion of P-wave > 1 mm in lead V1 from a baseline ECG, respectively. fQRS was defined as the presence of a notched R or S wave or the presence of ≥1 additional R waves (R') or; in the presence of a wide QRS complex (> 120 ms), > 2 notches in R or S waves in two contiguous leads corresponding to a myocardial region, respectively. RESULTS: Mean age of the patients was 59 (SD 14) years, 56/165 (33.9%) were female and the mean estimated glomerular filtration rate was 12.8 ml/min/1.73m2. Altogether 29/165 (17.6%) patients were observed with new-onset AF within median follow-up of 3 [IQR 3, range 2-6] years. At baseline, 137/165 (83.0%) and 144/165 (87.3%) patients were observed with LAE and fQRS, respectively. Furthermore, LAE and fQRS co-existed in 121/165 (73.3%) patients. Neither findings were associated with the risk of new-onset AF within follow-up. CONCLUSION: The prevalence of LAE and fQRS at baseline in this study on CKD stage 4-5 patients not on dialysis was very high. However, LAE or fQRS failed to predict occurrence of new-onset AF in these patients.
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Potenciais de Ação , Fibrilação Atrial/diagnóstico , Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Insuficiência Renal Crônica/diagnóstico , Idoso , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Função do Átrio Esquerdo , Remodelamento Atrial , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Índice de Gravidade de Doença , Fatores de TempoRESUMO
BACKGROUND: Diabetic kidney disease (DKD) remains one of the leading causes of premature death in diabetes. DKD is classified on albuminuria and reduced kidney function (estimated glomerular filtration rate (eGFR)) but these have modest value for predicting future renal status. There is an unmet need for biomarkers that can be used in clinical settings which also improve prediction of renal decline on top of routinely available data, particularly in the early stages. The iBEAt study of the BEAt-DKD project aims to determine whether renal imaging biomarkers (magnetic resonance imaging (MRI) and ultrasound (US)) provide insight into the pathogenesis and heterogeneity of DKD (primary aim) and whether they have potential as prognostic biomarkers in DKD (secondary aim). METHODS: iBEAt is a prospective multi-centre observational cohort study recruiting 500 patients with type 2 diabetes (T2D) and eGFR ≥30 ml/min/1.73m2. At baseline, blood and urine will be collected, clinical examinations will be performed, and medical history will be obtained. These assessments will be repeated annually for 3 years. At baseline each participant will also undergo quantitative renal MRI and US with central processing of MRI images. Biological samples will be stored in a central laboratory for biomarker and validation studies, and data in a central data depository. Data analysis will explore the potential associations between imaging biomarkers and renal function, and whether the imaging biomarkers improve the prediction of DKD progression. Ancillary substudies will: (1) validate imaging biomarkers against renal histopathology; (2) validate MRI based renal blood flow measurements against H2O15 positron-emission tomography (PET); (3) validate methods for (semi-)automated processing of renal MRI; (4) examine longitudinal changes in imaging biomarkers; (5) examine whether glycocalyx and microvascular measures are associated with imaging biomarkers and eGFR decline; (6) explore whether the findings in T2D can be extrapolated to type 1 diabetes. DISCUSSION: iBEAt is the largest DKD imaging study to date and will provide valuable insights into the progression and heterogeneity of DKD. The results may contribute to a more personalised approach to DKD management in patients with T2D. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT03716401 ).
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/diagnóstico por imagem , Rim/diagnóstico por imagem , Insuficiência Renal Crônica/diagnóstico por imagem , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/patologia , Progressão da Doença , Humanos , Rim/irrigação sanguínea , Rim/patologia , Imageamento por Ressonância Magnética , Estudos Observacionais como Assunto , Radioisótopos de Oxigênio , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Prospectivos , Circulação Renal , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/patologia , UltrassonografiaRESUMO
BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, 27â395 patients were enrolled to the COMPASS trial, of whom 24â824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012). INTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide. FUNDING: Bayer AG.
Assuntos
Aspirina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Doença da Artéria Coronariana/epidemiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Morbidade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
BACKGROUND: Despite improvement in short-term outcome of kidney transplants, the long-term survival of kidney transplants has not changed over past decades. Kidney biopsy is the gold standard of transplant pathology but it's invasive. Quantification of transplant blood flow could provide a novel non-invasive method to evaluate transplant pathology. The aim of this retrospective cross-sectional pilot study was to evaluate positron emission tomography (PET) as a method to measure kidney transplant perfusion and find out if there is correlation between transplant perfusion and histopathology. METHODS: Renal cortical perfusion of 19 kidney transplantation patients [average time from transplantation 33 (17-54) months; eGFR 55 (47-69) ml/min] and 10 healthy controls were studied by [15 O]H2O PET. Perfusion and Doppler resistance index (RI) of transplants were compared with histology of one-year protocol transplant biopsy. RESULTS: Renal cortical perfusion of healthy control subjects and transplant patients were 2.7 (2.4-4.0) ml min- 1 g- 1 and 2.2 (2.0-3.0) ml min- 1 g- 1, respectively (p = 0.1). Renal vascular resistance (RVR) of the patients was 47.0 (36.7-51.4) mmHg mL- 1min- 1g- 1 and that of the healthy 32.4 (24.6-39.6) mmHg mL- 1min-1g-1 (p = 0.01). There was a statistically significant correlation between Doppler RI and perfusion of transplants (r = - 0.51, p = 0.026). Transplant Doppler RI of the group of mild fibrotic changes [0.73 (0.70-0.76)] and the group of no fibrotic changes [0.66 (0.61-0.72)] differed statistically significantly (p = 0.03). No statistically significant correlation was found between cortical perfusion and fibrosis of transplants (p = 0.56). CONCLUSIONS: [15 O]H2O PET showed its capability as a method in measuring perfusion of kidney transplants. RVR of transplant patients with stage 2-3 chronic kidney disease was higher than that of the healthy, although kidney perfusion values didn't differ between the groups. Doppler based RI correlated with perfusion and fibrosis of transplants.
Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Imagem de Perfusão/métodos , Tomografia por Emissão de Pósitrons/métodos , Circulação Renal , Transplantes , Resistência Vascular , Biópsia/métodos , Correlação de Dados , Estudos Transversais , Feminino , Humanos , Testes de Função Renal/métodos , Transplante de Rim/métodos , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplantes/irrigação sanguínea , Transplantes/diagnóstico por imagem , Transplantes/patologiaRESUMO
Risk of cardiovascular events within the diabetic population has decreased and survival increased with patients living longer and thus facing the development of end-stage renal disease (ESRD). This calls for good care of patient with diabetes with a focus on hypertension. Patient data were collected from 42 Finnish primary care centres. Each was asked to enrol 10-12 consecutive patients with type-2 diabetes between March 2011 and August 2012. Along with the office blood pressure measurements and laboratory tests, the presence of albuminuria was measured and glomerular filtration rate estimated (eGFR). The 2013 ESH criteria for diabetic hypertensive patients (<140/85 mmHg) was reached by 39% of all 625 study patients and 38% of the pharmacologically treated 520 patients. The absence of detectable albumin in urine was significantly associated with the control of systolic blood pressure and achievement of treatment goals. Beta blockers were the most common antihypertensive agents and patients treated with them had lower eGFR compared to those not treated with these agents. The blood pressure of patients was not in full concordance with the present guideline recommendations. However, satisfactory improvement in blood pressure control, reduction of albuminuria and hence ESRD prevention was achieved.
Assuntos
Albuminúria , Pressão Sanguínea , Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Atenção Primária à Saúde , Adulto , Albuminúria/etiologia , Albuminúria/fisiopatologia , Albuminúria/terapia , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/terapia , Feminino , Finlândia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Urgent-start peritoneal dialysis (PD) carries a similar efficacy and safety profile compared to urgent-start haemodialysis (HD) but is only sparsely applied due to resource issues and concerns of complication risks. Furthermore, few data exist on adverse outcomes associated with central venous catheter (CVC) insertions in urgent-start HD patients. Thus, we sought to compare patient and dialysis-related outcomes in patients undergoing urgent-start PD or HD. METHODS: All patients initiating urgent-start PD in a tertiary research hospital in 2005-2018 were included in this retrospective, single-centre, comparative study and matched with urgent-start HD patients of similar age and chronic kidney disease aetiology. All urgent-start PDs were initiated within 72 h after catheter insertion, and urgent-start HDs were performed via a CVC. All analyses were performed at 3 months and at 1 year of follow-up, respectively. RESULTS: Thirty-three patients who commenced urgent-start PD and 58 matched urgent-start HD control patients were included. Altogether, 26 patients (29%; PD: 36%, HD 24%) died within the 1-year follow-up, and patient survival was similar at 3 months (hazard ratio (HR): 1.15, 95% confidence interval (CI): 0.35-3.81, p = 0.82) and at 1 year of follow-up (HR: 0.64, 95% CI: 0.30-1.39, p = 0.26) between the study groups. There were no differences in the total kidney replacement therapy (KRT)-related infection rate (p = 0.66) or cumulative first-year hospital care days (p = 0.43) between the treatment groups. Altogether, 139 CVCs were inserted during the 1-year follow-up. The number of CVCs per patient was associated with the emergence of blood culture-positive bacteraemia and increased cumulative first-year hospital care days. CONCLUSIONS: Patient survival, cumulative first-year hospital care days and total KRT-related infection rate at 3 months and 1-year follow-up are similar between urgent-start PD and urgent-start HD patients. Furthermore, CVC insertion rate is associated with incident blood culture-positive bacteraemia and increased cumulative first-year hospital care days.
RESUMO
AIMS: To study the association between risk factors and chronic kidney disease (CKD), and characterize medication use in Finnish primary care type 2 diabetes (T2D) patients. METHODS: Data on clinical characteristics, laboratory measurements, and medications were collected from medical records. The primary outcome measure was notable CKD (stage 3-5, eGFR <60 ml/min/1.73 m2) and/or increased albuminuria. The explanatory variables were individual risk factors and risk factor groups based on their number (0-2, 3-4, 5-6, >7). Spearman's rank correlation coefficient and risk ratio analysis were used to analyze the association between the number of risk factors and CKD stage, and between the number of risk factors and notable CKD, respectively. RESULTS: Altogether, 1335 patients with T2D in 60 Finnish primary care centers were recruited for this cross-sectional study. Three-quarters of T2D patients had 3 risk factors and 36% had ≥ 5 risk factors. Compared to patients with 0-2 risk factors, patients with 3-4, 5-6, and ≥ 7 risk factors had a 5.5-fold, 9.9-fold, and 15.9-fold risk of notable CKD (p < 0.001), respectively. Heart failure was most strongly associated with notable CKD (risk ratio, 3.7; p < 0.001). CONCLUSIONS: Number of risk factors was strongly associated with advanced-stage CKD.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Estudos Transversais , Taxa de Filtração Glomerular , Fatores de Risco , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologiaRESUMO
BACKGROUND: Only a small fraction of patients with atherosclerotic renovascular disease (ARVD) treated with revascularization have improved renal function after the procedure. It has been suggested that this may be due to effects of renal microvascular disease. Our aim was to measure the effect of renal artery stenosis (RAS) revascularization on renal perfusion in patients with renovascular disease. METHODS: Seventeen renovascular disease patients were treated by dilatation of unilateral (N = 8) or bilateral (N = 9) RAS (N = 23 kidneys), mainly because of uncontrolled or refractory hypertension. The patients were studied before and after (103 ± 29 days) the procedure. Renal perfusion was measured using quantitative positron emission tomography (PET) perfusion imaging. RESULTS: Although renal perfusion correlated inversely with the degree of RAS in patients with renovascular disease, it did not change after revascularization. CONCLUSIONS: Our data support the notion of former clinical trials that angiographic severity of RAS does not determine the response to revascularization. Quantitative PET perfusion imaging is a promising tool to noninvasively measure renal perfusion for the assessment of physiological impact of RAS.
Assuntos
Angioplastia/métodos , Aterosclerose/cirurgia , Hipertensão Renovascular/cirurgia , Obstrução da Artéria Renal/cirurgia , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/diagnóstico por imagem , Aterosclerose/fisiopatologia , Feminino , Humanos , Hipertensão Renovascular/diagnóstico por imagem , Hipertensão Renovascular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/fisiopatologia , Circulação RenalRESUMO
AIMS: To characterize clinical profiles, prevalence of chronic kidney disease (CKD), and treatment patterns in type 2 diabetes (T2D) and heart failure (HF) patients in Finnish primary care. METHODS: A total of 1385 patients (1196 with T2D, 50 with HF, and 139 with T2D and HF) in 60 Finnish primary care centers were recruited to this cross-sectional study. Data on demographic and clinical characteristics, laboratory measurements, and medications were collected retrospectively from medical records. T2D patients were classified according to their risk of cardiovascular (CV) events as very high-risk (62%) and other patients (38%). RESULTS: Of the T2D patients, 10% (139/1335) had a diagnosis of HF and 42% (457/1090) had stage 3-5 CKD and/or albuminuria based on laboratory measurement. Of the HF patients, 74% (139/189) had T2D and 78% (114/146) had stage 3-5 CKD and/or albuminuria. Metformin was the most frequently used medication in both very high-risk patients (74%) and other patients (86%). SGLT2 inhibitors and/or GLP-1 analogues were used by 37% of very high-risk patients compared to 42% in other patients. CONCLUSIONS: The majority of T2D patients in Finnish primary care are at very high risk of cardiovascular events. However, the implementation of treatments with proven cardioprotective effects in very high-risk patients is currently suboptimal.