RESUMO
BACKGROUND: Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain. METHODS: We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy). RESULTS: Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg; 95% CI, -4.4 to -0.2; P=0.03). CONCLUSIONS: Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.).
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Obstrução da Artéria Renal/terapia , Stents , Idoso , Anlodipino/uso terapêutico , Angioplastia com Balão , Anticolesterolemiantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Terapia Combinada , Combinação de Medicamentos , Feminino , Seguimentos , Ácidos Heptanoicos/uso terapêutico , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pirróis/uso terapêutico , Artéria Renal , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Falha de TratamentoRESUMO
PURPOSE: To describe the experience and results from the roll-in phase of the Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) study. MATERIALS AND METHODS: The CORAL roll-in database was used to describe the baseline characteristics of the patients in the roll-in cohort, all of whom underwent renal artery stent placement; to evaluate CORAL site performance; to compare estimates of lesion (stenosis) severity made by site interventionalists with the central CORAL angiographic core laboratory readings; and to report outcomes after renal artery stent placement. During the roll-in phase, 239 patients (mean age, 70.2 y ± 9.0; 49% male) underwent renal artery stent procedures. Angiographic core laboratory analysis of renal arteriograms was done, and participants were followed at 1 month and 9 months. RESULTS: Major angiographic complications were identified in 28 (13%) subjects. Kidney function remained unchanged at the short (2-4 weeks) follow-up interval. Improvement in systolic blood pressure with use of distal embolic protection devices (n = 161) did not show any clinical benefit over nonuse of such devices (n = 78) in this small series. At 9 months, there were significantly more endpoints reported by site in subjects with bilateral renal artery stenosis (P = .01) and prior history of stroke (P = .03). CONCLUSIONS: In the roll-in phase of the CORAL study, a significant number of angiographic complications were identified. No effect was seen on estimated glomerular filtration rate after renal artery stent placement, but systolic blood pressure decreased significantly.
Assuntos
Angioplastia com Balão , Aterosclerose/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde , Obstrução da Artéria Renal/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/instrumentação , Aterosclerose/diagnóstico , Aterosclerose/fisiopatologia , Pressão Sanguínea , Competência Clínica , Bases de Dados Factuais , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Hipertensão/terapia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Obstrução da Artéria Renal/diagnóstico , Obstrução da Artéria Renal/fisiopatologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Índice de Gravidade de Doença , Stents , Fatores de Tempo , Resultado do TratamentoRESUMO
Intradialytic hypotension continues to play a significant role in the morbidity and in some cases the mortality associated with maintenance hemodialysis. Greater precision in the determination of dry weight using bioimpedance technology and biofeedback systems designed to prevent rapid fluctuations in blood volume have recently been shown to decrease the frequency of this complication. Pharmacologic strategies designed to maintain peripheral vascular resistance in patients with insufficient release of endogenous vasoconstrictors continue to be explored. The sudden development of intradialytic hypotension may respond to specific antagonists to hypotensive mediators.
Assuntos
Determinação da Pressão Arterial , Hipotensão/etiologia , Hipotensão/prevenção & controle , Monitorização Fisiológica/métodos , Diálise Renal/efeitos adversos , Volume Sanguíneo , Humanos , Hipotensão/epidemiologia , Volume PlasmáticoRESUMO
Background Early rapid declines of kidney function may occur in patients with atherosclerotic renal artery stenosis with institution of medical therapy. The causes and consequences are not well understood. Methods and Results Patients enrolled in the medical therapy-only arm of the CORAL (Cardiovascular Outcomes With Renal Artery Lesions) study were assessed for a rapid decline (RD) in estimated glomerular filtration rate (eGFR), defined as a ≥30% decrease from baseline to either 3 months, 6 months, or both. In the medical therapy-only cohort, eGFR was available in 359 subjects at all time points, the subjects were followed for a median of 4.72 years, and 66 of 359 (18%) subjects experienced an early RD. Baseline log cystatin C (odds ratio, 1.78 [1.11-2.85]; P=0.02), age (odds ratio, 1.04 [1.00-1.07]; P<0.05), and Chronic Kidney Disease Epidemiology Collaboration creatinine eGFR (odds ratio, 1.86 [1.15-3.0]; P=0.01) were associated with an early RD. Despite continued medical therapy only, the RD group had an improvement in eGFR at 1 year (6.9%; P=0.04). The RD and nondecline groups were not significantly different for clinical events and all-cause mortality (P=0.78 and P=0.76, respectively). Similarly, renal replacement therapy occurred in 1 of 66 (1.5%) of the RD patients and in 6 of 294 (2%) of the nondecline patients. The regression to the mean of improvement in eGFR at 1 year in the RD group was estimated at 5.8±7.1%. Conclusions Early rapid declines in kidney function may occur in patients with renal artery stenosis when medical therapy is initiated, and their clinical outcomes are comparable to those without such a decline, when medical therapy only is continued.
Assuntos
Fármacos Cardiovasculares/uso terapêutico , Taxa de Filtração Glomerular , Rim/irrigação sanguínea , Rim/fisiopatologia , Obstrução da Artéria Renal/tratamento farmacológico , Idoso , Fármacos Cardiovasculares/efeitos adversos , Causas de Morte , Progressão da Doença , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/mortalidade , Obstrução da Artéria Renal/fisiopatologia , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Data derived from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study were analyzed in an effort to employ machine learning methods to predict the composite endpoint described in the original study. METHODS: We identified 573 CORAL subjects with complete baseline data and the presence or absence of a composite endpoint for the study. These data were subjected to several models including a generalized linear (logistic-linear) model, support vector machine, decision tree, feed-forward neural network, and random forest, in an effort to attempt to predict the composite endpoint. The subjects were arbitrarily divided into training and testing subsets according to an 80%:20% distribution with various seeds. Prediction models were optimized within the CARET package of R. RESULTS: The best performance of the different machine learning techniques was that of the random forest method which yielded a receiver operator curve (ROC) area of 68.1%±4.2% (mean ± SD) on the testing subset with ten different seed values used to separate training and testing subsets. The four most important variables in the random forest method were SBP, serum creatinine, glycosylated hemoglobin, and DBP. Each of these variables was also important in at least some of the other methods. The treatment assignment group was not consistently an important determinant in any of the models. CONCLUSION: Prediction of a composite cardiovascular outcome was difficult in the CORAL population, even when employing machine learning methods. Assignment to either the stenting or best medical therapy group did not serve as an important predictor of composite outcome. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00081731.
Assuntos
Insuficiência Renal Crônica/terapia , Anemia/tratamento farmacológico , Anemia/etiologia , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapia , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/complicações , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Proteinúria/tratamento farmacológico , Insuficiência Renal Crônica/classificação , Insuficiência Renal Crônica/etiologia , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731) clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931) were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p<0.001). In addition, patients who smoke were also more likely to have bilateral renal artery stenoses and peripheral vascular disease (PVD). Longitudinal analysis showed that smokers experienced composite endpoint events (defined as first occurrence of: stroke; cardiovascular or renal death; myocardial infarction; hospitalization for congestive heart failure; permanent renal replacement; and progressive renal insufficiency defined as 30% reduction of GFR from baseline sustained for ≥ 60 days) at a substantially younger age compared to non-smokers (67.1±9.0 versus 76.1±7.9, p<0.001). Using linear regression and generalized linear modeling analysis controlled by age, sex, and ethnicity, smokers had significantly higher cystatin C levels (1.3±0.7 vs 1.2±0.9, p<0.01) whereas creatinine and estimated glomerular filtration rate (eGFR) were not different from non-smokers. From these data we conclude that smoking has a significant association with deleterious cardio-renal outcomes in patients with renovascular hypertension.
Assuntos
Aterosclerose/complicações , Doenças Cardiovasculares/complicações , Nicotiana , Obstrução da Artéria Renal/complicações , Fumar , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Estudos de Casos e Controles , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Obstrução da Artéria Renal/fisiopatologiaRESUMO
BACKGROUND: Atherosclerotic renal artery stenosis is a problem with no consensus on diagnosis or therapy. The consequences of renal ischemia are neuroendocrine activation, hypertension, and renal insufficiency that can potentially result in acceleration of atherosclerosis, further renal dysfunction, myocardial infarction, heart failure, stroke, and death. Whether revascularization improves clinical outcomes when compared with optimum medical therapy is unknown. METHODS: CORAL is a randomized clinical trial contrasting optimum medical therapy alone to stenting with optimum medical therapy on a composite cardiovascular and renal end point: cardiovascular or renal death, myocardial infarction, hospitalization for congestive heart failure, stroke, doubling of serum creatinine, and need for renal replacement therapy. The secondary end points evaluate the effectiveness of revascularization in important subgroups of patients and with respect to all-cause mortality, kidney function, renal artery patency, microvascular renal function, and blood pressure control. We will also correlate stenosis severity with longitudinal renal function and determine the value of stenting from the perspectives of quality of life and cost-effectiveness. The primary entry criteria are (1) an atherosclerotic renal stenosis of > or = 60% with a 20 mm Hg systolic pressure gradient or > or = 80% with no gradient necessary and (2) systolic hypertension of > or = 155 mm Hg on > or = 2 antihypertensive medications. Randomization will occur in 1080 subjects. The study has 90% power to detect a 28% reduction in primary end point hazard rate. CONCLUSIONS: CORAL represents a unique opportunity to determine the incremental value of stent revascularization, in addition to optimal medical therapy, for the treatment of atherosclerotic renal artery stenosis.
Assuntos
Angioplastia com Balão , Doenças Cardiovasculares/etiologia , Obstrução da Artéria Renal/terapia , Stents , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Aterosclerose/terapia , Benzimidazóis/uso terapêutico , Compostos de Bifenilo , Doenças Cardiovasculares/prevenção & controle , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Hipertensão/etiologia , Hipertensão/prevenção & controle , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/fisiopatologia , Masculino , Seleção de Pacientes , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/mortalidade , Obstrução da Artéria Renal/fisiopatologia , Projetos de Pesquisa , Fatores de Risco , Tetrazóis/uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVES: Atherosclerotic renal artery stenosis may cause kidney function loss, but effects of stenting on eGFR and clinical events associated with CKD are uncertain. Our study objectives were to determine effects of stenting on eGFR and predictors of clinical events. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants (n=931) in the Cardiovascular Outcomes in Renal Artery Stenosis Trial (from May of 2005 to September of 2012) had >60% atherosclerotic renal artery stenosis and systolic hypertension on two or more antihypertensive drugs and/or stage ≥3 CKD. The intervention was stenting versus no stenting on a background of risk factor management: renin-angiotensin system inhibition, statin, antiplatelet therapy, and smoking cessation education. The effect of stenting on eGFR by the serum creatinine-cystatin C Chronic Kidney Disease Epidemiology Collaboration equation was the prespecified analysis of kidney function. Predictors of eGFR and CKD outcomes (≥30% eGFR loss, ESRD, and death) and cardiovascular disease outcomes (stroke, myocardial infarction, heart failure, and death) controlling for eGFR and albuminuria were also determined. RESULTS: eGFR was 59±24 ml/min per 1.73 m(2) (mean±SD) at baseline. Over 3 years, eGFR change, assessed by generalized estimating equations, was -1.5±7.0 ml/min per 1.73 m(2) per year in the stent group versus -2.3±6.3 ml/min per 1.73 m(2) per year in the medical therapy only group (P=0.18). eGFR predictors (multiple variable generalized estimating equations) were age, albuminuria, systolic BP, and diabetes (inverse associations) as well as men, total cholesterol, and HDL cholesterol (positive associations). CKD outcomes events occurred in 19% (175 of 931), and predictors (Cox proportional hazards models) included albuminuria (positive association), systolic BP (positive association), and HDL cholesterol (inverse association). Cardiovascular disease outcomes events occurred in 22% (207 of 931), and predictors included age, albuminuria, total cholesterol, prior cardiovascular disease, and bilateral atherosclerotic renal artery stenosis (positive associations). CONCLUSIONS: Stenting did not influence eGFR in participants with atherosclerotic renal artery stenosis receiving renin-angiotensin system inhibition-based therapy. Predictors of clinical events were traditional risk factors for CKD and cardiovascular disease.
Assuntos
Doenças Cardiovasculares/etiologia , Taxa de Filtração Glomerular , Obstrução da Artéria Renal/fisiopatologia , Obstrução da Artéria Renal/terapia , Insuficiência Renal Crônica/fisiopatologia , Stents , Fatores Etários , Idoso , Albuminúria/etiologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Pressão Sanguínea , HDL-Colesterol/sangue , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Estimativa de Kaplan-Meier , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Modelos de Riscos Proporcionais , Obstrução da Artéria Renal/etiologia , Insuficiência Renal Crônica/complicações , Fatores Sexuais , Abandono do Hábito de FumarRESUMO
Randomized clinical trials have not shown an additional clinical benefit of renal artery stent placement over optimal medical therapy alone. However, studies of renal artery stent placement have not examined the relationship of albuminuria and treatment group outcomes. The CORAL study (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) is a prospective clinical trial of 947 participants with atherosclerotic renal artery stenosis randomized to optimal medical therapy with or without renal artery stent which showed no treatment differences (3(5.8% and 35.1% event rate at mean 43-month follow-up). In a post hoc analysis, the study population was stratified by the median baseline urine albumin/creatinine ratio (n=826) and analyzed for the 5-year incidence of the primary end point (myocardial infarction, hospitalization for congestive heart failure, stroke, renal replacement therapy, progressive renal insufficiency, or cardiovascular disease- or kidney disease-related death), for each component of the primary end point, and overall survival. When baseline urine albumin/creatinine ratio was ≤ median (22.5 mg/g, n=413), renal artery stenting was associated with significantly better event-free survival from the primary composite end point (73% versus 59% at 5 years; P=0.02), cardiovascular disease-related death (93% versus 85%; P≤ 0.01), progressive renal insufficiency (91% versus 77%; P=0.03), and overall survival (89% versus 76%; P≤0.01), but not when baseline urine albumin/creatinine ratio was greater than median (n=413). These data suggest that low albuminuria may indicate a potentially large subgroup of those with renal artery stenosis that could experience improved event-free and overall-survival after renal artery stent placement plus optimal medical therapy compared with optimal medical therapy alone. Further research is needed to confirm these preliminary observations. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00081731.
Assuntos
Albuminúria/epidemiologia , Obstrução da Artéria Renal/epidemiologia , Obstrução da Artéria Renal/terapia , Stents , Vasodilatadores/administração & dosagem , Idoso , Albuminúria/diagnóstico , Albuminúria/terapia , Comorbidade , Intervalos de Confiança , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Obstrução da Artéria Renal/diagnóstico , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do TratamentoRESUMO
The goal of risk stratification of CVD inpatients with CKD is to lead to effective and early intervention and to prevent the adverse outcomes associated with this complex multisystem disease that is characteristic of growing number of patients with CKD in the general population and of patients receiving dialysis therapy or kidney transplantation. By 2030, there will be 2.24 million patients with ESRD in the United States, and approximately 1.3 million of these cases of ESRD will be caused by diabetes mellitus. Thus, CVD in this high-risk population presents a challenge for the nephrology and the cardiology community.
Assuntos
Doenças Cardiovasculares/etiologia , Nefropatias/complicações , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Doença Crônica , Humanos , Nefropatias/fisiopatologia , Nefropatias/terapia , Diálise Renal , Fatores de Risco , Índice de Gravidade de DoençaAssuntos
Comércio , Conflito de Interesses , Nefrologia , Política Organizacional , Sociedades Médicas/normas , HumanosRESUMO
BACKGROUND: Multiple randomized clinical trials comparing renal artery stent placement plus medical therapy with medical therapy alone have not shown any benefit of stent placement. However, debate continues whether patients with extreme pressure gradients, stenosis severity, or baseline blood pressure benefit from stent revascularization. OBJECTIVES: The study sought to test the hypothesis that pressure gradients, stenosis severity, and/or baseline blood pressure affects outcomes after renal artery stent placement. METHODS: Using data from 947 patients with a history of hypertension or chronic kidney disease from the largest randomized trial of renal artery stent placement, the CORAL (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) study, we performed exploratory analyses to determine if subsets of patients experienced better outcomes after stent placement than the overall cohort. We examined baseline stenosis severity, systolic blood pressure, and translesion pressure gradient (peak systolic and mean) and performed interaction tests and Cox proportional hazards analyses for the occurrence of the primary endpoint through all follow-up, to examine the effect of these variables on outcomes by treatment group. RESULTS: There were no statistically significant differences in outcomes based on the examined variables nor were there any consistent nonsignificant trends. CONCLUSIONS: Based on data from the CORAL randomized trial, there is no evidence of a significant treatment effect of the renal artery stent procedure compared with medical therapy alone based on stenosis severity, level of systolic blood pressure elevation, or according to the magnitude of the trans-stenotic pressure gradient. (Benefits of Medical Therapy Plus Stenting for Renal Atherosclerotic Lesions [CORAL]; NCT00081731).
Assuntos
Obstrução da Artéria Renal/fisiopatologia , Obstrução da Artéria Renal/terapia , Stents , Pressão Sanguínea/fisiologia , Estudos de Coortes , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertensão/terapia , Obstrução da Artéria Renal/patologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do TratamentoRESUMO
For people enrolled in Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL), we sought to examine whether variation exists in the baseline medical therapy of different geographic regions and if any variations in prescribing patterns were associated with physician specialty. Patients were grouped by location within the United States (US) and outside the US (OUS), which includes Canada, South America, Europe, South Africa, New Zealand, and Australia. When comparing US to OUS, participants in the US took fewer anti-hypertensive medications (1.9 ± 1.5 vs. 2.4 ± 1.4; P < .001) and were less likely to be treated with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (46% vs. 62%; P < .001), calcium channel antagonist (37% vs. 58%; P < .001), and statin (64% vs. 75%; P < .05). In CORAL, the identification of variations in baseline medical therapy suggests that substantial opportunities exist to improve the medical management of patients with atherosclerotic renal-artery stenosis.
Assuntos
Anti-Hipertensivos/uso terapêutico , Aterosclerose/patologia , Hipertensão Renal/diagnóstico , Hipertensão Renal/tratamento farmacológico , Obstrução da Artéria Renal/terapia , Idoso , Anti-Hipertensivos/farmacologia , Aterosclerose/terapia , Canadá , Gerenciamento Clínico , Europa (Continente) , Feminino , Humanos , Internacionalidade , Modelos Lineares , Masculino , Medicina , Pessoa de Meia-Idade , Análise Multivariada , Nova Zelândia , Padrões de Prática Médica , Estudos Prospectivos , Obstrução da Artéria Renal/patologia , Medição de Risco , Índice de Gravidade de Doença , África do Sul , América do Sul , Estados UnidosRESUMO
BACKGROUND: The cytochrome p450 (CYP) oxidative enzyme system, located primarily in the liver and small intestine, is responsible for metabolism and detoxification of numerous endogenous and exogenous substances. The most abundant CYP enzyme, CYP3A, is known to be involved in the metabolism of more than 200 commonly used medications. In experimental models of renal failure, both hepatic function and CYP enzyme content are reduced; however, direct evidence in humans is lacking. Evaluation of drug metabolism in patients with end-stage renal disease is important because these patients use a large number of medications and are at risk of adverse reactions and drug-drug interactions. METHODS: We measured hepatic CYP3A activity at baseline and after rifampin (INN, rifampicin) enzyme induction in 12 patients with end-stage renal disease and 12 healthy, age-matched controls. Hepatic CYP3A phenotype was characterized with the erythromycin breath test, and enzyme induction capacity was evaluated with a short course of rifampin (600 mg/d for 6 days). RESULTS: The end-stage renal disease group had 28% lower baseline erythromycin breath test values than controls (P <.05); however, enzyme induction capacity after rifampin administration was similar between groups (P =.70). CONCLUSION: The findings suggested that one mechanism by which patients with end-stage renal disease are at increased risk of drug toxicity is reduced activity of the CYP3A enzyme pathway.
Assuntos
Hidrocarboneto de Aril Hidroxilases/metabolismo , Falência Renal Crônica/enzimologia , Fígado/enzimologia , Oxirredutases N-Desmetilantes/metabolismo , Adulto , Idoso , Antibióticos Antituberculose/farmacologia , Hidrocarboneto de Aril Hidroxilases/biossíntese , Testes Respiratórios , Citocromo P-450 CYP3A , Indução Enzimática/efeitos dos fármacos , Eritromicina , Feminino , Humanos , Fígado/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Oxirredutases N-Desmetilantes/biossíntese , Fenótipo , Estudos Prospectivos , Inibidores da Síntese de Proteínas , Rifampina/farmacologiaRESUMO
CONTEXT: Cardiac troponin T (cTnT) and C-reactive protein (CRP) are prognostic markers in acute coronary syndromes. However, for patients with end-stage renal disease (ESRD) the ability of combinations of these markers to predict outcomes, and their association with cardiac pathology, are unclear. OBJECTIVE: To investigate the association between levels of cTnT and CRP and long-term risk of cardiac pathology and death in patients with ESRD. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study initiated February through June 1998 and enrolling 224 patients with ESRD from 5 hemodialysis centers in the Houston-Galveston region of Texas. Levels of cTnT and CRP were analyzed at study entry in patients without ischemic symptoms. MAIN OUTCOME MEASURES: All-cause mortality during a mean follow-up of 827 (range, 29-1327) days. Secondary outcomes in predefined substudies were coronary artery disease (CAD), decreased (< or =40%) left ventricular ejection fraction (LVEF), and presence of left ventricular hypertrophy (LVH). RESULTS: One hundred seventeen (52%) patients died during follow-up. For levels of cTnT and CRP, progressively higher levels predicted increased risk of death compared with the lowest quartile (for cTnT quartile 2: unadjusted hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.2-4.1; quartile 3: HR, 2.7; 95% CI, 1.5-4.9; quartile 4: HR, 3.0; 95% CI, 1.6-5.3. For CRP quartile 2: HR, 0.9; 95% CI, 0.5-1.6; quartile 3: HR, 1.8; 95% CI, 1.1-3.1; quartile 4: HR, 1.8; 95% CI, 1.1-3.2). Both cTnT and CRP remained independent predictors of death after adjusting for a number of potential confounders. The combination of cTnT and CRP results provided prognostic information when patients were divided into groups at or above and below the biomarker medians (high cTnT/high CRP levels vs low cTnT/low CRP levels for risk of death: HR, 2.5; 95% CI, 1.5-4.0). Elevated levels of cTnT, but not CRP, were strongly associated with diffuse CAD (n = 67; 0%, 25%, 50%, and 62% prevalence of multivessel CAD across progressive cTnT quartiles, P<.001). An LVEF of 40% or less was identified in 4 (9%), 3 (8%), 10 (27%), and 7 (19%) of patients across cTnT quartiles (P =.07). No trend for cTnT levels was found among patients with LVH (P =.45); similarly, no trend for CRP was found among patients with LVH (P =.65) or an LVEF of 40% or less (P =.75). CONCLUSIONS: Among stable patients with ESRD, increasing levels of cTnT and CRP are associated with increased risk of death. Furthermore, higher levels of cTnT may identify patients with severe angiographic coronary disease.
Assuntos
Proteína C-Reativa/metabolismo , Cardiomiopatias/sangue , Cardiomiopatias/epidemiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Diálise Renal , Troponina T/sangue , Idoso , Biomarcadores/sangue , Cardiomiopatias/complicações , Causas de Morte , Estudos de Coortes , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Ecocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/epidemiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Análise de Sobrevida , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/epidemiologiaRESUMO
BACKGROUND AND OBJECTIVES: People with atherosclerotic renal artery stenosis may benefit from renin-angiotensin inhibitors, angiotensin-converting enzyme inhibitors, and angiotensin-receptor blockers, but little is known about the factors associated with their use. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions study (ClinicalTrials.gov identified: NCT00081731) is a prospective, international, multicenter clinical trial that randomly assigned participants with atherosclerotic renal artery stenosis who received optimal medical therapy to stenting versus no stenting from May 2005 through January 2010. At baseline, medication information was available from 853 of 931 randomly assigned participants. Kidney function was measured by serum creatinine-based eGFR at a core laboratory. RESULTS: Before randomization, renin-angiotensin inhibitors were used in 419 (49%) of the 853 participants. Renin-angiotensin inhibitor use was lower in those with CKD (eGFR<60 ml/min per 1.73 m(2)) (58% versus 68%; P=0.004) and higher in individuals with diabetes (41% versus 27%; P<0.001). Presence of bilateral renal artery stenosis or congestive heart failure was not associated with renin-angiotensin inhibitor use. Although therapy with renin-angiotensin inhibitors varied by study site, differences in rates of use were not related to the characteristics of the site participants. Participants receiving a renin-angiotensin inhibitor had lower systolic BP (mean ± SD, 148 ± 23 versus 152 ± 23 mmHg; P=0.003) and more often had BP at goal (30% versus 22%; P=0.01). CONCLUSIONS: Kidney function and diabetes were associated with renin-angiotensin inhibitor use. However, these or other clinical characteristics did not explain variability among study sites. Patients with renal artery stenosis who received renin-angiotensin inhibitor treatment had lower BP and were more likely to be at treatment goal.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Aterosclerose/terapia , Obstrução da Artéria Renal/terapia , Sistema Renina-Angiotensina/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/diagnóstico , Aterosclerose/tratamento farmacológico , Aterosclerose/etnologia , Aterosclerose/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Comorbidade , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Obstrução da Artéria Renal/diagnóstico , Obstrução da Artéria Renal/tratamento farmacológico , Obstrução da Artéria Renal/etnologia , Obstrução da Artéria Renal/fisiopatologia , Fatores de Risco , Stents , Resultado do Tratamento , Estados Unidos/epidemiologiaAssuntos
Hipotensão , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Pressão Sanguínea/fisiologia , Volume Sanguíneo/fisiologia , Humanos , Hipotensão/epidemiologia , Hipotensão/etiologia , Hipotensão/fisiopatologia , Incidência , Prognóstico , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The safety and efficacy of different types of ß-blocker therapy in patients with non-dialysis-dependent chronic kidney disease (CKD) and systolic heart failure (HF) are not well described. We assessed whether treatment of systolic HF with carvedilol is efficacious and safe in adults with CKD. METHODS AND RESULTS: We performed a post hoc analysis of pooled individual patient data (n=4217) from 2 multinational, double-blinded, placebo-controlled, randomized trials, CAPRICORN (Carvedilol Postinfarct Survival Control in Left Ventricular Dysfunction Study) and COPERNICUS (Carvedilol Prospective Randomized, Cumulative Survival study). Primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, HF mortality, first HF hospitalization, the composite of cardiovascular mortality or first HF hospitalization, and sudden cardiac death. Non-dialysis-dependent CKD was defined by estimated glomerular filtration rate ≤60 mL/min/1.73 m(2), using the abbreviated Modification of Diet in Renal Disease equation. CKD was present in 2566 of 4217 (60.8%) of the cohort, 50.4% of whom were randomly assigned to carvedilol therapy. Within the CKD group, treatment with carvedilol decreased the risks of all-cause mortality (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63 to 0.93; P=0.007), cardiovascular mortality (HR, 0.76; 95% CI, 0.62 to 0.94; P=0.011), HF mortality (HR, 0.68; 95% CI, 0.52 to 0.88; P=0.003), first hospitalization for HF (HR, 0.74; 95% CI, 0.61 to 0.88; P=0.0009), and the composite of cardiovascular mortality or HF hospitalization (HR, 0.75; 95% CI, 0.65 to 0.87; P<0.001) but was without significant effect on sudden cardiac death (HR, 0.76; 95% CI, 0.56 to 1.05; P=0.098). There was no significant interaction between treatment arm and study type. Carvedilol was generally well tolerated by both groups of patients, with an increased relative incidence in transient increase in serum creatinine without need for dialysis and other electrolyte changes in the CKD patients. However, in a sensitivity analysis among HF subjects with estimated glomerular filtration rate <45 mL/min/1.73 m(2) (CKD stage 3b), the efficacy of carvedilol was not significantly different from placebo. CONCLUSIONS: This analysis suggests that the benefits of carvedilol therapy in patients with systolic left ventricular dysfunction with or without symptoms of HF are consistent even in the presence of mild to moderate CKD. Whether carvedilol therapy is similarly efficacious in HF patients with more advanced kidney disease requires further study.