RESUMEN
BACKGROUND AND AIM: Chronic kidney disease (CKD) affects gastrointestinal (GI) function and results in numerous adaptive and maladaptive responses. Disruption of the colonic microbiome and its attendant consequences-the loss of gut barrier integrity and increased generation of uremic toxins-has become well-recognized. However, less attention has been paid to characterizing the mechanisms behind dysfunction of the upper GI tract, largely owing to the difficulty of studying small bowel function in vivo. This present study was designed to comprehensively describe upper GI function in those with advanced renal impairment. METHODS: Thirty-five non-diabetic subjects (12 CKD stage 4/5 patients, 23 healthy controls) underwent detailed GI magnetic resonance imaging (MRI) in both fasted and fed states. Upper GI function was assessed by quantification of gastric emptying and intra-luminal small bowel water. Characterization of hydration and cardiovascular status was performed at baseline. Gut barrier integrity was assessed using serum endotoxin level. RESULTS: Chronic kidney disease was associated with dysmotility (gastric half-emptying time 96 ± 32 vs 74 ± 27 min, P = 0.04) and reduced fasting and post-prandial small bowel water (36 ± 22 mL vs 78 ± 42 mL, P < 0.001), reflecting abnormal digestive secretion, and absorption. This was related to the degree of endotoxemia (r = -0.60, P = 0.04) and poorer symptom scores, but not to disease severity, arterial stiffness or hydration status. CONCLUSION: Chronic kidney disease adversely affects digestive function. Abnormalities in digestive secretion and absorption may potentially have a broad impact in the prevention and treatment of both CKD and its complications. Further study is required to assess the factors that contribute to this dysfunction in a wider CKD population.
Asunto(s)
Endotoxinas/sangre , Enfermedades Gastrointestinales/etiología , Insuficiencia Renal Crónica/complicaciones , Adolescente , Adulto , Anciano , Agua Corporal/metabolismo , Digestión , Femenino , Vaciamiento Gástrico , Enfermedades Gastrointestinales/metabolismo , Enfermedades Gastrointestinales/fisiopatología , Humanos , Absorción Intestinal , Intestino Delgado/metabolismo , Masculino , Persona de Mediana Edad , Periodo Posprandial , Adulto JovenRESUMEN
BACKGROUND/AIMS: Endotoxaemia, a driver of systemic inflammation, appears to be driven by dialysis-induced circulatory stress in haemodialysis (HD) patients. More frequent HD regimens are associated with lower ultrafiltration requirements, improved haemodynamic stability and lower systemic inflammation. This study investigated the hypothesis that more frequently dialysed patients, with reduced exposure to dialysis-induced haemodynamic perturbation, would have lower circulating endotoxin (ET) levels. METHODS: A cross-sectional study of 86 established HD patients compared three groups: conventional HD 3× per week (HD3, n = 56), frequent HD 5-6× per week (SDHD, n = 20), and nocturnal HD (NHD, n = 10). Data collection included ultrafiltration volume and rate, serial blood pressures and blood sampling with quantification of ET, troponin T and high-sensitivity CRP (hsCRP). RESULTS: Pre-dialysis serum ET was highest in the conventional HD group (HD3 0.66 ± 0.29 EU/ml vs. NHD 0.08 ± 0.04 EU/ml). Across the study population, severity of endotoxaemia was associated with higher ultrafiltration rates, degree of intradialytic hypotension, troponin T and hsCRP levels. NHD patients had the lowest ultrafiltration requirements, the greatest haemodynamic stability and lower ET levels. CONCLUSION: More frequent HD regimens are associated with lower levels of circulating ET compared with conventional HD. Reduced ET translocation may be related to the greater haemodynamic stability of these treatments, with superior maintenance of splanchnic perfusion.
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Endotoxemia/sangre , Endotoxemia/prevención & control , Endotoxinas/sangre , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Diálisis Renal/métodos , Diálisis Renal/estadística & datos numéricos , Estudios Transversales , Humanos , Inflamación/sangre , Masculino , Persona de Mediana Edad , Troponina T/sangreRESUMEN
BACKGROUND/AIMS: Haemodialysis causes recurrent haemodynamic stress with subsequent ischaemic end-organ dysfunction. As dialysis prescriptions/schedules can be modified to lessen this circulatory stress, an easily applicable test to allow targeted interventions in vulnerable patients is urgently required. METHODS: Intra-dialytic central venous oxygen saturation (ScvO2) and clinical markers (including ultrafiltration, blood pressure) were measured in 18 prevalent haemodialysis patients. RESULTS: Pre-dialysis ScvO2 was 63.5 ± 13% and fell significantly to 56.4 ± 8% at end dialysis (p = 0.046). Ultrafiltration volume, a key driver of dialysis-induced myocardial ischaemia, inversely correlated to ScvO2 (r = -0.680, p = 0.015). CONCLUSIONS: This initial study demonstrates ScvO2 sampling is practical, with a potential clinical utility as an indicator of circulatory stress during dialysis.
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Circulación Sanguínea , Oxígeno/sangre , Diálisis Renal , Estrés Fisiológico , Anciano , Biomarcadores/sangre , Análisis de los Gases de la Sangre , Femenino , Humanos , Masculino , VenasRESUMEN
Psychologists practicing in Canada must decide which set of normative data to use for the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV). The purpose of this study was to compare the interpretive effects of applying American versus Canadian normative systems in a sample of 432 Canadian postsecondary-level students who were administered the WAIS-IV as part of an evaluation for a learning disability, attention-deficit hyperactivity disorder, or other mental health problems. Employing the Canadian normative system yielded IQ, Index, and subtest scores that were systematically lower than those obtained using the American norms. Furthermore, the percentage agreement in normative classifications, defined as American and Canadian index scores within five points or within the same classification range, was between 49% and 76%. Substantial differences are present between the American and Canadian WAIS-IV norms. Clinicians should consider carefully the implications regarding which normative system is most appropriate for specific types of evaluations.
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Escalas de Wechsler/estadística & datos numéricos , Adolescente , Adulto , Canadá , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND/OBJECTIVES: Translocated endotoxin derived from intestinal bacteria is a driver of systemic inflammation and oxidative stress. Severe endotoxaemia is an underappreciated, but characteristic finding in haemodialysis (HD) patients, and appears to be driven by acute repetitive dialysis induced circulatory stress. Resistance to erythropoietin (EPO) has been identified as a predictor of mortality risk, and associated with inflammation and malnutrition. This study aims to explore the potential link between previously unrecognised endotoxaemia and EPO Resistance Index (ERI) in HD patients. METHODOLOGY/PRINCIPAL FINDINGS: 50 established HD patients were studied at a routine dialysis session. Data collection included weight, BMI, ultrafiltration volume, weekly EPO dose, and blood sampling pre and post HD. ERI was calculated as ratio of total weekly EPO dose to body weight (U/kg) to haemoglobin level (g/dL). Mean haemoglobin (Hb) was 11.3±1.3 g/dL with a median EPO dose of 10,000 [IQR 7,500-20,000] u/wk and ERI of 13.7 [IQR 6.9-23.3] ((U/Kg)/(g/dL)). Mean pre-HD serum ET levels were significantly elevated at 0.69±0.30 EU/ml. Natural logarithm (Ln) of ERI correlated to predialysis ET levels (râ=â0.324, pâ=â0.03) with a trend towards association with hsCRP (râ=â0.280, pâ=â0.07). Ln ERI correlated with ultrafiltration volume, a driver of circulatory stress (râ=â0.295, pâ=â0.046), previously identified to be associated with increased intradialytic endotoxin translocation. Both serum ET and ultrafiltration volume corrected for body weight were independently associated with Ln ERI in multivariable analysis. CONCLUSIONS: This study suggests that endotoxaemia is a significant factor in setting levels of EPO requirement. It raises the possibility that elevated EPO doses may in part merely be identifying patients subjected to significant circulatory stress and suffering the myriad of negative biological consequences arising from sustained systemic exposure to endotoxin.
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Endotoxemia/etiología , Eritropoyetina/efectos adversos , Diálisis Renal/efectos adversos , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Análisis Multivariante , Factores de RiesgoRESUMEN
BACKGROUND AND OBJECTIVES: Endotoxin (ET) is recognized to cause adverse effects on cardiovascular (CV) structure. Circulatory translocation of gut bacterial ET is described in heart failure. Chronic kidney disease (CKD) is common in older people and aggressive BP control is the cornerstone of management. We therefore studied ET after improvement of the overall CV milieu with introduction of optimized antihypertensive therapy (AHT). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We recruited 40 hypertensive nondiabetic patients (≥70 years) with CKD stages 3 and 4 and hypertensive non-CKD matched controls. Assessment was performed after complete AHT washout and repeated after AHT reintroduction to target BP 130/80 mmHg. Pulse wave velocity (PWV) and analysis were assessed by applanation tonometry, central hemodynamics by continuous digital pulse wave analysis, vascular calcification (VC) by superficial femoral artery CT, and serum ET by Limulus Amebocyte assay. RESULTS: Mean age was 76 ± 5 years, estimated GFR (eGFR) (CKD group) was 40 ± 14 ml/min per 1.73 m(2), and achieved BP was 128/69 mmHg. Washout ET was 0.042 ± 0.011 EU/ml and was independent of renal function, gender, age, BP, VC, arterial stiffness, and high-sensitivity C-reactive protein. ET significantly decreased with AHT (to 0.020 ± 0.028 EU/ml; P < 0.001) and was associated with eGFR (R = -0.38; P = 0.02), arterial wave reflection (Augmentation Index R = -0.42; P = 0.01), and degree of tonic vasodilatation (total peripheral resistance R = -0.37; P = 0.03), but not VC, PWV, gender, age, BP, or high-sensitivity C-reactive protein. CONCLUSIONS: Elderly patients with hypertension have elevated serum ET. Improvement of their CV status with optimized AHT is associated with a significant reduction in endotoxemia. Further investigation of the potential pathophysiological mechanisms linking CV disease and CKD with this previously unappreciated effect of AHT appears warranted.
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Antihipertensivos/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Endotoxemia/prevención & control , Hipertensión/tratamiento farmacológico , Enfermedades Renales/complicaciones , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Presión Sanguínea/efectos de los fármacos , Proteína C-Reactiva/metabolismo , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Enfermedad Crónica , Progresión de la Enfermedad , Endotoxemia/sangre , Endotoxemia/complicaciones , Endotoxinas/sangre , Inglaterra , Femenino , Tasa de Filtración Glomerular , Hemodinámica/efectos de los fármacos , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Enfermedades Renales/fisiopatología , Masculino , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
BACKGROUND AND OBJECTIVES: Translocated endotoxin derived from intestinal bacteria has a wide range of adverse effects on cardiovascular (CV) structure and function, driving systemic inflammation, atherosclerosis and oxidative stress. This study's aim was to investigate endotoxemia across the spectrum of chronic kidney disease (CKD). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Circulating endotoxin was measured in 249 patients comprising CKD stage 3 to 5 and a comparator cohort of hypertensive patients without significant renal impairment. Patients underwent extended CV assessment, including pulse wave velocity and vascular calcification. Hemodialysis (HD) patients also received detailed echocardiographic-based intradialytic assessments. Patients were followed up for 1 year to assess survival. RESULTS: Circulating endotoxemia was most notable in those with the highest CV disease burden (increasing with CKD stage), and a sharp increase was observed after initiation of HD. In HD patients, predialysis endotoxin correlated with dialysis-induced hemodynamic stress (ultrafiltration volume, relative hypotension), myocardial stunning, serum cardiac troponin T, and high-sensitivity C-reactive protein. Endotoxemia was associated with risk of mortality. CONCLUSIONS: CKD patients are characteristically exposed to significant endotoxemia. In particular, HD-induced systemic circulatory stress and recurrent regional ischemia may lead to increased endotoxin translocation from the gut. Resultant endotoxemia is associated with systemic inflammation, markers of malnutrition, cardiac injury, and reduced survival. This represents a crucial missing link in understanding the pathophysiology of the grossly elevated CV disease risk in CKD patients, highlighting the potential toxicity of conventional HD and providing a novel set of potential therapeutic strategies to reduce CV mortality in CKD patients.