Impacto do acompanhamento com bioimpedância na predição de eventos cardiovasculares em pacientes em diálise crônica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

METABOLIC IMPLICATIONS OF PERITONEAL DIALYSIS IN PATIENTS WITH ACUTE KIDNEY INJURY

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Hipertensão pulmonar em pacientes com doença renal crônica dialítica está associada com hipervolemia e inflação

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Hipertensão pulmonar em pacientes com doença renal crônica dialítica está associada com hipervolemia e inflação

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Associates of an elevated natriuretic peptide level in stable heart failure patients:implications for targeted management

BACKGROUND: Persistently elevated natriuretic peptide (NP) levels in heart failure (HF) patients are associated with impaired prognosis. Recent work suggests that NP-guided therapy can improve outcome, but the mechanisms behind an elevated BNP remain unclear. Among the potential stimuli for NP in clinically stable patients are persistent occult fluid overload, wall stress, inflammation, fibrosis, and ischemia. The purpose of this study was to identify associates of B-type natriuretic peptide (BNP) in a stable HF population.

METHODS: In a prospective observational study of 179 stable HF patients, the association between BNP and markers of collagen metabolism, inflammation, and Doppler-echocardiographic parameters including left ventricular ejection fraction (LVEF), left atrial volume index (LAVI), and E/e prime (E/e') was measured.

RESULTS: Univariable associates of elevated BNP were age, LVEF, LAVI, E/e', creatinine, and markers of collagen turnover. In a multiple linear regression model, age, creatinine, and LVEF remained significant associates of BNP. E/e' and markers of collagen turnover had a persistent impact on BNP independent of these covariates.

CONCLUSION: Multiple variables are associated with persistently elevated BNP levels in stable HF patients. Clarification of the relative importance of NP stimuli may help refine NP-guided therapy, potentially improving outcome for this at-risk population.

Aportación de la bioimpedancia espectroscópica en el estado nutricional y de hidratación del paciente en hemodiálisis: impacto en la morbi-mortalidad

Aportación de la bioimpedancia espectroscópica en la valoración del estado de nutrición e hidratación del paciente en hemodiálisis. Impacto en la morbimortalidad. Los pacientes con enfermedad renal crónica tienen una mortalidad muy superior a la población general, siendo la principal causa la cardiovascular (Foley et al. 2005; Locatelli et al. 2004). Como consecuencia del gran impacto que tienen el estado nutricional ( Pifer et al. 2002; Gracia Iguacel et al. 2013) y la sobrehidratación (Kalantar Zadeh et al. 2009; Wizemann et al. 2009; Agarwal et al. 2010; Chazot et al. 2012) en la mortalidad, en los ultimos años se han desarrollado distintos métodos de análisis de la composición corporal, entre los cuales se encuentra la Bioimpedancia Espectroscópica (BIS). Esta herramienta permite cuantificar los diversos compartimentos del cuerpo (fundamentalmente masa magra, masa grasa y agua corporal) proporcionando al clínico información útil para la toma de decisiones, fundamentalmente en lo que respecta a la sobrecarga de volumen, aspecto fundamental en el manejo del paciente en hemodiálisis (López Gómez et al. 2011). La justificación de esta investigación se basa en existen pocos estudios longitudinales que analicen la evolución en el tiempo de marcadores nutricionales bioquímicos clásicos así como parámetros de bioimpedancia y su asociación con la morbimortalidad; no existiendo aún consenso sobre si los distintos marcadores pronósticos son mas predictivos con medidas basales o con medidas de seguimiento en el tiempo, por lo que nuestro trabajo puede contribuir a clarificar este aspecto. Además, existe un desconocimiento sobre el estado inflamatorio, la prevalencia de DPE y de sobrehidratación en la población en hemodiálisis de nuestro entorno por lo que consideramos importante analizarla para saber dónde estamos y en qué podemos mejorar. Objetivos: 1.- Impacto de la composición corporal así como de marcadores nutricionales bioquímicos e inflamatorios seguidos en el tiempo, sobre la morbimortalidad (evento compuesto muerte-hospitalización). 2.- Prevalencia del Síndrome de Desgaste Proteico Energético en función de distintas herramientas utilizadas para su valoración (criterios ISRNM, score MIS, y bioimpedancia).3.-Correlación entre los parámetros de bioimpedancia y parámetros bioquímicos nutricionales e inflamatorios. 4.- Análisis de la evolución en el tiempo de los parámetros bioquímicos, antropométricos y de bioimpedancia en el global de la muestra y en distintos grupos atendiendo al sexo, presencia de diabetes y grado de inflamación.. Diseño: Estudio observacional prospectivo de 15 meses de duración (Octubre/2013-Dic/2014) en pacientes prevalentes en hemodiálisis. Se ha realizado un corte transversal con los datos del primer mes de inclusión del paciente en el estudio (basal), a partir del cual se ha iniciado el seguimiento en el tiempo cada 2 meses. La mediana de seguimiento del estudio ha sido de 12 meses (RI 10-13 m). Pacientes y métodos: el nº de pacientes incluidos en el estudio fue de 169. Se incluyeron los pacientes estables, con mas de 3 meses en HD, excluyendose pacientes con ingreso reciente, proceso infeccioso o inflamatorio en 3 meses previos, neoplasia activa, marcapasos unipolar o con umbral de sensibilidad desconocido. Todos los pacientes firmaron el consentimiento informado. La prevalencia de DPE se analizó en el momento inicial y final del estudio. Para el análisis de la morbimortalidad se consideraron todos los ingresos de causa no programada, así como los éxitus por cualquier causa. Las funciones de supervivencia se calcularon mediante el análisis de Kaplan-Meier Para la identificación de las variables predictoras independientes del evento compuesto (muerte y / u hospitalización) se realizó un modelo de Cox univariante con las variables analíticas ( basal, media, mediana, máximo y mínimo) y demográficas y un modelo de Cox ajustado por edad,sexo e IMC con los parámetros de bioimpedancia . Las variables que dieron significativas en estos modelos (P < 0,05) se introdujeron en un modelo de Cox multivariante. Resultados. La prevalencia de DPE según criterios del ISRNM fue del 9.3 % en el momento basal, y del 4,3% en el momento de finalización del estudio. La prevalencia de sobrehidratación medida como AvROH fue del 20,1%. Durante el periodo de seguimiento se produjeron cambios significativos fundamentalmente en el índice de tejido graso (ITG) y en la sobrehidratación en los meses de verano (AvROH y TAFO). El 26% de la población de estudio tuvo al menos un ingreso hospitalario. 21 pacientes fallecieron durante el seguimiento (12,4% de la población). La principal causa de ingreso y éxitus fue la cardiovascular; consituyendo el 35% de los ingresos y el 57% de los éxitus. Los parámetros que presentaron asociación con el evento compuesto fueron: TAFO mínimo (HR 1.319: IC 95% 1.029-1.691; p= 0.029), PCR mediana (HR 1.032; IC 95% 1.014-1.050; p=0.001), albúmina máxima (HR 0.286; IC95% 0.085-0.966), colesterol total (HR 1.011; IC 95% 1.003-1.019; p=0.007) y nivel de 25 OH vit D (HR 0.947; IC 95% 0.915-0.981); p= 0.002). Conclusiones: El principal resultado de nuestro trabajo fue que la sobrehidratación, (medida como TAFO) se asoció de forma independiente con la morbimortalidad, y que las medidas seguidas en el tiempo (TAFO mínimo) tuvieron un mayor poder predictivo que las medidas basales. Adicionalmente; el estado nutricional e inflamatorio, medido mediante parámetros individuales, supuso un mayor impacto en la morbimortalidad que parámetros agrupados, como el score MIS o el síndrome DPE según criterios ISRNM. En nuestro estudio hemos encontrado importantes diferencias en la prevalencia de DPE en función de la herramienta utilizada (criterios ISRNM, MIS y parámetros de bioimpedancia). Finalmente, la periodicidad de la medición de las diferentes variables a lo largo del seguimiento nos ha permitido apreciar los cambios estacionales en los parámetros de bioimpedancia, los cuales se han acompañado de cambios en sentido inverso de algunos de los parámetros bioquímicos nutricionales.

Multi-organ support device for combined extracorporeal carbon dioxide removal and hemofiltration treatments with pump-free solution for ultrafiltration

The use of extracorporeal organ support (ECOS) devices is increasingly widespread, to temporarily sustain or replace the functions of impaired organs in critically ill patients. Among ECOS, respiratory functions are supplied by extracorporeal life support (ECLS) therapies like extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO2R), and renal replacement therapies (RRT) are used to support kidney functions. However, the leading cause of mortality in critically ill patients is multi-organ dysfunction syndrome (MODS), which requires a complex therapeutic strategy where extracorporeal treatments are often integrated to pharmacological approach. Recently, the concept of multi-organ support therapy (MOST) has been introduced, and several forms of isolated ECOS devices are sequentially connected to provide simultaneous support to different organ systems. The future of critical illness goes towards the development of extracorporeal devices offering multiple organ support therapies on demand by a single hardware platform, where treatment lines can be used alternately or in conjunction. The aim of this industrial PhD project is to design and validate a device for multi-organ support, developing an auxiliary line for renal replacement therapy (hemofiltration) to be integrated on a platform for ECCO2R. The intended purpose of the ancillary line, which can be connected on demand, is to remove excess fluids by ultrafiltration and achieve volume control by the infusion of a replacement solution, as patients undergoing respiratory support are particularly prone to develop fluid overload. Furthermore, an ultrafiltration regulation system shall be developed using a powered and software-modulated pinch-valve on the effluent line of the hemofilter, proposed as an alternative to the state-of-the-art solution with peristaltic pump.

ENaC-mediated alveolar fluid clearance and lung fluid balance depend on the channel-activating protease 1.

Sodium transport via epithelial sodium channels (ENaC) expressed in alveolar epithelial cells (AEC) provides the driving force for removal of fluid from the alveolar space. The membrane-bound channel-activating protease 1 (CAP1/Prss8) activates ENaC in vitro in various expression systems. To study the role of CAP1/Prss8 in alveolar sodium transport and lung fluid balance in vivo, we generated mice lacking CAP1/Prss8 in the alveolar epithelium using conditional Cre-loxP-mediated recombination. Deficiency of CAP1/Prss8 in AEC induced in vitro a 40% decrease in ENaC-mediated sodium currents. Sodium-driven alveolar fluid clearance (AFC) was reduced in CAP1/Prss8-deficient mice, due to a 48% decrease in amiloride-sensitive clearance, and was less sensitive to beta(2)-agonist treatment. Intra-alveolar treatment with neutrophil elastase, a soluble serine protease activating ENaC at the cell surface, fully restored basal AFC and the stimulation by beta(2)-agonists. Finally, acute volume-overload increased alveolar lining fluid volume in CAP1/Prss8-deficient mice. This study reveals that CAP1 plays a crucial role in the regulation of ENaC-mediated alveolar sodium and water transport and in mouse lung fluid balance.

Obesity Versus Osteoarthritis: Beyond The Mechanical Overload.

Obesity is currently considered a major public health problem in the world, already reaching epidemic characteristics, according to the World Health Organization. Excess weight is the major risk factor associated with various diseases, such as type 2 diabetes mellitus, hypertension, dyslipidemia and osteometabolic diseases, including osteoporosis and osteoarthritis. Osteoarthritis is the most prevalent rheumatic disease and the leading cause of physical disability and reduced quality of life of the population over 65 years. It mainly involves the joints that bear weight - knees and hips. However, along with the cases of obesity, its prevalence is increasing, and even in other joints, such as hands. Thus, it is assumed that the influence of obesity on the development of OA is beyond mechanical overload. The purpose of this review was to correlate the possible mechanisms underlying the genesis and development of these two diseases. Increased fat mass is directly proportional to excessive consumption of saturated fatty acids, responsible for systemic low-grade inflammation condition and insulin and leptin resistance. At high levels, leptin assumes inflammatory characteristics and acts in the articular cartilage, triggering the inflammatory process and changing homeostasis this tissue with consequent degeneration. We conclude that obesity is a risk factor for osteoarthritis and that physical activity and changes in diet composition can reverse the inflammatory and leptin resistance, reducing progression or preventing the onset of osteoarthritis.

Human Herpesvirus Infections Of The Central Nervous System: Laboratory Diagnosis Based On Dna Detection By Nested Pcr In Plasma And Cerebrospinal Fluid Samples.

Infections of the central nervous systems (CNS) present a diagnostic problem for which an accurate laboratory diagnosis is essential. Invasive practices, such as cerebral biopsy, have been replaced by obtaining a polymerase chain reaction (PCR) diagnosis using cerebral spinal fluid (CSF) as a reference method. Tests on DNA extracted from plasma are noninvasive, thus avoiding all of the collateral effects and patient risks associated with CSF collection. This study aimed to determine whether plasma can replace CSF in nested PCR analysis for the detection of CNS human herpesvirus (HHV) diseases by analysing the proportion of patients whose CSF nested PCR results were positive for CNS HHV who also had the same organism identified by plasma nested PCR. In this study, CSF DNA was used as the gold standard, and nested PCR was performed on both types of samples. Fifty-two patients with symptoms of nervous system infection were submitted to CSF and blood collection. For the eight HHV, one positive DNA result-in plasma and/or CSF nested PCR-was considered an active HHV infection, whereas the occurrence of two or more HHVs in the same sample was considered a coinfection. HHV infections were positively detected in 27/52 (51.9%) of the CSF and in 32/52 (61.5%) of the plasma, difference not significant, thus nested PCR can be performed on plasma instead of CSF. In conclusion, this findings suggest that plasma as a useful material for the diagnosis of cases where there is any difficulty to perform a CSF puncture.

Central nitrergic system regulation of neuroendocrine secretion, fluid intake and blood pressure induced by angiotensin-II

Background: Nitric oxide (NO) synthesis has been described in several circumventricular and hypothalamic structures in the central nervous system that are implicated in mediating central angiotensin-II (ANG-II) actions during water deprivation and hypovolemia. Neuroendocrine and cardiovascular responses, drinking behavior, and urinary excretions were examined following central angiotensinergic stimulation in awake freely-moving rats pretreated with intracerebroventricular injections of N omega-nitro-L-arginine methyl ester (L-NAME, 40 mu g), an inhibitor of NO synthase, and L-arginine (20 ug), a precursor of NO. Results: Injections of L-NAME or ANG-II produced an increase in plasma vasopressin (VP), oxytocin (OT) and atrial natriuretic peptide (ANP) levels, an increase in water and sodium intake, mean arterial blood pressure and sodium excretion, and a reduction of urinary volume. L-NAME pretreatment enhanced the ANG-II response, while L-arginine attenuated VP and OT release, thirst, appetite for sodium, antidiuresis, and natriuresis, as well as pressor responses induced by ANG-II. Discussion and conclusion: Thus, the central nitrergic system participates in the angiotensinergic responses evoked by water deprivation and hypovolemia to refrain neurohypophysial secretion, hydromineral balance, and blood pressure homeostasis.

Effects of Laser on the Synovial Fluid in the Inflammatory Process of the Knee Joint of the Rabbit

Objective: The purpose of this study was to evaluate the effects of low-level laser (LLL) energy on the clinical signs of inflammation and the cellular composition of synovial fluid (SF) in the inflamed knee of the rabbit. Background Data: There are few findings related to the effects of LLL on SF in inflammatory processes and there is little knowledge about the optimal parameters for reducing joint inflammation. Materials and Methods: Inflammation in the right knee of 36 rabbits was induced by intracapsular injection (0.2 mL) of Terebinthina commun (Tc). The animals were randomly assigned to three groups: acute experimental group (AEG), chronic experimental group (CEG), and control group (CG), which only received Tc. Each group was divided in two subgroups of six animals each. The AEG and CEG groups began to receive laser treatment 2 and 5 d after the induction of inflammation, respectively. Laser irradiation at a wavelength of 830 nm, power output of 77 mW, and power density of 27.5 W/cm(2) was applied daily for 7 d for either 0.12 sec or 0.32 sec, resulting in doses of 3.4 J/cm(2) and 8 J/cm(2), respectively. Body mass, joint perimeter, joint temperature, and the morphology of the SF were analyzed. Results: There was no statistically significant differences between groups in the body mass, joint perimeter, and SF morphology. Conclusion: Laser irradiation with the selected parameters produced only a few subtle differences in the inflammatory signs and the SF. The lack of effects may have been due to the short irradiation time.

Association of Trypanosoma vivax in extracellular sites with central nervous system lesions and changes in cerebrospinal fluid in experimentally infected goats

Changes in cerebrospinal fluid (CSF) and anatomical and histopathological central nervous system (CNS) lesions were evaluated, and the presence of Trypanosoma vivax in CNS tissues was investigated through PCR. Twelve adult male goats were divided into three groups (G): G1, infected with T. vivax and evaluated during the acute phase; G2, infected goats evaluated during the chronic phase; and G3, consisting of non-infected goats. Each goat from G1 and G2 was infected with 1.25 x 10(5) trypomastigotes. Cerebrospinal fluid (CSF) analysis and investigation of T. vivax was performed at the 15(th) day post-infection (dpi) in G1 goats and on the fifth day after the manifestation of nervous system infection signs in G2 goats. All goats were necropsied, and CNS fragments from G1 and G2 goats were evaluated by PCR for the determination of T. vivax. Hyperthermia, anemia and parasitemia were observed from the fifth dpi for G1 and G2, with the highest parasitemia peak between the seventh and 21(st) dpi. Nervous system infection signs were observed in three G2 goats between the 30(th) and 35(th) dpi. CSF analysis revealed the presence of T. vivax for G2. Meningitis and meningoencephalitis were diagnosed in G2. PCR were positive for T. vivax in all the samples tested. In conclusion, T. vivax may reach the nervous tissue resulting in immune response from the host, which is the cause of progressive clinical and pathological manifestations of the CNS in experimentally infected goats.

On the accuracy of two-fluid model predictions for a particular gas-solid riser flow

Literature presents a huge number of different simulations of gas-solid flows in risers applying two-fluid modeling. In spite of that, the related quantitative accuracy issue remains mostly untouched. This state of affairs seems to be mainly a consequence of modeling shortcomings, notably regarding the lack of realistic closures. In this article predictions from a two-fluid model are compared to other published two-fluid model predictions applying the same Closures, and to experimental data. A particular matter of concern is whether the predictions are generated or not inside the statistical steady state regime that characterizes the riser flows. The present simulation was performed inside the statistical steady state regime. Time-averaged results are presented for different time-averaging intervals of 5, 10, 15 and 20 s inside the statistical steady state regime. The independence of the averaged results regarding the time-averaging interval is addressed and the results averaged over the intervals of 10 and 20 s are compared to both experiment and other two-fluid predictions. It is concluded that the two-fluid model used is still very crude, and cannot provide quantitative accurate results, at least for the particular case that was considered. (C) 2009 Elsevier Inc. All rights reserved.

AnSBBR Applied to the Treatment of Metalworking Fluid Wastewater: Effect of Organic and Shock Load

An investigation was performed regarding the application of a mechanically stirred anaerobic sequencing batch biofilm reactor containing immobilized biomass on inert polyurethane foam (AnSBBR) to the treatment of soluble metalworking fluids to remove organic matter and produce methane. The effect of increasing organic matter and reactor fill time, as well as shock load, on reactor stability and efficiency have been analyzed. The 5-L AnSBBR was operated at 30 A degrees C in 8-h cycles, agitation of 400 rpm, and treated 2.0 L effluent per cycle. Organic matter was increased by increasing the influent concentration (500, 1,000, 2,000, and 3,000 mg chemical oxygen demand (COD)/L). Fill times investigated were in the batch mode (fill time 10 min) and fed-batch followed by batch (fill time 4 h). In the batch mode, organic matter removal efficiencies were 87%, 86%, and 80% for influent concentrations of 500, 1,000, and 2,000 mgCOD/L (1.50, 3.12, and 6.08 gCOD/L.d), respectively. At 3,000 mgCOD/L (9.38 gCOD/L.d), operational stability could not be achieved. The reactor managed to maintain stability when a shock load twice as high the feed concentration was applied, evidencing the robustness of the reactor to potential concentration variations in the wastewater being treated. Increasing the fill time to 4 h did not improve removal efficiency, which was 72% for 2,000 mgCOD/L. Thus, gradual feeding did not improve organic matter removal. The concentration of methane formed at 6.08 gCOD/L was 5.20 mmolCH(4), which corresponded to 78% of the biogas composition. The behavior of the reactor during batch and fed-batch feeding could be explained by a kinetic model that considers organic matter consumption, production, and consumption of total volatile acids and methane production.