RESUMO
INTRODUCTION: Haemodialysis (HD) allow depuration of uraemic toxins by diffusion, convection, and adsorption. Online haemodiafiltration (HDF) treatments add high convection to enhance removal. There are no prior studies on the relationship between convection and adsorption in HD membranes. The possible benefits conferred by intrinsic adsorption on protein-bound uraemic toxins (PBUTs) removal are unknown. METHODS: Twenty-two patients underwent their second 3-days per week HD sessions with randomly selected haemodialysers (polysulfone, polymethylmethacrylate, cellulose triacetate, and polyamide copolymer) in high-flux HD and HDF. Blood samples were taken at the beginning and at the end of the treatment to assess the reduction ratio (RR) in a wide range of molecular weight uraemic toxins. A mid-range removal score (GRS) was also calculated. An elution protocol was implemented to quantify the amount of adsorbed mass (Mads) for each molecule in every dialyser. RESULTS: All synthetic membranes achieved higher RR for all toxins when used in HDF, specially the polysulfone haemodialyser, resulting in a GRS = 0.66 ± 0.06 (p < 0.001 vs. cellulose triacetate and polyamide membranes). Adsorption was slightly enhanced by convection for all membranes. The polymethylmethacrylate membrane showed expected substantial adsorption of ß2-microglobulin (MadsHDF = 3.5 ± 2.1 mg vs. MadsHD = 2.1 ± 0.9 mg, p = 0.511), whereas total protein adsorption was pronounced in the cellulose triacetate membrane (MadsHDF = 427.2 ± 207.9 mg vs. MadsHD = 274.7 ± 138.3 mg, p = 0.586) without enhanced PBUT removal. DISCUSSION/CONCLUSION: Convection improves removal and slightly increases adsorption. Adsorbed proteins do not lead to enhanced PBUTs depuration and limit membrane efficiency due to fouling. Selection of the correct membrane for convective therapies is mandatory to optimize removal efficiency.
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Hemodiafiltração/instrumentação , Membranas Artificiais , Toxinas Urêmicas/isolamento & purificação , Adsorção , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Uremia/terapia , Toxinas Urêmicas/sangueRESUMO
INTRODUCTION: Interleukin-6 (IL-6) is one of the most important mediators of inflammation. It is also the culprit for a severe disease course in COVID-19. While COVID-19 has higher mortality in hemodialysis (HD) patients, medium cutoff (MCO) membranes were previously suggested as promising tools for better patient outcomes by purging inflammatory mediators. The aim of this study was to analyze changes in IL-6 levels of HD patients who were dialyzed via MCO membranes during their COVID-19 treatments. METHODS: This is an observational study on a group of HD patients who were admitted with COVID-19 diagnosis in a university hospital and intermittently dialyzed using MCO membranes during their hospital stay. IL-6 levels of the patients were measured before and after consecutive dialysis sessions by a commercial kit. Measurements were interpreted together with the clinical data. RESULTS: Nine patients with a total of 54 measurements were evaluated. IL-6 levels were significantly higher in patients who died (median and interquartile ranges [IQRs] of IL-6 levels for patients who died and survived were 112.0 pg/mL [48.3-399.4] and 5.3 pg/mL [2.2-27.4], respectively; p < 0.001). In the comparison of changes in IL-6 levels with dialysis sessions, patients who survived had lower post-dialysis levels (median: 4.5 pg/mL; IQR: 2.2-7.6). However, IL-6 levels had a tendency to increase with dialysis sessions in patients who could not survive COVID-19 (median: 237.0 pg/mL; IQR: 53.8-418.2). CONCLUSION: This study describes over time variations in IL-6 levels of COVID-19 patients undergoing HD with MCO membranes. The trend for the changes of IL-6 levels during dialysis sessions was not uniform for all patients. Surviving patients had decreasing levels of IL-6 with consecutive dialysis sessions, while nonsurvivors had an increasing trend.
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COVID-19 , Diálise Renal , Humanos , Interleucina-6 , COVID-19/terapia , Teste para COVID-19 , Membranas ArtificiaisRESUMO
INTRODUCTION: Removal of uremic toxins is a main objective of hemodialysis; however, whether high-flux and medium cut-off (MCO) membranes differ as regards removal of middle and large uremic toxins is not clear. OBJECTIVE: To compare medium cut-off and high-flux dialyzers as regards their intra- and interdialysis effect on circulating levels of middle and large uremic toxins and serum albumin. METHODS: Fifty-two patients were randomized to have hemodialysis with either 3 months of high-flux dialyzer followed by 3 months of MCO or vice versa. Blood samples were taken before and after dialysis at the first and last sessions of each dialyzer for analyses of middle and large uremic toxins including inflammatory mediators and vascular endothelial growth factor (VEGF), and serum albumin. RESULTS: Reduction rates were higher, and postdialysis levels of ß-2 microglobulin, free kappa and lambda light chains, and myoglobulin were lower at the first and last sessions with MCO dialyzers compared to high-flux dialyzers (p < 0.05 for all). Last session predialysis levels of ß-2 microglobulin, free kappa light chain, and free lambda light chain were lower than first session predialysis levels in MCO dialyzers as compared to high-flux dialyzers (p < 0.05 for all). Last session levels of interleukin-6, interleukin-10, interleukin-17, and interferon-gamma did not differ between dialyzers (p > 0.05 for all). VEGF level was lower in the MCO group compared to the high-flux group (p = 0.043). Last session level of serum albumin with MCO dialyzers was lower than that with high-flux dialyzers (3.62 [3.45-3.88] vs. 3.78 [3.58-4.02] g/L) (p = 0.04) and 6.7% lower (p < 0.001) than at the first session of MCO dialyzers. CONCLUSION: The decline in circulating levels of several middle and large uremic toxins including VEGF following hemodialysis was more pronounced when using MCO membranes as compared to high-flux membranes while their effect on inflammatory molecules was similar.
Assuntos
Hemodiafiltração , Membranas Artificiais , Diálise Renal , Toxinas Biológicas/sangue , Uremia/sangue , Adulto , Idoso , Biomarcadores , Comorbidade , Citocinas/metabolismo , Feminino , Hemodiafiltração/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal/métodos , Albumina Sérica , Uremia/etiologia , Uremia/terapia , Fator A de Crescimento do Endotélio Vascular/sangue , Microglobulina beta-2/sangueRESUMO
BACKGROUND: Patients undergoing maintenance hemodialysis (HD) exhibit increased levels of uremic toxins, which are associated with poor outcomes. Recently, new dialysis membranes have allowed clearance of solutes with higher molecular weight, without significant albumin losses high-retention-onset-HD (HRO-HD). METHODS: Prospective crossover trial, in which 16 prevalent patients switched from high-flux HD (HF-HD) to online hemodiafiltration (olHDF) and HRO-HD for 4 weeks. The following variables were evaluated: pre- and post-dialysis serum concentrations of albumin, urea, phosphate (P), beta-2 microglobulin (ß2M), and total mass (TM) extraction and dialyzer clearance of urea, P, and ß2M. RESULTS: Comparing HF-HD, olHDF, and HRO-HD, respectively, there were no differences regarding pre-dialysis serum concentrations of albumin (3.94 ± 0.36, 4.06 ± 0.22, and 3.93 ± 0.41 g/dL, p = 0.495), urea (166 ± 29, 167 ± 30, and 164 ± 27 mg/dL, p = 0.971), P (4.9 ± 2.1, 5.2 ± 1.6, and 4.9 ± 2.1 mg/dL, p = 0.879), and ß2M (31.3 ± 7.1, 32.6 ± 8.6, and 33.7 ± 5.9 µg/mL, p = 0.646). ß2M clearance was significantly lower in HF-HD in comparison to both olHDF and HRO-HD: 43 (37-53) versus 64 (48-85) mL/min, p = 0.013, and 69 (58-86) mL/min, p = 0.015, respectively. Post-dialysis ß2M serum concentration was higher in HF-HD in comparison to olHDF and HRO-HD: 11.6 (9.6-12.4) vs. 5.7 (4.5-7.0) µg/mL, p = 0.001, and 5.6 (5.3-7.6) µg/mL, p = 0.001, respectively. TM extraction of urea, P, and ß2M were similar across the 3 dialysis modalities. CONCLUSIONS: olHDF and HRO-HD were superior to HF-HD regarding ß2M clearance, leading to lower post-dialysis ß2M levels.
Assuntos
Hemodiafiltração , Membranas Artificiais , Ureia/metabolismo , Microglobulina beta-2/metabolismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: A new class of dialysis membrane, the mid cut-off (MCO) dialyzer, has been developed to improve the clearance of uremic toxins in hemodialysis (HD). The a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) study aimed to determine if regular use of MCO dialyzer was safe and specifically did not result in a significant loss of albumin. METHODS: This investigator initiated, crossover, longitudinal, device study was conducted across 9 centers in Australia and New Zealand (n = 89). Participants had a 4-week wash-in with high-flux HD, followed by 24-week intervention with MCO HD and a subsequent 4-week wash-out with high-flux HD. The primary outcome was change in serum albumin between weeks 4 and 28. Secondary outcomes included trends in serum albumin, changes in kappa- and lambda-free light chains (FLC), 6-min walk test (6MWT), malnutrition inflammation score (MIS), restless legs score and quality of life. RESULTS: Participants had a mean age of 66 ± 14 years, 62% were men, 45% were anuric, and 51% had -diabetes. There was no reduction in serum albumin following treatment with MCO HD (mean reduction -0.7 g/L, 95% CI -1.5 to 0.1). A sustained, unexplained reduction in serum albumin (>25%) was not observed in any participant. A reduction in FLC was observed 2 weeks into MCO HD (lambda-FLC: Δ -9.1 mg/L, 95% CI -14.4 to -3.7; kappa-FLC: Δ -5.7 mg/L, 95% CI -9.8 to -1.6) and was sustained for the rest of the study intervention. Both FLC increased after the cessation of MCO use. There was no improvement in restless legs symptoms, quality of life, 6MWT or MIS scores. CONCLUSIONS: Regular HD using the MCO dialyzer did not result in a significant fall in serum albumin. There were no effects on quality of life, functional status or nutrition. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482.
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Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Membranas Artificiais , Diálise Renal/instrumentação , Albumina Sérica Humana/análise , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Diálise Renal/efeitos adversosRESUMO
BACKGROUND: There is no obvious evidence regarding biological variation of procalcitonin (PCT) levels in hemodialysis (HD) patients without infections. The aim of this study was to determine the within- and between-person biological variation of PCT levels in HD patients without infections. METHODS: A multicenter, prospective, cohort study enrolled 123 HD patients without any signs of infectious disease. Baseline PCT levels were determined pre- and post-HD, and then repeated pre-HD PCT measurements were performed at 2, 4, 8, 12, 16, 20, and 24 weeks after baseline blood-sampling, regardless of the presence or absence of infectious disease. Analytical variation (CVa), the within-person biological variation (CVi), between-person biological variation (CVb), individual index (II), and the reference change value (RCV) were calculated. RESULTS: The mean age was 62.4 years, 76.4% were male, and 32.5% had diabetes. The mean duration of HD was 87 months. The median value for baseline pre-HD PCT was 0.23 ng/mL, which is much higher than the reference level for healthy individuals. PCT levels decreased of 46.6% after a single HD session. CVi was 24.9%, CVb was 54.2%, II was 0.46, and RCV was calculated as 96.4% with 99% probability. CONCLUSIONS: The PCT level was significantly higher in stable HD patients without manifest bacterial infection. CVb was more variable than CVi in HD patients, which indicates that relative change is more important than absolute PCT levels for diagnosing bacterial infection, and doubling or more of the baseline PCT level may imply the presence of a bacterial infection in HD patients.
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Pró-Calcitonina/sangue , Diálise Renal , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The aim of this study was to establish a novel approach to in vitro dissolution evaluation using a combination of the paddle method and a dialysis membrane, both to predict the overall in vivo performance of tacrolimus microspheres and also to identify a suitable dissolution test method to describe the in vivo initial burst phenomenon. This new dissolution method for evaluating the release of tacrolimus from microspheres consisted of rotating a customized paddle inside a dialysis membrane using a conventional paddle apparatus. Findings were compared with a method in which the paddle was rotated outside the dialysis membrane, the conventional paddle method, and the flow-through cell method. We concluded that the paddle method with a dialysis membrane and internal agitation, which was designed to mimic in vivo conditions, predicted the overall pharmacokinetic (PK) profile of tacrolimus microspheres whereas the conventional paddle method described the initial burst. These findings suggest that it may not be possible to predict both the PK profile and initial burst using a single analysis method. We therefore recommend that evaluation of the initial burst be performed separately. In conclusion, we propose that combination of the paddle method with a dialysis membrane and internal agitation to evaluate the overall PK profile, together with the paddle method to describe the in vivo initial burst, represents a novel approach to in vitro dissolution evaluation for microsphere formulations.
Assuntos
Portadores de Fármacos/química , Imunossupressores/química , Poliésteres/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Tacrolimo/química , Química Farmacêutica/instrumentação , Liberação Controlada de Fármacos , Desenho de Equipamento , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Membranas Artificiais , Microesferas , Modelos Químicos , Solubilidade , Tacrolimo/administração & dosagem , Tacrolimo/farmacocinéticaRESUMO
BACKGROUND: Inadequate removal of molecules between 5 and 50 KDa may cause long-term complication in chronic hemodialysis. Medium cut-off (MCO) is a new class of membranes with enhanced sieving properties and negligible albumin loss. MCO membrane makes it possible to perform expanded hemodialysis (HDx), a technique based on high internal filtration (IF).The present study is designed to quantify IF in 2 MCO dialyzers (Theranova 400 and 500, Baxter, Deerfield, USA) using a nuclear imaging technique previously validated. METHODS: Blood and dialysate compartment pressure drop along with transmembrane pressure; they were measured in a closed in vitro circuit with human blood (blood flow [QB] = 300 and 400 mL/min; dialysate flow 500 mL/min; net ultrafiltration rate 0 mL/min). A non-diffusible marker molecule (albumin macro-aggregates labeled with 99Tc metastable) was injected in the blood compartment and nuclear emission was recorded by a gamma camera. Relative variations in the concentration of the marker molecule along the length of the filter were used to calculate local cross filtration. RESULTS: Based on marker concentration profiles, IF was estimated. For Theranova 400, IF were 29.7 and 41.6 mL/min for QB of 300 and 400 mL/min. For Theranova 500, IF were 31.6 and 53.1 mL/min for QB of 300 and 400 mL/min respectively. CONCLUSIONS: MCO membrane provides significant amounts of IF due to the particular combination between hydraulic permeability of the membrane and reduced inner diameter of the fibers. High IF combined with enhanced sieving profile of MCO membrane leads to improved removal of a wider spectrum of uremia retention molecules in HDx, without requiring complex equipment.
Assuntos
Membranas Artificiais , Diálise Renal/instrumentação , Filtração , Humanos , Diálise Renal/métodosRESUMO
BACKGROUND: The initial part of process development involves extensive screening programs to identify optimal biological systems and cultivation conditions. For a successful scale-up, the operation mode on screening and production scale must be as close as possible. To enable screening under fed-batch conditions, the membrane-based fed-batch shake flask was developed. It is a shake flask mounted with a central feed reservoir with an integrated rotating membrane tip for a controlled substrate release. Building on the previously provided proof of principle for this tool, this work extends its application by constructive modifications and improved methodology to ensure reproducible performance. RESULTS: The previously limited operation window was expanded by a systematic analysis of reservoir set-up variations for cultivations with the fast-growing organism Escherichia coli. Modifying the initial glucose concentration in the reservoir as well as interchanging the built-in membrane, resulted in glucose release rates and oxygen transfer rate levels during the fed-batch phase varying up to a factor of five. The range of utilizable membranes was extended from dialysis membranes to porous microfiltration membranes with the design of an appropriate membrane tip. The alteration of the membrane area, molecular weight cut-off and liquid volume in the reservoir offered additional parameters to fine-tune the duration of the initial batch phase, the oxygen transfer rate level of the fed-batch phase and the duration of feeding. It was shown that a homogeneous composition of the reservoir without a concentration gradient is ensured up to an initial glucose concentration of 750 g/L. Finally, the experimental validity of fed-batch shake flask cultivations was verified with comparable results obtained in a parallel fed-batch cultivation in a laboratory-scale stirred tank reactor. CONCLUSIONS: The membrane-based fed-batch shake flask is a reliable tool for small-scale screening under fed-batch conditions filling the gap between microtiter plates and scaled-down stirred tank reactors. The implemented reservoir system offers various set-up possibilities, which provide a wide range of process settings for diverse biological systems. As a screening tool, it accurately reflects the cultivation conditions in a fed-batch stirred tank reactor and enables a more efficient bioprocess development.
Assuntos
Técnicas de Cultura Celular por Lotes/instrumentação , Técnicas de Cultura Celular por Lotes/métodos , Reatores Biológicos , Diálise , Escherichia coli/crescimento & desenvolvimento , Filtração , Glucose/metabolismo , Microbiologia Industrial/métodos , Membranas ArtificiaisRESUMO
Blood adsorption onto the inside surface of hollow fiber dialysis membranes was investigated by means of time-of-flight secondary ion mass spectrometry (TOF-SIMS) and near-field infrared microscopy (NFIR) in order to evaluate the biocompatibility and permeability of dialysis membranes. TOF-SIMS is useful for the imaging of particular molecules with a high spatial resolution of approximately 100 nm. In contrast, infrared spectra provide quantitative information and NFIR enables analysis with a high spatial resolution of less than 1 µm, which is close to the resolution of TOF-SIMS. A comparison was made of one of the most widely used dialysis membranes made of polysulfone (PSf), that has an asymmetric and inhomogeneous pore structure, and a newly developed asymmetric cellulose triacetate (ATA) membrane that also has an asymmetric pore structure, even though the conventional cellulose triacetate membrane has a symmetric and homogeneous pore structure. As a result, it was demonstrated that blood adsorption on the inside surface of the ATA membrane is more reduced than that on the PSf membrane. Graphical abstract Analysis of blood adsorption on inside surface of hollow fiber membrane.
Assuntos
Materiais Biocompatíveis/química , Análise Química do Sangue , Celulose/análogos & derivados , Membranas Artificiais , Polímeros/química , Diálise Renal/instrumentação , Sulfonas/química , Adsorção , Sangue , Celulose/química , Humanos , Raios Infravermelhos , Teste de Materiais/métodos , Microscopia/métodos , Permeabilidade , Porosidade , Espectrometria de Massa de Íon Secundário/métodosRESUMO
OBJECTIVES: To investigate the contribution of direct electron transfer mechanisms to electricity production in microbial fuel cells by physically retaining Shewanella oneidensis cells close to or away from the anode electrode. RESULTS: A maximum power output of 114 ± 6 mWm(-2) was obtained when cells were retained close to the anode using a dialysis membrane. This was 3.5 times more than when the cells were separated away from the anode. Without the membrane the maximum power output was 129 ± 6 mWm(-2). The direct mechanisms of electron transfer contributed significantly to overall electron transfer from S. oneidensis to electrodes, a result that was corroborated by another experiment where S. oneidensis cells were entrapped in alginate gels. CONCLUSION: S. oneidensis transfers electrons primarily by direct electron transfer as opposed to mediated electron transfer.
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Fontes de Energia Bioelétrica/microbiologia , Shewanella/metabolismo , Transporte de Elétrons/fisiologiaRESUMO
Hemodialysis-associated eosinophilia (HAE) is believed to be associated with allergic reactions to dialyzer materials. This study aimed to investigate the use of Polyflux membranes to improve HAE. Thirty-one patients suffering from HAE were included. Patients were dialyzed with polysulfone membranes when they developed HAE. After that, patients were dialyzed with Polyflux membranes three times every week, 4 h every time without changing the dialysis parameters and medication. Levels of peripheral eosinophils, hsCRP, IgE, C3a, IL-5 and peripheral CD4+ lymphocytes and CD8+ lymphocytes were assessed before Polyflux treatment, and at 4th, 8th and 12th weeks of treatment. Any symptoms including chest tightness and skin itching were observed during the study period. After 12 weeks of Polyflux membrane dialysis and compared with polysulfone membrane dialysis, levels of peripheral eosinophils were significantly decreased (1.26 ± 0.61 vs. 0.71 ± 0.29 × 10(9)/L, p < 0.001); serum IL-5 levels were significantly decreased (24.43 ± 10.21 vs. 9.11 ± 4.21 pg/mL, p < 0.001); and chest tightness and skin itching were significantly improved (45.2% vs. 19.4%, p = 0.028). After 12 weeks, there was no significant change in serum levels of hsCRP (2.00 ± 0.94 vs. 1.81 ± 0.79 mg/L, p = 0.352), IgE (104.61 ± 98.79 vs. 114.95 ± 101.07 IU/mL, p = 0.422) and C3a (121.61 ± 34.04 vs. 120.29 ± 32.81 µg/L, p = 0.316), and in peripheral levels of CD4+ (589 ± 181 vs. 569 ± 171 cells/mm(3), p = 0.672) and CD8+ (443 ± 123 vs. 414 ± 140 cells/mm(3), p = 0.395) cells. Eosinophil count was correlated with serum IL-5 levels (r = 0.873, p < 0.001). Changing to a Polyflux membrane may alleviate HAE and reduce serum IL-5 levels. Therefore, this could be a strategy to manage HAE in the clinical practice.
Assuntos
Eosinofilia/prevenção & controle , Membranas Artificiais , Diálise Renal/efeitos adversos , Idoso , Proteína C-Reativa/metabolismo , Complemento C3a/metabolismo , Eosinofilia/sangue , Eosinofilia/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Interleucina-5/metabolismo , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Diálise Renal/instrumentaçãoRESUMO
BACKGROUND: In 2006, NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) published clinical practice guidelines for hemodialysis adequacy. Recent studies evaluating hemodialysis adequacy as determined by initiation timing, frequency, duration, and membrane type and prompted an update to the guideline. STUDY DESIGN: Systematic review and evidence synthesis. SETTING & POPULATION: Patients with advanced chronic kidney disease receiving hemodialysis. SELECTION CRITERIA FOR STUDIES: We screened publications from 2000 to March 2014, systematic reviews, and references and consulted the NKF-KDOQI Hemodialysis Adequacy Work Group members. We included randomized or controlled clinical trials in patients undergoing long-term hemodialysis if they reported outcomes of interest. INTERVENTIONS: Early versus late dialysis therapy initiation; more frequent (>3 times a week) or longer duration (>4.5 hours) compared to conventional hemodialysis; low- versus high-flux dialyzer membranes. OUTCOMES: All-cause and cardiovascular mortality, myocardial infarction, stroke, hospitalizations, quality of life, depression or cognitive function scores, blood pressure, number of antihypertensive medications, left ventricular mass, interdialytic weight gain, and harms or complications related to vascular access or the process of dialysis. RESULTS: We included 32 articles reporting on 19 trials. Moderate-quality evidence indicated that earlier dialysis therapy initiation (at estimated creatinine clearance [eClcr] of 10-14mL/min) did not reduce mortality compared to later initiation (eClcr of 5-7mL/min). More than thrice-weekly hemodialysis and extended-length hemodialysis during a short follow-up did not improve clinical outcomes compared to conventional hemodialysis and resulted in a greater number of vascular access procedures (very low-quality evidence). Hemodialysis using high-flux membranes did not reduce all-cause mortality, but reduced cardiovascular mortality compared to hemodialysis using low-flux membranes (moderate-quality evidence). LIMITATIONS: Few studies were adequately powered to evaluate mortality. Heterogeneity of study designs and interventions precluded pooling data for most outcomes. CONCLUSIONS: Limited data indicate that earlier dialysis therapy initiation and more frequent and longer hemodialysis did not improve clinical outcomes compared to conventional hemodialysis.
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Falência Renal Crônica/terapia , Guias de Prática Clínica como Assunto , Diálise Renal/métodos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Depressão/epidemiologia , Intervenção Médica Precoce , Hospitalização/estatística & dados numéricos , Humanos , Falência Renal Crônica/mortalidade , Infarto do Miocárdio/epidemiologia , Qualidade de Vida , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
The retention of a number of solutes that may cause adverse biochemical/biological effects, called uremic toxins, characterizes uremic syndrome. Uremia therapy is based on renal replacement therapy, hemodialysis being the most commonly used modality. The membrane contained in the hemodialyzer represents the ultimate determinant of the success and quality of hemodialysis therapy. Membrane's performance can be evaluated in terms of removal efficiency for unwanted solutes and excess fluid, and minimization of negative interactions between the membrane material and blood components that define the membrane's bio(in)compatibility. Given the high concentration of plasma proteins and the complexity of structural functional relationships of this class of molecules, the performance of a membrane is highly influenced by its interaction with the plasma protein repertoire. Proteomic investigations have been increasingly applied to describe the protein uremic milieu, to compare the blood purification efficiency of different dialyzer membranes or different extracorporeal techniques, and to evaluate the adsorption of plasma proteins onto hemodialysis membranes. In this article, we aim to highlight investigations in the hemodialysis setting making use of recent developments in proteomic technologies. Examples are presented of why proteomics may be helpful to nephrology and may possibly affect future directions in renal research.
Assuntos
Falência Renal Crônica/terapia , Proteoma/metabolismo , Diálise Renal/instrumentação , Adsorção , Materiais Biocompatíveis , Proteínas Sanguíneas/metabolismo , Humanos , Falência Renal Crônica/sangue , Membranas Artificiais , ProteômicaRESUMO
The presence of estrogens residues in dairy products is a growing concern due to their potential health risk. Herein, in this study, we have developed a membrane-protected magnetic solid-phase extraction (MP-MSPE) method that utilized a magnetic adsorbent (Fe3O4@COF-LZU1) with in-situ growth for the efficient extraction of estrone (E1), 17ß-estradiol (E2), and estriol (E3). When combined with HPLC-FLD, this method allows for the efficient detection of estrogens in dairy products. The stability of the MP-MSPE was improved by the presence of a dialysis membrane, which remained a high extraction efficiency (90 %) even after ten reuse cycles. The hydrogen bonding, π-π interactions and pore size effect contribute to the excellent adsorption of three estrogens onto Fe3O4@COF-LZU1. Under optimal conditions, the method exhibits a low detection limit (0.01-0.15 µg L-1), wide linear range (0.1-800 µg L-1), and favorable recoveries (77.3 %-109.4 %) at three concentration levels (10, 50 and 100 µg L-1). This proposed method is characterized by its simplicity, high efficiency and eco-friendliness, making it a promising approach for extracting estrogens from dairy products.
Assuntos
Estrogênios , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Diálise Renal , Extração em Fase Sólida/métodos , Laticínios , Cromatografia Líquida de Alta Pressão , Fenômenos Magnéticos , Limite de DetecçãoRESUMO
Monitoring phosphorus fertilization is crucial for controlling the concentration of biologically available soil P. Over the years, several methodologies have been used, including successive cropping in a greenhouse or field, as well as extractions employing P sink procedures. The latter procedures are ideal laboratory experiments to show the soil's ability to supply P and to explore the P-residual release kinetics. Following these methodologies, long-term P desorption studies have been developed using dialysis membrane tubes filled with nanomaterial solutions. In this study, a magnetic nanocomposite (Fe3O4/Al2O3/MnO2) was synthesized and characterized utilizing cutting-edge instruments such as XRD, FTIR, FAAS, BET, SEM, and EDX. The resulting material had a crystalline size and surface area of 22.75 nm and 203.69 m2/g, respectively, and was employed for long-term P-desorption and kinetics experiments while filled in dialysis membrane tubes. The P-desorption experiment was conducted on four separate acidic soil samples that were cultured for 122 days with four different P concentrations. The findings demonstrated a direct relationship between P-desorbed and P-treatment, as well as with desorption time. The minimum desorption was obtained from the control of Boji Dirmaji soil P0 (1.16-9.36) and the highest desorption from Nedjo soil with P3 (5.23-30.35 mg/kg) treatment over 1-28 days. The rate of P release from soil to solution or diffusion through the membrane was determined by pseudo-first-order kinetics with a rate constant (0.021-0.028 hr-1). This method has the potential to measure fixed-P availability by mimicking it as a plant would, with high P-desorption efficiency and quick P-release capacity.
RESUMO
Performance evaluation of new dialysis membranes is primarily performed in vitro, which can lead to differences in clinical results. Currently, data on dialysis membrane performance and safety are available only for haemodialysis patients. Herein, we aimed to establish an in vivo animal model of dialysis that could be extrapolated to humans. We created a bilateral nephrectomy pig model of renal failure, which placed a double-lumen catheter with the hub exposed dorsally. Haemodialysis was performed in the same manner as in humans, during which clinically relevant physiologic data were evaluated. Next, to evaluate the utility of this model, the biocompatibility of two kinds of membranes coated with or without vitamin E used in haemodiafiltration therapy were compared. Haemodialysis treatment was successfully performed in nephrectomized pigs under the same dialysis conditions (4 h per session, every other day, for 2 weeks). In accordance with human clinical data, regular dialysis alleviated renal failure in pigs. The vitamin E-coated membrane showed a significant reduction rate of advanced oxidation protein products during dialysis than non-coated membrane. In conclusion, this model mimics the pathophysiology and dialysis condition of patients undergoing haemodialysis. This dialysis treatment model of renal failure will be useful for evaluating the performance and safety of dialysis membranes.
Assuntos
Modelos Animais de Doenças , Membranas Artificiais , Diálise Renal , Animais , Diálise Renal/instrumentação , Suínos , Vitamina E , Teste de Materiais , Materiais Revestidos Biocompatíveis , Nefrectomia , Hemodiafiltração/instrumentação , Hemodiafiltração/métodosRESUMO
Patients undergoing hemodialysis (HD) experience serious cardiovascular complications, through malnutrition, inflammation, and atherosclerosis. Amputation for peripheral arterial disease (PAD) is more prevalent in patients undergoing HD than in the general population. In addition, revascularization procedures in dialysis patients are often associated with subsequent amputation and high mortality rates. To improve the prognosis of dialysis patients, malnutrition and inflammation must be properly treated, which necessitates a better understanding of the characteristics of dialysis membranes. Herein, the characteristics of several dialysis membranes were studied, with a special reference to the AN69 membrane, noting several similarities to low-density lipoprotein (LDL)-apheresis, which is also applicable for the treatment of PAD. Both systems (LDL-apheresis and AN69) have anti-inflammatory and anti-thrombogenic effects because they use a negatively charged surface for extracorporeal adsorptive filtration from the blood/plasma, and contact phase activation. The concomitant use of both these therapeutic systems may have additive therapeutic benefits in HD patients. Here, we reviewed the characteristics of dialysis membranes and benefits of the AN69 membrane in dialysis patients.
RESUMO
In addition to being the core factor in thrombosis, thrombin is involved in various inflammatory disease responses, but few studies have examined whether and how it is involved in membrane-related inflammation. In this study, the thrombin inhibitor dabigatran is used to modify a polyethersulfone dialysis membrane. The modified membrane shows good hydrophilic properties and dialysis performance. It reduces the thrombin level in a targeted manner, thereby significantly inhibiting coagulation factor activation (based on the prothrombin time, international normalized ratio, activated partial thromboplastin time and thrombin time) and reducing the fibrinogen level and platelet adhesion. On thromboelastography, it shows excellent dynamic antithrombotic capacity. The modified membrane inhibited membrane-related inflammation by inhibiting the production of the inflammatory mediators C-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) via the thrombin/complement C5a pathway. Moreover, it is found to be safe in an in vivo study. Thus, the dabigatran-modified polyethersulfone membrane may reduce dialysis-related complications through its dual antithrombotic and anti-inflammatory effects.
Assuntos
Dabigatrana , Trombina , Humanos , Trombina/metabolismo , Fibrinolíticos/farmacologia , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológicoRESUMO
Saquinavir mesylate (SQV) is a protease inhibitor commonly employed for the treatment of human immunodeficiency virus-1 infection. It is generally administered orally as tablets in combination with other antiviral drugs. Another promising route of administration can be represented by the vaginal one through topically applied formulations. This delivery can reduce the first-pass effect in the case of systemic drug adsorption or prevent HIV infection. We propose the formulation of a Carbopol® 974 (C974) hydrogel containing biodegradable mPEG-PL(L)GA nanoparticles (NPs) for the vaginal delivery of SQV, intended both as a prevention and a therapeutic strategy. mPEG-PL(L)GA NPs were incorporated into the C974 polymeric matrix, leading to a reduction of the hydrogel consistency dependent on NPs and C974 concentrations. Despite the moderate drug loading into NPs, the presence of the NPs had an impact on the in vitro release of the drug from the hydrogel at pH 5.5 using immersion cells. A higher amount of the drug was released, probably due to the effect of NPs in promoting the incorporation of the drug into the hydrogel at a high SQV dose. These findings can be useful for the development of topically applied hydrogels for SQV delivery, possibly having improved in vivo therapeutic outcomes.