Construction of Kevlar nanofiber/graphene oxide composite beads as safe, self-anticoagulant, and highly efficient hemoperfusion adsorbents.

Recently emerged hemoperfusion absorbents, e.g. ion-exchange resin, activated carbon, and other porous materials, provide numerous novel possibilities to cure chronic liver failure (CLF) and renal failure (CRF). However, the limited adsorption performance and unsatisfactory blood compatibility significantly impede the development of the absorbents. Hence, designing safe and self-anticoagulant hemoperfusion absorbents with robust toxin clearance remains a considerable challenge. Here, brand new Kevlar-based composite gel beads for hemoperfusion are prepared by interface assembly based on π-π interaction. First, Kevlar nanofiber-graphene oxide (K-GO) beads are produced by liquid-liquid phase separation. Then, sodium p-styrenesulfonate (SS) is adsorbed onto the K-GO interface by π-π interaction and initiated to achieve the composite gel (K-GO/PSS) beads with an interfacial crosslinked structure. Such composite gel beads possess superior mechanical strength and self-anticoagulation capability, owing to the dual-network structure and heparin-mimicking gel structure, respectively. Furthermore, the K-GO/PSS beads show robust adsorption capacities for different kinds of toxins due to their strong charge and π-π interactions. A simulated hemoperfusion experiment in vitro demonstrates that the concentrations of the toxins in the blood can be restored to normal values within 30 minutes. In general, we envision that such composite gel beads will provide new strategies for future clinical CLF and CRF treatments.

Rapid and low-cost quantitative detection of creatinine in human urine with a portable Raman spectrometer.

The creatinine concentration of human urine is closely related to human kidney health and its rapid, quantitative, and low-cost detection has always been demanded. Herein, a surface-enhanced Raman spectroscopic (SERS) method for rapid and cost-effective quantification of creatinine concentrations in human urine was developed. A Au nanoparticle solution (Au sol) was used as a SERS substrate and the influence of different agglomerating salts on its sensitivity toward detecting creatinine concentrations was studied and optimized, as well as the effect of both the salt and Au sol concentrations. The variation in creatinine spectra over time on different substrates was also examined, demonstrating reproducible quantitative analysis of creatinine concentrations in solution. By adjusting the pH, a simple liquid-liquid solvent extraction procedure, which extracted creatinine from human urine, was used to increase the SERS detection selectivity toward creatinine in complex matrices. The quantitative results were compared to those obtained with a clinically validated enzymatic "creatinine kit (CK)." The limit of detection (LOD) for the SERS technique was 1.45 mg L-1, compared with 3.4 mg L-1 for the CK method. Furthermore, cross-comparing the results from the two methods, the average difference was 5.84% and the whole SERS detection process could be completed within 2 min compared with 11 min for the CK, indicating the practicality of the quantitative SERS technique. This novel quantitative technique shows promises as a high-throughput platform for relevant clinical and forensic analysis.

Bioinspired Microfluidic Device by Integrating a Porous Membrane and Heterostructured Nanoporous Particles for Biomolecule Cleaning.

Mimicking the structures and functions of biological systems is considered as a promising approach to construct artificial materials, which have great potential in energy, the environment, and health. Here, we demonstrate a conceptually distinct design by synergistically combining a kidney-inspired porous membrane and natural sponge-inspired heterostructured nanoporous particles to fabricate a bioinspired biomolecule cleaning device, achieving highly efficient biomolecule cleaning spanning from small molecules to macromolecules. The bioinspired biomolecule cleaning device is a two-layer microfluidic device that integrates a polyamide porous membrane and heterostructured nanoporous poly(acrylic acid)-poly(styrene divinylbenzene) particles. The former as a filtration membrane isolates the upper sample liquid and the latter fixed onto the bottom of the underlying channel acts as an active sorbent, particularly enhancing the clearance of macromolecules. As a proof-of-concept, we demonstrate that typical molecules, including urea, creatinine, lysozyme, and ß2-microglobulin, can be efficiently cleaned from simulant liquid and even whole blood. This study provides a method to fabricate a bioinspired biomolecule cleaning device for highly efficient biomolecule cleaning. We believe that our bioinspired synergistic design may expand to other fields for the fabrication of integrated functional devices, creating opportunities in a wide variety of applications.

Medium Cut-Off Dialyzer versus Eight Hemodiafiltration Dialyzers: Comparison Using a Global Removal Score.

BACKGROUND: A novel class of membranes, medium cut-off (MCO) membranes, has recently been designed to achieve interesting removal capacities for middle and large middle molecules in hemodialysis (HD) treatments. The few studies published to date have reported contradictory results regarding middle-sized molecules when comparing MCO dialyzers versus dialyzers used in online hemodiafiltration (OL-HDF). METHODS: A prospective, single-center study was carried out in 22 patients. Each patient underwent 9 dialysis sessions with routine dialysis parameters, one with an MCO dialyzer in HD and the other 8 with different dialyzers in OL-HDF. The removal ratio (RR) of urea, creatinine, ß2-microglobulin, myoglobin, prolactin, α1-microglobulin, α1-acid glycoprotein, and albumin was intraindividually compared. Albumin loss in dialysate was measured. We propose a global removal score ([ureaRR + ß2-microglobulinRR + myoglobinRR + prolactinRR + α1-microglobulinRR + α1-acid glycoproteinRR]/6 - albuminRR) as a new tool for measuring dialyzer effectiveness. RESULTS: No significant differences in the RRs of small and middle molecular range molecules were observed between the MCO vs. OL-HDF dialyzers (range 60-80%). Lower RRs were found for α1-microglobulin and α1-acid glycoprotein without significant differences. The albumin RR was < 11% and dialysate albumin loss was < 3.5 g in all situations without significant differences. The global removal score was 54.9 ± 4.8% with the MCO dialyzer without significant differences. CONCLUSIONS: Removal of a wide range of molecular weights, calculated with the proposed global removal score, was almost equal with the MCO dialyzer in HD treatment compared with 8 high-flux dialyzers in high-volume OL-HDF without relevant changes in albumin loss. The global removal score could be a new tool to evaluate the effectiveness of dialyzers and/or different treatment modalities.

Modern creatinine (Bio)sensing: Challenges of point-of-care platforms.

The importance of knowing creatinine levels in the human body is related to the possible association with renal, muscular and thyroid dysfunction. Thus, the accurate detection of creatinine may indirectly provide information surrounding those functional processes, therefore contributing to the management of the health status of the individual and early diagnosis of acute diseases. The questions at this point are: to what extent is creatinine information clinically relevant?; and do modern creatinine (bio)sensing strategies fulfil the real needs of healthcare applications? The present review addresses these questions by means of a deep analysis of the creatinine sensors reported in the literature over the last five years. There is a wide range of techniques for detecting creatinine, most of them based on optical readouts (20 of the 33 papers collected in this review). However, the use of electrochemical techniques (13 of the 33 papers) is recently emerging in alignment with the search for a definitive and trustworthy creatinine detection at the point-of-care level. In this sense, biosensors (7 of the 33 papers) are being established as the most promising alternative over the years. While creatinine levels in the blood seem to provide better information about patient status, none of the reported sensors display adequate selectivity in such a complex matrix. In contrast, the analysis of other types of biological samples (e.g., saliva and urine) seems to be more viable in terms of simplicity, cross-selectivity and (bio)fouling, besides the fact that its extraction does not disturb individual's well-being. Consequently, simple tests may likely be used for the initial check of the individual in routine analysis, and then, more accurate blood detection of creatinine could be necessary to provide a more genuine diagnosis and/or support the corresponding decision-making by the physician. Herein, we provide a critical discussion of the advantages of current methods of (bio)sensing of creatinine, as well as an overview of the drawbacks that impede their definitive point-of-care establishment.

Biosensing methods for determination of creatinine: A review.

Creatinine is a metabolic product of creatine phosphate in muscles, which provides energy to muscle tissues. Creatinine has been considered as indicator of renal function specifically after dialysis, thyroid malfunction and muscle damage. The normal level of creatinine in the serum and its excretion through urine in apparently healthy individuals is 45-140 µM and 0.8-2.0 gm/day respectively. The level of creatinine reaches >1000 µM in serum during renal, thyroid and kidney dysfunction or muscle disorder. A number of conventional methods such as colorimetric, spectrophotometric and chromatographic are available for determination of creatinine. Besides the advantages of being highly sensitive and selective, these methods have some drawbacks like time-consuming, requirement of sample pre-treatment, high cost instrumental set-up and skilled persons to operate. The sensors/biosensors overcome these drawbacks, as these are fast, easy, cost effective and highly sensitive. This review article describes the classification, operating principles, merits and demerits of various creatinine sensors/biosensors, specifically nanomaterials based biosensors. Creatinine biosensors work optimally within 2-900 s, potential range 0.1-1.0 V, pH range 4.0-10.0, temperature range 25-35 °C and had linear range, 0.004-30000 µM for creatinine with the detection limit between 0.01.01 µM and 520 µM. These biosensors measured creatinine level in sera and urine samples and had storage stability between 4 and 390 days, while being stored dry at 4 °C. The future perspective for further improvement and commercialization of creatinine biosensors are discussed.

Nanofibrous Tubular Membrane for Blood Hemodialysis.

As the most important components of a hemodialysis device, nanofibrous membranes enjoy high interconnected porosity and specific surface area as well as excellect permeability. In this study, a tubular nanofibrous membrane of polysulfone nanofibers was produced via electrospinning method to remove urea and creatinine from urine and blood serums of dialysis patients. Nanofibrous membranes were electrospun at a concentration of 11.5 wt% of polysulfone (PS) and dimethylformamide (DMF)/tetrahydrofuran (THF) with a ratio of 70/30. The effects of the rotational speed of collectors, electrospinning duration, and inner diameter of the tubular nanofibrous membrane on the urea and creatinine removal efficiency of the tubular membrane were investigated through the hemodialysis simulation experiments. It was found that the tubular membrane with an inner diameter of 3 mm elecrospun at shorter duration with lower collecting speed had the highest urea and creatinine removal efficiency. The hemodialysis simulation experiment showed that the urea and creatinine removal efficiency of the tubular membrane with a diameter of 3 mm were 90.4 and 100%, respectively. Also, three patients' blood serums were tested with the nanofibrous membrane. The results showed that the creatinine and urea removal rates were 93.2 and 90.3%, respectively.

Chemiluminescence of creatinine/H2O2/Co(2+) and its application for selective creatinine detection.

Creatinine is an important biomarker in clinical diagnosis and biomonitoring programs as well as urinary metabolomic/metabonomics research. Current methods are either nonselective, time consuming or require heavy and expensive instruments. In this study, chemiluminescence of creatinine with hydrogen peroxide has been reported for the first time, and its chemiluminescence is remarkably enhanced in the presence of cobalt ions. By utilizing these phenomena, we have developed a sensitive and selective chemiluminescence method for creatinine determination by coupling with flow injection analysis. The calibration curve is linear in the range of 1×10(-7)-3×10(-5)mol/L with a limit of detection (S/N=3) of 7.2×10(-8)mol/L, which is adequate for detecting creatinine in the clinically accepted range. The relative standard deviation for seven measurements of 3×10(-5)mol/L creatinine is 1.2%. The chemiluminescence method was then utilized to detect creatinine in human urine samples after simple dilution with water. It takes less than 1min each measurement and the recoveries for spiked urine samples were 100-103%. The interference study demonstrates that some common species in urine, such as amino acids, ascorbic acid and creatine, have negligible effects on creatinine detection. The present method does not use expensive instruments, enzymes and separation technique. This method has the advantages of sensitivity, selectivity, simplicity, rapidity, and low cost. It holds great promise for basic or comprehensive metabolic panel, drug screening, anti-dopping, and urinary metabolomic/metabonomics research.

Creatinina en flujo vaginal para el diagnóstico de rotura prematura de membranas / Creatinine in vaginal fluid for the diagnosis of premature rupture of membranes

Objetivo: Establecer la eficacia diagnóstica de la determinación de creatinina en flujo vaginal para el diagnóstico de la rotura prematura de membranas. Métodos: Se realizó una investigación de tipo prospectivo en una muestra de 270 embarazadas que asistieron al Hospital Central Dr. Urquinaona. Los grupos consistieron en pacientes con rotura prematura de membranas (grupo A: n = 135) y embarazadas con membranas íntegras (grupo B: n = 135), consideradas como controles. Se evaluaron las características generales, valores de creatinina en flujo vaginal y efectividad diagnóstica. Resultados: La edad gestacional al momento de la determinación de las concentraciones de creatinina en flujo vaginal fue de 32,9 ± 1,6 semanas para el grupo A y 33,1 ± 1,9 semanas para el grupo B (p = ns). No se encontraron diferencias estadísticamente significativas en la edad materna ni en la frecuencia de paridad entre ambos grupos de tratamiento (p = ns). Las pacientes del grupo A presentaron concentraciones significativamente más altas de creatinina en flujo vaginal (1,09 ± 0,35 mg/dl) comparadas con las embarazadas del grupo B (0,36 ± 0,17 mg/dl, p < 0,05). Un valor de corte de 0,45 mg/dl presentó un valor por debajo de la curva de 0,87 con una sensibilidad del 78,3%, especificidad del 78,7%, valor predictivo positivo del 80,6% y valor predictivo negativo del 76,4%. Conclusión: La determinación de las concentraciones de creatinina en el flujo vaginal es una técnica diagnóstica útil para la rotura prematura de membranas

Objective: To establish the diagnostic efficacy of determining creatinine concentrations in vaginal fluid for the diagnosis of premature rupture of membranes. Methods: A prospective study was performed in a sample of 270 pregnant women attending the Dr. Urquinaona Central Hospital. Group A consisted of patients with premature rupture of membranes (n = 135) and group B of pregnant women with intact membranes (n = 135), considered as controls. We evaluated general characteristics, creatinine values in vaginal fluid, and diagnostic efficacy. Results: Gestational age at creatinine determination in vaginal fluid was 32.9 ± 1.6 weeks in group A and 33.1 ± 1.9 weeks in group B (p = ns). There were no significant differences in maternal age or the frequency of parity between the 2 groups (p = ns). Creatinine concentrations in vaginal fluid were significantly higher in group A (1.09 ± 0.35 mg/dl) than in group B (0.36 ± 0.17 mg/dl; P<.05). A cut-off point of 0.45 mg/dl showed an under the curve value of 0.87, with a sensitivity of 78.3%, a specificity of 78.7%, a positive predictive value of 80.6%, and a negative predictive value of 76.4%. Conclusions: Determination of creatinine concentrations in vaginal fluid is a useful diagnostic tool for premature rupture of membranes

Recomendaciones de pruebas preoperatorias en el paciente adulto para procedimientos en régimen de cirugía ambulatoria / Preoperative tests recommendations in adult patients for ambulatory surgery

Tradicionalmente, la valoración anestésica ha incluido una serie de pruebas de laboratorio con la intención de detectar patologías no diagnosticadas y garantizar que el paciente concurre a la cirugía bajo unos criterios de seguridad. Estas pruebas sin una indicación clínica específica suponen un gasto innecesario, de cuestionable valor diagnóstico y son en general inútiles. En el contexto de la cirugía sin ingreso, recientes evidencias sugieren que los pacientes de cualquier edad y sin comorbilidad importante, estado físico ASA I y II, no necesitan pruebas preoperatorias complementarias de forma rutinaria. El objetivo de estas recomendaciones es determinar las indicaciones generales de las pruebas a realizar antes de la cirugía en el paciente adulto ASA I y II que se va a intervenir en cirugía ambulatoria (AU)

Anesthetic assessment traditionally included a series of laboratory tests intended to detect undiagnosed diseases, and to ensure that the patient undergoes surgery following safety criteria. These tests, without a specific clinical indication, are expensive, of questionable diagnostic value and often useless. In the context of outpatient surgery, recent evidence suggests that patients of any age without significant comorbidity, ASA physical status grade i and grade ii, do not need additional preoperative tests routinely. The aim of the present recommendations is to determine the general indications in which these tests should be performed in ASA grade i and grade ii patients undergoing ambulatory surgery (AU)

Innovative strategy with potential to increase hemodialysis efficiency and safety.

Uremic toxins are mainly represented by blood urine nitrogen (BUN) and creatinine (Crea) whose removal is critically important in hemodialysis (HD) for kidney disease. Patients undergoing HD have a complex illness, resulting from: inadequate removal of organic waste, dialysis-induced oxidative stress and membrane-induced inflammation. Here we report innovative breakthroughs for efficient and safe HD by using a plasmon-induced dialysate comprising Au nanoparticles (NPs)-treated (AuNT) water that is distinguishable from conventional deionized (DI) water. The diffusion coefficient of K3Fe(CN)6 in saline solution can be significantly increased from 2.76, to 4.62 × 10(-6) cm s(-1), by using AuNT water prepared under illumination by green light-emitting diodes (LED). In vitro HD experiments suggest that the treatment times for the removals of 70% BUN and Crea are reduced by 47 and 59%, respectively, using AuNT water instead of DI water in dialysate, while additionally suppressing NO release from lipopolysaccharide (LPS)-induced inflammatory cells.

Association between sodium intake and hydration status amongst community-dwelling elderly people / Asociación entre la ingesta de sodio y el estado de hidratación en personas mayores que viven en centros comunitarios

Dehydration is a common condition in older people and it has been associated with the development of many diseases. The aim of this study was to assess the association between hydration status in community-dwelling elderly people. Data were gathered in 74 community-dwelling elderly individuals (28 males) and included the collection of 24-h urine samples, which were screened for validity using 24-h urinary creatinine excretion in relation to body weight, anthropometric, physical activity, and sociodemographic variables. Hydration status was assessed using urinary indicators (24-h volume, osmolality and urine specific gravity) and sodium intake was assessed by 24-h urinary sodium excretion. Linear regression analysis was performed to quantify the association between sodium excretion (independent variables) and hydration biomarkers (dependent variables). No significant differences were found between males and females in 24-h urine volume (1,982.5 ± 654.5 mL vs 1,832.0 ± 655.8 mL, p = 0.341), 24-h urine osmolality (454.0 ± 158.5 mOsm/kg vs 402.7 ± 149.4 mOsm/kg, p = 0.204) and 24-h urine specific gravity (1.015 ± 0.006 vs 1.013 ± 0.005, p = 0.131). Urine volume and osmolality showed a positive and significant association with sodium excretion (= 0.314, 95%CI: 0.095,0.562 and = 0.390, 95%CI: 0.195,0.679, respectively), even after adjusting for confounders (age, sex, body mass index, and physical activity). Our findings showed that community-dwelling elderly individuals with a higher level of sodium intake had a higher 24-h urine volume and a higher 24-h urine osmolality. These findings suggest that a higher sodium intake is associated with a poorer hydration status in this elderly population, assessed by urine osmolality (AU)

La deshidratación es un problema común en las personas mayores y ha sido asociado con el desarrollo de muchas enfermedades. El objetivo de este estudio consiste en la evaluación de la asociación entre la ingesta de socio y el estado de hidratación en personas mayores que viven en centros comunitarios. Los datos fueron recopilados a partir de 74 personas mayores que vivían en centros comunitarios (28 varones) e incluyeron tomas de muestras de orina de 24h, que fueron examinadas para determinar su validez empleando excreción urinaria de creatinina de 24h en relación con variables de peso corporal, antropometría, actividad física y variables sociodemográficas. El estado de hidratación fue evaluado empleando indicadores urinarios (volumen en 24h, osmolalidad y gravedad específica de la orina) y la ingesta de sodio fue evaluada mediante excreción urinaria de sodio de 24h. Se realizó un análisis de regresión lineal para cuantificar la asociación entre excreción de sodio (variables independientes) y biomarcadores de hidratación (variables dependientes). No se encontraron diferencias significativas entre varones y mujeres en el volumen de orina de 24h (1.982,5 ± 654,5 mL vs 1.832,0 ± 655,8 mL, p = 0,341), 24-h orina osmolalidad (454,0 ± 158,5 mOsm/kg vs 402,7 ± 149,4 mOsm/kg, p= 0,204) y gravedad específica de la orina en 24h (1,015 ±0,006 vs 1,013 ± 0,005, p = 0,131). El volumen de orina y la osmolalidad mostraron una asociación positiva y significativa con la excreción de sodio (= 0,314, 95% CI: 0,095, 0,562 y = 0,390, 95% CI: 0,195, 0,679, respectivamente), incluso después de ajustar factores de distorsión (edad, sexo, índice de masa corporal y actividad física). Nuestros resultados demostraron que las personas mayores en centros comunitarios, con un mayor nivel de ingesta de sodio, tenían un mayor volumen de orina de 24h y una mayor osmolalidad de la orina de 24-h. Estos resultados sugieren que una mayor ingesta de sodio estaría asociada a un peor estado de hidratación en esta población de mayores, evaluado mediante la osmolalidad de la orina (AU)

Tracing and separating plasma components causing matrix effects in hydrophilic interaction chromatography-electrospray ionization mass spectrometry.

Matrix effects on electrospray ionization were investigated for plasma samples analysed by hydrophilic interaction chromatography (HILIC) in gradient elution mode, and HILIC columns of different chemistries were tested for separation of plasma components and model analytes. By combining mass spectral data with post-column infusion traces, the following components of protein-precipitated plasma were identified and found to have significant effect on ionization: urea, creatinine, phosphocholine, lysophosphocholine, sphingomyelin, sodium ion, chloride ion, choline and proline betaine. The observed effect on ionization was both matrix-component and analyte dependent. The separation of identified plasma components and model analytes on eight columns was compared, using pair-wise linear correlation analysis and principal component analysis (PCA). Large changes in selectivity could be obtained by change of column, while smaller changes were seen when the mobile phase buffer was changed from ammonium formate pH 3.0 to ammonium acetate pH 4.5. While results from PCA and linear correlation analysis were largely in accord, linear correlation analysis was judged to be more straight-forward in terms of conduction and interpretation.

Estandarización de los procedimientos de medida de creatinina: estado actual / Standardization of creatinine measurement methods: current status

La implementación de las ecuaciones de estimación del filtrado glomerular (FG) en los informes del laboratorio clínico ha colocado en el punto de mira las limitaciones de la medida de creatinina y promovido la puesta en marcha de un programa internacional para su estandarización. Hemos analizado el estado actual de implementación de dicho programa respecto a la trazabilidad, la conmutabilidad, la imprecisión, el error sistemático, así como la información acerca del tipo de ecuación a utilizar y sobre los valores de referencia, de los reactivos de creatinina más utilizados en los laboratorios españoles. La mayoría de los procedimientos de medida presentan trazabilidad al método de referencia y satisfacen los requerimientos de imprecisión; sin embargo, la información disponible sobre la inexactitud, el error total de medida, la verificación de la conmutabilidad de los materiales de calibración utilizados, la ecuación de FG a utilizar y los valores de referencia en población pediátrica es insuficiente o inexistente en la mayoría de las firmas comerciales evaluadas (AU)

The implementation of equations for estimating glomerular filtration rate (GFR) in clinical laboratory reports has placed the spotlight on the limitations of creatinine measurements and has promoted the establishment of an international program for standardisation. We have analysed the current state of implementation of this program with regard to traceability, commutability, imprecision, systematic error, as well as information on the type of equation to use and reference values, as well as the creatinine reagents commonly used in Spanish laboratories. Most of the measurement procedures have traceability to the reference method, and meet the requirements of imprecision. The available information available on the inaccuracy, the total error of measurement, verification of the commutability of calibration materials used, the glomerular filtration equation to use, and reference values in the paediatric population is unsatisfactory or non-existent in most commercial firms evaluated (AU)

A novel approach for blood purification: mixed-matrix membranes combining diffusion and adsorption in one step.

Hemodialysis is a commonly used blood purification technique in patients requiring kidney replacement therapy. Sorbents could increase uremic retention solute removal efficiency but, because of poor biocompatibility, their use is often limited to the treatment of patients with acute poisoning. This paper proposes a novel membrane concept for combining diffusion and adsorption of uremic retention solutes in one step: the so-called mixed-matrix membrane (MMM). In this concept, adsorptive particles are incorporated in a macro-porous membrane layer whereas an extra particle-free membrane layer is introduced on the blood-contacting side of the membrane to improve hemocompatibility and prevent particle release. These dual-layer mixed-matrix membranes have high clean-water permeance and high creatinine adsorption from creatinine model solutions. In human plasma, the removal of creatinine and of the protein-bound solute para-aminohippuric acid (PAH) by single and dual-layer membranes is in agreement with the removal achieved by the activated carbon particles alone, showing that under these experimental conditions the accessibility of the particles in the MMM is excellent. This study proves that the combination of diffusion and adsorption in a single step is possible and paves the way for the development of more efficient blood purification devices, excellently combining the advantages of both techniques.

A simple screening method using ion chromatography for the diagnosis of cerebral creatine deficiency syndromes.

Cerebral creatine deficiency syndromes (CCDS) are caused by genetic defects in L-arginine:glycine amidinotransferase, guanidinoacetate methyltransferase or creatine transporter 1. CCDS are characterized by abnormal concentrations of urinary creatine (CR), guanidinoacetic acid (GA), or creatinine (CN). In this study, we describe a simple HPLC method to determine the concentrations of CR, GA, and CN using a weak-acid ion chromatography column with a UV detector without any derivatization. CR, GA, and CN were separated clearly with the retention times (mean ± SD, n = 3) of 5.54 ± 0.0035 min for CR, 6.41 ± 0.0079 min for GA, and 13.53 ± 0.046 min for CN. This new method should provide a simple screening test for the diagnosis of CCDS.

Benefits of first-half intensive haemodiafiltration for the removal of uraemic solutes.

AIM: Haemodiafiltration (HDF) is the most efficient blood purification method and can remove a wide spectrum of solutes of different molecular weights (MW). The purpose of this study was to investigate whether the removed amounts of solutes, especially the larger molecules, could be increased by changing the HDF filtration procedure. METHODS: A new first-half intensive HDF treatment (F-HDF) was designed, whereby convective clearance is intensively forced during the first half of a HDF session. We compared the removed amounts of solutes in the same group of nine patients treated by F-HDF, constant rate-replacing HDF (C-HDF) and a high-flux haemodialysis (HD). RESULTS: F-HDF can remove significantly larger amounts of α(1) -microglobulin (MG), molecular weight (MW) 33,000, compared with HD and C-HDF (30.1 ± 15.1 vs 12.4 ± 0.3, 15.0 ± 3.1 mg, P < 0.01). Regarding the removal amounts and clear space of ß(2) MG, MW 11,800, there were no significant differences between the three treatment modalities. Regarding amounts of creatinine, urea nitrogen and phosphorus, there were no significant differences between the three treatment modalities. CONCLUSION: In post-replacement HDF with a high-flux membrane dialyzer, the method used in the present study in which replacement is completed during the first half of the process, is associated with a greater rate of larger molecule removal than the conventional uniform replacement method.

Effect of packing density of hollow fibers on solute removal performances of dialyzers.

Solute removal performances of dialyzers are dependent not only on the solute permeabilities of the membrane but also on the module design. We have investigated how the packing density of hollow fiber (PDF) affects the solute removal performances. A series of 4 polyester polymer alloy membrane test dialyzers were assembled with varying PDFs of 29.6%, 35.3%, 44.1%, and 53.1%. Clearances (C(L)) were measured in vitro for creatinine (MW113), vitamin B(12) (MW1355), and chymotrypsin (MW25300) with various Q(B)=100 to 400 and Q(D)=350 to 650 mL/min in the absence of net ultrafiltration. When Q(B) was 44.1%, which was also considered to be due to the internal filtration. Packing density of hollow fiber can be optimized in terms of solute removal performances when the target solute and therapeutic conditions are specified.

Mechanisms of solute and fluid removal in hemodiafiltration.

BACKGROUND: Prescribing therapeutic conditions for online predilution hemodiafiltration (HDF) with fixed total dialysate flow rate Q(Dtotal) is not straightforward, since the increase in the substitution fl ow rate Q(S) is compensated by the decrease in the net dialysate flow rate Q(Dnet). METHODS: Clearances of various solutes under online predilution HDF were clinically evaluated with fixed Q(Dtotal) (= 520 ml/min) divided into Q(Dnet) and Q(S). Three polysulfone membrane dialyzers and 5 polyester polymer alloy membrane dialyzers were chosen to measure sieving coefficients (SC) for albumin in vitro at 37 degrees C to predict when the albumin loss is greatest during clinical treatment. RESULTS: Clearances of small solutes such as urea and creatinine increased in vivo with the increase in blood flow. These values, however, slightly but steadily decreased with the increase in Q(S) because the increase in Q(S) decreased Q(Dnet). Clearances of beta2-microglobulin and alpha1-microglobuin increased with the increase in Q(S) and decreased with the increase in Q(Dnet), because clearances of larger solutes were more strongly dependent on ultrafiltration than on diffusion. The SC for albumin in vitro showed a peak at the beginning of the experiment in those membranes with large proportions of polyvinylpyrroridone (PVP), which may lead to large amounts of albumin loss at the beginning of the treatment. CONCLUSIONS: Dialysis prescription in online predilution HDF in terms of maximizing clearance for the solute of interest may be different for each target solute. The amount of albumin loss may be closely related to the amount of PVP included in the membrane.