Influence of ultrafiltration conditions on the measurement of unbound drug concentrations: flucloxacillin as an example.

BACKGROUND: When performing therapeutic drug monitoring (TDM) for flucloxacillin, it is advised to measure the unbound, not the total, flucloxacillin concentration. To be able to accurately quantify unbound flucloxacillin concentrations, a reliable analytical method is indispensable. OBJECTIVE: To determine the influence of temperature and pH of the sample during ultrafiltration on the measured unbound fraction of flucloxacillin. MATERIALS AND METHODS: We performed three different experiments. In a single laboratory experiment, we investigated the influence of ultrafiltration temperature (10°C, room temperature and 37°C) on the measured unbound fraction of flucloxacillin for three concentration levels. In a multiple laboratory experiment, the results of eight laboratories participating in an international quality control programme measuring unbound flucloxacillin concentrations were analysed. In the third experiment, patient samples were ultrafiltrated using four different conditions: (i) physiological pH and room temperature; (ii) unadjusted pH (pH 9 after freezing) and room temperature; (iii) physiological pH and 37°C and (iv) unadjusted pH and 37°C. RESULTS: For all experiments, measurement of samples that were ultrafiltrated at room temperature resulted in a substantially lower unbound fraction compared to samples that were ultrafiltrated at 37°C. Adjusting the pH to physiological pH only had a minimal impact on the measured unbound fraction. CONCLUSIONS: On the basis of these findings and considering the need for fast, simple and reproducible sample pretreatment for TDM purposes, we conclude that ultrafiltration of flucloxacillin should be performed at physiological temperature (37°C), but adjustment of pH does not seem to be necessary.

Development of a virus-based affinity ultrafiltration method for screening virus-surface-protein-targeted compounds from complex matrixes: Herbal medicines as a case study.

Herbal medicines (HMs) are one of the main sources for the development of lead antiviral compounds. However, due to the complex composition of HMs, the screening of active compounds within these is inefficient and requires a significant time investment. We report a novel and efficient virus-based screening method for antiviral active compounds in HMs. This method involves the centrifugal ultrafiltration of viruses, known as the virus-based affinity ultrafiltration method (VAUM). This method is suitable to identify virus specific active compounds from complex matrices such as HMs. The effectiveness of the VAUM was evaluated using influenza A virus (IAV) H1N1. Using this method, four compounds that bind to the surface protein of H1N1 were identified from dried fruits of Terminalia chebula (TC). Through competitive inhibition assays, the influenza surface protein, neuraminidase (NA), was identified as the target protein of these four TC-derived compounds. Three compounds were identified by high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS), and their anti-H1N1 activities were verified by examining the cytopathic effect (CPE) and by performing a virus yield reduction assay. Further mechanistic studies demonstrated that these three compounds directly bind to NA and inhibit its activity. In summary, we describe here a VAUM that we designed, one that can be used to accurately screen antiviral active compounds in HMs and also help improve the efficiency of screening antiviral drugs found in natural products.

Development of a new miniaturized system for ultrafiltration.

Acute decompensated heart failure and fluid overload are the most common causes of hospitalization in heart failure patients, and often, they contribute to disease progression. Initial treatment encompasses intravenous diuretics although there might be a percentual of patients refractory to this pharmacological approach. New technologies have been developed to perform extracorporeal ultrafiltration in fluid overloaded patients. Current equipment allows to perform ultrafiltration in most hospital and acute care settings. Extracorporeal ultrafiltration is then prescribed and conducted by specialized teams, and fluid removal is planned to restore a status of hydration close to normal. Recent clinical trials and European and North American practice guidelines suggest that ultrafiltration is indicated for patients with refractory congestion not responding to medical therapy. Close interaction between nephrologists and cardiologists may be the key to a collaborative therapeutic effort in heart failure patients. Further studies are today suggesting that wearable technologies might become available soon to treat patients in ambulatory and de-hospitalized settings. These new technologies may help to cope with the increasing demand for the care of chronic heart failure patients. Herein, we provide a state-of-the-art review on extracorporeal ultrafiltration and describe the steps in the development of a new miniaturized system for ultrafiltration, called AD1 (Artificial Diuresis).

Decongestion (instead of ultrafiltration?).

PURPOSE OF REVIEW: To summarize the contemporary evidence on decongestion strategies in patients with acute heart failure (AHF). RECENT FINDINGS: While loop diuretic therapy has remained the backbone of decongestive treatment in AHF, multiple randomized clinical trials suggest that early combination with other diuretic classes or molecules with diuretic properties should be considered. Mineralocorticoid receptor antagonists and sodium-glucose co-transporter-2 inhibitors are disease-modifying drugs in heart failure that favourably influence prognosis early on, advocating their start as soon as possible in the absence of any compelling contraindications. Short-term upfront use of acetazolamide in adjunction to intravenous loop diuretic therapy relieves congestion faster, avoids diuretic resistance, and may shorten hospitalization length. Thiazide-like diuretics remain a good option to break diuretic resistance. Currently, ultrafiltration in AHF remains mainly reserved for patient with an inadequate response to pharmacological treatment. SUMMARY: In most patients with AHF, decongestion can be achieved effectively and safely through combination diuretic therapies. Appropriate diuretic therapy may shorten hospitalization length and improve quality of life, but has not yet proven to reduce death or heart failure readmissions. Ultrafiltration currently has a limited role in AHF, mainly as bail-out strategy, but evidence for a more upfront use remains inconclusive.

Utilization of aquapheresis among hospitalized patients with end-stage liver disease: A case series and literature review.

Third-spacing of fluid is a common complication in hospitalized patients with decompensated cirrhosis. In addition to ascites, patients with advanced cirrhosis may develop significant peripheral edema, which may limit mobility and exacerbate debility and muscle wasting. Concomitant kidney failure and cardiac dysfunction may lead to worsening hypervolemia, which may ultimately result in pulmonary edema and respiratory compromise. Diuretic use in such patients may be limited by kidney dysfunction and electrolyte abnormalities, including hyponatremia and hypokalemia. A slow, continuous form of ultrafiltration known as aquapheresis is a method of extracorporeal fluid removal whereby a pump generates a transmembrane pressure that forces an isotonic ultrafiltrate across a semipermeable membrane. This leads to removal of an ultrafiltrate that is isotonic to blood without the need for dialysate or replacement fluid as is necessary in other forms of continuous kidney replacement therapy. This technique has been utilized in other conditions including acute decompensated heart failure, with trials showing mixed, but generally favorable results. Herein, we present a series of our own experience using aquapheresis among patients with cirrhosis, review the literature regarding its use in other hypervolemic states, and discuss how we may apply lessons learned from use of aquapheresis in heart failure to patients with end-stage liver disease.

The Future of Municipal Wastewater Reuse Concentrate Management: Drivers, Challenges, and Opportunities.

Water reuse is rapidly becoming an integral feature of resilient water systems, where municipal wastewater undergoes advanced treatment, typically involving a sequence of ultrafiltration (UF), reverse osmosis (RO), and an advanced oxidation process (AOP). When RO is used, a concentrated waste stream is produced that is elevated in not only total dissolved solids but also metals, nutrients, and micropollutants that have passed through conventional wastewater treatment. Management of this RO concentrate─dubbed municipal wastewater reuse concentrate (MWRC)─will be critical to address, especially as water reuse practices become more widespread. Building on existing brine management practices, this review explores MWRC management options by identifying infrastructural needs and opportunities for multi-beneficial disposal. To safeguard environmental systems from the potential hazards of MWRC, disposal, monitoring, and regulatory techniques are discussed to promote the safety and affordability of implementing MWRC management. Furthermore, opportunities for resource recovery and valorization are differentiated, while economic techniques to revamp cost-benefit analysis for MWRC management are examined. The goal of this critical review is to create a common foundation for researchers, practitioners, and regulators by providing an interdisciplinary set of tools and frameworks to address the impending challenges and emerging opportunities of MWRC management.

Excessive Ozonation Stress Triggers Severe Membrane Biofilm Accumulation and Fouling.

The established benefits of ozone on microbial pathogen inactivation, natural organic matter degradation, and inorganic/organic contaminant oxidation have favored its application in drinking water treatment. However, viable bacteria are still present after the ozonation of raw water, bringing a potential risk to membrane filtration systems in terms of biofilm accumulation and fouling. In this study, we shed light on the role of the specific ozone dose (0.5 mg-O3/mg-C) in biofilm accumulation during long-term membrane ultrafiltration. Results demonstrated that ozonation transformed the molecular structure of influent dissolved organic matter (DOM), producing fractions that were highly bioavailable at a specific ozone dose of 0.5, which was inferred to be a turning point. With the increase of the specific ozone dose, the biofilm microbial consortium was substantially shifted, demonstrating a decrease in richness and diversity. Unexpectedly, the opportunistic pathogen Legionella was stimulated and occurred in approximately 40% relative abundance at the higher specific ozone dose of 1. Accordingly, the membrane filtration system with a specific ozone dose of 0.5 presented a lower biofilm thickness, a weaker fluorescence intensity, smaller concentrations of polysaccharides and proteins, and a lower Raman activity, leading to a lower hydraulic resistance, compared to that with a specific ozone dose of 1. Our findings highlight the interaction mechanism between molecular-level DOM composition, biofilm microbial consortium, and membrane filtration performance, which provides an in-depth understanding of the impact of ozonation on biofilm accumulation.

Development of target-based cell membrane affinity ultrafiltration technology for a simplified approach to discovering potential bioactive compounds in natural products.

Target-based drug discovery technology based on cell membrane targets has gained significant traction and has been steadily advancing. However, current methods still face certain limitations that need to be addressed. One of the challenges is the laborious preparation process of screening materials, which can be time-consuming and resource-intensive. Additionally, there is a potential issue of non-specific adsorption caused by carrier materials, which can result in false-positive results and compromise the accuracy of the screening process. To address these challenges, this paper proposes a target-based cell membrane affinity ultrafiltration technology for active ingredient discovery in natural products. In this technique, the cell membranes of human lung adenocarcinoma epithelial cells (A549) with a high expression of epidermal growth factor receptor (EGFR) were incubated with candidate drugs and then transferred to an ultrafiltration tube. Through centrifugation, components that interacted with EGFR were retained in the ultrafiltration tube as "EGFR-ligand" complex, while the components that did not interact with EGFR were separated. After thorough washing and eluting, the components interacting with EGFR were dissociated and further identified using LC-MS, enabling the discovery of bioactive compounds. Moreover, the target-based cell membrane affinity ultrafiltration technology exhibited commendable binding capacity and selectivity. Ultimately, this technology successfully screened and identified two major components from the Curcumae Rhizoma-Sparganii Rhizoma (CS) herb pair extracts, which were further validated for their potential anti-tumor activity through pharmacological experiments. By eliminating the need for laborious preparation of screening materials and the potential non-specific adsorption caused by carriers, the development of target-based cell membrane affinity ultrafiltration technology provides a simplified approach and method for bioactive compounds discovery in natural sources.

Sodium removal per ultrafiltration volume in automated peritoneal dialysis in pediatric patients.

BACKGROUND: The standard rate of sodium removal in adult anuric patients on continuous ambulatory peritoneal dialysis (CAPD) is 7.5 g/L of ultrafiltration volume (UFV). Although automated PD (APD) is widely used in pediatric patients, no attempt has yet been made to estimate sodium removal in APD. METHODS: The present, retrospective cohort study included pediatric patients with APD who were managed at Tokyo Metropolitan Children's Medical Center between July 2010 and November 2017. The patients underwent a peritoneal equilibrium test (PET) at our hospital. Sodium removal per UFV was calculated by peritoneal function and dwell time using samples from patients on APD with 1- and 2-h dwell effluent within three months of PET and 4- and 10-h dwell effluent at PET. RESULTS: In total, 217 samples from 18 patients were included, with 63, 81, and 73 of the samples corresponding to the High [H], High-average [HA], and Low-average [LA] PET category, respectively. Sodium removal per UFV (g/L in salt equivalent) for dwell times of one, two, four, and ten hours was 5.2, 8.8, 8.0, and 11.5 for PET [H], 5.3, 5.8, 5.6, and 8.1 for PET [HA], and 4.6, 5.1, 5.1, and 7.1 for PET [LA], respectively. CONCLUSIONS: Sodium removal per UFV in pediatric APD was less than the standard adult CAPD and tended to be lower with shorter dwell times, leading to sodium accumulation. Therefore, salt intake should be restricted in combination with one or more long daytime dwells, especially in anuric patients.

Rapid identifying of COX-2 inhibitors from turmeric (Curcuma longa) by bioaffinity ultrafiltration coupled with UPLC-Q Exactive-Orbitrap-MS and zebrafish-based in vivo validation.

Turmeric (Curcuma longa), a typical source with recognized anti-inflammatory activity, is one such medicine-food homology source, yet its anti-inflammatory mechanisms and specific component combinations remain unclear. In this study, a net fishing method combining bio-affinity ultrafiltration and ultra-high performance liquid chromatography-mass spectrometry (AUF-LC/MS) was employed and 13 potential COX-2 inhibitors were screened out from C. longa. 5 of them (C1, 17, 20, 22, 25) were accurately isolated and identified. Initially, their IC50 values were measured (IC50 of C1, 17, 20, 22 and 25 is 55.08, 48.26, 29.13, 111.28 and 150.48 µM, respectively), and their downregulation of COX-2 under safe concentrations (400, 40, 120, 50 and 400 µM for C1, 17, 20, 22 and 25, respectively) was confirmed on RAW 264.7 cells. Further, in transgenic zebrafish (Danio rerio), significant anti-inflammatory activity at safe concentrations (15, 3, 1.5, 1.5 and 3 µg/mL for C1, 17, 20, 22 and 25, respectively) were observed in a dose-dependent manner. More importantly, molecular docking analysis further revealed the mode of interaction between them and the key active site residues of COX-2. This study screened out and verified unreported COX-2 ligands, potentially accelerating the discovery of new bioactive compounds in other functional foods.

Environmental impact assessment via life cycle analysis on ultrafiltration membrane fabricated from polyethylene terephthalate waste to treat microalgal cultivation wastewater for reusability.

The current study had conducted the life cycle analysis (LCA) to assess the environmental impact of microalgal wastewater treatment via an integrated membrane bioreactor. The functional unit selected for this analysis was 1 kg of treated microalgal wastewater with contaminants eliminated by ultrafiltration membrane fabricated from recycled polyethylene terephthalate waste. Meanwhile, the applied system boundary in this study was distinguished based on two scenarios, namely, cradle-to-gate encompassed wastewater treatment only and cradle-to-cradle which included the reutilization of treated wastewater to cultivate microalgae again. The environmental impacts and hotspots associated with the different stages of the wastewater treatment process had clearly elucidated that membrane treatment had ensued the highest impact, followed by microalgal harvesting, and finally cultivation. Among the environmental impact categories, water-related impact was found to be prominent in the following series: freshwater ecotoxicity, freshwater eutrophication and marine ecotoxicity. Notably, the key performance indicator of all environmental impact, i.e., the global warming potential was found to be very much lower at 2.94 × 10-4 kg CO2 eq as opposed to other literatures reported on the LCA of wastewater treatments using membranes. Overall, this study had proffered insights into the environmental impact of microalgal wastewater treatment and its stimulus for sustainable wastewater management. The findings of this study can be instrumental in making informed decision for optimizing microalgal wastewater treatment and reutilization assisted by membrane technology with an ultimate goal of enhancing sustainability.

ß-cyclodextrin modified GO ultrafiltration membranes with enhanced antifouling property for water purification.

The study investigated the influence of additives on the fabrication of mixed matrix membranes comprising polyethersulfone (PES), with a specific focus on hydrophilicity, flux, morphology, and antifouling properties. Carboxymethyl modified ß-cyclodextrin (CMß-CD) was used to enhance the dispersion and hydrophilicity of graphene oxide (GO), leading to the formation of a hydrophilic and stable composite nanoparticle (CMCD@GO). The hydrophilicity (WCA <51.5°) and water flux (32.6 L m-2.h-1) of the modified PES membranes (MCDGO-x) were improved by the incorporation of CMCD@GO nanoparticles, while that of PES membrane was 79.7° and 10.6 L m-2.h-1. The rate of backscattered light intensity (ΔBS) of MCDGO-x suspensions remains stable, suggesting stable dispersion of CMCD@GO in organic solvents. Compared to the bare PES membrane, the MCDGO-x membrane exhibits a thinner active layer and a finger-like structure. The MCDGO-x membrane exhibited excellent naphthenic acids (NAs) rejection (>93.2%) due to reduced roughness and higher hydrophilicity, while the GO-modified PES membrane (MGO-5) exhibited lower NAs rejection (87.2%). Furthermore, the MCDGO-5 membrane showed higher flux recovery ratio (FRR) of 79.3% compared to MGO-5 membrane (68.5%) after three cycles, indicating the antifouling performance of MCDGO-x for NAs was significantly improved. The combination of CMß-CD and GO enhance the flux and antifouling properties of PES ultrafiltration membranes, suggesting significant potential for applications in the purification of oil sands process water and the treatment of oily wastewater.

Target-guided isolation and purification of cyclooxygenase-2 inhibitors from Meconopsis integrifolia (Maxim.) Franch. by high-speed counter-current chromatography combined with ultrafiltration liquid chromatography.

Meconopsis integrifolia (Maxim.) Franch. is used extensively in traditional Tibetan medicine for its potent anti-inflammatory properties. In this study, six cyclooxygenase-2 (COX-2) inhibitors were purified from M. integrifolia using high-speed counter-current chromatography guided by ultrafiltration liquid chromatography (ultrafiltration-LC). First, ultrafiltration-LC was performed to profile the COX-2 inhibitors in M. integrifolia. The reflux extraction conditions were further optimized using response surface methodology, and the results showed that the targeted COX-2 inhibitors could be well enriched under the optimized extraction conditions. Then the six target COX-2 inhibitors were separated by high-speed countercurrent chromatography with a solvent system composed of ethyl acetate/n-butanol/water (4:1:4, v/v/v. Finally, the six COX-2 inhibitors, including 21.2 mg of 8-hydroxyluteolin 7-sophoroside, 29.6 mg of 8-hydroxyluteolin 7-[6'''-acetylallosyl-(1→2)-glucoside], 42.5 mg of Sinocrassoside D3, 54.1 mg of Hypolaetin 7-[6'''-acetylallosyll-(l→2)-3''-acetylglucoside, 30.6 mg of Hypolaetin 7-[6'''-acetylallosyll-(l→2)-6''-acetylglucoside and 17.8 mg of Hypolaetin were obtained from 500 mg of sample. Their structures were elucidated by 1 H-NMR spectroscopy. This study reveals that ultrafiltration-LC combined with high-speed counter-current chromatography is a robust and efficient strategy for target-guided isolation and purification of bioactive molecules. It also enhances the scientific understanding of the anti-inflammatory properties of M. integrifolia but also paves the way for its further medicinal applications.

Rapid identification of chemical components and screening of acetylcholinesterase inhibitors from Dalbergia odorifera based on mass defect and diagnostic ion filtering strategy, affinity ultrafiltration, and liquid chromatography-tandem mass spectrometry.

Dalbergia odorifera is a natural product rich in pharmacological ingredients, but the comprehensive characterization and rapid profiling of active components remain a challenge. Thus, an integrated data mining and identification strategy was exploited to efficiently identify the chemical constituents and screen acetylcholinesterase inhibitors (AChEIs) through affinity ultrafiltration and ultra-high-performance liquid chromatography-mass spectrometry (AUF-UHPLC-MS). As a result, polygonal mass defect filtering, diagnostic product ions, and neutral loss rules were created for rapid structural classification and component identification. A total of 140 flavonoids were tentatively characterized, including 41 isoflavonoids, 23 flavanones, 21 isoflavans, 19 flavones and flavonols, 13 neoflavonoids, 11 isoflavanones, seven flavone glycosides, and five chalcones. Subsequently, six natural AChEIs including tectorigenin, fisetin, dalbergin, pterostilbene, isoliquiritigenin, and biochanin A were screened out using AUF-UHPLC-MS and molecular docking. Meanwhile, the AChE inhibitory activities of the six compounds were assessed in vitro, tectorigenin, fisetinand, and dalbergin have moderate inhibitory activity. In conclusion, a novel strategy for systematic characterization and further screening of active compounds in natural products was established, which provides a material basis for quality control of Dalbergia odorifera.

Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED).

BACKGROUND: Volume overload is common and associated with high mortality in patients on peritoneal dialysis (PD). Traditional strategies including diuretics, water/salt restriction, and icodextrin-based solutions cannot always fully correct this condition, necessitating novel alternative strategies. Recent studies confirmed the expression of sodium-glucose cotransporter 2 (SGLT2) in the human peritoneum. Experimental data suggest that SGLT2 inhibitors decrease glucose absorption from the PD solution, thereby increasing the ultrafiltration volume. This trial aims to assess whether SGLT2 inhibitors increase the ultrafiltration volume in patients on PD. METHODS: The EMPOWERED trial (trial registration: jRCTs051230081) is a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Patients with clinically diagnosed chronic heart failure are eligible regardless of the presence of diabetes if they use at least 3 L/day glucose-based PD solutions. Participants will be randomly assigned (1:1) to receive empagliflozin 10 mg once daily and then placebo or vice versa. Each treatment period will last 8 weeks with a 4-week washout period. This study will recruit at least 36 randomized participants. The primary endpoint is the change in the daily ultrafiltration volume from baseline to week 8 in each intervention period. The key secondary endpoints include changes in the biomarkers of drained PD solutions, renal residual function, and anemia-related parameters. CONCLUSIONS: This trial aims to assess the benefit of SGLT2 inhibitors in fluid management with a novel mechanism of action in patients on PD. It will also provide insights into the effects of SGLT2 inhibitors on solute transport across the peritoneal membrane and residual renal function.

Ultrafiltration Tolerance: A Phenotype That We Need to Recognize.

BACKGROUND: The evaluation and management of fluid balance are key challenges in critical care patients who require renal replacement therapies because cumulative fluid balance is an independent factor that increases morbidity and mortality in different clinical scenarios. SUMMARY: One of the strategies when fluid overload is refractory to diuretics is extracorporeal fluid removal (i.e., net ultrafiltration [UFNET] during kidney replacement therapy). However, problems with UFNET without individualized assessment are cardiovascular events and intradialytic hypotension, events that contribute to decreasing organ perfusion and sympathetic stress. Therefore, we must consider and try to predict the best timing for the start of ultrafiltration and find the point where the patient is most tolerant to ultrafiltration, making a simile to the concept of fluid tolerance. KEY MESSAGES: UFNET is a continuous and dynamic process, going through moments of tolerance and intolerance to ultrafiltration; as nephrologists, we must take the necessary measures to move through this period.

The Changes in Relative Blood Volume during Dialysis Are Characterized by Ultrafiltration Rate and Predialysis Blood Test Values.

INTRODUCTION: Continuous monitoring of relative blood volume (percentage BV) in hemodialysis (HD) is critical for determining dry weight and preventing intradialytic hypotension. However, the cause of the BV variation remains unknown. This research aimed to examine factors that influence the percentage BV. METHODS: We devised a formula based on coefficients ("a," "τ," and "b") to predict changes in percentage BV. "a" denotes a significant decrease in percentage BV in the early stages of HD. "τ" represents the transition from early to late phase of HD. "b" denotes the slope of the decrease in percentage BV in the late phase of HD. We measured the percentage BV in 18 patients with end-stage renal disease. The coefficients were estimated by fitting experimental data from patients using a least squares optimization algorithm. A correlation analysis of these parameters and patient predialysis data was performed. RESULTS: Ultrafiltration rate (UFR) was found to be negatively correlated with "b" (r = -0.851, p < 0.01). However, UFR was not significantly related to "a." Predialysis serum total protein level was negatively correlated with "a" (r = -0.531, p = 0.042). Predialysis serum albumin and predialysis sodium were not significantly correlated with "a" and "τ." Plasma osmolarity did not have a significant relationship with "a" and "τ." DISCUSSION/CONCLUSION: UFR influenced the decrease in percentage BV in the late phase but did not influence the decrease of percentage BV in the early phase. "a" was associated with predialysis serum total protein level but not with plasma osmolality or predialysis sodium. This implies that colloid oncotic pressure is important for plasma refilling immediately after dialysis begins. During the change of percentage BV, the decrease in the early phase of dialysis was not related to UFR, but related to other parameters, especially predialysis total protein level. A decrease in the late phase of dialysis is related to UFR.

Determinants of Urine Output Using Advanced Hemodynamic Monitoring in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

INTRODUCTION: Low cardiac output and hypovolemia are candidate macrocirculatory mechanisms explanatory of de novo anuria in intensive care unit (ICU) patients undergoing continuous renal replacement therapy (CRRT). We aimed to determine the hemodynamic parameters and CRRT settings associated with the longitudinal course of UO during CRRT. METHODS: This is an ancillary analysis of the PRELOAD CRRT observational, single-center study (NCT03139123). Enrolled adult patients had severe acute kidney injury treated with CRRT for less than 24 h and were monitored with a calibrated continuous cardiac output monitoring device. Hemodynamics (including stroke volume index [SVI] and preload-dependence, identified by continuous cardiac index variation during postural maneuvers), net ultrafiltration (UFNET), and UO were reported 4-hourly, over 7 days. Two study groups were defined at inclusion: non-anuric participants if the cumulative 24 h UO at inclusion was ≥0.05 mL kg-1 h-1, and anuric otherwise. Quantitative data were reported by its median [interquartile range]. RESULTS: Forty-two patients (age 68 [58-76] years) were enrolled. At inclusion, 32 patients (76%) were not anuric. During follow-up, UO decreased significantly in non-anuric patients, with 25/32 (78%) progressing to anuria within 19 [10-50] hours. Mean arterial pressure (MAP) and UFNET did not significantly differ between study groups during follow-up, while SVI and preload-dependence were significantly associated with the interaction of study group and time since inclusion. Higher UFNET flow rates were significantly associated with higher systemic vascular resistances and lower cardiac output during follow-up. Multivariate analyses showed that (1) lower UO was significantly associated with lower SVI, lower MAP, and preload-independence; and (2) higher UFNET was significantly associated with lower UO. CONCLUSIONS: In ICU patients treated with CRRT, those without anuria showed a rapid loss of diuresis after CRRT initiation. Hemodynamic indicators of renal perfusion and effective volemia were the principal determinants of UO during follow-up, in relation with the hemodynamic impact of UFNET setting.

Biodegradable ultrafiltration membrane enhanced with anti-biofouling agent from Anacardium occidentale extract.

Our research focuses on developing environmentally friendly biodegradable ultrafiltration (UF) membranes for small-scale water purification in areas lacking infrastructure or during emergencies. To address biofouling challenges without resorting to harmful chemicals, we incorporate bio-based extracts, such as methyl gallate from A. occidentale leaves, a Malaysian ulam herb, known for its quorum sensing inhibition (QSI) properties. The methyl gallate enriched extract was purified by solvent partitioning and integrated into cellulose-based UF membranes (0 to 7.5% w w-1) through phase inversion technique. The resulting membranes exhibited enhanced anti-organic fouling and anti-biofouling properties, with flux recovery ratio (FRR) of 87.84 ± 2.00% against bovine serum albumin and FRRs of 76.67 ± 1.89% and 69.57 ± 1.77% against E. coli and S. aureus, respectively. The CA/MG-5 membrane showed a 224% improvement in pure water flux (PWF) compared to the neat CA membrane. Our innovative approach significantly improves PWF, presenting an environmentally friendly method for biofouling prevention in UF membrane applications.

Dapagliflozin in peritoneal dialysis patients: a pilot study evaluating peritoneal membrane function.

BACKGROUND: Patients taking SGLT-2 inhibitors may experience delayed peritoneal fibrosis, better ultrafiltration of water and toxins, and higher survival rates. We aimed to evaluate the possible effects of Dapagliflozin in changing the peritoneal solute transfer rate, reducing peritoneal glucose absorption, and, hence, increasing ultrafiltration. METHODOLOGY: A pilot pre-post interventional study was used to evaluate 20 patients on continuous ambulatory peritoneal dialysis (CAPD) enrolled in a one-month self-controlled study [Trial#: NCT04923295]. Inclusion criteria included being over 18, and having a Peritoneal Dialysis (PD) vintage of at least six months. All participants were classified as having high or average high transport status based on their Peritoneal Equilibrium Test with a D0/D4 > 0.39. and using at least two exchanges with 2.35% dextrose over the previous three months before enrollment. RESULTS: Following the treatment, 13 patients had an increase in median D4/D0 from 0.26 [0.17-0.38] to 0.31 [0.23-0.40], while seven patients had a decline from 0.28 [0.17-0.38] to 0.23 [0.14-0.33]. Additionally, nine patients had a decrease in median D/P from 0.88 [0.67-0.92] to 0.81 [0.54-0.85], while 11 patients had an increase from 0.70 [0.6-0.83] to 0.76 [0.63-0.91]. CONCLUSION: According to the findings of this study, Dapagliflozin usage in peritoneal dialysis patients did not result in a reduction in glucose absorption across the peritoneal membrane. Additionally, Dapagliflozin was also associated with a small increase in sodium dip, a decrease in peritoneal VEGF, and a decrease in systemic IL-6 levels all of which were not statistically significant. Further large-scale studies are required to corroborate these conclusions.