Colloidal Photonic Crystal-Enhanced Fluorescence of Gold Nanoclusters: A Highly Sensitive Solid-state Fluorescent Probe for Creatinine.

Gold nanoclusters (AuNCs) are an intensely pursued class of fluorophores with excellent biocompatibility, high water solubility, and ease of further conjugation. However, their low quantum yield limits their applications, such as ultra-sensitive chemical or molecular sensing. To address this problem, various strategies have been adopted for augmenting their fluorescence intensity. Herein, we report a facile and scalable approach for the fluorescence enhancement of bovine serum albumin (BSA) capped AuNCs (BSA-AuNCs) using periodic, close-packed polystyrene colloidal photonic crystals (CPCs). The slow photon effect at the bandgap edges is utilized for the increased light-matter interactions and thereby enhancing the fluorescence intensity of the BSA-AuNCs. Compared to the planar polystyrene control sample, the CPC film yielded a 14-fold enhancement in fluorescence intensity. Further, we demonstrated the as-prepared BSA-AuNCs-CPC as a solid-state platform for the highly sensitive and selective fluorescence turn-off detection of creatinine at nanomolar level.

Portable smartphone integrated 3D-Printed electrochemical sensor for nonenzymatic determination of creatinine in human urine.

3D printing technologies are an attractive for fabricating electrochemical sensors due to their ease of operation, freedom of design, fast prototyping, low waste, and low cost. We report the fabrication of a simple 3D-printed electrochemical sensing device for non-enzymatic detection of creatinine, an important indicator of renal function. To create the 3D-printed electrodes (3DE), carbon black/polylactic acid (CB/PLA) composite filament was used. The 3DE was activated using 0.5 M NaOH via amperometry prior to use to improve electrochemical performance. To give selectivity for creatinine, the activated 3DE was modified with a copper oxide nanoparticle-ionic liquid/reduced graphene oxide (CuO-IL/rGO) composite. The modified 3DE was characterized using microscopy and electrochemistry. Cyclic voltammetry and amperometry were used to evaluate sensor performance. The modified 3DE provided electrocatalytic activity towards creatinine without enzymes. Under optimal conditions, the modified 3DE directly coupled with a portable smartphone potentiostat exhibited the linear detection range of 0.5-35.0 mM, and the limit of detection was 37.3 µM, which is sufficient for detecting creatinine in human urine samples. Furthermore, the other physiological compounds present in human urine were not detected on the modified 3DE. Therefore, the modified 3DE could be a tool for effective creatinine screening in the urine.

Cell-Free Hemoglobin in Acute Kidney Injury after Lung Transplantation and Experimental Renal Ischemia/Reperfusion.

Cell-free hemoglobin (CFH), a pro-oxidant and cytotoxic compound that is released in hemolysis, has been associated with nephrotoxicity. Lung transplantation (LuTx) is a clinical condition with a high incidence of acute kidney injury (AKI). In this study, we investigated the plasma levels of CFH and haptoglobin, a CFH-binding serum protein, in prospectively enrolled LuTx patients (n = 20) with and without AKI. LuTx patients with postoperative AKI had higher CFH plasma levels at the end of surgery compared with no-AKI patients, and CFH correlated with serum creatinine at 48 h. Moreover, CFH levels inversely correlated with haptoglobin levels, which were significantly reduced at the end of surgery in LuTx patients with AKI. Because multiple other factors can contribute to AKI development in the complex clinical setting of LuTx, we next investigated the role of exogenous CFH administration in a mouse model of mild bilateral renal ischemia reperfusion injury (IRI). Exogenous administration of CFH after reperfusion caused overt AKI with creatinine increase, tubular injury, and enhanced markers of renal inflammation compared with vehicle-treated animals. In conclusion, CFH is a possible factor contributing to postoperative AKI after LuTx and promotes AKI in an experimental model of mild transient renal ischemia. Targeting CFH might be a therapeutic option to prevent AKI after LuTx.

Synergistic Inhibitory Effects of Selected Amino Acids on the Formation of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in both Benzaldehyde- and Phenylacetaldehyde-Creatinine Model Systems.

Although various inhibitors have been employed to react with phenylacetaldehyde to form adducts and thus interrupt the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), high concentrations of PhIP remain in the final system. It remains unknown whether other critical aldehyde or ketone intermediates are involved in the generation of PhIP, and scavenging these reactive carbonyls simultaneously may achieve higher inhibitory efficiency of PhIP. In this study, reactive carbonyls in a glucose/creatinine/phenylalanine model system were first identified by gas chromatography-mass spectrometry (GC-MS), and then the single and synergistic effects of nonprecursor amino acids (cysteine, methionine, proline, histidine, arginine, and leucine) on scavenging reactive carbonyls were investigated to find out promising combination partners. The obtained results showed that the concentrations of benzaldehyde and phenylacetaldehyde in the glucose/creatinine/phenylalanine model system reached 0.49 ± 0.01 and 6.22 ± 0.21 µg/mL, respectively. Heating these carbonyl compounds in the presence of creatinine resulted in the quantity of PhIP produced increasing linearly with the added quantity of benzaldehyde (r = 0.9733, P = 0.0002) and phenylacetaldehyde (r = 0.9746, P = 0.0002), indicating that both compounds are key intermediates for PhIP generation. Among the investigated amino acids, histidine produced the maximum inhibition of PhIP formation (78-99%) in the benzaldehyde/creatinine model system, and proline produced the maximum inhibition of PhIP formation (13-97%) in the phenylacetaldehyde/creatinine model system, where both compounds decreased PhIP formation in a dose-dependent manner. Histidine in combination with proline enhanced the inhibitory effect against PhIP formation at a low addition level, where the highest inhibitory efficiency was obtained using a 1:3 mass ratio of histidine to proline (2 mg/mL in total), reducing PhIP formation by 96%. These findings suggest that histidine-proline combinations can scavenge benzaldehyde and phenylacetaldehyde simultaneously, enhancing the suppression of PhIP formation.

Measurement of kidney function in Malawi, South Africa, and Uganda: a multicentre cohort study.

BACKGROUND: The burden of kidney disease in many African countries is unknown. Equations used to estimate kidney function from serum creatinine have limited regional validation. We sought to determine the most accurate way to measure kidney function and thus estimate the prevalence of impaired kidney function in African populations. METHODS: We measured serum creatinine, cystatin C, and glomerular filtration rate (GFR) using the slope-intercept method for iohexol plasma clearance (mGFR) in population cohorts from Malawi, Uganda, and South Africa. We compared performance of creatinine and cystatin C-based estimating equations to mGFR, modelled and validated a new creatinine-based equation, and developed a multiple imputation model trained on the mGFR sample using age, sex, and creatinine as the variables to predict the population prevalence of impaired kidney function in west, east, and southern Africa. FINDINGS: Of 3025 people who underwent measured GFR testing (Malawi n=1020, South Africa n=986, and Uganda n=1019), we analysed data for 2578 participants who had complete data and adequate quality measurements. Among 2578 included participants, creatinine-based equations overestimated kidney function compared with mGFR, worsened by use of ethnicity coefficients. The greatest bias occurred at low kidney function, such that the proportion with GFR of less than 60 mL/min per 1·73 m2 either directly measured or estimated by cystatin C was more than double that estimated from creatinine. A new creatinine-based equation did not outperform existing equations, and no equation, including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 race-neutral equation, estimated GFR within plus or minus 30% of mGFR for 75% or more of the participants. Using a model to impute kidney function based on mGFR, the estimated prevalence of impaired kidney function was more than two-times higher than creatinine-based estimates in populations across six countries in Africa. INTERPRETATION: Estimating GFR using serum creatinine substantially underestimates the individual and population-level burden of impaired kidney function in Africa with implications for understanding disease progression and complications, clinical care, and service provision. Scalable and affordable ways to accurately identify impaired kidney function in Africa are urgently needed. FUNDING: The GSK Africa Non-Communicable Disease Open Lab. TRANSLATIONS: For the Luganda, Chichewa and Xitsonga translations of the abstract see Supplementary Materials section.

Insight into mechanisms of creatinine optical sensing using fluorescein-gold complex.

Creatinine level in biological fluids is a clinically relevant parameter to monitor vital functions and it is well assessed that measuring creatinine levels in the human body can be of great utility to evaluate renal, muscular, or thyroid dysfunctions. The accurate detection of creatinine levels may have a critical role in providing information on health status and represents a tool for the early diagnosis of severe pathologies. Among different methods for creatinine detection that have been introduced and that are evolving with increasing speed, fluorescence-based and colorimetric sensors represent one of the best alternatives, thanks to their affordability, sensitivity and easy readability. In this work, we demonstrate that the fluorescein-Au3+complex provides a rapid, selective, and sensitive tool for the quantification of creatinine concentrations in ranges typical of sweat and urine. UV-visible absorption, diffuse reflectance spectroscopy, steady state and time resolved fluorescence spectroscopy were used to shed light on the molecular mechanisms involved in the changes of optical properties, which underlie the multiplexed sensor analytical reply. Interestingly, sensing can be performed in solution or on solid nylon support accessing different physiological concentrations from micromolar to millimolar range. As a proof-of-concept, the nylon-based platform was used to demonstrate its effectiveness in creatinine detection on a solid and flexible substrate, showing its analytical colorimetric properties as an easy and disposable creatinine point-of-care test.

Hemimycalins C-E; Cytotoxic and Antimicrobial Alkaloids with Hydantoin and 2-Iminoimidazolidin-4-one Backbones from the Red Sea Marine Sponge Hemimycale sp.

In the course of our continuing efforts to identify bioactive secondary metabolites from Red Sea marine sponges, we have investigated the sponge Hemimycale sp. The cytotoxic fraction of the organic extract of the sponge afforded three new compounds, hemimycalins C-E (1-3). Their structural assignments were obtained via analyses of their one- and two-dimensional NMR spectra and HRESI mass spectrometry. Hemimycalin C was found to differ from the reported hydantoin compounds in the configuration of the olefinic moiety at C-5-C-6, while hemimycalins D and E were found to contain an 2-iminoimidazolidin-4-one moiety instead of the hydantoin moiety in previously reported compounds from the sponge. Hemimycalins C-E showed significant antimicrobial activity against Escherichia coli and Candida albicans and cytotoxic effects against colorectal carcinoma (HCT 116) and the triple-negative breast cancer (MDA-MB-231) cells.

Association between type of anesthesia and length of hospital stay in primary unilateral total knee arthroplasty patients: a single-center retrospective study.

OBJECTIVE: This study explored the risk factors influencing the length of hospital stay (LOS) and establish whether the type of anesthesia is independently associated with the LOS in patients after primary unilateral total knee arthroplasty (TKA). METHODS: In this retrospective cohort study, 2309 patients undergoing unilateral TKA were recruited between January 2013 and June 2014 in a tertiary academic medical center in Singapore. Univariate and multivariate linear regression analyses were used to identify the independent risk factors associated with LOS. Besides, subgroup and interaction analyses were performed to evaluate the relationship between the type of anesthesia and LOS. RESULT: In total, 2309 patients were identified. Out of these, 791 patients underwent general anesthesia, whereas 1518 patients underwent regional anesthesia. Multivariate regression analyses revealed that prolonged LOS was significantly associated with age ≥ 65 years (ß = 0.48; 95% CI, 0.09-0.87; P = 0.015), diabetes mellitus (DM) (ß = 0.8; 95% CI, 0.33-1.27; P = 0.001), congestive cardiac failure (CCF) (ß = 4.1; 95% CI, 2.02-6.17; P < 0.001), perioperative blood transfusion (ß = 5.71; 95% CI, 4.86-6.56; P < 0.001), creatinine > 2 mg/dL (ß = 4.54; 95% CI, 2.46-6.62; P < 0.001), ASA status (III) (ß = 1.72; 95% CI, 0.72-2.71; P = 0.001), general anesthesia (ß = 0.78; 95% CI, 0.41-1.66; P < 0.001). The LOS further decreased among participants receiving regional anesthesia at advanced age (age ≥ 65 years) (ß = - 1.12; 95% CI, - 1.66 to - 0.58; P < 0.001), patients with BMI ≤ 25 kg/m2 (ß = - 1.92; 95% CI, - 2.73 to - 1.11; P < 0.001) or ≥ 30 kg/m2 (ß = - 0.58; 95% CI, - 1.1 to - 0.06; P = 0.029). CONCLUSION: Our findings demonstrated that age ≥ 65 years, DM, CCF, perioperative blood transfusion, creatinine > 2 mg/dL, ASA status (III), general anesthesia are associated with a prolonged LOS after primary TKA. Elderly patients (age ≥ 65 years) and patients with BMI ≤ 25 kg/m2 or ≥ 30 kg/m2 receiving regional anesthesia have a further reduced LOS. Therefore, when TKA is performed, priority for regional anesthesia is given to the elderly patients (age ≥ 65 years old) and those with BMI ≤ 25 kg/m2 or ≥ 30 kg/m2.

Fabrication and dialysis performance of functionalized multiwall carbon nanotubes integrated cellulose acetate/poly(vinylpyrrolidone) membranes.

Mixed matrix membranes (MMMs) of cellulose acetate/poly(vinylpyrrolidone) (CA/PVP) infused with acid functionalized multiwall carbon nanotubes (f-MWCNTs) were fabricated by an immersion phase separation technique for hemodialysis application. Membranes were characterized using FTIR, water uptake, contact angle, TGA, DMA and SEM analysis. The FTIR was used to confirm the bonding interaction between CA/PVP membrane matrix and f-MWCNTs. Upon addition of f-MWCNTs, TGA thermograms and glass transition temperature indicated improved thermal stability of MMMs. The surface morphological analysis demonstrated revealed uniform distribution of f-MWCNTs and asymmetric membrane structure. The water uptake and contact angle confirmed that hydrophilicity was increased after incorporation of f-MWCNTs. The membranes demonstrated enhancement in water permeate flux, bovine serum albumin (BSA) rejection with the infusion of f-MWCNTs; whereas BSA based anti-fouling analysis using flux recovery ratio test shown up to 8.4% improvement. The urea and creatinine clearance performance of MMMs were evaluated by dialysis experiment. It has been found that f-MWCNTs integrated membranes demonstrated the higher urea and creatinine clearance with increase of 12.6% and 10.5% in comparison to the neat CA/PVP membrane. Thus, the prepared CA/PVP membranes embedded with f-MWCNTs can be employed for wide range of dialysis applications.

Fabrication and performance evaluation of polymeric membrane using blood compatible hydroxyapatite for artificial kidney application.

In the current study, a phase inversion scheme was employed to fabricate hydroxyapatite (HA)/polysulfone (PSF)-based asymmetric membranes using a film applicator with water as a solvent and nonsolvent exchanging medium. Fourier Transform Infrared (FTIR) and X-ray diffraction (XRD) spectroscopic studies were conducted to confirm the bonding chemistry and purity of filler. The inherent thick nature of PSF generated sponge-like shape while the instantaneous demixing process produced finger-like pore networks in HA/PSF-based asymmetric membranes as exhibited by scanning electron microscope (SEM) micrographs. The FTIR spectra confirmed noncovalent weak attractions toward the polymer surface. The leaching ratio was evaluated to observe the dispersion behavior of HA filler in membrane composition. Hydrophilicity, pore profile, pure water permeation (PWP) flux, and molecular weight cutoff (MWCO) values of all formulated membranes were also calculated. Antifouling results revealed that HA modified PSF membranes exhibited 43% less adhesion of bovine serum albumin (BSA) together with >86% recovery of flux. Membrane composition showed 74% total resistance, out of which 60% was reversible resistance. Biocompatibility evaluation revealed that the modified membranes exhibited prothrombin time (PT), and thrombin time (TT) comparable with typical blood plasma, whereas proliferation of living cells over membrane surface proved its nontoxic behavior toward biomedical application. The urea and creatinine showed effective adsorption aptitude toward HA loaded PSF membranes.

Liposomal Delivery of Cyclocreatine Impairs Cancer Cell Bioenergetics Mediating Apoptosis.

Creatine kinase (CK) enzyme overexpression has been suggested to play a role in the process of tumorigenesis and metastasis. Cyclocreatine (CCR) is a substrate analog of creatine kinase (CK), where its phosphorylated form is a poor phosphate donor in comparison with native bioenergetic molecule, creatine phosphate (Cr-P). The compound CCR has been shown to markedly inhibit the growth of a broad spectrum of cancers, both in vitro and in vivo. Intracellularly, CCR is phosphorylated by CK to yield a synthetic phosphagen [(N-phosphorylcyclocreatine (CCR ~P)], with thermodynamic and kinetic properties distinct from those of creatine phosphate (Cr-P). Distinct inhibition of tumor growth and metastasis has been attributed to CCR accumulation as CCR ~P in tumor cells, especially in those expressing a high level of CK protein, with minimal adverse effects. Unfortunately, the clinical use of CCR against malignancies is quite limited due to its amphoteric nature, which accounts for most of its extremely low membrane permeability, as well as limited oral bioavailability (BA) and poor systemic pharmacokinetics (PK).Our current work describes the encapsulation of CCR , utilizing freeze and thaw vesicles (FTV )-composed mostly of saturated PC, DOPE, and Chol-into stealth™ liposomes , postcoated with 4.5 M% PEG-PE. Following physicochemical characterization, in vitro release and cellular uptake kinetics confirmed efficient delivery of liposomal CCR (CCR-Lip), leading to intracellular accumulation of its CC-P metabolic product. Successful delivery of CCR to cancer cell effectively depleted low energetic cancer cells of ATP significantly mediating myc-induced metabolic changes. CCR-Lip showed significant antimetastatic and anticancer effectiveness against both MCF-7 and PC-3 human carcinoma models (p < 0.05-0.01), with 4- to 6-fold lower IC50 values vs. closest drug control. Such shift in bioenergetics was coupled via AMPK and phospho-p53 to the mitochondrial apoptosis effector Bak , thus inducing a cell-intrinsic mechanism to counteract uncontrolled neoplastic proliferation, in target cancer cells. Our novel liposomal delivery system of the CCR substrate analog demonstrated strong inhibition of malignant cell bioenergetics, leading to significant antineoplastic and proapoptotic actions, against different cancers.

Perspective on New Equations for Estimating Glomerular Filtration Rate.

The Kidney Disease Improving Global Outcomes 2012 Clinical Practice Guideline on Chronic Kidney Disease (1) recommends calculating estimated glomerular filtration rate (eGFR) using equations developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for adults ≥18 years (2) and by the Chronic Kidney Disease in Children (CKiD) for ages <18 years (3). These equations were recommended because they used readily available information, serum/plasma/blood creatinine, plus age, sex, and race for adults, and height for children; and have been validated in large and diverse cohorts of people who had measured glomerular filtration rate (mGFR) as a basis for establishing accuracy.

The validation of molecular interaction among dimer chitosan with urea and creatinine using density functional theory: In application for hemodyalisis membrane.

The formation of chitosan dimer and its interaction with urea and creatinine have been investigated at the density functional theory (DFT) level (B3LYP-D3/6-31++G**) to study the transport phenomena in hemodialysis membrane. The interaction energy of chitosan-creatinine and chitosan-urea complexes are in range -4 kcal/mol < interaction energy <-20 kcal/mol which were classified in medium hydrogen bond interaction. The chemical reactivity parameter proved that creatinine was more electrophilic and easier to bind chitosan than urea. The energy gap of HOMO-LUMO of chitosan-creatinine complex was lower than chitosan-urea complex that indicating chitosan-creatinine complex was more reactive and easier to transport electron than chitosan-urea complex. Moreover, the natural bond orbital (NBO) analysis showed a high contribution of hydrogen bond between chitosan-creatinine and chitosan-urea. The chitosan-creatinine interaction has a stronger hydrogen bond than chitosan-urea through the interaction O18-H34....N56 with stabilizing energy = -13 kcal/mol. The quantum theory atom in molecule (QTAIM) also supported NBO data. All data presented that creatinine can make hydrogen bond interaction stronger with chitosan than urea, that indicated creatinine easier to transport in the chitosan membrane than urea during hemodialysis process.

Identification of acrolein as the reactive carbonyl responsible for the formation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx).

Reaction mixtures of reactive carbonyls and creatinine were submitted to high temperature and studied to identify the reactive carbonyl(s) responsible for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) formation. MeIQx was produced by reaction of acrolein and creatinine within a wide pH range and with an activation energy of 81.1 ± 1.4 kJ/mol. No additional reactants were required, although methylglyoxal, ammonia, and formaldehyde also participated in the reaction. Nevertheless, these additional reactants were produced in situ from either acrolein or creatinine. A reaction pathway that both explains the formation of MeIQx and is valid for the formation of other heterocyclic aromatic amines (HAAs) with the structure of quinoxaline is proposed. Obtained results demonstrate the key role of reactive carbonyls present in foods (the food carbonylome) on HAA formation. Because creatinine is ubiquitous in proteinaceous foods, the control of the food carbonylome seems to be the key point to control HAA formation in foods.

Adsorption of Uremic Toxins Using Ti3C2Tx MXene for Dialysate Regeneration.

The COVID-19 pandemic has become a major worldwide crisis. Although respiratory symptoms are a key feature of the disease, many people who are hospitalized with COVID-19 also suffer acute kidney injury, a condition that exacerbates patient mortality and may have to be treated through renal replacement therapy. Much of the focus on hospital capacity during the pandemic has centered on the availability of ventilators. However, supplies for dialysis treatment, including dialysate, have also run dangerously low in hospitals at the epicenter of the pandemic. Therefore, there is an urgent need to develop materials that can efficiently and rapidly regenerate dialysate, removing toxins and restoring electrolyte concentrations so that this vital resource remains readily available. In this work, Ti3C2Tx, a two-dimensional transition-metal carbide (MXene) that is known to efficiently adsorb urea, was used to remove creatinine and uric acid from an aqueous solution and dialysate, with a maximum adsorption capacity of 45.7 and 17.0 mg/g, respectively. We systematically analyzed and modeled the adsorption kinetics, isotherms, and thermodynamics, thus determining the rate-limiting step and adsorption mechanism. A fixed-bed column loaded with Ti3C2Tx was designed to further evaluate the adsorption performance under continuous fluid-flow conditions, mirroring conditions of continuous renal replacement therapy modalities. The maximum capacity and 50% breakthrough volume were calculated to further approach the practical application of Ti3C2Tx for removal of uremic toxins. Our findings suggest that Ti3C2Tx has the potential to be used as an efficient sorbent for the regeneration of dialysate, allowing for accelerated dialysate regeneration by removing filtered toxins and leading to more portable dialysis devices.

Adsorption Capacity of Vitamin B12 and Creatinine on Highly-Mesoporous Activated Carbons Obtained from Lignocellulosic Raw Materials.

Enterosorbents are widely-used materials for human body detoxification, which function by immobilizing and eliminating endogenous and exogenous toxins. Here, activated carbons, obtained from the lignocellulosic raw vegetal materials of indigenous provenance, have been studied. Walnut shell and wood from local species of nuts and apple-trees were carbonized, and further activated at high temperatures with water vapors in a rotary kiln. A second activation was carried out, in a fluidized bed reactor, but for shorter times. The textural properties of the samples were determined from the adsorption isotherms of nitrogen at 77 K, allowing the obtaining of highly mesoporous materials, while the adsorption capacity permitted an essential rise of six to seven times in the maximal adsorption values of the metabolites, which was determined by the reactivation process. A kinetic study of vitamin B12 and creatinine immobilization was performed, the optimal immobilization time for the apple-tree wood reactivated carbons being 2 times longer than for those originating from walnut shells. An additional investigation was also performed in specific conditions that simulate the real environment of immobilization: the temperature of a febrile human body (at the temperature T = 38 °C) and the characteristic acidity of the urinary tract and stomach (at the pH of 5.68 and 2.53, respectively). The activated carbonic adsorbents studied here, together with the results of the immobilization studies, show that these procedures can conduct a good incorporation of some endogenous metabolic products, such as vitamin B12 and creatinine, therefore presenting a good opportunity for their use as forthcoming commercial enterosorbents.

Co-Adsorptive Removal of Creatinine and Urea by a Three-Component Dual-Layer Hollow Fiber Membrane.

The development of wearable artificial kidney demands an efficient dialysate recovery, which relies upon the adsorption process. This study proposes a solution to solve the problem of competitive adsorption between the uremic toxins by employing two adsorptive components in a membrane separation process. Dual-layer hollow fiber (DLHF) membranes, which are composed of a polysulfone (PSf)/activated carbon (AC) inner layer and a PSf/poly(methyl methacrylate) (PMMA) outer layer, were prepared for co-adsorptive removal of creatinine and urea from aqueous solution. The DLHF membranes were characterized in terms of morphological, physicochemical, water transport, and creatinine adsorption properties. The membrane was then subjected to an ultrafiltration adsorption study for performance evaluation. The incorporation of AC in membrane, as confirmed by microscopic and surface analyses, has improved the pure water flux up to 25.2 L/(m2 h). A membrane with optimum AC loading (9 wt %) demonstrated the highest maximum creatinine adsorption capacity (86.2 mg/g) based on the Langmuir adsorption isotherm model. In the ultrafiltration adsorption experiment, the membrane removed creatinine and urea with a combined average percent removal of 29.3%. Moreover, the membrane exhibited creatinine and urea uptake recoveries of 98.8 and 81.2%, respectively. The combined action of PMMA and AC in the PSf DLHF membrane has made the adsorption of multiple uremic toxins possible during dialysate recovery.

Reactive carbonyls and the formation of the heterocyclic aromatic amine 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ).

Reactions involving reactive carbonyls, creatinine, and ammonia-producing compounds were investigated in order to clarify the formation of the heterocyclic aromatic amine (HAA) 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ). Obtained results showed that MeIQ was only produced when 2-butenal (crotonaldehyde) was present. Reaction yields depended on the pH, with a maximum around pH 6.5, and on concentrations of crotonaldehyde and creatinine. Ammonia was also required for MeIQ formation, but ammonia was produced by creatinine decomposition. The amount of MeIQ formed increased with reaction time, temperature, and oxygen content in the reaction atmosphere. Activation energy for MeIQ formation from crotonaldehyde, creatinine, and glutamine was 72.2 ± 0.4 kJ·mol-1. A reaction pathway that explains MeIQ formation is proposed. Obtained results suggest a main role of reactive carbonyls formed in foods (the food carbonylome) on HAA formation. In addition, they provide scientific basis for the understanding of how HAAs are formed and could be mitigated.