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Activated carbon (AC) is widely used to removing hazardous pollutants from air and water, owing to its exceptional adsorption properties. However, the high affinity of water molecules with the surface oxygen-containing functional groups can adversely affect the adsorption performance of AC. In this study, a facile and efficient method is presented for fabrication of hydrophobic AC through surface monolayer silanation. Compared to initial AC, the hydrophobic AC improves the water contact angle from 29.7° to 123.5° while maintaining high specific surface area and enhances the removal capacity of multi-phase pollutants (emulsified oil and toluene). Additionally, the hydrophobic AC exhibits excellent adsorption capability to harmful algal bloom species (Chlorella) (97.56%) and algal organic matter (AOM) (96.23%) owing to electrostatic interactions and surface hydrophobicity. The study demonstrates that this method of surface monolayer silanation can effectively weaken the effect of water molecules on AC adsorption capacity, which has significant potential for practical use in air and water purification, as well as in the control of harmful algal blooms.

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Many hypotheses could explain the mortality decrease observed using hemodiafiltration, such as reduction of intradialytic hypotension and more efficient toxin removal. We led a systematic analysis of representative uremic toxin removal with hemodialysis (HD), online postdilution hemodiafiltration (postHDF) and online predilution hemodiafiltration (preHDF), in a single-center crossover and prospective observational study. The primary outcome was the reduction ratio of uremic toxins of the three categories defined by the Eutox group. Twenty-six patients were treated by those three techniques of extra renal epuration. Mean Kt/Vurea was not different between the treatment methods. Mean reduction ratio of beta2microglobulin was significantly higher for both HDF treatments than for HD (p < 0.001). Myoglobin, kappa, and lambda free light chain reduction ratio was significantly different between the modes: 37.75 ± 11.95%, 45.31 ± 11% and 61.22 ± 10.56%/57.21 ± 12.5%, 63.53 ± 7.93%, and 68.40 ± 11.79%/29.12 ± 8.44%, 34.73 ± 9.01%, and 45.55 ± 12.31% HD, preHDF, and postHDF, respectively (p < 0.001). Mean protein-bound solutes reduction ratio was not different between the different treatments except for PCS with a higher reduction ratio during HDF treatments. Mean albumin loss was always less than 2 g. HDF improved removal of middle molecules but had no effect on indoles concentration without any difference between synthetic dialysis membranes.

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BACKGROUND: Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes. Due to the lack of randomized control trials, most of the data pertaining to the clinical course, therapeutic interventions and outcomes of patients with metformin induced toxicity has come from case reports or series. AIM: To analyse the symptomology, clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series. METHODS: We performed a systematic search from PubMed, Science Direct, Reference Citation Analysis (https://www.referencecitationanalysis.com/) and Google Scholar databases using the terms "metformin" AND "toxicity" OR "overdose" OR "lactic acidosis" OR "hyperlactatemia". The inclusion criteria were: (1) Case reports or case series with individual patient details; and (2) Reported toxicity or overdose of metformin in adults, published in the English language. Data regarding baseline demographics, clinical presentation, therapeutic interventions, intensive care unit course and overall outcome were collected. RESULTS: Two hundred forty-two individual cases were analysed, from 158 case reports and 26 case series, with a cumulative mortality of 19.8%. 214 (88.4%) patients were diabetics on metformin. 57 (23.6%) had acute ingestion, but a great majority (76.4%) were on metformin in therapeutic doses when they developed toxicity. Metformin associated lactic acidosis (MALA) was the most commonly reported adverse effect present in 224 (92.6%) patients. Most of the patients presented with gastrointestinal and neurological symptoms and a significant number of patients had severe metabolic acidosis and hyperlactatemia. The organ support used was renal replacement therapy (RRT) (68.6%), vaso-pressors (58.7%) and invasive mechanical ventilation (52.9%). A majority of patients (68.6%) received RRT for toxin removal, renal dysfunction and correction of MALA. Patients with lowest pH and highest serum lactate and metformin levels also had favourable outcomes with use of RRT. CONCLUSION: Most of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal functions. These patients may develop severe lactic acidosis, leading to significant morbidity and need for organ support. Despite severe MALA and the need for multiple organ support, they may have good outcomes, especially when RRT is used. The dose of metformin, serum pH, lactate and metformin levels may indicate the severity of toxicity and the need for aggressive therapeutic measures but may not necessarily indicate poor outcomes.

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Mycotoxins are toxic metabolites of filamentous fungi; they are common contaminants in numerous foods and beverages. Cyclodextrins are ring-shaped oligosaccharides, which can form host-guest type complexes with certain mycotoxins. Insoluble beta-cyclodextrin bead polymer (BBP) extracted successfully some mycotoxins (e.g., alternariol and zearalenone) from aqueous solutions, including beverages. Therefore, in this study, we aimed to examine the ability of BBP to remove other 12 mycotoxins (including aflatoxin B1, aflatoxin M1, citrinin, dihydrocitrinone, cyclopiazonic acid, deoxynivalenol, ochratoxin A, patulin, sterigmatocystin, zearalanone, α-zearalanol, and ß-zearalanol) from different buffers (pH 3.0, 5.0, and 7.0). Our results showed that BBP can effectively extract citrinin, dihydrocitrinone, sterigmatocystin, zearalanone, α-zearalanol, and ß-zearalanol at each pH tested. However, for the removal of ochratoxin A, BBP was far the most effective at pH 3.0. Based on these observations, BBP may be a suitable mycotoxin binder to extract certain mycotoxins from aqueous solutions for decontamination and/or for analytical purposes.

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Poisoning is a common problem in the United States. Acid-base disturbances, electrolyte derangements, or acute kidney injury result from severe poisoning from toxic alcohols, salicylates, metformin, and acetaminophen. Lithium is highly sensitive to small changes in kidney function. These poisonings and drug overdoses often require the nephrologist's expertise in diagnosis and treatment, which may require correction of acidosis, administration of selective enzyme inhibitors, or timely hemodialysis. The clinical and laboratory abnormalities associated with the poisonings and drug overdoses can develop rapidly and lead to severe cellular dysfunction and death. Understanding the pathophysiology of the disturbances and their clinical and laboratory findings is essential for the nephrologist to rapidly recognize the poisonings and establish an effective treatment plan. This installment of AJKD's Core Curriculum in Nephrology presents illustrative cases of individual poisonings and drug overdoses and summarizes up to date information on their prevalence, clinical and laboratory findings, pathophysiology, diagnosis, and treatment.

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More than three million patients are treated for kidney failure world-wide. Haemodialysis, the most commonly used treatment, requires large amounts of water and generates mountains of non-recyclable plastic waste. To improve the environmental footprint, dialysis treatments need to develop absorbents to regenerate the waste dialysate. Whereas conventional dialysis clears water-soluble toxins, it is not so effective in clearing protein-bound uraemic toxins (PBUTs), such as indoxyl sulfate (IS). Thus, developing absorption devices to remove both water-soluble toxins and PBUTs would be advantageous. Vapour induced phase separation (VIPS) has been used in this work to produce polycaprolactone/chitosan (PCL/CS) composite symmetric porous monoliths with extra porous carbon additives to increase creatinine and albumin-bound IS absorption. Moreover, these easy-to-fabricate porous monoliths can be formed into the required geometry. The PCL/CS porous monoliths absorbed 436 µg/g of albumin-bound IS and 2865 µg/g of creatinine in a single-pass perfusion model within 1 h. This porous PCL/CS monolith could potentially be used to absorb uraemic toxins, including PBUTs, and thus allow the regeneration of waste dialysate and the development of a new generation of environmentally sustainable dialysis treatments, including wearable devices.

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OBJECTIVES: Accurate management of metabolic decompensation in maple syrup urine disease (MSUD) has a crucial role, as acute attacks can cause neurological sequels and can be life threatening. Here, we aimed to evaluate effect of sodium phenylbutyrate (NaPBA) in acute management of MSUD attacks. METHODS: Episodes with an initial plasma leucine (Leu) level above 750 µmoL/L and that require hospitalization due to clinical findings of Leu neurotoxicity and/or feeding difficulties were included to the study. Patients who had no molecular diagnosis and a regular follow-up were excluded. Clinical findings, laboratory results and therapy responses were reviewed, retrospectively. RESULTS: Ten patients who experienced 19 distinct episodes of MSUD attacks were enrolled. Initial median Leu level was 901.67 (range 756-1989.11) and 33.9 µmoL/L (range 7.91-347.3 µmoL/L) at the end of therapy. None of our patients underwent extracorporeal toxin removal during the course of attack. In patients with serial plasma quantitative amino acid sampling, mean Leu reduction rate was calculated to be 529.68 ± 250.08 µmoL/L/day at the 24th h of treatment and 318.72 ± 191.52 µmoL/L/day at the 48th h of treatment. CONCLUSIONS: This study is the first original study that investigates the effect of NaPBA in management of acute attacks of MSUD patients from Turkey. We suggest that NaPBA treatment in MSUD attacks can ameliorate clinical and biochemical findings. This therapeutic option should be considered especially in smaller centers without the toxin removal chance and for patients who were not appropriate for extracorporeal toxin removal like hemodynamic instability.

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Extracorporeal treatments create opportunity for removing disease causing solutes within blood. Intoxications, renal failure, and immune-mediated diseases may be managed with these treatments, often providing new hope for patients with severe or refractory disease. Understanding solute pharmacokinetics and the limitations of each type of extracorporeal technique can allow for the selection of the optimal treatment modality.

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Pore-forming and hemolytic toxins are bacterial cytotoxic proteins required for virulence in many pathogens, including staphylococci and streptococci, and are notably associated with clinical manifestations of disease. Inspired by adsorption properties of naturally occurring aluminosilicates, we engineered inexpensive, laboratory-synthesized, aluminosilicate geopolymers with controllable pore and surface characteristics to remove pathogenic or cytotoxic material from the surrounding environment. In this study, macroporous and mesoporous geopolymers were produced with and without stearic acid surface modifications. Geopolymer binding efficacies were assessed by measuring adsorption of methicillin-resistant Staphylococcus aureus (MRSA) culture filtrate proteins, α-hemolysin and streptolysin-O toxins, MRSA whole cells, and antibiotics. Macroporous and mesoporous geopolymers were strong non-selective adsorbents for bacterial protein, protein toxins, and bacteria. Although some geopolymers adsorbed antibiotics, these synthesized geopolymers could potentially be used in non-selective adsorptive applications and optimized for adsorption of specific biomolecules.

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Ground shells of almonds (ALM), hazelnuts (HAZ), walnuts (WAL), and chestnuts (CHE), coconut fiber (COC), spent coffee grounds (COF), and clementine peel (CLE) were used to remove ochratoxin A (OTA) from both water and an ethanol/water mixture (14:86, v/v). Other very efficient adsorbents like wood biochar (BC) and hydrochar (HC) and a humic acid (HA) were also adopted as a comparison. In batch experiments, sorption of OTA from water followed the trend BC (100% removed) > HA > CLE > COC > HC > COF > ALM > HAZ > CHE > WAL (8% removed), whereas sorption of OTA from ethanol/water mixture (14:86, v/v) onto only the raw materials was COC (54% removed) > CLE > HAZ > ALM > COF > CHE > WAL (0.4% removed). The desorption of the toxin from all materials in water was rather low. Afterwards, sorption kinetics and isotherms of OTA onto CLE, COC, and COF were performed. The three materials adsorbed OTA in about 2 h according to a pseudo-second-order kinetic model, thus indicating the occurrence of a chemisorption mechanism. Equilibrium sorption data of OTA onto CLE followed preferentially the Freundlich model, whereas those on COC and COF fitted well both Freundlich and Langmuir isotherms (r > 0.996). The values of Freundlich sorption constants, KFads, for CLE, COC, and COF were 313, 202, and 98 L kg-1, respectively. OTA desorption from each of the three materials showed hysteretic effects. Overall findings of this work suggest that raw plant wastes could be effectively used as biosorbents to abate the level of OTA in liquid media.

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AIMS: To assess recommendations provided by the EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup on extracorporeal toxin removal (ECTR) in lithium poisoning. METHODS: Retrospective assessment in a 128 lithium-poisoned patient cohort previously used to identify ECTR initiation criteria that could improve outcome (Paris criteria). ECTR requirement using EXTRIP criteria was compared to the actual practice or if Paris criteria were used. The potential impact on outcome if these different criteria were used was investigated. RESULTS: Using the recommended (Rec-EXTRIP) or recommended + suggested (All-EXTRIP) EXTRIP criteria, ECTR would have been indicated in more patients than was actually done (P < .001), or if Paris criteria were used (P < .01). The non-actually ECTR-treated patients fulfilling Rec-EXTRIP or All-EXTRIP criteria had shorter intensive care unit stay (P < .05) and no significant increase in fatalities and neurological impairment on discharge in comparison to the actually ECTR-treated patients. ECTR requirements using EXTRIP vs Paris criteria were not concordant (P < .001). In the non-actually ECTR-treated patients, 31/106 and 55/106 patients fulfilled Rec-EXTRIP or All-EXTRIP but not Paris criteria, respectively. Those patients had longer stay (P < .01) but no worse neurological impairment on discharge than the patients not fulfilling any of these criteria (50/106 and 26/106, respectively). In the non-actually ECTR-treated patients, 7/106 fulfilled Paris but not Rec-EXTRIP criteria. Those patients had longer stay (P < .05) and worse neurological impairment on discharge (P < .01) than the 50/106 patients not fulfilling any of these criteria. CONCLUSION: In this cohort of lithium poisonings, EXTRIP criteria may lead to more ECTR than actually performed or if the Paris criteria were used, with no demonstrated improvement in outcome.

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Alternariol is an Alternaria mycotoxin that appears in fruits, tomatoes, oilseeds, and corresponding products. Chronic exposure to it can induce carcinogenic and xenoestrogenic effects. Cyclodextrins (CDs) are ring-shaped molecules built up by glucose units, which form host-guest type complexes with some mycotoxins. Furthermore, insoluble CD polymers seem suitable for the extraction/removal of mycotoxins from aqueous solutions. In this study, the interactions of alternariol with ß- and γ-CDs were tested by employing fluorescence spectroscopic and modeling studies. Moreover, the removal of alternariol from aqueous solutions by insoluble ß-CD bead polymer (BBP) was examined. Our major observations/conclusions are the following: (1) CDs strongly increased the fluorescence of alternariol, the strongest enhancement was induced by the native γ-CD at pH 7.4. (2) Alternariol formed the most stable complexes with the native γ-CD (logK = 3.2) and the quaternary ammonium derivatives (logK = 3.4-3.6) at acidic/physiological pH and at pH 10.0, respectively. (3) BBP effectively removed alternariol from aqueous solution. (4) The alternariol-binding ability of ß-CD polymers was significantly higher than was expected based on their ß-CD content. (5) CD technology seems a promising tool to improve the fluorescence detection of alternariol and/or to develop new mycotoxin binders to decrease alternariol exposure.

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Zearalenone (ZEN) is a Fusarium-derived xenoestrogenic mycotoxin. In plants, zearalenone-14-O-ß-d-glucoside (Z14G) is the major conjugated metabolite of ZEN, and is a masked mycotoxin. Masked mycotoxins are plant-modified derivatives, which are not routinely screened in food and feed samples. Cyclodextrins (CDs) are cyclic oligosaccharides built up from D-glucopyranose units. CDs can form stable host-guest type complexes with lipophilic molecules (e.g., with some mycotoxins). In this study, the interaction of Z14G with native and chemically modified ß- and γ-CDs was examined employing fluorescence spectroscopy and molecular modeling. Furthermore, the removal of Z14G from aqueous solution by insoluble ß-CD bead polymer (BBP) was also tested. Our results demonstrate that Z14G forms the most stable complexes with γ-CDs under acidic and neutral conditions (K ≈ 103 L/mol). Among the CDs tested, randomly methylated γ-CD induced the highest increase in the fluorescence of Z14G (7.1-fold) and formed the most stable complexes with the mycotoxin (K = 2 × 103 L/mol). Furthermore, BBP considerably reduced the Z14G content of aqueous solution. Based on these observations, CD technology seems a promising tool to improve the fluorescence analytical detection of Z14G and to discover new mycotoxin binders which can also remove masked mycotoxins (e.g., Z14G).

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A new extracorporeal circuit for hemodialysis was designed with the goal of improving the middle and high molecular weight toxins removal. A recirculation pathway was added to the hemodialysis circuit and relevant pressure regulation was performed along the circuit in order to keep the ultrafiltration rate as zero. The influence of increasing the recirculation to dialysate flow rate ratio on the removal of urea, vitamin B12, and hemoglobin was investigated. This removal was also modeled by an analytical method and solved by MATLAB software. A significant increase in removal of vitamin B12 (34%) and especially hemoglobin (228%) was achieved using the recirculation flow in an adjusted hemodialysis circuit. The model showed an acceptable agreement with the experimental results which shows its applicability for prediction of different toxin removal in this circuit.

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Zearalenone (ZEN) is a Fusarium-derived mycotoxin, exerting xenoestrogenic effects in animals and humans. ZEN and its derivatives commonly occur in cereals and cereal-based products. During the biotransformation of ZEN, its reduced metabolites, α-zearalenol (α-ZEL) and ß-zearalenol (ß-ZEL), are formed; α-ZEL is even more toxic than the parent compound ZEN. Since previous studies demonstrated that ZEN and ZELs form stable complexes with ß-cyclodextrins, it is reasonable to hypothesize that cyclodextrin polymers may be suitable for mycotoxin removal from aqueous solutions. In this study, the extraction of ZEN and ZELs from water, buffers, and corn beer was investigated, employing insoluble ß-cyclodextrin bead polymer (BBP) as a mycotoxin-binder. Our results demonstrate that even relatively small amounts of BBP can strongly decrease the mycotoxin content of aqueous solutions (including beer). After the first application of BBP for mycotoxin binding, BBP could be completely reactivated through the elimination of ZEN from the cyclodextrin cavities by washing with a 50 v/v% ethanol-water mixture. Therefore, our study suggests that insoluble cyclodextrin polymers may be suitable tools in the future to deplete mycotoxins from contaminated drinks.

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In this article, we review approaches for decreasing uremic solute concentrations in chronic kidney disease and in particular, in end-stage renal disease (ESRD). The rationale to do so is the straightforward relation between concentration and biological (toxic) effect for most toxins. The first section is devoted to extracorporeal strategies (kidney replacement therapy). In the context of high-flux hemodialysis and hemodiafiltration, we discuss increasing dialyzer blood and dialysate flows, frequent and/or extended dialysis, adsorption, bioartificial kidney, and changing physical conditions within the dialyzer (especially for protein-bound toxins). The next section focuses on the intestinal generation of uremic toxins, which in return is stimulated by uremic conditions. Therapeutic options are probiotics, prebiotics, synbiotics, and intestinal sorbents. Current data are conflicting, and these issues need further study before useful therapeutic concepts are developed. The following section is devoted to preservation of (residual) kidney function. Although many therapeutic options may overlap with therapies provided before ESRD, we focus on specific aspects of ESRD treatment, such as the risks of too-strict blood pressure and glycemic regulation and hemodynamic changes during dialysis. Finally, some recommendations are given on how research might be organized with regard to uremic toxins and their effects, removal, and impact on outcomes of uremic patients.

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