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Antioxidants (Basel, Switzerland) Nov 2023In this study, bile acid-based vesicles and nanoparticles (i.e., bilosomes and biloparticles) are studied to improve the water solubility of lipophilic drugs....
In this study, bile acid-based vesicles and nanoparticles (i.e., bilosomes and biloparticles) are studied to improve the water solubility of lipophilic drugs. Ursodeoxycholic acid, sodium cholate, sodium taurocholate and budesonide were used as bile acids and model drugs, respectively. Bilosomes and biloparticles were prepared following standard protocols with minor changes, after a preformulation study. The obtained systems showed good encapsulation efficiency and dimensional stability. Particularly, for biloparticles, the increase in encapsulation efficiency followed the order ursodeoxycholic acid < sodium cholate < sodium taurocholate. The in vitro release of budesonide from both bilosytems was performed by means of dialysis using either a nylon membrane or a portion of Wistar rat small intestine and two receiving solutions (i.e., simulated gastric and intestinal fluids). Both in gastric and intestinal fluid, budesonide was released from bilosystems more slowly than the reference solution, while biloparticles showed a significant improvement in the passage of budesonide into aqueous solution. Immunofluorescence experiments indicated that ursodeoxycholic acid bilosomes containing budesonide are effective in reducing the inflammatory response induced by glucose oxidase stimuli and counteract ox-inflammatory damage within intestinal cells.
PubMed: 38136145
DOI: 10.3390/antiox12122025 -
Kidney Medicine Mar 2024Dialysis comes with a substantial treatment burden, so patients must select care plans that align with their preferences. We aimed to deepen the understanding of...
RATIONALE & OBJECTIVE
Dialysis comes with a substantial treatment burden, so patients must select care plans that align with their preferences. We aimed to deepen the understanding of decisional regret with dialysis choices.
STUDY DESIGN
This study had a mixed-methods explanatory sequential design.
SETTING & PARTICIPANTS
All patients from a single academic medical center prescribed maintenance in-center hemodialysis or presenting for home hemodialysis or peritoneal dialysis check-up during 3 weeks were approached for survey. A total of 78 patients agreed to participate. Patients with the highest (15 patients) and lowest decisional regret (20 patients) were invited to semistructured interviews.
PREDICTORS
Decisional regret scale and illness intrusiveness scale were used in this study.
ANALYTICAL APPROACH
Quantitatively, we examined correlations between the decision regret scale and illness intrusiveness scale and sorted patients into the highest and lowest decision regret scale quartiles for further interviews; then, we compared patient characteristics between those that consented to interview in high and low decisional regret. Qualitatively, we used an adapted grounded theory approach to examine differences between interviewed patients with high and low decisional regret.
RESULTS
Of patients invited to participate in the interviews, 21 patients (8 high regret, 13 low regret) agreed. We observed that patients with high decisional regret displayed resignation toward dialysis, disruption of their sense of self and social roles, and self-blame, whereas patients with low decisional regret demonstrated positivity, integration of dialysis into their identity, and self-compassion.
LIMITATIONS
Patients with the highest levels of decisional regret may have already withdrawn from dialysis. Patients could complete interviews in any location (eg, home, dialysis unit, and clinical office), which may have influenced patient disclosure.
CONCLUSIONS
Although all patients experienced disruption after dialysis initiation, patients' approach to adversity differs between patients experiencing high versus low regret. This study identifies emotional responses to dialysis that may be modifiable through patient-support interventions.
PubMed: 38435065
DOI: 10.1016/j.xkme.2023.100785 -
Kidney International Supplements Apr 2024The International Society of Nephrology Global Kidney Health Atlas charts the availability and capacity of kidney care globally. In the North America and the Caribbean... (Review)
Review
Capacity for the management of kidney failure in the International Society of Nephrology North America and the Caribbean region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).
The International Society of Nephrology Global Kidney Health Atlas charts the availability and capacity of kidney care globally. In the North America and the Caribbean region, the Atlas can identify opportunities for kidney care improvement, particularly in Caribbean countries where structures for systematic data collection are lacking. In this third iteration, respondents from 12 of 18 countries from the region reported a 2-fold higher than global median prevalence of dialysis and transplantation, and a 3-fold higher than global median prevalence of dialysis centers. The peritoneal dialysis prevalence was lower than the global median, and transplantation data were missing from 6 of the 10 Caribbean countries. Government-funded payments predominated for dialysis modalities, with greater heterogeneity in transplantation payor mix. Services for chronic kidney disease, such as monitoring of anemia and blood pressure, and diagnostic capability relying on serum creatinine and urinalyses were universally available. Notable exceptions in Caribbean countries included non-calcium-based phosphate binders and kidney biopsy services. Personnel shortages were reported across the region. Kidney failure was identified as a governmental priority more commonly than was chronic kidney disease or acute kidney injury. In this generally affluent region, patients have better access to kidney replacement therapy and chronic kidney disease-related services than in much of the world. Yet clear heterogeneity exists, especially among the Caribbean countries struggling with dialysis and personnel capacity. Important steps to improve kidney care in the region include increased emphasis on preventive care, a focus on home-based modalities and transplantation, and solutions to train and retain specialized allied health professionals.
PubMed: 38618503
DOI: 10.1016/j.kisu.2024.01.003 -
Peritoneal Dialysis International :... Jan 2024Long-term peritoneal dialysis is associated with the development of peritoneal membrane alterations, both in morphology and function. Impaired ultrafiltration (UF) is... (Review)
Review
Long-term peritoneal dialysis is associated with the development of peritoneal membrane alterations, both in morphology and function. Impaired ultrafiltration (UF) is the most important functional change, and peritoneal fibrosis is the major morphological alteration. Both are caused by the continuous exposure to dialysis solutions that are different from plasma water with regard to the buffer substance and the extremely high-glucose concentrations. Glucose has been incriminated as the major cause of long-term peritoneal membrane changes, but the precise mechanism has not been identified. We argue that glucose causes the membrane alterations by peritoneal pseudohypoxia and by the formation of advanced glycosylation end products (AGEs). After a summary of UF kinetics including the role of glucose transporters (GLUT), and a discussion on morphologic alterations, relationships between function and morphology and a survey of the pathogenesis of UF failure (UFF), it will be argued that impaired UF is partly caused by a reduction in small pore fluid transport as a consequence of AGE-related vasculopathy and - more importantly - in diminished free water transport due to pseudohypoxia, caused by increased peritoneal cellular expression of GLUT-1. The metabolism of intracellular glucose will be reviewed. This occurs in the glycolysis and in the polyol/sorbitol pathway, the latter is activated in case of a large supply. In both pathways the ratio between the reduced and oxidised form of nicotinamide dinucleotide (NADH/NAD ratio) will increase, especially because normal compensatory mechanisms may be impaired, and activate expression of hypoxia-inducible factor-1 (HIF-1). The latter gene activates various profibrotic factors and GLUT-1. Besides replacement of glucose as an osmotic agent, medical treatment/prevention is currently limited to tamoxifen and possibly Renin/angiotensis/aldosteron (RAA) inhibitors.
Topics: Humans; Peritoneal Dialysis; Glucose; Glycosylation; Peritoneum; Dialysis Solutions; Water; Ultrafiltration
PubMed: 37723976
DOI: 10.1177/08968608231196033 -
Transplant International : Official... 2024An increasing number of sensitized patients awaiting transplantation face limited options, leading to fatalities during dialysis and higher costs. The absence of...
An increasing number of sensitized patients awaiting transplantation face limited options, leading to fatalities during dialysis and higher costs. The absence of established evidence highlights the need for collaborative consensus. Donor-specific antibodies (DSA)-triggered antibody-mediated rejection (AMR) significantly contributes to kidney graft failure, especially in sensitized patients. The European Society for Organ Transplantation (ESOT) launched the ENGAGE initiative, categorizing sensitized candidates by AMR risk to improve patient care. A systematic review assessed induction and maintenance regimens as well as antibody removal strategies, with statements subjected to the Delphi methodology. A Likert-scale survey was distributed to 53 European experts (Nephrologists, Transplant surgeons and Immunologists) with experience in kidney transplant recipient care. A rate ≥75% with the same answer was considered consensus. Consensus was achieved in 95.3% of statements. While most recommendations aligned, two statements related to complement inhibitors for AMR prophylaxis lacked consensus. The ENGAGE consensus presents contemporary recommendations for desensitization and immunomodulation strategies, grounded in predefined risk categories. The adoption of tailored, patient-specific measures is anticipated to streamline the care of sensitized recipients undergoing renal allografts. While this approach holds the promise of enhancing transplant accessibility and fostering long-term success in transplantation outcomes, its efficacy will need to be assessed through dedicated studies.
Topics: Humans; Kidney Transplantation; Delphi Technique; Graft Rejection; Consensus; Europe; Isoantibodies; Transplant Recipients
PubMed: 38665475
DOI: 10.3389/ti.2024.12475 -
Kidney360 Aug 2023
Topics: Humans; Renal Dialysis; Kidney Failure, Chronic; Graft Occlusion, Vascular; Africa, Eastern
PubMed: 37424062
DOI: 10.34067/KID.0000000000000211 -
Cardiovascular Drugs and Therapy Jan 2024Hyperkalaemia is one of the most common electrolyte disorders in patients with cardiovascular disease (CVD). The true burden of hyperkalaemia in the real-world setting... (Review)
Review
Hyperkalaemia is one of the most common electrolyte disorders in patients with cardiovascular disease (CVD). The true burden of hyperkalaemia in the real-world setting can be difficult to assess, but in population-based cohort studies up to 4 in 10 patients developed hyperkalaemia. In addition to drugs interfering with potassium metabolism and food intake, several conditions can cause or worsen hyperkalaemia, such as advanced age, diabetes, and chronic kidney disease. Mortality, cardiovascular morbidity, and hospitalisation are higher in patients with hyperkalaemia. Hyperkalaemia represents a major contraindication or a withholding cause for disease-modifying therapies like renin-angiotensin-aldosterone inhibitors (RAASi), mainly mineralocorticoid receptor antagonists. Hyperkalaemia can be also classified as acute and chronic, according to the onset. Acute hyperkalaemia is often a life-threatening emergency requiring immediate treatment to avoid lethal arrhythmias. Therapy goal is cell membrane stabilisation by calcium administration, cellular intake, shift of extracellular potassium to the intracellular space (insulin, beta-adrenergic agents, sodium bicarbonate), and increased elimination with diuretics or dialysis. Chronic hyperkalaemia was often managed with dietary counselling to prevent potassium-rich food intake and tapering of potassium-increasing drugs, mostly RAASi. Sodium polystyrene sulphonate, a potassium binder, was the only therapeutic option. Recently, new drugs such as patiromer and sodium zirconium cyclosilicate give new opportunities for the treatment of hyperkalaemia, as they proved to be safe, well tolerated, and effective. Aim of this review is to describe the burden of hyperkalaemia in cardiovascular patients, its direct and indirect effects, and the therapeutic options now available in the acute and chronic setting.
PubMed: 38289453
DOI: 10.1007/s10557-024-07551-7 -
Turkish Journal of Medical Sciences 2023There are over 60,000 hemodialysis (HD) patients in Türkiye, and the number of patients is increasing yearly. Dialysate flow rate (Qd) is a factor in HD adequacy....
BACKGROUND AND AIM
There are over 60,000 hemodialysis (HD) patients in Türkiye, and the number of patients is increasing yearly. Dialysate flow rate (Qd) is a factor in HD adequacy. Approximately 150 L of water are consumed per session to prepare the dialysate. We aimed to investigate whether HD effectiveness can be achieved at a low Qd in different patient groups for the purpose of saving water.
MATERIALS AND METHODS
This prospective study included 81 HD patients from 2 centers. The patients underwent an aggregate total of 486 HD sessions, including 3 sessions at a Qd of 500 mL/min and 3 sessions at a Qd of 300 mL/min for each patient. We used online Kt/V readings recorded at the end of each dialysis session to compare the effectiveness of these 2 types of HD session performed at a different Qd.
RESULTS
The online Kt/V readings were similar between the standard (500) and low (300) Qd HD (1.51 ± 0.41 and 1.49 ± 0.44, respectively, p = 0.069). In the subgroup analyses, men had higher online Kt/V values at the standard Qd compared to the low Qd (1.35 ± 0.30 and 1.30 ± 0.32, respectively, p = 0.019), but the Kt/V values were not different for women. While the low Qd did not reduce online Kt/V in patients using small surface area dialysis membranes (1.75 ± 0.35 for 300 Qd and 1.75 ± 0.32 for 500 Qd, p = 0.931), it was associated with reduced online Kt/V in patients using large surface area dialysis membranes (1.12 ± 0.25 for 300 Qd and 1.17 ± 0.24 for 500 Qd, p = 0.006). The low Qd did not result in differences in online Kt/V among low-weight patients. However, online Kt/V values were better with the standard Qd in patients weighing 65 kg and above.
CONCLUSION
In our study, dialysis adequacy at a reduced dialysate flow was not inferior for women, patients with low body weight, or patients using small surface area membranes. Individualized HD at a reduced Qd of 300 mL/min in eligible patients can save 48 L of water per HD session and an average of 7500 L of water per year.
Topics: Humans; Renal Dialysis; Female; Male; Prospective Studies; Middle Aged; Aged; Water; Adult; Dialysis Solutions; Kidney Failure, Chronic
PubMed: 38813487
DOI: 10.55730/1300-0144.5756 -
Journal of Mass Spectrometry and... Aug 2023Free thyroxine (FT4) measurement is one of the most requested tests in patient care for diagnosing and treating thyroid-related illnesses. Equilibrium dialysis (ED) is...
BACKGROUND
Free thyroxine (FT4) measurement is one of the most requested tests in patient care for diagnosing and treating thyroid-related illnesses. Equilibrium dialysis (ED) is considered the "gold standard" for FT4 measurement; however, several factors have a profound effect on the reliability of FT4 assays and require special consideration.
METHODS
In the current study, we focused on evaluating critical factors that could contribute to reporting errors, such as adsorption of thyroxine (T4) to labware surfaces, stability of serum samples, stock solutions, and calibrator storage conditions, as well as the solvents used to prepare T4 solutions.
RESULTS
The adsorption of T4 in ethanolic solutions and dialysates to labware surfaces can be reduced with the careful selection of pipette tips, test tubes, and 96-well plates. Adding pH modifiers to neat T4 solutions can improve its stability. FT4 in serum samples remains stable after exposure to four freeze-thaw cycles, 5 °C for 18-20 h, or -70 °C for a minimum of three years.
CONCLUSION
The presented study has demonstrated that the loss of analyte due to pre-analytical and analytical factors during operation of the FT4 reference measurement procedure (RMP) can be minimized by careful selection of all labware for sample preparation. It was found that the accuracy and imprecision of FT4 assays can be influenced by different types of dialysis devices, but acceptable alternatives to ED membranes were identified. This study demonstrates approaches to establish a FT4 method that is independent from specific suppliers and addresses critical pre-analytical and analytical factors important for FT4 measurements.
PubMed: 37449264
DOI: 10.1016/j.jmsacl.2023.06.001 -
Minerva Anestesiologica Sep 2023Extracorporeal carbon dioxide removal (ECCO
2 R) promotes protective ventilation in patients with acute respiratory failure, but devices with high...BACKGROUND
Extracorporeal carbon dioxide removal (ECCO
2 R) promotes protective ventilation in patients with acute respiratory failure, but devices with high CO2 extraction capacity are required for clinically relevant impact. This study evaluates three novel low-flow techniques based on dialysate acidification, also combined with renal replacement therapy, and metabolic control.METHODS
Eight swine were connected to a low-flow (350 mL/min) extracorporeal circuit including a dialyzer with a closed-loop dialysate circuit, and two membrane lungs on blood (ML
b ) and dialysate (MLd ), respectively. The following 2-hour steps were performed: 1) MLb -start (MLb ventilated); 2) MLbd -start (MLb and MLd ventilated); 3) HLac (lactic acid infusion before MLd ); 4) HCl-NaLac (hydrochloric acid infusion before MLd combined with renal replacement therapy and reinfusion of sodium lactate); 5) HCl-βHB-NaLac (hydrochloric acid infusion before MLd combined with renal replacement therapy and reinfusion of sodium lactate and sodium 3-hydroxybutyrate). Caloric and fluid inputs, temperature, blood glucose and arterial carbon dioxide pressure were kept constant.RESULTS
The total MLs CO
2 removal in HLac (130±25 mL/min), HCl-NaLac (130±21 mL/min) and HCl-βHB-NaLac (124±18 mL/min) were higher compared with MLbd -start (81±15 mL/min, P<0.05) and MLb -start (55±7 mL/min, P<0.05). Minute ventilation in HLac (4.3±0.9 L/min), HCl-NaLac (3.6±0.8 L/min) and HCl-βHB-NaLac (3.6±0.8 L/min) were lower compared to MLb -start (6.2±1.1 L/min, P<0.05) and MLbd -start (5.8±2.1 L/min, P<0.05). Arterial pH was 7.40±0.03 at MLb -start and decreased only during HCl-βHB-NaLac (7.35±0.03, P<0.05). No relevant changes in electrolyte concentrations, hemodynamics and significant adverse events were detected.CONCLUSIONS
The three techniques achieved a significant extracorporeal CO
2 removal allowing a relevant reduction in minute ventilation with a sufficient safety profile.Topics: Animals; Swine; Carbon Dioxide; Respiration, Artificial; Sodium Lactate; Hydrochloric Acid; Hydrogen-Ion Concentration; Dialysis Solutions
PubMed: 36951601
DOI: 10.23736/S0375-9393.23.17142-2