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International Journal of Molecular... Apr 2024Chronic kidney disease (CKD) is a global health concern affecting approximately one billion individuals worldwide. End-stage kidney disease (ESKD), the most severe form...
Chronic kidney disease (CKD) is a global health concern affecting approximately one billion individuals worldwide. End-stage kidney disease (ESKD), the most severe form of CKD, is often accompanied by anemia. Peritoneal dialysis (PD), a common treatment for ESKD, utilizes the peritoneum for solute transfer but is associated with complications including protein loss, including transferrin (Tf) a key protein involved in iron transport. This study investigated Tf characteristics in ESKD patients compared to healthy individuals using lectin microarray, spectroscopic techniques and immunocytochemical analysis to assess Tf interaction with transferrin receptors (TfRs). ESKD patients exhibited altered Tf glycosylation patterns, evidenced by significant changes in lectin reactivity compared to healthy controls. However, structural analyses revealed no significant differences in the Tf secondary or tertiary structures between the two groups. A functional analysis demonstrated comparable Tf-TfR interaction in both PD and healthy samples. Despite significant alterations in Tf glycosylation, structural integrity and Tf-TfR interaction remained preserved in PD patients. These findings suggest that while glycosylation changes may influence iron metabolism, they do not impair Tf function. The study highlights the importance of a glucose-free dialysis solutions in managing anemia exacerbation in PD patients with poorly controlled anemia, potentially offering a targeted therapeutic approach to improve patient outcomes.
Topics: Humans; Transferrin; Glycosylation; Kidney Failure, Chronic; Male; Female; Middle Aged; Receptors, Transferrin; Peritoneal Dialysis; Aged; Adult; Iron
PubMed: 38731843
DOI: 10.3390/ijms25094625 -
Advances in Therapy Jul 2024Limitations in physical functioning are common in patients with late-stage chronic kidney disease (CKD) and can greatly affect their lives. Using patient interviews,...
INTRODUCTION
Limitations in physical functioning are common in patients with late-stage chronic kidney disease (CKD) and can greatly affect their lives. Using patient interviews, this study reports experiences associated with physical functioning limitations for patients with late-stage CKD.
METHODS
A preliminary conceptual model on concepts relevant to physical functioning limitations in patients with CKD was developed using data from a targeted literature review (patients with CKD stages IV-V) and previous interviews (patients with CKD stages IIIa-IIIb). The preliminary conceptual model informed a semi-structured interview guide designed to capture experiences of physical functioning limitations in patients with CKD. Patients with CKD stages IV-V who were not receiving dialysis were interviewed; their responses were used to develop a comprehensive conceptual model summarizing their experiences associated with physical functioning limitations.
RESULTS
A total of 25 patients with CKD stage IV (n = 19) or V (n = 6) were interviewed. Based on patient responses, the reported concepts were grouped into one of six categories: physical functioning limitations/difficulties, behavioural impacts, activity participation restrictions, symptoms attributed to physical functioning limitations, impacts on sleep and emotional functioning impacts related to physical functioning limitations. Twenty-three patients reported concepts associated with physical functioning limitations, most frequently 'walking up and down stairs' (83%) and 'walking distances' (74%). All 23 patients also reported behavioural impacts, including 'need to rest/subsequent periods of rest' (100%) and 'participation in fewer activities' (91%). As well as summarizing the reported concepts, the comprehensive conceptual model shows how concepts may relate to one another; for example, challenging symptoms or difficulty completing tasks can lead to changes in patient behaviour such as purposely reducing or avoiding activities.
CONCLUSIONS
This study found that patients with late-stage CKD not receiving dialysis who experience physical functioning limitations report a range of impacts on their daily lives. The comprehensive conceptual model summarizes the concepts reported and the relationships between them, providing a holistic understanding of how patients with late-stage CKD are affected by physical functioning limitations. Infographic available for this article. INFOGRAPHIC.
Topics: Humans; Male; Female; Aged; Renal Insufficiency, Chronic; Middle Aged; Qualitative Research; Activities of Daily Living; Aged, 80 and over; Interviews as Topic; Quality of Life; Severity of Illness Index
PubMed: 38722538
DOI: 10.1007/s12325-024-02853-6 -
Renal Failure Dec 2024Increasing evidence suggests that peritoneal fibrosis induced by peritoneal dialysis (PD) is linked to oxidative stress. However, there are currently no effective...
Increasing evidence suggests that peritoneal fibrosis induced by peritoneal dialysis (PD) is linked to oxidative stress. However, there are currently no effective interventions for peritoneal fibrosis. In the present study, we explored whether adding caffeic acid phenethyl ester (CAPE) to peritoneal dialysis fluid (PDF) improved peritoneal fibrosis caused by PD and explored the molecular mechanism. We established a peritoneal fibrosis model in Sprague-Dawley rats through intraperitoneal injection of PDF and lipopolysaccharide (LPS). Rats in the PD group showed increased peritoneal thickness, submesothelial collagen deposition, and the expression of TGFβ1 and α-SMA. Adding CAPE to PDF significantly inhibited PD-induced submesothelial thickening, reduced TGFβ1 and α-SMA expression, alleviated peritoneal fibrosis, and improved the peritoneal ultrafiltration function. , peritoneal mesothelial cells (PMCs) treated with PDF showed inhibition of the AMPK/SIRT1 pathway, mitochondrial membrane potential depolarization, overproduction of mitochondrial reactive oxygen species (ROS), decreased ATP synthesis, and induction of mesothelial-mesenchymal transition (MMT). CAPE activated the AMPK/SIRT1 pathway, thereby inhibiting mitochondrial membrane potential depolarization, reducing mitochondrial ROS generation, and maintaining ATP synthesis. However, the beneficial effects of CAPE were counteracted by an AMPK inhibitor and siSIRT1. Our results suggest that CAPE maintains mitochondrial homeostasis by upregulating the AMPK/SIRT1 pathway, which alleviates oxidative stress and MMT, thereby mitigating the damage to the peritoneal structure and function caused by PD. These findings suggest that adding CAPE to PDF may prevent and treat peritoneal fibrosis.
Topics: Animals; Rats; AMP-Activated Protein Kinases; Caffeic Acids; Dialysis Solutions; Disease Models, Animal; Homeostasis; Membrane Potential, Mitochondrial; Mitochondria; Oxidative Stress; Peritoneal Dialysis; Peritoneal Fibrosis; Peritoneum; Phenylethyl Alcohol; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction; Sirtuin 1; Transforming Growth Factor beta1
PubMed: 38721924
DOI: 10.1080/0886022X.2024.2350235 -
Artificial Organs Jul 2024Regional anticoagulation in hemodialysis avoids the use of heparin, which is responsible for both hemorrhagic and non-hemorrhagic complications. Typically, blood is... (Review)
Review
BACKGROUND
Regional anticoagulation in hemodialysis avoids the use of heparin, which is responsible for both hemorrhagic and non-hemorrhagic complications. Typically, blood is decalcified by injecting citrate into the arterial line of the extracorporeal circuit. Calcium-free dialysate improves anticoagulation efficacy but requires injection of a calcium-containing solution into the venous line and strict monitoring of blood calcium levels. Recent improvements have made regional anticoagulation with calcium-free dialysate safer and easier.
OBSERVATIONS
(1) Adjusting the calcium injection rate to ionic dialysance avoids the risk of dyscalcemia, thus making unnecessary the monitoring of blood calcium levels. This adjustment could be carried out automatically by the hemodialysis monitor. (2) As calcium-free dialysate reduces the amount of citrate required, this can be supplied by dialysate obtained from currently available concentrates containing citric acid. This avoids the need for citrate injection and the risk of citrate overload. (3) Calcium-free dialysate no longer needs the dialysate acidification required for avoiding calcium carbonate precipitation in bicarbonate-containing dialysate.
CONCLUSIONS
Regional anticoagulation with calcium-free dialysate enables an acid- and heparin-free procedure that is more biocompatible and environmentally friendly than conventional bicarbonate hemodialysis. The availability of specific acid-free concentrates and adapted hemodialysis monitors is required to extend this procedure to maintenance hemodialysis.
Topics: Humans; Renal Dialysis; Anticoagulants; Calcium; Dialysis Solutions; Citric Acid; Blood Coagulation; Hemodialysis Solutions
PubMed: 38716639
DOI: 10.1111/aor.14764 -
New Biotechnology Sep 2024Given the necessity for bioprocesses scaling-up, the present study aims to explore the potential of three marine cyanobacteria and a consortium, cultivated in...
Given the necessity for bioprocesses scaling-up, the present study aims to explore the potential of three marine cyanobacteria and a consortium, cultivated in semi-continuous mode, as a green approach for i) continuous exopolysaccharide-rich biomass production and ii) removal of positively charged metals (Cu, Ni, Zn) from mono and multi-metallic solutions. To ensure the effectiveness of both cellular and released exopolysaccharides, weekly harvested whole cultures were confined in dialysis tubings. The results revealed that all the tested cyanobacteria have a stronger affinity towards Cu in mono and three-metal systems. Despite the amount of metals removed per gram of biomass decreased with higher biosorbent dosage, the more soluble carbohydrates were produced, the greater was the metal uptake, underscoring the pivotal role of released exopolysaccharides in metal biosorption. According to this, Dactylococcopsis salina 16Som2 showed the highest carbohydrate productivity (142 mg L d) and metal uptake (84 mg Cu g biomass) representing a promising candidate for further studies. The semi-continuous cultivation of marine cyanobacteria here reported assures a schedulable production of exopolysaccharide-rich biosorbents with high metal removal and recovery potential, even from multi-metallic solutions, as a step forward in the industrial application of cyanobacteria.
Topics: Cyanobacteria; Extracellular Polymeric Substance Matrix; Biomass; Biotechnology; Metals; Green Chemistry Technology
PubMed: 38714292
DOI: 10.1016/j.nbt.2024.04.004 -
International Journal of Molecular... Apr 2024Although several therapeutic effects have been attributed to wild blackthorn fruits, their use is still negligible. Purification of the antioxidant-active fraction,...
Although several therapeutic effects have been attributed to wild blackthorn fruits, their use is still negligible. Purification of the antioxidant-active fraction, obtained from wild blackthorn fruits by hot ammonium oxalate extraction (Ao), yielded seven fractions after successive elution with water, sodium chloride and sodium hydroxide solutions. The purified fractions differ in carbohydrates, proteins, and phenolics. About 60% of the applied Ao material was recovered from the column, with the highest yields eluted with 0.25 M NaCl solution, accounting for up to 70 wt% of all eluted material. Analyses have shown that two dominant fractions (3Fa and 3Fb) contain 72.8-81.1 wt% of galacturonic acids, indicating the prevalence of homogalacturonans (HG) with a low acetyl content and a high degree of esterification. The low content of rhamnose, arabinose and galactose residues in both fractions indicates the presence of RG-I associated with arabinogalactan. In terms of yield, the alkali-eluted fraction was also significant, as a dark brown-coloured material with a yield of ~15 wt% with the highest content of phenolic compounds of all fractions. However, it differs from other fractions in its powdery nature, which indicates a high content of salts that could not be removed by dialysis.
Topics: Antioxidants; Fruit; Polysaccharides; Oxalates; Plant Extracts; Pectins; Phenols; Galactans
PubMed: 38674109
DOI: 10.3390/ijms25084519 -
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 -
Frontiers in Pediatrics 2024The predominant use of intravenous catheters as primary access type in the pediatric hemodialysis population is associated with an increased risk of catheter related... (Review)
Review
The predominant use of intravenous catheters as primary access type in the pediatric hemodialysis population is associated with an increased risk of catheter related blood stream infections. While strict adherence to catheter placement and long-term care guidelines have helped to decrease the incidence of these infections, blood stream infections remain an infection burden in pediatric patients with long term hemodialysis catheters. The formation of biofilms on the surfaces of these catheters has been shown to be a source of microbes causing blood stream infections. One of the strategies for preventing bacterial colonization, inhibiting microbial multiplication, and suppressing the seeding of these microbes from biofilms upon maturation, has been the use of antibiotic-based lock solutions in-between dialysis treatments. Although clinical guidelines for the use of antibiotic lock solutions are yet to be developed, available evidence suggests a beneficial role of antibiotic lock solutions in the management of catheter related blood stream infections. Additionally, a clear understanding of how biofilms are formed and their role in the pathogenesis of catheter related bloodstream infection will facilitate the development of solutions that can prevent biofilm formation and inhibit their multiplication, maturation and seeding into the bloodstream.
PubMed: 38665376
DOI: 10.3389/fped.2024.1379895 -
Journal of Pharmaceutical and... Aug 2024Niraparib is a potent and orally bioavailable inhibitor of poly (ADP-ribose) polymerase (PARP) with high specificity for isoforms 1 and 2. It has been approved by the...
Niraparib is a potent and orally bioavailable inhibitor of poly (ADP-ribose) polymerase (PARP) with high specificity for isoforms 1 and 2. It has been approved by the U.S. Food and Drug Administration for ovarian cancer maintenance therapy and is currently under development for various cancers, including glioblastoma. To assess central nervous system (CNS) penetration of niraparib in glioblastoma patients, a novel bioanalytical method was developed to measure total and unbound niraparib levels in human brain tumor tissue and cerebrospinal fluid (CSF). The method was validated using plasma as a surrogate matrix over the concentration range of 1-10,000 nM on an LC-MS/MS system. The MS/MS detection was conducted in positive electrospray ionization mode, while chromatography was performed using a Kinetex™ PS C18 column with a total 3.5-minute gradient elution run time. The maximum coefficient of variation for both intra- and inter-day precision was 10.6%, with accuracy ranging from 92.8% - 118.5% across all matrices. Niraparib was stable in human brain homogenate for at least 6 hours at room temperature (RT) and 32 days at -20°C, as well as in stock and working solutions for at least 21 hours (RT) and 278 days (4°C). Equilibrium dialysis experiments revealed the fractions unbound of 0.05 and 0.16 for niraparib in human brain and plasma, respectively. The validated method is currently employed to assess niraparib levels in human glioblastoma tissue, CSF, and plasma in an ongoing trial on newly diagnosed glioblastoma and recurrent IDH1/2(+) ATRX mutant glioma patients (NCT05076513). Initial results of calculated total (K) and unbound (K) tumor-to-plasma partition coefficients indicate significant brain penetration ability of niraparib in glioblastoma patients.
Topics: Humans; Piperidines; Indazoles; Tandem Mass Spectrometry; Brain Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Chromatography, Liquid; Glioblastoma; Reproducibility of Results; Brain; Sulfonamides; Liquid Chromatography-Mass Spectrometry
PubMed: 38657366
DOI: 10.1016/j.jpba.2024.116150 -
World Journal of Urology Apr 2024An abnormal lower urinary tract poses significant challenges for transplant surgeons. Besides the ureteral anastomosis to an ileal conduit, there are diverse complex...
PURPOSE
An abnormal lower urinary tract poses significant challenges for transplant surgeons. Besides the ureteral anastomosis to an ileal conduit, there are diverse complex reconstructive solutions. Due to its rarity, standardization and teaching of complex urinary diversion is extremely difficult.
METHODS
The indications and outcomes of complex urinary diversions after kidney transplantation (KT) were retrospectively investigated at eight urologic transplant centers including a current follow-up.
RESULTS
Of 37 patients with 21 (56%) males, vesicoureteral reflux (24%), spina bifida (22%), and glomerulonephritis (12%) were the most common causes of terminal renal failure. In 30 (81%) patients, urinary diversion was performed before KT, at a median of 107.5 (range, 10; 545) months before. Transplantations were held at a median patient age of 43 (10; 68) years, including six (16%) living donations. Urinary diversion was modified during 12 (32%) transplantations. After KT, the ileal conduit was the most common incontinent urinary diversion in 25 (67%) patients; a Mainz pouch I and bladder augmentation were the most frequent continent diversions (each n = 3). At a median follow-up of 120 months (range 0; 444), 12 (32%) patients had a graft failure with a 5-year graft survival of 79% (95%CI 61; 90). The median overall survival was 227 months (168; 286) and the 5-year overall survival 89% (69.3; 96.4).
CONCLUSION
The mid-term kidney transplant function with complex urinary diversion appears to be comparable to transplants with regular urinary diversions. Hence, complex urinary diversion should always be considered as a surgical option, even during transplantation, if necessary.
Topics: Female; Humans; Male; Kidney Transplantation; Plastic Surgery Procedures; Retrospective Studies; Surgeons; Urinary Diversion; Adult
PubMed: 38630278
DOI: 10.1007/s00345-024-04934-1