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International Journal of Molecular... Sep 2023Zr-based metal-organic framework materials (Zr-MOFs) with increased specific surface area and pore volume were obtained using chemical (two materials, and ) and...
Zr-based metal-organic framework materials (Zr-MOFs) with increased specific surface area and pore volume were obtained using chemical (two materials, and ) and solvothermal () synthesis methods and investigated via FT-IR spectroscopy, TGA, SANS, PXRD, and SEM methods. The difference between and lies in the addition of reactants during synthesis. Nitrogen porosimetry data indicated the presence of pores with average dimensions of ~4 nm; using SANS, the average size of the nanocrystals was suggested to be approximately 30 nm. The patterns obtained through PXRD were characterized by similar features that point to well-crystallized phases specific for the UIO-66 type materials; SEM also revealed that the materials were composed of small and agglomerate crystals. Thermogravimetric analysis revealed that both materials had approximately two linker deficiencies per Zr formula unit. Captopril and ibuprofen loading and release experiments in different buffered solutions were performed using the obtained Zr-based metal-organic frameworks as drug carriers envisaged for controlled drug release. The carriers demonstrated enhanced drug-loading capacity and showed relatively good results in drug delivery. The cumulative percentage of drug release in phosphate-buffered solution at pH 7.4 was higher than that in buffered solution at pH 1.2. The release rate could be controlled by changing the pH of the releasing solution. Different captopril release behaviors were observed when the experiments were performed using a permeable dialysis membrane.
PubMed: 37762192
DOI: 10.3390/ijms241813887 -
Toxins Sep 2023Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans....
Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans. While models exist for the induction of renal failure, none are optimized for the implantation of devices to the retroperitoneal vasculature. We successfully piloted an embolization-to-implantation protocol enabling the first implant of a silicon nanopore membrane hemodialyzer (SNMHD) in a swine renal failure model. Renal arterial embolization is a non-invasive approach to near-total nephrectomy that preserves retroperitoneal anatomy for device implants. Silicon nanopore membranes (SNM) are efficient blood-compatible membranes that enable novel approaches to RRT. Yucatan minipigs underwent staged bilateral renal arterial embolization to induce renal failure, managed by intermittent hemodialysis. A small-scale arteriovenous SNMHD prototype was implanted into the retroperitoneum. Dialysate catheters were tunneled externally for connection to a dialysate recirculation pump. SNMHD clearance was determined by intermittent sampling of recirculating dialysate. Creatinine and urea clearance through the SNMHD were 76-105 mL/min/m and 140-165 mL/min/m, respectively, without albumin leakage. Normalized creatinine and urea clearance measured in the SNMHD may translate to a fully implantable clinical-scale device. This pilot study establishes a path toward therapeutic testing of the clinical-scale SNMHD and other implantable RRT devices.
Topics: Humans; Swine; Animals; Kidneys, Artificial; Creatinine; Pilot Projects; Silicon; Swine, Miniature; Renal Insufficiency; Dialysis Solutions; Urea
PubMed: 37755973
DOI: 10.3390/toxins15090547 -
Blood Purification 2023Hyperammonemia is a life-threatening condition mainly due to the neurotoxicity of ammonia. Ammonia scavengers may be insufficient, and extracorporeal treatment may be... (Review)
Review
Hyperammonemia is a life-threatening condition mainly due to the neurotoxicity of ammonia. Ammonia scavengers may be insufficient, and extracorporeal treatment may be required. Continuous treatments are preferred, and a high-dose continuous renal replacement therapy (CRRT) must be prescribed to ensure a fast ammonia depletion. Many of the children with hyperammonemia are newborns, with lower blood volume than older children. The majority of the CRRT systems are adult-based, with large extracorporeal priming volumes and inadequate UF control. Recent strides have been made in the development of CRRT systems more suitable for young children with smaller sets to use in adult machines and dedicated monitors for neonates and infants. The main advantage of the machines for adults is the higher dialysis fluid flows, however with greater hemodynamic risks. Pediatric monitors have been designed to reduce the extracorporeal volume and to increase the precision of the treatment. However, they have substantial limitation in clearance performances. In this review, we discuss on current strategies to provide CRRT in newborns and small infants with hyperammonemia. We also presented our experience with the use of CARPEDIEM™ implemented in a CVVHDF modality, boosting the diffusive clearance with a post-replacement convective mechanism.
Topics: Infant, Newborn; Infant; Humans; Child; Adolescent; Child, Preschool; Renal Replacement Therapy; Hyperammonemia; Ammonia; Continuous Renal Replacement Therapy; Dialysis Solutions; Acute Kidney Injury
PubMed: 37725911
DOI: 10.1159/000533486 -
Renal Failure 2023To investigate the role of segmental bioelectrical impedance technique (SBIA) in the assessment of intraperitoneal ultrafiltration volume with peritoneal dialysis...
OBJECTIVE
To investigate the role of segmental bioelectrical impedance technique (SBIA) in the assessment of intraperitoneal ultrafiltration volume with peritoneal dialysis patients.
METHOD
We selected the patients at the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University and measured the segmental bioelectrical impedance by a German Fresenius body composition analyzer (the Fresenius whole body composition measurement (BCM) machine was used as a segmental machine in this study). An alternating current (5 kHz, 0.05-0.7 mA) was continuously released during the measurement. The released current penetrated the peritoneal cavity on both sides of the body, from which the segmental resistance at a frequency of 5 kHz was obtained from the multifrequency data (R5/Ω). Baseline BIA measurements were initiated after the patient entered the supine position for 5-10 min, then dialysate was instilled into the peritoneal cavity. BIA measurements were performed at 10-min intervals during the retention of dialysate in the abdomen and finally ended when dialysate drainage was complete. Real-time intraperitoneal volume estimated by SBIA (IPV)and ultrafiltration volume estimated by SBIA(UFV) was calculated. At the same time, the actual ultrafiltration volume at the end of peritoneal dialysis was weighed and measured (UFV).
RESULTS
A total of 30 patients were included in the study, 9 patients withdrew from the study due to subjective factors during the measurement process, and 21 patients completed the study. The correlation coefficient of UFV and UFV was 0.21 ( < 0.05). Bland-Altman analysis showed that the bias of UFV to the actual UFV was 0.12 L, and the 95% agreement limit was between -0.5 L and 0.74 L, which confirmed that UFV measured by electrical impedance method and UFV measured by weighing method were in good agreement. The time required to reach the maximum ultrafiltration volume (UFV) was 108 ± 68 min, and the mean value of the maximum ultrafiltration volume (Max UFV) was 1.16 ± 0.60 L.
CONCLUSION
The segmental bioelectrical impedance technique can be used to assess the intraperitoneal ultrafiltration volume of peritoneal dialysis patients in real-time and effectively. This method may guide the dialysis fluid retention time and the maximum ultrafiltration volume in PD patients.
Topics: Humans; Ultrafiltration; Electric Impedance; Peritoneal Dialysis; Dialysis Solutions; Renal Dialysis
PubMed: 37724525
DOI: 10.1080/0886022X.2023.2255678 -
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 -
Biomedicine & Pharmacotherapy =... Nov 2023Kidney transplantation is the treatment of choice for patients with kidney failure. Compared to dialysis therapy, it provides better quality of life and confers... (Review)
Review
Kidney transplantation is the treatment of choice for patients with kidney failure. Compared to dialysis therapy, it provides better quality of life and confers significant survival advantage at a relatively lower cost. However, the long-term success of this life-saving intervention is severely hampered by an inexorable clinical problem referred to as ischemia-reperfusion injury (IRI), and increases the incidence of post-transplant complications including loss of renal graft function and death of transplant recipients. Burgeoning evidence shows that nitric oxide (NO), a poisonous gas at high concentrations, and with a historic negative public image as an environmental pollutant, has emerged as a potential candidate that holds clinical promise in mitigating IRI and preventing acute and chronic graft rejection when it is added to kidney preservation solutions at low concentrations or when administered to the kidney donor prior to kidney procurement and to the recipient or to the reperfusion circuit at the start and during reperfusion after renal graft preservation. Interestingly, dysregulated or abnormal endogenous production and metabolism of NO is associated with IRI in kidney transplantation. From experimental and clinical perspectives, this review presents endogenous enzymatic production of NO as well as its exogenous sources, and then discusses protective effects of constitutive nitric oxide synthase (NOS)-derived NO against IRI in kidney transplantation via several signaling pathways. The review also highlights a few isolated studies of renal graft protection by NO produced by inducible NOS.
Topics: Humans; Kidney Transplantation; Nitric Oxide; Quality of Life; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Kidney; Reperfusion Injury; Nitric Oxide Synthase Type III
PubMed: 37722191
DOI: 10.1016/j.biopha.2023.115530 -
BMC Nephrology Sep 2023Few drug dosing recommendations for patients receiving home hemodialysis (HHD) have been published which has hindered the adoption of HHD. HHD regimens vary widely and...
BACKGROUND
Few drug dosing recommendations for patients receiving home hemodialysis (HHD) have been published which has hindered the adoption of HHD. HHD regimens vary widely and differ considerably from conventional, thrice weekly, in-center hemodialysis in terms of treatment frequency, duration and blood and dialysate flow rates. Consequently, vancomycin and daptomycin clearances in HHD are also likely to be different, consequently HHD dosing regimens must be developed to ensure efficacy and minimize toxicity when these antibiotics are used. Many HHD regimens are used clinically, this study modeled ten common HHD regimens and determined optimal vancomycin and daptomycin dosing for each HHD regimen.
METHODS
Monte Carlo simulations using pharmacokinetic data derived from the literature and demographic data from a large HHD program treating patients with end stage kidney disease were incorporated into a one-compartment pharmacokinetic model. Virtual vancomycin and daptomycin doses were administered post-HHD and drug exposures were determined in 5,000 virtual patients receiving ten different HHD regimens. Serum concentration monitoring with subsequent dose changes was incorporated into the vancomycin models. Pharmacodynamic target attainment rates were determined for each studied dose. The lowest possible doses that met predefined targets in virtual patients were chosen as optimal doses.
RESULTS
HHD frequency, total dialysate volumes and HHD durations influenced drug exposure and led to different dosing regimens to meet targets. Antibiotic dosing regimens were identified that could meet targets for 3- and 7-h HHD regimens occurring every other day or 4-5 days/week. HHD regimens with 3-day interdialytic periods required higher doses prior to the 3-day period. The addition of vancomycin serum concentration monitoring allowed for calculation of necessary dosing changes which increased the number of virtual subjects meeting pharmacodynamic targets.
CONCLUSIONS
Doses of vancomycin and daptomycin that will meet desired pharmacodynamic targets in HHD are dependent on patient and HHD-specific factors. Doses used in conventional thrice weekly hemodialysis are unlikely to meet treatment goals. The antibiotic regimens paired with the HHD parameters studied in this analysis are likely to meet goals but require clinical validation.
Topics: Humans; Vancomycin; Daptomycin; Hemodialysis, Home; Monte Carlo Method; Anti-Bacterial Agents; Dialysis Solutions
PubMed: 37710245
DOI: 10.1186/s12882-023-03314-y -
Journal of Translational Medicine Sep 2023Peritoneal dialysis (PD) remains limited due to dialysis failure caused by peritoneal fibrosis. Tamoxifen (TAM), an inhibitor of estrogen receptor 1 (ESR1), has been...
BACKGROUND
Peritoneal dialysis (PD) remains limited due to dialysis failure caused by peritoneal fibrosis. Tamoxifen (TAM), an inhibitor of estrogen receptor 1 (ESR1), has been reported to treat fibrosis, but the underlying mechanism remains unknown. In this study, we sought to explore whether tamoxifen played an anti-fibrotic role by affecting transcription factor ESR1.
METHODS
ESR1 expression was detected in the human peritoneum. Mice were daily intraperitoneally injected with 4.25% glucose PD dialysate containing 40 mM methylglyoxal for 2 weeks to establish PD-induced peritoneal fibrosis. Tamoxifen was administrated by daily gavage, at the dose of 10 mg/kg. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay were performed to validate ESR1 bound H19 promoter. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of H19 on the mesothelial-mesenchymal transition (MMT) of human peritoneal mesothelial cells (HPMCs). Intraperitoneal injection of nanomaterial-wrapped 2'-O-Me-modified small interfering RNA was applied to suppress H19 in the mouse peritoneum. RNA immunoprecipitation and RNA pull-down assays demonstrated binding between H19 and p300. Exfoliated peritoneal cells were obtained from peritoneal dialysis effluent to analyze the correlations between ESR1 (or H19) and peritoneal solute transfer rate (PSTR).
RESULTS
ESR1 was increased significantly in the peritoneum after long-term exposure to PD dialysate. Tamoxifen treatment ameliorated high glucose-induced MMT of HPMCs, improved ultrafiltration rate, and decreased PSTR of mouse peritoneum. Tamoxifen reduced the H19 level by decreasing the ESR1 transcription of H19. Depletion of H19 reversed the pro-fibrotic effect of high glucose while ectopic expression of H19 exacerbated fibrotic pathological changes. Intraperitoneal injection of nanomaterial-wrapped 2'-O-Me-modified siRNAs targeting H19 mitigated PD-related fibrosis in mice. RNA immunoprecipitation (RIP) and RNA pull-down results delineated that H19 activated VEGFA expression by binding p300 to the VEGFA promoter and inducing histone acetylation of the VEGFA promoter. ESR1 and H19 were promising targets to predict peritoneal function.
CONCLUSIONS
High glucose-induced MMT of peritoneal mesothelial cells in peritoneal dialysis via activating ESR1. In peritoneal mesothelial cells, ESR1 transcribed the H19 and H19 binds to transcription cofactor p300 to activate the VEGFA. Targeting ESR1/H19/VEGFA pathway provided new hope for patients undergoing peritoneal dialysis.
Topics: Animals; Humans; Mice; Dialysis Solutions; Fibrosis; Glucose; Peritoneum; RNA; Vascular Endothelial Growth Factor A; Tamoxifen
PubMed: 37697303
DOI: 10.1186/s12967-023-04470-3 -
Internal Medicine (Tokyo, Japan) Apr 2024A hypercalcemic crisis due to primary hyperparathyroidism is a life-threatening condition. We herein report a 71-years-old man with hypercalcemic crisis due to primary...
A hypercalcemic crisis due to primary hyperparathyroidism is a life-threatening condition. We herein report a 71-years-old man with hypercalcemic crisis due to primary hyperparathyroidism with parathyroid adenoma. Generally, hemodialysis or continuous hemodiafiltration using calcium-free or low-calcium dialysate is performed early for hypercalcemic crisis. In this case, continuous hemodialysis with a common calcium concentration dialysate improved the hypercalcemic crisis, and parathyroidectomy was performed. The patient recovered sufficiently. Prediction of hypercalcemia crisis, appropriate introduction and methods of blood purification therapy, and timing decisions for parathyroidectomy are required for therapeutic management of hypercalcemic crisis with parathyroid adenoma.
Topics: Male; Humans; Aged; Calcium; Hypercalcemia; Parathyroid Neoplasms; Hyperparathyroidism, Primary; Dialysis Solutions; Calcium, Dietary; Renal Dialysis
PubMed: 37690849
DOI: 10.2169/internalmedicine.1764-23 -
PloS One 2023Diffuse midline gliomas (DMG) are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates <10%. Treatment failure is due in... (Clinical Trial)
Clinical Trial
Diffuse midline gliomas (DMG) are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates <10%. Treatment failure is due in part to the function of the BBB. Intratumoral microdialysis sampling is an effective tool to determine brain entry of varied agents and could help to provide a better understanding of the relationship of drug permeability to DMG treatment responsivity. This is a non-randomized, single-center, phase 1 clinical trial. Up to seven young adult (18-39 years) patients with recurrent high-grade or diffuse midline glioma will be enrolled with the goal of 5 patients completing the trial over an anticipated 24 months. All patients will take abemaciclib pre-operatively for 4.5 days at twice daily dosing. Patients will undergo resection or biopsy, placement of a microdialysis catheter, and 48 hours of dialysate sampling coupled with timed plasma collections. If intratumoral tumor or brain dialysate sampling concentrations are >10nmol/L, or tumor tissue studies demonstrate CDK inhibition, then restart of abemaciclib therapy along with temozolomide will be administered for maintenance therapy and discontinued with evidence of radiologic or clinical disease progression. The poor survival associated with diffuse midline gliomas underscore the need for improved means to evaluate efficacy of drug delivery to tumor and peritumoral tissue. The findings of this novel study, will provide real-time measurements of BBB function which have the potential to influence future prognostic and diagnostic decisions in such a lethal disease with limited treatment options. Trial registration: Clinicaltrials.gov, NCT05413304. Registered June 10, 2022, Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis.
Topics: Young Adult; Humans; Feasibility Studies; Microdialysis; Clinical Protocols; Dialysis Solutions; Glioma
PubMed: 37682953
DOI: 10.1371/journal.pone.0291068