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The Analyst Apr 2024Monitoring the concentration fluctuations of neurotransmitters is valuable for elucidating the chemical signals that underlie brain functions. Microdialysis sampling is...
Monitoring the concentration fluctuations of neurotransmitters is valuable for elucidating the chemical signals that underlie brain functions. Microdialysis sampling is a widely used tool for monitoring neurochemicals . The volume requirements of most techniques that have been coupled to microdialysis, such as HPLC, result in fraction collection times of minutes, thus limiting the temporal resolution possible. Further the time of analysis can become long for cases where many fractions are collected. Previously we have used direct analysis of dialysate by low-flow electrospray ionization-tandem mass spectrometry (ESI-MS/MS) on a triple quadrupole mass spectrometer to monitor acetylcholine, glutamate, and γ-amino-butyric acid to achieve multiplexed monitoring with temporal resolution of seconds. Here, we have expanded this approach to adenosine, dopamine, and serotonin. The method achieved limits of detection down to 2 nM, enabling basal concentrations of all these compounds, except serotonin, to be measured . Comparative analysis with LC-MS/MS showed accurate results for all compounds except for glutamate, possibly due to interference for this compound . Pairing this analysis with droplet microfluidics yields 11 s temporal resolution and can generate dialysate fractions down to 3 nL at rates up to 3 fractions per s from a microdialysis probe. The system is applied to multiplexed monitoring of neurotransmitter dynamics in response to stimulation by 100 mM K and amphetamine. These applications demonstrate the suitability of the droplet ESI-MS/MS method for monitoring short-term dynamics of up to six neurotransmitters simultaneously.
Topics: Tandem Mass Spectrometry; Chromatography, Liquid; Microfluidics; Microdialysis; Serotonin; Glutamic Acid; Neurotransmitter Agents; Dialysis Solutions
PubMed: 38488040
DOI: 10.1039/d4an00112e -
International Journal of Antimicrobial... May 2024Peritonitis remains the major infectious complication in the setting of peritoneal dialysis (PD). Despite known only moderate pathogenicity, the most frequently detected...
INTRODUCTION
Peritonitis remains the major infectious complication in the setting of peritoneal dialysis (PD). Despite known only moderate pathogenicity, the most frequently detected pathogens in PD-related peritonitis are surprisingly coagulase-negative staphylococci. However, this could be explained, at least in part, by Staphylococcus aureus small colony variants (SCVs) induced by PD fluids (PDFs) and misidentified by routinely used microbiological methods.
MATERIAL AND METHODS
Bacteria were exposed to commonly used PDFs in various regimens designed to simulate daily use as closely as possible. Wild-type isolates and SCVs were subsequently used to determine minimum inhibitory concentrations (MICs), in vitro biofilm formation capacities, and auxotrophies. Underlying genetic alterations were investigated using whole-genome sequencing, and various microbial identification methods were tested to determine their performance for wild-types and SCVs.
RESULTS
Stable SCVs could be isolated most successfully after exposure to glucose-containing PDFs alone. The reading of MICs was significantly affected by the reduced growth of SCVs, resulting in lower MIC values in 44% of all tests. Nonsynonymous mutations were found in all but one SCV, while only two isolates showed typical auxotrophic responses. While MALDI-TOF, PCR and Pastorex Staph-Plus correctly identified all S. aureus SCVs, API-Staph and VITEK-2 yielded identification rates of only 40% and 10%, respectively.
CONCLUSIONS
Overall, the present study has shown that commercially available PDFs induce S. aureus SCVs in vitro, which are difficult to identify and test for antimicrobial susceptibility and can potentially lead to recurrent or persistent infections. Thus, they represent a potentially underappreciated challenge not only for microbiologists, but also for clinicians.
Topics: Peritoneal Dialysis; Microbial Sensitivity Tests; Humans; Staphylococcus aureus; Staphylococcal Infections; Peritonitis; Anti-Bacterial Agents; Biofilms; Whole Genome Sequencing; Dialysis Solutions
PubMed: 38458357
DOI: 10.1016/j.ijantimicag.2024.107135 -
Journal of Hospice and Palliative Care Mar 2024This article underscores the importance of integrating comprehensive palliative care for noncancer patients who are undergoing hemodialysis, with an emphasis on the... (Review)
Review
This article underscores the importance of integrating comprehensive palliative care for noncancer patients who are undergoing hemodialysis, with an emphasis on the aging populations in Asian nations such as Taiwan, Japan, the Republic of Korea, and China. As the global demographic landscape shifts towards an aging society and healthcare continues to advance, a marked increase has been observed in patients undergoing hemodialysis who require palliative care. This necessitates an immediate paradigm shift to incorporate this care, addressing the intricate physical, psychosocial, and spiritual challenges faced by these individuals and their families. Numerous challenges impede the provision of effective palliative care, including difficulties in prognosis, delayed referrals, cultural misconceptions, lack of clinician confidence, and insufficient collaboration among healthcare professionals. The article proposes potential solutions, such as targeted training for clinicians, the use of telemedicine to facilitate shared decision-making, and the introduction of time-limited trials for dialysis to overcome these obstacles. The integration of palliative care into routine renal treatment and the promotion of transparent communication among healthcare professionals represent key strategies to enhance the quality of life and end-of-life care for people on hemodialysis. By embracing innovative strategies and fostering collaboration, healthcare providers can deliver more patient-centered, holistic care that meets the complex needs of seriously ill patients within an aging population undergoing hemodialysis.
PubMed: 38449832
DOI: 10.14475/jhpc.2024.27.1.1 -
Heliyon Mar 2024Monitoring phosphorus fertilization is crucial for controlling the concentration of biologically available soil P. Over the years, several methodologies have been used,...
Monitoring phosphorus fertilization is crucial for controlling the concentration of biologically available soil P. Over the years, several methodologies have been used, including successive cropping in a greenhouse or field, as well as extractions employing P sink procedures. The latter procedures are ideal laboratory experiments to show the soil's ability to supply P and to explore the P-residual release kinetics. Following these methodologies, long-term P desorption studies have been developed using dialysis membrane tubes filled with nanomaterial solutions. In this study, a magnetic nanocomposite (FeO/AlO/MnO) was synthesized and characterized utilizing cutting-edge instruments such as XRD, FTIR, FAAS, BET, SEM, and EDX. The resulting material had a crystalline size and surface area of 22.75 nm and 203.69 m/g, respectively, and was employed for long-term P-desorption and kinetics experiments while filled in dialysis membrane tubes. The P-desorption experiment was conducted on four separate acidic soil samples that were cultured for 122 days with four different P concentrations. The findings demonstrated a direct relationship between P-desorbed and P-treatment, as well as with desorption time. The minimum desorption was obtained from the control of Boji Dirmaji soil P0 (1.16-9.36) and the highest desorption from Nedjo soil with P3 (5.23-30.35 mg/kg) treatment over 1-28 days. The rate of P release from soil to solution or diffusion through the membrane was determined by pseudo-first-order kinetics with a rate constant (0.021-0.028 hr). This method has the potential to measure fixed-P availability by mimicking it as a plant would, with high P-desorption efficiency and quick P-release capacity.
PubMed: 38449605
DOI: 10.1016/j.heliyon.2024.e27235 -
International Urology and Nephrology Jul 2024The present systematic review and meta-analysis aimed at evaluating the effect of low dialysate sodium concentration on interdialytic weight gain (IDWG) in chronic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The present systematic review and meta-analysis aimed at evaluating the effect of low dialysate sodium concentration on interdialytic weight gain (IDWG) in chronic hemodialysis patients.
METHODS
Studies were eligible for inclusion if they were English language papers published in a peer-reviewed journal and met the following inclusion criteria: (1) studies in adult patients (over 18 years of age), (2) included patients on chronic hemodialysis since at least 6 months; (3) compared standard (138-140 mmol/l) or high (> 140 mmol/l) dialysate sodium concentration with low (< 138 mmol/l) dialysate sodium concentration; (4) Included one outcome of interest: interdialytic weight gain. Medline, PubMed, Web of Science, and the Cochrane Library were searched for the quality of reporting for each study was performed using the Quality Assessment Tool of Controlled Intervention Studies of the National Institutes of Health. The quality of reporting of each cross-over study was performed using the Revised Cochrane Risk of Bias (RoB) tool for cross-over trials as proposed by Ding et al. RESULTS: Nineteen studies (710 patients) were included in the analysis: 15 were cross-over and 4 parallel randomized controlled studies. In cross-over studies, pooled analysis revealed that dialysate sodium concentration reduced IDWG with a pooled MD of - 0.40 kg (95% CI - 0.50 to - 0.30; p < 0.001). The systematic review of four parallel, randomized, studies revealed that the use of a low dialysate sodium concentration was associated with a significant reduction of the IDWG in two studies, sustained and almost significant (p = 0.05) reduction in one study, and not significant reduction in one study.
CONCLUSION
Low dialysate sodium concentration reduces the IDWG in prevalent patients on chronic hemodialysis.
Topics: Humans; Renal Dialysis; Sodium; Weight Gain; Dialysis Solutions; Kidney Failure, Chronic; Hemodialysis Solutions
PubMed: 38446246
DOI: 10.1007/s11255-024-03972-3 -
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 -
Canadian Journal of Kidney Health and... 2024A key barrier to becoming a living kidney donor is an inefficient evaluation process, requiring more than 30 tests (eg, laboratory and diagnostic tests), questionnaires,...
PURPOSE OF PROGRAM
A key barrier to becoming a living kidney donor is an inefficient evaluation process, requiring more than 30 tests (eg, laboratory and diagnostic tests), questionnaires, and specialist consultations. Donor candidates make several trips to hospitals and clinics, and often spend months waiting for appointments and test results. The median evaluation time for a donor candidate in Ontario, Canada, is nearly 1 year. Longer wait times are associated with poorer outcomes for the kidney transplant recipient and higher health care costs. A shorter, more efficient donor evaluation process may help more patients with kidney failure receive a transplant, including a pre-emptive kidney transplant (ie, avoiding the need for dialysis). In this report, we describe the development of a quality improvement intervention to improve the efficiency, effectiveness, and patient-centeredness of the donor candidate evaluation process. We developed a One-Day Living Kidney Donor Assessment Clinic, a condensed clinic where interested donor candidates complete all testing and consultations within 1 day.
SOURCES OF INFORMATION
The One-Day Living Kidney Donor Assessment Clinic was developed after performing a comprehensive review of the literature, receiving feedback from patients who have successfully donated, and meetings with transplant program leadership from St. Joseph's Healthcare Hamilton. A multistakeholder team was formed that included health care staff from nephrology, transplant surgery, radiology, cardiology, social work, nuclear medicine, and patients with the prior lived experience of kidney donation. In the planning stages, the team met regularly to determine the objectives of the clinic, criteria for participation, clinic schedule, patient flow, and clinic metrics.
METHODS
Donor candidates entered the One-Day Clinic if they completed initial laboratory testing and agreed to an expedited process. If additional testing was required, it was completed on a different day. Donor candidates were reviewed by the nephrologist, transplant surgeon, and donor coordinator approximately 2 weeks after the clinic for final approval. The team continues to meet regularly to review donor feedback, discuss challenges, and brainstorm solutions.
KEY FINDINGS
The One-Day Clinic was implemented in March 2019, and has now been running for 4 years, making iterative improvements through continuous patient and provider feedback. To date, we have evaluated more than 150 donor candidates in this clinic. Feedback from donors has been uniformly positive (98% of donors stated they were very satisfied with the clinic), with most noting that the clinic was efficient and minimally impacted work and family obligations. Hospital leadership, including the health care professionals from each participating department, continue to show support and collaborate to create a seamless experience for donor candidates attending the One-Day Clinic.
LIMITATIONS
Clinic spots are limited, meaning some interested donor candidates may not be able to enter a One-Day Clinic the same month they come forward.
IMPLICATIONS
This patient-centered quality improvement intervention is designed to improve the efficiency and experience of the living kidney donor evaluation, result in better outcomes for kidney transplant recipients, and potentially increase living donation. Our next step is to conduct a formal evaluation of the clinic, measuring qualitative feedback from health care professionals working in the clinic and donor candidates attending the clinic, and measuring key process and outcome measures in donor candidates who completed the one-day assessment compared with those who underwent the usual care assessment. This program evaluation will provide reliable, regionally relevant evidence that will inform transplant centers across the country as they consider incorporating a similar one-day assessment model.
PubMed: 38410167
DOI: 10.1177/20543581241231462 -
Clinical and Experimental Nephrology Jul 2024Volume overload is common and associated with high mortality in patients on peritoneal dialysis (PD). Traditional strategies including diuretics, water/salt restriction,...
Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED).
BACKGROUND
Volume overload is common and associated with high mortality in patients on peritoneal dialysis (PD). Traditional strategies including diuretics, water/salt restriction, and icodextrin-based solutions cannot always fully correct this condition, necessitating novel alternative strategies. Recent studies confirmed the expression of sodium-glucose cotransporter 2 (SGLT2) in the human peritoneum. Experimental data suggest that SGLT2 inhibitors decrease glucose absorption from the PD solution, thereby increasing the ultrafiltration volume. This trial aims to assess whether SGLT2 inhibitors increase the ultrafiltration volume in patients on PD.
METHODS
The EMPOWERED trial (trial registration: jRCTs051230081) is a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Patients with clinically diagnosed chronic heart failure are eligible regardless of the presence of diabetes if they use at least 3 L/day glucose-based PD solutions. Participants will be randomly assigned (1:1) to receive empagliflozin 10 mg once daily and then placebo or vice versa. Each treatment period will last 8 weeks with a 4-week washout period. This study will recruit at least 36 randomized participants. The primary endpoint is the change in the daily ultrafiltration volume from baseline to week 8 in each intervention period. The key secondary endpoints include changes in the biomarkers of drained PD solutions, renal residual function, and anemia-related parameters.
CONCLUSIONS
This trial aims to assess the benefit of SGLT2 inhibitors in fluid management with a novel mechanism of action in patients on PD. It will also provide insights into the effects of SGLT2 inhibitors on solute transport across the peritoneal membrane and residual renal function.
Topics: Humans; Peritoneal Dialysis; Sodium-Glucose Transporter 2 Inhibitors; Cross-Over Studies; Double-Blind Method; Glucosides; Ultrafiltration; Benzhydryl Compounds; Randomized Controlled Trials as Topic; Heart Failure; Multicenter Studies as Topic; Dialysis Solutions; Treatment Outcome
PubMed: 38402502
DOI: 10.1007/s10157-024-02467-w -
Nature Medicine Feb 2024Individuals with kidney failure undergoing hemodialysis are at elevated risk for thromboembolic events. Factor (F) XI, which is in the intrinsic pathway of coagulation,... (Randomized Controlled Trial)
Randomized Controlled Trial
Individuals with kidney failure undergoing hemodialysis are at elevated risk for thromboembolic events. Factor (F) XI, which is in the intrinsic pathway of coagulation, is emerging as an attractive target for new anticoagulants that may be safer than existing agents. Osocimab-an inhibitory FXIa antibody-is a potential treatment option for such patients. We conducted a phase 2b, double-blind, placebo-controlled trial, in which 704 participants (448 male, 256 female) with kidney failure undergoing hemodialysis were randomized to receive lower- or higher-dose osocimab or placebo. In total, 686 participants (436 male, 250 female) received treatment for ≤18 months (planned minimal treatment period of 6 months). The co-primary outcomes were clinically relevant bleeding (a composite of major and clinically relevant nonmajor bleeding) and a composite of the incidence of moderate, severe or serious adverse events. Clinically relevant bleeding occurred in 16/232 (6.9%) and 11/224 (4.9%) participants who received lower- and higher-dose osocimab, respectively, and in 18/230 participants (7.8%) who received a placebo. For the composite adverse event endpoint, incidences were 51%, 47% and 43% in the lower-dose osocimab, higher-dose osocimab and placebo groups, respectively. These results suggest that osocimab is associated with a low risk of bleeding and is generally well tolerated in this population; findings that require confirmation in larger trials. ClinicalTrials.gov identifier, NCT04523220 .
Topics: Humans; Male; Female; Blood Coagulation; Anticoagulants; Hemorrhage; Renal Insufficiency; Renal Dialysis; Double-Blind Method; Antibodies, Monoclonal, Humanized
PubMed: 38365952
DOI: 10.1038/s41591-023-02794-7 -
BMC Nephrology Feb 2024Autosomal dominant polycystic kidney disease (ADPKD) is the leading inheritable cause of end-stage renal disease (ESRD). Mortality data specific to patients with ADPKD...
BACKGROUND
Autosomal dominant polycystic kidney disease (ADPKD) is the leading inheritable cause of end-stage renal disease (ESRD). Mortality data specific to patients with ADPKD is currently lacking; thus, the aim of this study was to estimate mortality in patients with ADPKD.
METHODS
We analyzed data from the United States Renal Data System (USRDS) for patients with ADPKD available during the study period of 01/01/2014-12/31/2016, which included a cohort of patients with non-ESRD chronic kidney disease (CKD) and a cohort of patients with ESRD. Mortality rates with 95% confidence intervals (CIs) were calculated overall and by age group, sex, and race for the full dataset and for a subset of patients aged ≥ 65 years. Adjusted mortality hazard ratios (HRs) were calculated using Cox regression modeling by age group, sex, race, and CKD stage (i.e., non-ESRD CKD stages 1-5) or ESRD treatment (i.e., dialysis and transplant).
RESULTS
A total of 1,936 patients with ADPKD and non-ESRD CKD and 37,461 patients with ADPKD and ESRD were included in the analysis. Age-adjusted mortality was 18.4 deaths per 1,000 patient-years in the non-ESRD CKD cohort and 37.4 deaths per 1,000 patient-years in the ESRD cohort. As expected, among the non-ESRD CKD cohort, patients in CKD stages 4 and 5 had a higher risk of death than patients in stage 3 (HR = 1.59 for stage 4 and HR = 2.71 for stage 5). Among the ESRD cohort, patients receiving dialysis were more likely to experience death than patients who received transplant (HR = 2.36). Age-adjusted mortality among patients aged ≥ 65 years in the non-ESRD CKD cohort was highest for Black patients (82.7 deaths per 1,000 patient-years), whereas age-adjusted mortality among patients aged ≥ 65 years in the ESRD cohort was highest for White patients (136.1 deaths per 1,000 patient-years).
CONCLUSIONS
Mortality rates specific to patients aged ≥ 65 years suggest racial differences in mortality among these patients in both non-ESRD CKD and ESRD cohorts. These data fill an important knowledge gap in mortality estimates for patients with ADPKD in the United States.
Topics: Humans; United States; Polycystic Kidney, Autosomal Dominant; Renal Dialysis; Kidney Failure, Chronic; Kidney; Renal Insufficiency, Chronic; Disease Progression
PubMed: 38365638
DOI: 10.1186/s12882-024-03484-3