Preferences in treating polyomavirus infection in kidney transplant recipients: A discrete choice experiment with patients, caregivers, and clinicians.

Background: Treatment strategies for BK polyomavirus (BKPyV) infection in kidney transplant recipients are heterogeneous among clinicians. We aimed to identify the treatment preferences of key stakeholders for BKPyV infection and measure the trade-offs between treatment outcomes.

Methods: Adult kidney transplant recipients, caregivers, and clinicians were eligible to participate in a discrete choice experiment between February 2021 and June 2022.

Role of Cholesterol Metabolic Enzyme CYP46A1 and Its Metabolite 24S-Hydroxycholesterol in Ischemic Stroke.

Background: For several decades, it has been recognized that overactivation of the glutamate-gated N-methyl-D-aspartate receptors (NMDARs) and subsequent Ca toxicity play a critical role in ischemic brain injury. 24S-hydroxycholesterol (24S-HC) is a major cholesterol metabolite in the brain, which has been identified as a potent positive allosteric modulator of NMDAR in rat hippocampal neurons. We hypothesize that 24S-HC worsens ischemic brain injury via its potentiation of the NMDAR, and reducing the production of 24S-HC by targeting its synthetic enzyme CYP46A1 provides neuroprotection.

Long-term effect of increasing water intake on repeated self-assessed health-related quality of life (HRQoL) in autosomal dominant polycystic kidney disease.

Background: The aim of this study was to determine the long-term effect of increasing water intake in patients with autosomal dominant polycystic kidney disease (ADPKD) on longitudinal changes in health-related quality of life (HRQoL) in the setting of a clinical trial.

Methods: Self-completed HRQoL (using the KDQoL-SF, v.1.

Cholestane-3β,5α,6β-Triol Inhibits Acid-Sensing Ion Channels and Reduces Acidosis-Mediated Ischemic Brain Injury.

Background: Activation of the acid-sensing ion channels (ASICs) by tissue acidosis, a common feature of brain ischemia, contributes to ischemic brain injury, while blockade of ASICs results in protection. Cholestane-3β,5α,6β-triol (Triol), a major cholesterol metabolite, has been demonstrated as an endogenous neuroprotectant; however, the mechanism underlying its neuroprotective activity remains elusive. In this study, we tested the hypothesis that inhibition of ASICs is a potential mechanism.

Participant Perceptions in a Long-term Clinical Trial of Autosomal Dominant Polycystic Kidney Disease.

Rationale & Objective: The development of new therapies for autosomal dominant polycystic kidney disease requires clinical trials to be conducted efficiently. In this study, the factors affecting the recruitment and retention of participants enrolled in a 3-year randomized controlled trial in autosomal dominant polycystic kidney disease were investigated.

Study Design: Qualitative study.

Patients' Perspectives, Factors, and Patterns of eHealth Use in Kidney Transplant Recipients.

Introduction: eHealth supports the delivery of relevant health information and management of chronic disease. However, little is known about patients' perspectives and the determinants of eHealth use among kidney transplant recipients.

Methods: Kidney transplant recipients aged 18 years and older from 3 transplant units in Australia and the Better Evidence and Translation in Chronic Kidney Disease consumer network completed a survey with free-text responses relating to eHealth uptake.

Inhibition of Acid-Sensing Ion Channels by KB-R7943, a Reverse Na/Ca Exchanger Inhibitor.

KB-R7943, an isothiourea derivative, is widely used as a pharmacological inhibitor of reverse sodium-calcium exchanger (NCX). It has been shown to have neuroprotective and analgesic effects in animal models; however, the detailed molecular mechanisms remain elusive. In the current study, we investigated whether KB-R7943 modulates acid-sensing ion channels (ASICs), a group of proton-gated cation channels implicated in the pathophysiology of various neurological disorders, using the whole-cell patch clamp techniques.

Perspectives of Kidney Transplant Recipients on eHealth: Semistructured Interviews.

Unlabelled: The acceptability and impact of eHealth on patient outcomes may be limited if their concerns and priorities are not addressed. This study aimed to describe the perspectives and experiences of eHealth among kidney transplant recipients.

Methods: Face-to-face semistructured interviews were conducted with 30 adult kidney transplant recipients from New South Wales, Australia (urban and regional), in ambulatory clinics.

Changes in NMDA Receptor Function in Rapid Ischemic Tolerance: A Potential Role for Tri-Heteromeric NMDA Receptors.

In this study, we characterize biophysical changes in NMDA receptor function in response to brief non-injurious ischemic stress (ischemic preconditioning). Electrophysiological studies show NMDA receptor function is reduced following preconditioning in cultured rat cortical neurons. This functional change is not due to changes in the reversal potential of the receptor, but an increase in desensitization.

pH and proton-sensitive receptors in brain ischemia.

Extracellular proton concentration is at 40 nM when pH is 7.4. In disease conditions such as brain ischemia, proton concentration can reach µM range.

Whole Blood Transcriptome Analysis in Children with Sickle Cell Anemia.

Whole transcriptome RNA-sequencing was performed to quantify RNA expression changes in whole blood samples collected from steady state sickle cell anemia (SCA) and control subjects. Pediatric SCA and control subjects were recruited from Atlanta (GA)-based hospital(s) systems and consented for RNA sequencing. RNA sequencing was performed on an Ion Torrent S5 sequencer, using the Ion Total RNA-seq v2 protocol.

Prescribed Water Intake in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Arginine vasopressin promotes kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). Increased water intake reduces arginine vasopressin and urine osmolality and may slow kidney cyst growth. METHODS: In this randomized controlled 3-year clinical trial, we randomly assigned adults with ADPKD who had a height-corrected total kidney volume in Mayo imaging subclass categories 1B to 1E and an estimated glomerular filtration rate of 30 ml/min/1.

Kidney Transplant Cortical Necrosis Observed During Pelvic Radiation Therapy.

A 61 year-old female kidney transplant recipient developed radiologic and biopsy-confirmed cortical necrosis in her transplant with elevated serum creatinine levels during concurrent chemoradiation therapy for anal squamous cell carcinoma. Acute anatomic and pathologic changes within a transplanted kidney during chemoradiation therapy have not been described previously in the literature. Further research is required to ascertain the potential significance and long-term clinical consequences of such findings.

Factors Associated With Advanced Colorectal Neoplasia in Patients With CKD.

Rationale & Objective: The risk of developing colorectal cancer in patients with chronic kidney disease (CKD) is twice that of the general population, but the factors associated with colorectal cancer are poorly understood. The aim of this study was to identify factors associated with advanced colorectal neoplasia in patients with CKD.

Study Design: Prospective cohort study.

Roxadustat for CKD-related Anemia in Non-dialysis Patients.

Introduction: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and improves iron metabolism. We assessed the efficacy and tolerability of roxadustat in patients with chronic kidney disease (CKD)-related anemia not on dialysis.

Methods: ANDES was a global Phase 3 randomized study in which adults with stage 3-5 CKD not on dialysis received roxadustat or placebo.

Health-Related Quality of Life in People Across the Spectrum of CKD.

Introduction: People with chronic kidney disease (CKD) experience reduced quality of life (QoL) because of the high symptom and treatment burden. Limited data exist on the factors associated with overall and domain-specific QoL across all CKD stages.

Methods: Using data from a prospective, multinational study (Australia, New Zealand, Canada, and Spain) in 1696 participants with CKD, we measured overall and domain-specific QoL (pain, self-care, activity, mobility, anxiety/depression) using the EuroQoL, 5 dimension, 3 level.

Clinical Management of Hyperkalemia.

Hyperkalemia is an electrolyte abnormality with potentially life-threatening consequences. Despite various guidelines, no universally accepted consensus exists on best practices for hyperkalemia monitoring, with variations in precise potassium (K) concentration thresholds or for the management of acute or chronic hyperkalemia. Based on the available evidence, this review identifies several critical issues and unmet needs with regard to the management of hyperkalemia.

Assessment of Dietary Sodium Intake Using the Scored Salt Questionnaire in Autosomal Dominant Polycystic Kidney Disease.

The excess intake of dietary sodium is a key modifiable factor for reducing disease progression in autosomal dominant polycystic kidney disease (ADPKD). The aim of this study was to test the hypothesis that the scored salt questionnaire (SSQ; a frequency questionnaire of nine sodium-rich food types) is a valid instrument to identify high dietary salt intake in ADPKD. The performance of the SSQ was evaluated in adults with ADPKD with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.

GPR68 Is a Neuroprotective Proton Receptor in Brain Ischemia.

Background And Purpose: Brain acidosis is prevalent in stroke and other neurological diseases. Acidosis can have paradoxical injurious and protective effects. The purpose of this study is to determine whether a proton receptor exists in neurons to counteract acidosis-induced injury.

Sodium zirconium cyclosilicate increases serum bicarbonate concentrations among patients with hyperkalaemia: exploratory analyses from three randomized, multi-dose, placebo-controlled trials.

Background: Sodium zirconium cyclosilicate (SZC) binds potassium and ammonium in the gastrointestinal tract. In addition to serum potassium reduction, Phase 2 trial data have shown increased serum bicarbonate with SZC, which may be clinically beneficial because maintaining serum bicarbonate ≥22 mmol/L preserves kidney function. This exploratory analysis examined serum bicarbonate and urea, and urine pH data from three SZC randomized, placebo-controlled Phase 3 studies among patients with hyperkalaemia [ZS-003 (n = 753), HARMONIZE (n = 258) and HARMONIZE-Global (n = 267)].

Deletion of a Neuronal Drp1 Activator Protects against Cerebral Ischemia.

Mitochondrial fission catalyzed by dynamin-related protein 1 (Drp1) is necessary for mitochondrial biogenesis and maintenance of healthy mitochondria. However, excessive fission has been associated with multiple neurodegenerative disorders, and we recently reported that mice with smaller mitochondria are sensitized to ischemic stroke injury. Although pharmacological Drp1 inhibition has been put forward as neuroprotective, the specificity and mechanism of the inhibitor used is controversial.

Hippocampal changes in mice lacking an active prohormone convertase 2.

Prohormone convertase 2 (PC2) is essential for the biosynthesis of many neuropeptides, including several of them in hippocampus. In mouse brain, lacking an enzymatically active PC2 (PC2-null) causes accumulation of many neuropeptides in their precursor or intermediate forms. Little is known about how a PC2-null state may affect the function of the hippocampus.