Inhibition of Calcium Release-Activated Calcium Channels to Treat Acute Kidney Injury: Design and Rationale of the KOURAGE Study a Randomized Trial.

Introduction: Patients with severe acute kidney injury (AKI) with associated acute hypoxemic respiratory failure (AHRF) experience poorer outcomes, including higher rates of in-hospital mortality, relative to patients with less severe AKI, or those without associated AHRF. Zegocractin is a calcium release-activated calcium (CRAC) channel inhibitor with potent anti-inflammatory and pulmonary endothelial protective properties. Preclinical and early phase clinical studies suggest that zegocractin may be an effective agent for the treatment of AKI.

Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial.

Background: Calcium release-activated calcium (CRAC) channel inhibitors block proinflammatory cytokine release, preserve endothelial integrity and may effectively treat patients with severe COVID-19 pneumonia.

Methods: CARDEA was a phase 2, randomized, double-blind, placebo-controlled trial evaluating the addition of Auxora, a CRAC channel inhibitor, to corticosteroids and standard of care in adults with severe COVID-19 pneumonia. Eligible patients were adults with ≥ 1 symptom consistent with COVID-19 infection, a diagnosis of COVID-19 confirmed by laboratory testing using polymerase chain reaction or other assay, and pneumonia documented by chest imaging.

Auxora for the Treatment of Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome: Clinical Development of a Calcium Release-Activated Calcium Channel Inhibitor.

Objectives: To assess the safety of Auxora in patients with acute pancreatitis (AP), systemic inflammatory response syndrome (SIRS), and hypoxemia, and identify efficacy endpoints to prospectively test in future studies.

Methods: This phase 2, open-label, dose-response study randomized patients with AP, accompanying SIRS, and hypoxemia (n = 21) to receive low-dose or high-dose Auxora plus standard of care (SOC) or SOC alone. All patients received pancreatic contrast-enhanced computed tomography scans at screenings, day 5/discharge, and as clinically required 90 days postrandomization; scans were blinded and centrally read to determine AP severity using computed tomography severity index.

Derivation and validation of the ED-SAS score for very early prediction of mortality and morbidity with acute pancreatitis: a retrospective observational study.

Background: Existing scoring systems to predict mortality in acute pancreatitis may not be directly applicable to the emergency department (ED). The objective of this study was to derive and validate the ED-SAS, a simple scoring score using variables readily available in the ED to predict mortality in patients with acute pancreatitis.

Methods: This retrospective observational study was performed based on patient data collected from electronic health records across 2 independent health systems; 1 was used for the derivation cohort and the other for the validation cohort.

Auxora versus standard of care for the treatment of severe or critical COVID-19 pneumonia: results from a randomized controlled trial.

Background: Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia.

Methods: A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia.

Microglial Calcium Release-Activated Calcium Channel Inhibition Improves Outcome from Experimental Traumatic Brain Injury and Microglia-Induced Neuronal Death.

Store-operated Ca entry (SOCE) mediated by calcium release-activated calcium (CRAC) channels contributes to calcium signaling. The resulting intracellular calcium increases activate calcineurin, which in turn activates immune transcription factor nuclear factor of activated T cells (NFAT). Microglia contain CRAC channels, but little is known whether these channels play a role in acute brain insults.

Distinguishing benign from malignant pelvic mass utilizing an algorithm with HE4, menopausal status, and ultrasound findings.

Objective: The purpose of this study was to develop a risk prediction score for distinguishing benign ovarian mass from malignant tumors using CA-125, human epididymis protein 4 (HE4), ultrasound findings, and menopausal status. The risk prediction score was compared to the risk of malignancy index and risk of ovarian malignancy algorithm (ROMA).

Methods: This was a prospective, multicenter (n=6) study with patients from six Asian countries.

The use of HE4 in the prediction of ovarian cancer in Asian women with a pelvic mass.

Objective: The purpose of this study was to evaluate the performance of human epididymis protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) for distinguishing between benign and malignant pelvis masses in Asian women.

Methods: This was a prospective, multicenter (n=6) study with patients from six Asian countries. Patients had a pelvic mass on imaging and were scheduled to undergo surgery.

Bardoxolone methyl decreases megalin and activates nrf2 in the kidney.

Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression.

Prospective safety study of bardoxolone methyl in patients with type 2 diabetes mellitus, end-stage renal disease and peritoneal dialysis.

Patients on peritoneal dialysis experience inflammation associated with advanced chronic kidney disease and the therapy itself. An important consequence of the inflammation may be acceleration of the rate of decline in residual renal function. The decline in residual renal function has been associated with an increased mortality for patients in this population.

Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study.

Objectives: This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department.

Background: Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI.

Adverse drug reaction driven immunosuppressive drug manipulations: a single-center comparison of enteric-coated mycophenolate sodium vs. mycophenolate mofetil.

Unlabelled: Enteric-coated mycophenolate sodium (MPS) has been developed to help circumvent the upper gastrointestinal side-effects of mycophenolic acid by facilitating drug release in the small intestine. Many questions regarding the side-effect profile of MPS remain. Therefore, the purpose of this study is to review a single-center's experience with mycophenolate mofetil (MMF) and MPS.

Medication prescribing patterns in ambulatory haemodialysis patients: comparisons of USRDS to a large not-for-profit dialysis provider.

Background: End-stage renal disease (ESRD) patients are prescribed numerous medications. The United States Renal Data System (USRDS) reported on medication prescribing patterns in 1998. Since then, several new medications, treatment guidelines and recommendations have been introduced.

Factors associated with medication-related problems in ambulatory hemodialysis patients.

Background: Hemodialysis (HD) patients are at risk for medication-related problems. Patient characteristics associated with the number of medication-related problems in HD patients have not been investigated.

Methods: Patient records were reviewed to identify medical problems, prescribed medications, medication indication(s), and medication-related problems.