Noninvasive Quantification Of Tissue Sodium Concentration In The Kidney Disease Spectrum Using 23na Magnetic Resonance Imaging, Fabio R. Salerno

Electronic Thesis and Dissertation Repository

Chronic kidney disease (CKD), especially when requiring kidney replacement therapy (hemodialysis (HD) and peritoneal dialysis (PD)), is associated with extracellular water expansion with increased total body sodium. Sodium can also be accumulated in tissues independently of extracellular water. Sodium-23 magnetic resonance imaging (²³Na MRI) can quantify the concentration of sodium nuclei in tissues. Applied to the human leg, quantification of tissue sodium concentrations mainly at the skin and muscle level is possible. We hypothesized that increased tissue sodium concentrations exert toxic effects in CKD and dialysis. We aimed to (1) compare tissue sodium concentrations in adults, children and …

Exploration Of The Pathophysiological Mechanisms Underlying Hemodialysis Associated Cardiac Ischemic Injury, Lisa Yun Jeong Hur

Electronic Thesis and Dissertation Repository

Hemodialysis (HD) provides life-saving treatment in individuals with kidney failure. However, HD is associated with poor quality of life and extremely high mortality rates mainly caused by cardiovascular disease due to heart failure and sudden cardiac death. Standard pharmacological treatment developed within the non-kidney disease community are largely ineffective in HD patients because of the difference in pathophysiology of cardiovascular mortality. HD treatment causes hypotension and recurrent ischemic injury to multiple vascular beds including the heart, leading to heart failure. These injuries can be abrogated by improving the patient’s tolerability of the treatment. To apply interventions that may improve hemodynamic …

Technical Adaptations For Cardiac Sodium Mri, Taylor L. Marcus

Electronic Thesis and Dissertation Repository

Cardiac sodium (Na⁺) MRI has the potential to unveil relationships between chronic kidney disease (CKD) and cardiovascular disease (CVD). Unfortunately, this modality requires many technical adaptations before it’s possible to extract and compare image data between individuals. This study investigated whether cardiac electrocardiogram (ECG) gating could improve image quality, and whether a uniform phantom could increase signal uniformity if a surface coil is used to acquire the image. Healthy participants were imaged with a custom-built surface coil and 3.0-T MR system. Cardiac gated images presented with a decreased signal-to-noise ratio (SNR), but intensity correction significantly increased image signal …

Differential Effects Of Kim-1 In Subcutaneous And Orthotopic Renca Models Of Kidney Cancer, Demitra M. Yotis Dy

Electronic Thesis and Dissertation Repository

Renal Cell Carcinoma (RCC) is the most common and fatal type of kidney cancer. Over 30% of patients that are diagnosed with RCC exhibit metastases. Almost 88% of patients with distant metastases succumb to the disease within 5 years of diagnosis. Kidney Injury Molecule-1 (KIM-1) is a cell surface glycoprotein that is not expressed in a healthy kidney but becomes highly expressed on proximal tubular epithelial cells (PTECs) following injury. Data from the Cancer Genome Atlas (TCGA) reveals that >90% of RCC tumours express KIM-1 mRNA and that higher expression levels correlate with increased overall survival rates of patients. The …

Beta Blocker Dialyzability And Effectiveness In Chronic Hemodialysis Patients, Alvin Tieu

Electronic Thesis and Dissertation Repository

Of the minimal information describing drug dialyzability, the majority was obtained prior to modern hemodialysis membranes. This study characterized the dialyzability of the most commonly prescribed beta blockers in patients undergoing high-flux hemodialysis. Eight subjects were recruited to a pharmacokinetic, 4-way crossover trial. Drug concentrations were measured using mass spectrometry and dialyzability determined by the arterial-venous difference and recovery clearance methods. A provincial-wide retrospective cohort study was designed to determine the effect of dialyzability on adverse clinical outcomes. Beta blocker efficacy can be hindered if substantial clearance occurs during dialysis. Our results demonstrate atenolol and metoprolol are extensively cleared during …

Acute Kidney Injury Biomarkers: A Prospective Cohort Study In Urological Patients, Daniel Olvera-Posada

Electronic Thesis and Dissertation Repository

Several recent studies have assessed the use of biomarkers of Acute Kidney Injury (AKI), but the information among patients with stone disease and those with obstructive uropathy is limited. For this reason, we conducted a prospective cohort study to determine the urinary levels of KIM-1, Total and Monomeric NGAL in patients with hydronephrosis secondary to renal stone disease, congenital ureteropelvic junction obstruction or ureteral stricture, and in a group of healthy controls in our health care center. Urinary biomarker concentrations were evaluated before and after surgical treatment. Patients with hydronephrosis showed significantly higher baseline levels of KIM-1 compared to those …

Kidney Injury Molecule-1 Signalling In Ischemic Acute Kidney Injury And Phagocytosis, Ola Z. Ismail

Electronic Thesis and Dissertation Repository

Acute kidney injury (AKI) is defined by the rapid loss of kidney function due to tissue damage. It affects 10-30 % of hospitalized patients and is independently associated with increased morbidity and mortality. Ischemia-reperfusion injury (IRI) is the most common pathoetiological mechanism of AKI, whereby tissue injury is mediated by reactive oxygen species. Ischemic AKI leads to the rapid upregulation of a transmembrane protein, kidney injury molecule-1 (KIM-1) on the apical membrane of proximal tubular epithelial cells (TECs). Previous work from our group and others demonstrated that the extracellular domain of KIM-1 specifically binds to phosphatidylserine on apoptotic cells, thereby …

Cell Death Regulates Injury And Inflammation During Renal Allograft Transplantation, Arthur Lau

Electronic Thesis and Dissertation Repository

Renal transplantation invariably results in tissue injury resulting from ischemia reperfusion injury (IRI), inflammation, drug toxicity, and rejection. Tubular epithelial cells (TEC) comprise the majority of renal parenchyma and are susceptible to cell death and injury during diverse forms of inflammation, which has direct and indirect effects on long term allograft function. Renal TEC have the unique ability to attenuate inflammation and alloimmune injury through the expression of various mediators of cell death and inflammatory molecules. Inhibition of cell death pathways in renal allografts may influence outcomes of alloimmune responses and graft survival. In this body of investigation, alteration of …

Effect Of Fluid Loss Following Hemodialysis On Tibialis Anterior Muscle Strength In People With End-Stage Renal Disease, Anuradha Sawant

Electronic Thesis and Dissertation Repository

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the effect of fluid loss following hemodialysis (HD) on tibialis anterior (TA) strength in participants with end-stage renal disease. Issues concerning measures of skeletal muscle hydration and efficacy of exercise as an anabolic intervention were also addressed.

METHODS: Data from published literature were combined in a meta-analysis to establish efficacy of exercise in participants on HD. Three clinical studies were undertaken using data acquired from healthy volunteers and participants on HD. Hydration of the calf muscles was estimated using bioelectrical impedance spectroscopy (BIS) [extracellular (ECF) and intracellular (ICF) fluid] …