Fracture Prediction And Prevention In Individuals With Chronic Kidney Disease, Andrea C.J. Cowan

Electronic Thesis and Dissertation Repository

Patients with chronic kidney disease (CKD) face increased fracture risk yet our understanding and management of this risk remains poor. We conducted three studies using retrospective cohort analysis in Ontario, Canada. We developed a 3-year fracture prediction model for patients receiving dialysis. Secondly, we contrasted fracture rates among patients on SGLT2i or DPP4i medications, stratified by kidney function. Lastly, we examined hypocalcemia incidence post-denosumab prescription, stratified by kidney function.

Findings: The fracture risk tool, incorporating demographic and lab data, performed well (AUC 0.72). SGLT2i did not elevate fracture risk vs. DPP4i (HR 0.95 [95% CI 0.79,1.13]). In those prescribed denosumab, …

About Dying And Death: Thanatology's Place In Medical Curriculum, Jill Dombroski

Electronic Thesis and Dissertation Repository

This study explored how healthcare providers engage in advance care planning and end-of-life care conversations. The research explored what shapes their understanding and the extent to which concepts from thanatology they intuitively bring in, explicitly bring in, and maybe fail to recognize. To achieve this, constructivist grounded theory (CGT) methodology guided the design, data collection, analysis, and interpretation of the findings, which allowed for iteration across interviews and analysis with existing theories and data in the literature. The CGT design encouraged further engagement with the literature in an ongoing iterative fashion as well as with the analysis of the data. …

Fluoroscopic Guided Peritoneal Dialysis Catheter Placement: An Analysis Of Pelvic Catheter Positioning And Early Catheter Flow Dysfunction, David Clark

Electronic Thesis and Dissertation Repository

Fluoroscopic peritoneal dialysis catheter (FPDC) positioning has not been thoroughly evaluated. Using a retrospective cohort of adult patients who underwent FPDC insertion in London, Ontario (Feb 1, 2010 - Aug 1, 2017); we retrieved procedural radiographs measuring the level of intraabdominal radiocontrast to pubic symphysis (IRPS), and catheter tip to pubic symphysis (CTPS). The median (Q1-Q3) distance (millimeters) of IRPS was larger in females [35(25-44)] than males [28(19-37); P=0.001]; but this distance was not associated with variables: Age (years), BMI (Kg/m²), Race, PKD, abdominopelvic surgeries, in correlation/regression analyses. CTPS distance increased with BMI [(β; 95% Confidence Interval …

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 …

21°C Is The Emerging Ideal Temperature For Kidney Preservation In The Presence Of Hydrogen Sulfide, Smriti Juriasingani

Electronic Thesis and Dissertation Repository

Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. However, the shortage of transplantable kidneys has led to ever-increasing waiting lists. As a result, kidneys obtained via donation after cardiac death (DCD) are being used more frequently for transplantation. However, they exhibit poorer outcomes due to ischemia-reperfusion injury (IRI) and cold preservation methods, such as static cold storage (SCS). Supplementing cold preservation solutions with hydrogen sulfide donors, such as AP39, has been shown to improve renal IRI and graft outcomes, but the injury associated with cold preservation remains. This thesis evaluates the effect of subnormothermic kidney …

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 …

Characteristics And Outcomes Of Patients Discharged Home From An Emergency Department With Acute Kidney Injury: A Population-Based Cohort Study, Rey Acedillo

Electronic Thesis and Dissertation Repository

We designed a population-based cohort study to describe the characteristics and outcomes of 6346 adults discharged home from an emergency department (ED) with acute kidney injury (AKI). Within 30 days of discharge, 149 (2.3%) patients died (stage 1: 2.1%, stage 2: 5.2%, and stage 3 AKI: 15.9%). We also compared 30-day mortality to patients hospitalized with AKI and patients discharged home with no AKI in two separate propensity score-matched analyses. An ED discharge versus hospitalization was associated with lower 30-day mortality (3.0% vs. 11.9%, relative risk (RR): 0.25, 95% confidence interval (CI): 0.21-0.30). An ED discharge home with AKI versus …

Measuring The Efficiency Of The Living Kidney Donor Candidate Evaluation Process, Steven Habbous

Electronic Thesis and Dissertation Repository

Background: Living kidney donation is the ideal treatment for many patients with kidney failure. However, the living donor evaluation process has been criticized by patients and healthcare providers as inefficient. In the present research, we evaluated the inefficiency of the living donor evaluation process.

Methods: We conducted a scoping review of the literature and obtained data from large administrative datasets (1256 living donors) and medical chart review (849 prospectively recruited living donors across 12 transplant centres plus retrospective analysis of 1065 living donor candidates from a single centre).

Results: The median time to complete the entire evaluation was 9-11 months …

Risk Factors For Bk Virus Infection After Kidney Transplantation, London, Ontario 2016, Seyed M Hosseini-Moghaddam

Electronic Thesis and Dissertation Repository

Our objective was to determine the risk factors for BK virus infection in renal allograft recipients in the first year after transplantation. In this cohort, we included all patients who received renal allograft at London Health Sciences Centre (LHSC) between 2012 and 2014. We continued post-transplantation follow-up for one year. Of 175 patients (37% female) with median age (range) of 53 (14-82) years, 40 (22.9%) developed BK viremia (median interval:100 days, range: 35-264). Recipient age, recipient gender, hemodialysis (HD) vs peritoneal dialysis (PD), Human Leukocyte Antigens A1, B35 and Cw4 increased the risk of post-transplant BKV infection. However, donor gender, …

Incidence, Characteristics, And Outcomes Of Acute Kidney Injury Treated With Dialysis During Pregnancy And The Postpartum Period, Ainslie M. Hildebrand

Electronic Thesis and Dissertation Repository

Pregnancy-related acute kidney injury (AKI) may be associated with significant morbidity and mortality in young and often otherwise healthy women. We conducted a retrospective cohort study of all consecutive pregnancies between 1997 and 2011 in Ontario and describe the incidence, characteristics, and outcomes of AKI treated with dialysis (AKI-D) during pregnancy or within 12 weeks postpartum. Of 1,918,789 pregnancies, 188 were complicated by AKI-D (incidence proportion: 1 per 10,000, 95% confidence interval 0.8 to 1.1). Eight women died (4.3% versus 0.01% in the general population) and seven (3.9%) survivors remained dialysis-dependent four months after delivery. The presence of AKI-D was …

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] …

Patency And Complication Rates Of The Arteriovenous Fistula: A Systematic Review, Ahmed A. Al-Jaishi

Electronic Thesis and Dissertation Repository

Advantages of fistulas, which include long patency and low complication rates, were ascertained over two decades ago and may not apply to the contemporary dialysis population. We conducted a systematic review to summarize the patency and complication rates of fistulas from literature published after 1999. We screened 7,008 citations and 62 articles met our criteria. The risk of primary failure was 27% (95% confidence interval (CI): 23–32%). When primary failures were included, the primary and secondary patency rates were 59% (CI 53–64%) and 66% (CI 58–74%) at one year, respectively. The median rates of infection, ischemic steal syndrome, and thrombosis …

Adverse Drug Events And Renal Function, Matthew A. Weir

Electronic Thesis and Dissertation Repository

The objective of this thesis was to use health administrative data to investigate two important adverse drug reactions (ADRs) related to renal function. The first study examined the risk of hyperkalemia associated with the antibiotic trimethoprim-sulfamethoxazole (TMP-SMX) and its interaction with beta-adrenergic receptor blockers (“beta blockers”). The second study evaluated the effect of impaired kidney function on the risk of hypoglycemia conferred by the anti-diabetic drug glyburide. The simultaneous use of beta adrenergic receptor blockers (β-blockers) and trimethoprim-sulfamethoxazole (TMP-SMX) may confer a high risk of hyperkalemia. We conducted two nested case-control studies to examine the association between hospitalization for hyperkalemia …

Preoperative Angiotensin Converting Enzyme Inhibitor Or Angiotensin Receptor Blocker Use And Acute Dialysis: A Population Based Cohort Study, Mitesh K. Shah

Electronic Thesis and Dissertation Repository

Angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use prior to major surgery is controversial. We performed a population based retrospective cohort study of 237,208 elderly patients (of whom 101,494 (42.8%) were ACEi or ARB users) who underwent major elective surgery from 1995 to 2010 in Ontario, Canada. The primary outcome was acute kidney injury treated with dialysis (AKI-D) within 14 days following surgery (810 (0.34%) patients). The secondary outcome was all-cause mortality within 90 days following surgery (11,089 (4.67%) patients). After adjusting for potential confounders, preoperative ACEi or ARB use was associated with a lower relative risk …

The Characteristics Of Successful Evidence Retrieval By Nephrologists And The Impact Of Pubmed Search Filters, Salimah Shariff

Electronic Thesis and Dissertation Repository

Background: Clinicians frequently search PubMed to guide patient care. This study investigated the factors that impact successful searching and the utility of PubMed search filters.

Methods: A random sample of nephrologists was surveyed between 2008 and 2010; 160 valid responses were received (72% response rate). One group of 60 respondents was presented with the same two clinical questions, while the other 100 were each presented with a unique clinical question. The clinical questions were based on recently published systematic reviews. Respondents provided the search terms they would type into PubMed to address their clinical question(s). All physician-provided searches …