Nephrology Commons^™

Exploring The Effect Of Social Determinants Of Health (Sdoh) Factors On The Time To Kidney Transplant Evaluation Completion For African American End Stage Renal Disease (Esrd) Patients, Kesha Levesque

MUSC Theses and Dissertations

Purpose – The purpose of this dissertation is to investigate the relationship between demographics and Social Determinants of Health (SDOH) variables on diagnostic testing time completion in patients being evaluated for kidney transplant waitlisting.

Aims - Compared to White Americans, African Americans who are eligible to receive a kidney transplant are less likely to complete the required testing in order to be placed on the kidney transplant waiting list which puts African Americans at risk for morbidity and mortality due to prolonged exposure to dialysis. The COVID-19 pandemic was directly associated with a decrease in the number of patients placed …

Mechanisms Of Mitochondrial Dysfunction In Sepsis-Induced Kidney Injury, Joshua Andrew Smith

MUSC Theses and Dissertations

Mitochondrial dysfunction is a well-characterized pathophysiological feature of acute kidney injury (AKI). Our laboratory has previously implicated suppression of mitochondrial biogenesis, the process by which cells generate new and functional mitochondria, as an important contributor to development of mitochondrial dysfunction in multiple experimental models of AKI. However, relatively little is known about the molecular mechanisms responsible for disruption of biogenesis in renal cells. The primary goals of this project were to define signaling pathways mediating acute suppression of renal cortical mitochondrial biogenesis and to characterize changes in glycolytic metabolism that might support both cellular and organ function following sepsis-induced AKI. …

Discovery Of Pharmacological Compounds That Stimulate Renal Mitochondrial Biogenesis And Restore Kidney Function, Sean Robert Jesinkey

MUSC Theses and Dissertations

Dysfunctional mitochondria are a primary pathological consequence of acute kidney injury (AKI). Mitochondrial homeostasis is disrupted up to 144 h after ischemia-reperfusion (I/R) induced-AKI in the renal cortical tissue of mice. Stimulation of mitochondrial biogenesis in renal cells after oxidant injury restores mitochondrial function. The primary goals of this project were to identify novel pharmacological compounds capable of inducing mitochondrial biogenesis in the renal proximal tubule and evaluate if this induction would promote the recovery of mitochondrial and/or renal function after in vivo AKI. The secondary goal was to employ our mitochondrial approach for drug discovery towards identifying a novel …

Serotonergic Stimulation Of Mitochondrial Biogenesis And Their Cheminformatic Models, Richard Edwin Trager Iii

MUSC Theses and Dissertations

Kidney disease and toxicity is increasingly being tied to mitochondrial dysfunction. Cheminformatic modeling and high-throughput phenotypic screens can discover discrete subsets of selective ligands that correlate with mitochondrial biogenesis (MB) and accelerate recovery from acute kidney injury (AKI). Serotonergic (5-HT) stimulation has been shown to cause MB. Subtype specific ligands for 5-HT1F and 5-HTA/C receptors show increased uncoupled oxygen consumption rate (OCR). Our overall goal, in a screening assay, is to discover small molecules that increase MB to be used as drugs in the treatment of diseases that exhibit mitochondrial dysfunction. To achieve this goal we created pharmacophore models of …

Discovery Of Novel Prognostic Biomarkers Of Acute Kidney Injury, Joseph Lee Alge

MUSC Theses and Dissertations

Background: Acute kidney injury is a cause of significant morbidity and mortality in hospitalized patients. Prognostic biomarkers that predict at the time of diagnosis which patients will develop severe AKI and its complications would facilitate timely intervention and could lead to improved outcomes. The urinary proteome is a logical source of candidate biomarkers of kidney injury. Methods: Urine was collected from rodents and human subjects with AKI secondary to diverse etiologies, including cardiac surgery, ischemic/hypoxic injury, and nephrotoxicity. Shotgun proteomics was used to identify candidate biomarkers in four separate discovery phase experiments. These candidates were then verified in a larger …

Endoplasmic Reticulum Calcium-Independent Phospholipase A2 Gamma (Er-Ipla2Γ): Role In Oxidative Stress-Induced Lipid Peroxidation, Ca2+ Release, Phospholipid Homeostasis And Cell Death In The Kidney, Andre Chioke Eaddy

MUSC Theses and Dissertations

Acute kidney injury and chronic kidney disease are becoming more prevalent and have high morbidity and mortality, and despite several therapies targeted towards treating or preventing kidney injury, outcomes have been unchanged for many years. Calcium­independent phospholipase A2y (iPLA2γ) is one of seven Ca2+-independent PLA2 enzymes and represents a potential therapeutic target in kidney disease because of its unique subcellular localization and its potential as the putative membrane remodeling/repair enzyme. Studies in our laboratory suggest iPLA2γ is cytoprotective during oxidant injury by preventing and/or repairing oxidant-induced lipid peroxidation and pointed to ER-iPLA2γ as the major component of membrane repair and …

Promoting Mitochondrial Biogenesis With The Sirti Activator Srt1720 To Improve Mitochondrial And Renal Function After Acute Kidney Injury, Jason Allen Funk

MUSC Theses and Dissertations

Mitochondrial dysfunction is a primary pathological consequence of acute kidney injury (AKI). Induction of mitochondrial biogenesis via the nuclear coactivator of transcription PPARγ-coactivator-1α (PGC-1α), the master regulator of mitochondrial biogenesis, rescues mitochondrial function in renal cells after oxidant injury. The primary goal of this project was to evaluate the recovery of mitochondrial function after in vivo AKI, and to determine the influence of mitochondrial biogenesis during the repair process. Deacetylation of PGC-1α by the class III HDAC SIRT1 produces a more active form of the protein and stimulates mitochondrial biogenesis. The potent SIRT1 activator SRT1720 induced deacetylation of PGC-1α, increased …

Heterogeneous Macromolecular Composition Of Renal Basement Membranes In Health, Diabetes And Glomerulonephritis, Douglas K. Brees

MUSC Theses and Dissertations

Although basement membranes are ubiquitous structures throughout the body, basement membranes have distinct compositions that are specific to their location. This basement membrane heterogeneity may, in part, reflect functional differences among various basement membranes. We examined basement membrane heterogeneity in normal, healthy mouse kidneys to assess the similarities and differences between glomerular and tubular basement membrane composition. It was demonstrated that mouse glomerular and tubular basement membrane share similar compositions but differ with respect to specific amounts of some components. In diabetes mellitus and passive Heymann nephritis (PHN), damage to the glomerular barrier occurs and is accompanied by an increase …