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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

The Incidence of Contrast Induced Nephropathy in Trauma Patients.

Cordeiro, Samuel 04 1900 (has links)
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / PURPOSE: Contrast-induced nephropathy (CIN) has been recognized as a potential adverse outcome in patients receiving contrast dye for CT evaluation for over 50 years. Despite the time and resources dedicated to better identifying at-risk patients and implementing preventative measures, contrast induced nephropathy continues to be a significant cause of hospital acquired renal insufficiency. This study was aimed to evaluate the incidence and factors associated with contrast-induced nephropathy in the trauma patient population. MATERIALS AND METHODS: A retrospective institutional review of 563 patients admitted to the trauma service at St. Joseph’s Hospital and Medical Center were evaluated. Data were recorded for each patient including demographics, injury severity score (ISS), clinical prediction score (CPS), laboratory values on admission, 24, 48 and 72 hours including hematocrit, blood urea nitrogen, creatinine and eGFR, IV fluid volume given, contrast volume given, systolic blood pressure (SBP), urine output (UOP), intensive care unit length of stay (ICU LoS) and total hospital length of stay (tot LoS). Contrast induced nephropathy was considered to be present if the patient received contrast material for CT scan and 24-48 hour creatinine increased by an absolute value of 0.5mg/dl or if there was a 25% increase in 24-48 hour creatinine when compared to admission creatinine. Contrast volumes given to each patient before CT scan were determined by the Department of Radiology. RESULTS: As seen in table 1 results of univariate analysis demonstrate the following significant data: CIN vs age (p 0.004), CIN vs ISS (p <0.000), CIN vs CPS (p <0.000), CIN vs ICU length of stay (p 0.006), CIN vs total length of stay (p 0.002), CIN vs SBP (p <0.000), CIN vs IVF volume given in the 2nd 24 hours (p <0.000) and CIN vs IVF volume given in the first 48hrs (p <0.000). Data from multivariate analysis demonstrate the following significant data: CIN vs CPS (p <0.000, CI 1.92E-2 – 3.93E-2), CIN vs SBP (p 0.003 CI 8.61E-4 – 4.41E-3) and CIN vs IVF vol 2nd 24 hours (p 0.001, CI 1.47E-5 – 5.91E-5). The mean data for patients who did and did not develop CIN respectively were CPS: 9.09 and 3.12, SBP 84mmHg and 99mmHg, and IVF vol 2nd 24 hrs 2504ml and 5931ml CONCLUSION: Contrast induced nephropathy continues to be a significant problem in many hospital populations including trauma patients. Certain patient groups including those with higher CPS, hypotension or receiving decreased IV fluids may benefit from aggressive mindfulness of the risk of contrast induced kidney injury and continued investigation is needed to better identify trauma patients at increased risk.
2

The role of hypoxia for the development of diabetic nephropathy : Temporal relationship and involvement of endothelin receptor signaling

Franzén, Stephanie January 2016 (has links)
Diabetic nephropathy is one of the most common causes of end stage renal disease and develops in approximately one third of all diabetes patients. Disease progression is characterized by deteriorating glomerular filtration rate and escalating urinary albumin/protein excretion; both are used as clinical markers for disease progression. Recently, it has been proposed that intrarenal hypoxia is a unifying mechanism for chronic kidney disease, including diabetic nephropathy. Several mechanistic pathways have been linked to the development of intrarenal hypoxia and diabetic nephropathy including increased angiotensin II signaling, oxidative stress and hyperglycemia per se. Furthermore, pathological endothelin signaling has recently immerged as a possible contributing factor for chronic kidney disease and diabetic nephropathy. The overall aims of this thesis were therefore to determine the temporal relationship between development of intrarenal hypoxia and kidney disease as well as elucidate the potential link between endothelin signaling, intrarenal hypoxia and kidney disease in experimental insulinopenic diabetes. It is well established that different mouse strains have different susceptibility for kidney and cardiovascular disease. The first step was therefore to compare four commonly used mouse strains with regards to development of kidney disease after onset of insulinopenic diabetes. From the results of this study, we concluded that the NMRI mouse strain has a disease progression closest to the human disease and this strain was chosen in the subsequent studies in mice. The next step was to adapt and optimize a suitable method for repetitive measurements of intrarenal oxygen tension during the course of disease development. Electron paramagnetic resonance (EPR) oximetry had previously been used in tumor biology and was now adapted and optimized for measurements of kidney oxygenation in our diabetic mouse model. EPR oximetry in normoglycemic control mice recorded cortical oxygen tension values similar to previous reports using invasive techniques. Surprisingly, intrarenal hypoxia developed already within the first 72h after induction of hyperglycemia and persisted throughout the two-week study period. Importantly, this was well before albuminuria developed. The final part of this thesis was to investigate the role of endothelin signaling for the intrarenal hypoxia in a diabetic rat model. Endothelin 1 signals via two distinctly different receptor-mediated pathways. In normal physiology, endothelin 1 binding to endothelin receptor type A (ETA) induces vasoconstriction, which can be blocked by the specific ETA antagonist BQ123, whereas endothelin 1 binding to endothelin receptor type B (ETB) induces nitric oxide-dependent vasodilation. ETB receptors can be selectively activated by Sarafotoxin 6c. The results from blocking ETA and activating ETB receptors demonstrated that endothelin 1 signaling via ETA receptors contributes to intrarenal hypoxia in the rat diabetic kidney, and that ETB stimulation significantly reduces the diabetes-induced intrarenal hypoxia. The beneficial effects on kidney oxygen availability in diabetes by ETA blockade or ETB stimulation were mainly linked to hemodynamic improvements rather than direct effects on kidney oxygen consumption or oxidative stress status. In conclusion, by applying EPR oximetry in a mouse model of insulinopenic diabetes mimicking the human disease, we demonstrated intrarenal hypoxia already within the first couple of days after the onset of hyperglycemia, which is well before detectable signs of kidney disease development. Furthermore, blockade of ETA or activation of ETB receptors significantly reduced intrarenal hypoxia in the diabetic kidney. These results demonstrate involvement of ETA receptor signaling in diabetes-induced intrarenal hypoxia and ETA blockade or ETB activation might provide new therapeutical targets to reduce kidney hypoxia and disease progression in diabetes.
3

Sub-clinical manifestations of microvascular disease in childhood onset insulin dependent diabetes mellitus (IDDM) : a follow up study on the 'Avon Childhood Diabetes Cohort'

Hamilton-Shield, J. P. January 1997 (has links)
No description available.
4

The investigation of early physiological changes in renal function in childhood diabetes

Campbell, Fiona M. January 1998 (has links)
No description available.
5

The effects of angiotensin-converting enzyme inhibition on glomerular morphology in acute experimental diabetes

Mackin, Paul January 1998 (has links)
No description available.
6

A profile of patients with minimal change nephropathy between 2001 and 2010 at the Witwatersrand Academic Complex

Mkandawire, Mercy Juliet 07 September 2015 (has links)
A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Medicine in Internal Medicine Johannesburg, 2015 / Available literature on primary minimal change nephropathy (MCN) predominantly reflects Western and Asian populations, with little data describing the disease in black patients. We therefore studied the demographic and clinical profile of patients presenting with MCN at the Witwatersrand Academic Complex. The results of 1,618 renal biopsies performed at our centre between 2001 and 2010 were reviewed; 47 patients with MCN were identified (prevalence of 2.9%).The patients were predominantly of black race (83%), the male : female ratio was 1.04:1 and the mean age was 31.8± 12.1 years. The majority of patients (90%) fitted the criteria for the nephrotic syndrome. 18% of patients had elevated serum creatinine levels and 6.4% had associated hypertension. An association was found between gender and age; with a predominance of males amongst younger patients (less than 30 years) compared to a predominance of females amongst the older patients. Records of treatment and outcomes were available for 28 patients, all of whom received initial corticosteroid therapy (average dose of prednisone 0.8mg /kg/day). The average duration of therapy was 29 weeks. 57.1% achieved remission with no further relapse. No clinical or demographic parameters were identified that predicted response to corticosteroid therapy. 39.2% of patients had probable steroid dependance/resistance. Of these patients, 58.3% had a single relapse and 41.7% had double relapses. The mean time to relapse was 27.8±19.4 months with 83% of patients relapsing within 48 months; the mean time to relapse was longer in males (39.3±17.5 months) as compared to females who relapsed in 18±16.9 months, which was significant at the 10% level (P = 0.09). MCN is rare amongst Black Africans but should be considered in the differential diagnosis of nephrotic syndrome. The disorder in these patients may be less responsive to corticosteroids and a longer course of therapy may be required to induce remission. Males may be more likely to remain in remission for a longer time period.
7

Characterization of novel antigens in membranous nephropathy

Coles, Paige 17 June 2016 (has links)
INTRODUCTION: Membranous nephropathy is an autoimmune disease that targets glomeruli of the kidney. Previous discoveries in membranous nephropathy include the discovery of megalin as an antigen in the proximal tubular brush border fraction (Fx1A) and glomeruli of Heymann nephritis rats, identification of neutral endopeptidase in alloimmune neonatal nephropathy, and discovery of PLA2R and THSD7A as causal antigens in approximately 80-85% of primary membranous nephropathy cases. It was then recognized that there must be other antigens responsible for the remaining 15-20% of cases. OBJECTIVES: The current study aims to screen membranous nephropathy patient serum samples via Western blotting for reactivity with potential antigens in protein extracts of normal human glomeruli, purify potential membranous nephropathy antigens, identify them with mass spectrometry, and validate these identifications with immunoprecipitation and immunohistochemical analysis. Previously, work had been done to identify one novel, 58 kDa antigen. A second novel antigen had been shown in the proximal tubule brush border. Finally, a third protein, CR1, was shown to contain corresponding antibodies in the antibody preparation used in the rat model of membranous nephropathy, making the antigen a protein of interest in human primary membranous nephropathy. METHODS: Using human glomeruli obtained by detergent extraction, we isolated extracellular domains and identified two novel antigens, called 58-kDa and brush-border, with patient serum. We attempted to further purify the 58-kDa antigen with lectin binding columns and partition phase separation. Upon the identification of a small cohort of cases associated with autoimmune tubulointerstitial nephritis, we set out to determine if these sera recognized a novel antigen. Prior to screening human glomerular extract with these sera, we exposed it to partial proteolysis with trypsin, reducing agent β-mercaptoethanol, and tubular elements to further characterize the antigen before it was pulled down with anti-brush-border antigen+ and control IgG4 and analyzed by mass spectrometry. The third and final antigen we investigated was CR1, which we screened with membranous nephropathy sera and immunoblotted its antibody against different protein preparations. RESULTS: Labeling of the extracellular portions of the 58-kDa and brush-border antigens with biotin was successful. It was determined that the 58-kDa antigen was not glycosylated due to its inability to bind lectin columns. The 58-kDa antigen was present in the hydrophilic layer when separated with tritonX-114 detergent. Partial proteolysis of the brush-border antigen with trypsin yielded bands at 140 kDa, 120 kDa and 95 kDa. The brush-border antigen was destroyed under reducing conditions. Candidate proteins for the brush-border antigen as determined by mass spectrometry include megalin and SVEP1. Membranous nephropathy sera were shown to be negative for anti-CR1+ antibody, and anti-CR1+ antibody was reactive with glomeruli and the TBS supernatant fraction. CONCLUSIONS: This study suggests that the 58-kDa antigen which has antibodies in some human primary membranous nephropathy sera contains extracellular portion(s), is not glycosylated, but is membrane-associated. The data indicate that there is also potential for a membranous nephropathy antigen in the tubular brush border with an immunoreactive element around 95 kDa in size, that is sensitive to reducing conditions. Preliminary mass spectrometry information points toward megalin as the identification of this antigen. CR1 does not appear to be a causal antigen in human primary membranous nephropathy.
8

Studies on Angiotensin Converting Enzyme 2, Angiotensin-(1-7), and p47phox-Dependent NADPH Oxidase and their Roles in Diabetic Nephropathy

Liu, George 17 December 2012 (has links)
Diabetic nephropathy is the leading cause of end-stage renal disease, yet the mechanisms responsible for hyperglycemia-induced kidney injury have not been fully elucidated. Activation of the renin-angiotensin system and NADPH oxidase-dependent generation of reactive oxygen species are important mediators of chronic kidney disease. I first studied the effect of ACE2, an important enzyme in the renin-angiotensin system, in diabetic kidney injury in the Akita mouse and related the effect to angiotensin peptide and NADPH oxidase. I then demonstrated the interaction between Angiotensin II, the main substrate, and angiotensin-(1-7), the main product of ACE2, respectively, on cell signaling in mesangial cells to better understand the in vitro effect of ACE2. Finally I studied the effect of deletion of p47phox, a regulatory subunit of the NADPH oxidase, on initiation and progression of diabetic nephropathy in the Akita mouse and mesangial cell. Administration of human recombinant ACE2 decreased angiotensin II levels, increased angiotensin-(1-7) levels, normalized NADPH oxidase activity in the Akita mice, and ameliorated diabetes-induced kidney injury. In vitro, hrACE2 attenuated both high glucose and ANG II–induced oxidative stress and NADPH oxidase activity in mesangial cells. Ang-(1–7)-induced ERK1/2 phosphorylation in mesangial cells in a mas receptor-cAMP-PKA-dependent manner. This effect of ang-(1-7) on ERK1/2 phosphorylation is not mediated by AT1R, AT2R, epidermal growth factor or NADPH oxidase. Pre-treatment with Ang-(1-7) attenuated Ang II-induced NADPH oxidase activity and ERK1/2 activation also in a cAMP-PKA-dependent manner. Deletion of p47phox not only reduced diabetes-induced kidney injury but also reduced hyperglycemia by increasing pancreatic and circulating insulin concentrations. p47phox-/- mice exhibited improved glucose tolerance but modestly decreased insulin sensitivity. Deletion of p47phox attenuated high glucose-induced activation of NADPH oxidase and pro-fibrotic gene expression in mesangial cells. There was a positive correlation between p47phox and collagen Iα1 mRNA levels in renal biopsy samples from control subjects and subjects with diabetic nephropathy. The data generated in this thesis strongly suggest a protective role of ACE2, via Ang-(1-7), and a deleterious role of p47phox in diabetic nephropathy. Future therapeutic strategies should include enhancing ACE2 activity in the kidney and inhibiting p47phox-dependent activation of NADPH oxidase in both the kidney and the pancreas.
9

Investigation of vasoactive factors in clinical and experimental diabetic renal disease

Harron, Joanne Camille January 1998 (has links)
No description available.
10

Studies on Angiotensin Converting Enzyme 2, Angiotensin-(1-7), and p47phox-Dependent NADPH Oxidase and their Roles in Diabetic Nephropathy

Liu, George 17 December 2012 (has links)
Diabetic nephropathy is the leading cause of end-stage renal disease, yet the mechanisms responsible for hyperglycemia-induced kidney injury have not been fully elucidated. Activation of the renin-angiotensin system and NADPH oxidase-dependent generation of reactive oxygen species are important mediators of chronic kidney disease. I first studied the effect of ACE2, an important enzyme in the renin-angiotensin system, in diabetic kidney injury in the Akita mouse and related the effect to angiotensin peptide and NADPH oxidase. I then demonstrated the interaction between Angiotensin II, the main substrate, and angiotensin-(1-7), the main product of ACE2, respectively, on cell signaling in mesangial cells to better understand the in vitro effect of ACE2. Finally I studied the effect of deletion of p47phox, a regulatory subunit of the NADPH oxidase, on initiation and progression of diabetic nephropathy in the Akita mouse and mesangial cell. Administration of human recombinant ACE2 decreased angiotensin II levels, increased angiotensin-(1-7) levels, normalized NADPH oxidase activity in the Akita mice, and ameliorated diabetes-induced kidney injury. In vitro, hrACE2 attenuated both high glucose and ANG II–induced oxidative stress and NADPH oxidase activity in mesangial cells. Ang-(1–7)-induced ERK1/2 phosphorylation in mesangial cells in a mas receptor-cAMP-PKA-dependent manner. This effect of ang-(1-7) on ERK1/2 phosphorylation is not mediated by AT1R, AT2R, epidermal growth factor or NADPH oxidase. Pre-treatment with Ang-(1-7) attenuated Ang II-induced NADPH oxidase activity and ERK1/2 activation also in a cAMP-PKA-dependent manner. Deletion of p47phox not only reduced diabetes-induced kidney injury but also reduced hyperglycemia by increasing pancreatic and circulating insulin concentrations. p47phox-/- mice exhibited improved glucose tolerance but modestly decreased insulin sensitivity. Deletion of p47phox attenuated high glucose-induced activation of NADPH oxidase and pro-fibrotic gene expression in mesangial cells. There was a positive correlation between p47phox and collagen Iα1 mRNA levels in renal biopsy samples from control subjects and subjects with diabetic nephropathy. The data generated in this thesis strongly suggest a protective role of ACE2, via Ang-(1-7), and a deleterious role of p47phox in diabetic nephropathy. Future therapeutic strategies should include enhancing ACE2 activity in the kidney and inhibiting p47phox-dependent activation of NADPH oxidase in both the kidney and the pancreas.

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