Vascular calcification is a prominent cardiovascular condition found worldwide. This condition is predominantly found in the elderly population, and patients who suffer from chronic kidney disease, due to an imbalance of serum phosphate and calcium levels. For many years, vascular calcification was believed to be a passive pathological process which develops with ageing and/or lifestyle. Little has been documented about the disease until the 20th century, when interest in cardiovascular research grew amongst scientists. Indeed, vascular calcification underpins severe clinical outcomes and cardiovascular diseases have been labelled the global leading cause of death. Calcific aortic valve diseases (CAVD) is a progressive degenerative condition characterised by the development of lipo-calcification around the aortic valve leaflets leading to severe aortic stenosis and aortic regurgitation, which may ultimately lead to heart failure. At present there are no pharmaceutical therapies that can stop its progression and its molecular mechanisms are not fully understood. Recent findings have suggested that vascular smooth muscle cell (VSMC) calcification shares many common features with physiological skeletogenesis via the release of matrix vesicles (MVs), which are specialised structures that initiate mineralisation during bone formation. The ability for MVs to nucleate calcium and phosphate highly depend on their protein composition, as this may vary depending on active cell signalling and the microenvironment. This mechanism involving MV-regulated calcification has yet to be examined in CAVD. In this study, examined whether calcium and/or phosphate regulate VIC-derived MVs to induce calcification in the aortic valve. I used a primary rat valve interstitial cell (VIC) model, coupled with stenotic human valve tissues to characterise and study the mechanisms underpinning CAVD. X-ray fluorescence and diffraction analysis showed the mineral found in calcified human aortic valves to be hydroxyapatite (HA), the main component in bone. Additional imaging studies employing transmission electron microscopy (TEM) revealed particles that were similar in size and morphology to skeletal MVs. To further characterise VIC-derived MVs in vitro, I harvested MVs from rat VICs, and subsequently studied their protein composition using Isobaric tag for relative and absolute quantitation (iTRAQ) mass spectrometry. The data obtained from the proteomics analysis was compared to previous published studies on MV proteins derived from osteoblasts and VSMCs. The results showed the upregulation of numerous calcification regulators in MVs isolated from all 3 cell types, in particular, the Annexin family, which are known calcium binding proteins. Further studies conducted with Annexin 6, an established calcium regulator in arterial calcification, revealed its colocalisation with MV-enriched areas in calcified human aortic valve tissue suggesting it may play an important role in calcium regulation during CAVD.

Submitted by Jorge Silva (jorgelmsilva@ufrrj.br) on 2018-03-15T19:04:01Z No. of bitstreams: 1 2017 - Juliana de Abreu Pereira.pdf: 2216195 bytes, checksum: 788fd1f8f4db4f3012004d0eec09d439 (MD5) / Made available in DSpace on 2018-03-15T19:04:01Z (GMT). No. of bitstreams: 1 2017 - Juliana de Abreu Pereira.pdf: 2216195 bytes, checksum: 788fd1f8f4db4f3012004d0eec09d439 (MD5) Previous issue date: 2017-04-27 / CAPES / Prebiotics, such as lactulosis, may favor the switch on the fermentative pattern of the colonic microbiota from proteolytic to saccharolytic, which allows bigger assimilation of nitrogenous compounds by the microrganisms of the colon. The present study aimed to evaluate, in dogs with CKD, the effect of the continued orally use of lactulosis over the nitrogenous compounds metabolisms?, the iron metabolism and on serum levels of albumin, magnesium, calcium and phosphorus. Twenty-one animals with CKD in IRIS II and III stages, under normal handling and feeding, were clinically and laboratorially evaluated by a 28 days period; divided in three groups according to treatment: T1 ? lactulosis + therapeutic diet, T2 ? lactulosis + standard treatment + therapeutic diet, T3 ? standard treatment + therapeutic diet . For the three groups (T1, T2 and T3), clinical parameters indicated anaemia and body score from regular to bad, according to the disease?s degree, during the hole treatment. The haematological and biochemical?s averages are consistent with common laboratorial findings in nephrophatic patients, with high levels of urea and creatinine; and low leves of haematocrit. For all the evaluated parameters in this study, the averages? variations during the period didn?t show any significant difference between times and treatments, with the exception of the calcemia averages that were greater for T1 group; which may indicate that for this animals? group the monotherapy with lactulosis could have increased the absorption of this mineral in those patients. With regard to iron metabolism, this study?s data revealed that the anaemia found in the dogs throughout the experimental period presented chronicity features, since the groups? means remained within the iron and transferrin references, besides high ferritin averages, without significant differences between groups and moments. The obtained data allowed to conclude that there was no difference between the proposed treatments in relation to clinical state and the biochemical and mineral profiles, such as iron metabolism; which justifies that the action mechanisms of prebiotics in nephrophatic patients should be evaluated with more details. / Prebi?ticos, como a lactulose, podem favorecer a altera??o do padr?o fermentativo da microbiota col?nica de proteol?tico para sacarol?tico; o que possibilita maior assimila??o de compostos nitrogenados pelos microrganismos do c?lon. O presente estudo teve por objetivo avaliar, em c?es com DRC, o efeito da utiliza??o continuada de lactulose por via oral, sobre o metabolismo de compostos nitrogenados; o metabolismo do ferro, e sobre as concentra??es s?ricas de albumina, magn?sio, c?lcio e f?sforo. Vinte e um animais portadores de DRC em est?gios IRIS II e III, com manejo e alimenta??o normais, foram avaliados clinicamente e laboratorialmente por um per?odo de 28 dias; divididos em tr?s grupos conforme o tratamento: T1 ? lactulose + ra??o terap?utica, T2 ? lactulose + tratamento convencional + ra??o terap?utica, T3 ? tratamento convencional + ra??o terap?utica. Para os tr?s grupos (T1, T2 e T3), os par?metros cl?nicos foram indicativos de anemia e escore corporal de regular a ruim, de acordo com o grau da enfermidade, ao longo de todo tratamento. As m?dias dos par?metros hematol?gicos e bioqu?micos s?o condizentes com achados laboratoriais comuns em nefropatas; com elevados valores de ureia e creatinina e valores decrescidos de hemat?crito. Para todos os par?metros as varia??es durante o per?odo n?o apresentaram diferen?a significativa entre os tempos e tratamentos, ? exce??o das m?dias de calcemia que foram maiores para o grupo T1; o que pode indicar que para os animais deste grupo a monoterapia com lactulose pode ter aumentado a absor??o deste mineral. Com rela??o ao metabolismo de ferro, os dados revelaram que a anemia encontrada nos c?es em todo o per?odo experimental apresentou caracter?sticas de cronicidade, uma vez que as m?dias dos grupos permaneceram dentro dos intervalos de refer?ncia para ferro e transferrina; al?m de m?dias elevadas de ferritina, sem diferen?as significativas entre grupos e momentos. Os dados obtidos permitiram concluir que n?o houve diferen?a entre os tratamentos propostos com rela??o ao estado cl?nico e aos perfis bioqu?micos e minerais, bem como ao metabolismo de ferro; o que justifica que os mecanismos de a??o dos prebi?ticos em nefropatas devem ser avaliados com maiores detalhes.

Doença renal crônica é uma afecção comum em cães e gatos, especialmente em gatos senis, e importante causa de morbidade e mortalidade. Além da idade avançada, fatores como alterações congênitas, alimentação inadequada, utilização de drogas nefrotóxicas, intoxicações e doenças infecciosas predispõem às lesões do parênquima renal. Em felinos a descrição histopatológica mais frequente é a nefrite tubulointersticial difusa. Independente da causa do dano ao néfron, a doença renal crônica é uma afecção irreversível e geralmente progressiva. Este estudo teve por objetivo realizar uma análise da contribuição da ultrassonografia utilizando-se o modo B e Doppler colorido e pulsado para o diagnóstico e estagiamento da doença renal crônica em 45 felinos. Sendo 16 do grupo controle, felinos que não portavam manifestações clínicas relacionadas ao sistema urinário, apresentavam concentração sérica de creatinina inferior a 1,6mg/dL; quatro do estágio 1, felinos com taxas de creatinina sérica inferior a 1,6mg/dL com alterações ultrassonográficas; 17 do estágio II, felinos com taxas de creatinina 1,6 a 2,8mg/dL; oito do estágio III / IV, felinos com taxa de creatinina sérica de 2,9 a 5,0mg/dL agrupados aos felinos com taxa de creatinina sérica acima de 5,0mg/dL. Os rins foram avaliados ultrassonograficamente por meio das características: ecogenicidade da cortical, regularidade de contorno e definição corticomedular no modo B; comprimento, largura e altura nos cortes longitudinal, transversal e dorsal no modo B; preenchimento das artérias interlobares, arqueadas e interlobulares por meio do Doppler colorido; e índice de resistividade dos vasos intrarenais por meio do Doppler pulsado. Foi determinada a relação comprimento do rim pelo diâmetro luminal da aorta nos felinos normais e nefropatas. Conclui-se que o aumento da ecogenicidade da cortical demonstrou-se uma característica relevante a ser considerada na avaliação ultrassonográfica da doença renal crônica. O Doppler colorido mostrou-se uma ferramenta importante no diagnóstico da doença renal crônica, especialmente quando as alterações detectadas à avaliação ultrassonográfica pelo modo B não eram expressivas. O índice de resistividade não se apresentou acima do limite da normalidade nos estágios iniciais da doença renal crônica, sugerindo não ser útil como preditor da nefropatia crônica. As alterações na avaliação ultrassonográfica modo B associadas ao aumento do índice de resistividade podem indicar um pior prognóstico da evolução da doença renal crônica. Achados ultrassonográficos como ecogenicidade da cortical aumentada, irregularidade de contorno, indefinição corticomedular, diminuição do preenchimento vascular pelo Doppler colorido e aumento do índice de resistividade são elementos importantes a serem considerados no estabelecimento do diagnostico da doença renal crônica em felinos. / Chronic kidney disease is common in dogs and cats, especially in older cats, and an important cause of morbidity and mortality. Factors like advanced age, congenital alterations, inappropriate nutrition, use of nephrotoxic drugs, intoxications and infectious disease may lead to parenchymal lesions in kidney. The most frequent histopathologic change in cats is diffuse tubulointertitial nephritis. Independent of the cause of the nephron damage, the chronic renal disease is an irreversible and usually progressive affection. This study aim to analyze the contribution of ultrasography in the diagnosis and staging of chronic kidney diseases using B mode, color Doppler and spectral Doppler. Sixteen presenting no manifestation of urinary disease and serum creatinine levels less than 1,6mg/dL served at control group; four cats represented stage I, with serum creatinine levels less than 1,6mg/dL and ultrasonographic changes; 17 cats represented stage II, with serum creatinine levels between 1,6 and 2,8mg/dL; eight cats represented stage III/IV, with serum creatinine levels between 2,9 e 5,0mg/dL, grouped with the felines with serum creatinine levels above 5,0mg/dL. The kidneys underwent an ultrasonographic examination observing: cortical echogenicity, regularity of the contour and corticomedullary definition in the B mode; length, width and height in the longitudinal, transverse and dorsal planes in the B mode; filling of the interlobars, arcuate and interlobulars arteries by the color Doppler; and resistive index of the intrarenal vessels using the pulsed Doppler. The ratio between the length of the kidney and the luminal diameter of the aorta in normal felines and in felines with kidney disease was established. The increase in echogenicity of the cortex showed to be a relevant characteristic to be considered in the ultrasonographic evaluation of chronic kidney disease. The color Doppler showed to be an important tool in the diagnosis of the chronic kidney disease, especially when the alterations in the B mode werent expressive. The resistive index did not present itself above of the normal limits in the initial stages of the chronic kidney disease, suggesting its uselessness as a predictor of the chronic kidney disease. Changes in B mode associated with increase in resistive index may indicate a poor prognostics of the chronic kidney disease. Increase in the echogenicity of the cortical, contour irregularity, corticomedullary indefinition, reduced vascular filling detected by color Doppler and the increase in the resistive index were important elements to be considered in the diagnosis of the chronic kidney disease.

A Insuficiência Renal Crônica (IRC) é uma alteração sistêmica, relativamente comum, onde os principais fatores de risco estão representados pelo diabetes e pela hipertensão. A disfunção acarreta redução ou limitação da capacidade de filtração glomerular dos rins, causando uremia, alterações sistêmicas diversas, especialmente cardiovasculares (hipertensão arterial, aterosclerose, pericardites, cardiomiopatias, arritmias cardíacas e hipertensão pulmonar), anemia, problemas hemostáticos e linfocitopenia. Também podem ser observadas alterações ósseas e bioquímicas, além de distúrbios gastrintestinais e dermatológicos. No âmbito bucal várias alterações tem sido descritas, tanto em tecidos moles quanto em tecidos duros (hálito urêmico, pH salivar mais alcalino; aumento na capacidade-tampão, elevada formação de cálculo dentário, aumento do número de cáries e incidência de doença periodontal), associadas aos distúrbios fisiológicos. Além disso, os pacientes portadores de enfermidades crônicas são frequentemente afetados por maiores níveis de estresse emocional, decorrente da necessidade de tratamento contínuo e limitação de suas atividades sociais, com consequente prejuízo de sua qualidade de vida. Este trabalho teve como objetivo caracterizar as manifestações orais destes pacientes, buscando estabelecer correlações entre o estado de ansiedade e depressão, qualidade de vida, valorização da saúde oral; características biodemográficas e status da insuficiência renal dos indivíduos incluídos no estudo. Nosso plano foi o de examinar pacientes que frequentam instituições especializadas em hemodiálise (duas) e, paralelamente, compor grupo controle, não portador de IRC, tabulando as variáveis propostas na investigação. A metodologia desenvolveu-se com a aplicação de questionários referentes a qualidade de vida (Sf36), indicativo de depressão (Inventário de Beck) e percepção de saúde bucal ( OHIP-14). Os dados foram coletados com o auxílio de ficha clínica específica. Os resultados indicaram níveis maiores de ansiedade e depressão, declínio na qualidade de vida e percepção de saúde bucal. Houve diferença estatisticamente significante no índice PSR quando comparados grupo teste (GT) e controle (GC). Houve maior número de queixas bucais nas mulheres do GC. Em ambos os grupos e gêneros houve relação inversa entre escore de xerostomia e nível de fluxo salivar. Conclui-se que a menor qualidade de vida influencia negativamente o sintoma de depressão que, por sua vez, reduz a percepção de saúde oral. O ciclo se fecha pela influencia negativa do distúrbio metabólico (e as sequelas medicamentosas) sobre a saúde bucal. / Chronic Kidney Disease (CKD) is a relatively common systemic dysfunction which main risk factors are represented by diabetes and hypertension. CKD implies in reduction or limitation of kidneys\' glomerular filtration capacity, causing uremia, various systemic disturbances, particularly cardiovascular (hypertension, atherosclerosis, pericarditis, cardiomyopathies, cardiac arrhythmias and pulmonary hypertension), anemia, lymphopenia and hemostatic problems. Biochemical changes in calcium metabolism can also be observed, as well as gastrointestinal and dermatological disturbances. Oral cavity disturbances may be represented either by soft tissue as hard tissue diseases (uremic breath, more alkaline saliva pH, increase in buffering capacity, high formation of dental calculus, increase in the incidence of tooth decay and periodontal disease). In addition, patients with chronic diseases are often affected by higher levels of emotional stress as a result of the need of continuous treatment that limits their social activities, impairing their quality of life as a consequence. This study aimed to characterize oral and systemic manifestations of these patients in order to establish correlations among anxiety and depression state, quality of life, appreciation of oral health, biodemographic data and the status of renal failure of the individuals included in the study. Our plan was to examine patients attending specialized institutions in hemodialysis and compare this population to a control group, no IRC. The data collected were discussed descriptively and analyzed according to appropriate statistical tests. The methodology was developed with the use of questionnaires regarding quality of life (SF36), indicative of depression (Beck Depression Inventory), and perception of oral health (OHIP-14). Data were collected with the assistance of medical record. The results indicated higher levels of anxiety and depression, impairment of quality of life and perception of oral health. There was a statistical significant difference when compared with the PSR index test (GT) and control group (CG). There was a higher number of oral complaints in women in CG. In both groups and genders there was an inverse relationship between scores of xerostomia and salivary flow rate. We conclude that the lower quality of life negatively influences depression level which, in turn, reduces the perception of oral health. The cycle completes by the negative influence of metabolic (and drug sequels) on oral health quality.

A insuficiência renal crônica (IRC) é uma afecção clínica frequente em gatos domésticos. É caracterizada por inflamação tubulointersticial, vascular, glomerular e fibrose severa. Estudos em modelos de IRC induzida em roedores têm revelado uma redução e estabilização do quadro clínico, evidenciados pela melhora nos parâmetros de função renal e redução da inflamação e da fibrose renal. Neste estudo foi testada a segurança e o efeito do transplante alogênico intra-renal e endovenosa das células-tronco mesenquimais derivadas da membrana amniótica felina (AMSCs) em gatos acometidos pela IRC natural. As AMSCs foram isoladas de âmnio de embriões coletadas em campanhas rotineiras de castração. Dez gatos, machos e fêmeas, foram incluídos neste estudo. Um gato hígido recebeu injeção intra-renal das AMSCs guiada por ultrassom em ambos rins (5x105 células/rim). Nove gatos com IRC natural receberam injeção endovenosa das AMSCs (2x106 células x 2 tratamentos). A avaliação da evolução clínica foi baseada na mensuração dos parâmetros do hemograma, bioquímica, hemogasometria, urinálise e ultrassonografia. Foi efetuada análise de variância (ANOVA) comparar diferenças entre as fases de tratamento seguido de teste de Tukey para comparação das médias entre os grupos. Na injeção intra-renal, não houve variação nos parâmetros clínicos, porém foi necessária a sedação e anestesia geral. Foi registrado elevado estresse de manipulação e ligeira hematúria após o procedimento. Os gatos com IRC que receberam injeção endovenosa das AMSCs, registraram uma variação significativa nos parâmetros de função renal (redução dos níveis de creatinina sérica, redução da proteinúria e aumento da densidade urinária). A arquitetura e morfologia renal não teve variação com o tratamento. Conclui-se que as AMSCs felinas têm um efeito renoprotetor e melhoram a função renal em gatos acometidos pela IRC, estabilizando o quadro clínico e a progressão da doença. A injeção endovenosa das AMSCs constitui uma ferramenta importante para proporcionar boa qualidade de vida aos gatos com IRC / Chronic kidney disease (CKD) is a common clinical condition in domestic cats. It is characterized by tubulointerstitial, vascular, glomerular inflammation and severe fibrosis. Studies in rodent model of induced CKD have been shown a decrease and stabilization of the clinical condition, evidenced by renal function improvement and by inflammation and renal fibrosis reduction. In this study was evaluated the safety and effect of intra-renal and intravenous infusion of allogeneic mesenchymal stem cells derived from feline amniotic membrane (AMSCs) in cats with naturally occurring CKD. The AMSCs were isolated from fetal membranes collected after routine castrations. Ten cats, male and female, were enrolled and included in this study. A healthy cat received intrarenal injection of AMSCs guided by ultrasound in both kidneys (5x105 cells/kidney). Nine cats with naturally CDK received intravenous injection of AMSCs (2x106 cells x 2 treatments). The evaluation of the clinical condition was based on the measurement of complete blood count, blood biochemistry, blood gases, urinalysis and ultrasound. Analysis of variance (ANOVA) was performed to compare differences between the phases of treatment followed by Tukey test to compare means between groups. The clinical parameters of the healthy cat (intrarenal injection) did not change, but sedation and general anesthesia was required. The number of interventions stressed the animal and he developed transient hematuria after AMSCs injection. Cats with CDK, registered a significant improvement of renal function (decrease in serum creatinine and urine protein concentrations and increase in urine specific gravity). The kidney architecture and morphology did not change with the treatment. We conclude that the feline AMSCs have a renoprotective effect and improve renal function in cats with naturally occurring CKD, stabilizing the clinical condition and disease progression. Intravenous injection of AMSCs is an important tool to provide general well-being for cats with CDK

Thesis (M.Sc. (Medical Sciences)) -- University of Limpopo, 2018 / Microalbuminuria (MA) is considered to be a strong and independent risk factor for cardiovascular disease (CVD), chronic kidney disease (CKD) and end-stage renal disease (ESRD). Cross sectional studies have indicated that microalbuminuria is also associated with cardiovascular risk factors such as dyslipidaemia and low grade inflammation. Hence, the aim of this study was to investigate the association of microalbuminuria with serum lipids [Total cholesterol (TC), Triglycerides (TG), High Density Lipoproteins Cholesterol (HDL-C), Low Density Lipoproteins Cholesterol (LDL-C), Lipoprotein a (Lp (a)] and inflammatory markers [C-reactive protein (CRP) and Interleukin-6 (IL-6)] in a rural black population. Methods: This is a cross-sectional study conducted in Dikgale Health and Demographic Surveillance System (HDSS) site and quantitative methods were used. The present study is part of a study titled “Prevention, control and integrated management of chronic diseases in a rural area, South Africa” conducted in the Department of Medical Sciences, University of Limpopo. In the above study blood samples were collected from 816 people aged 15 years and above. For the present study participants with HIV, macroalbuminuria, creatinine ≥170 μmol/land diabetes mellitus were excluded from the 816 people. Six hundred and two (602) participants fitted the inclusion criteria of the present study. Of the 602 participants 255 were men and 377 were women. From these participants, creatinine and albumin concentrations were measured in a morning spot urine sample and the albumin/creatinine ratio (ACR) was calculated. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using OMRON M5-I. Serum lipids (TC, TG, HDL-C, and LDL-C) and glucose were determined using ILAB 300 plus. Lp (a) and hs-CRP were determined using IMMAGE 800 Immunochemistry System. Insulin and IL-6 were determined using ACCESS 2 Chemistry System. Data was analysed using SPSS version 22.0. Statistical tests used included Student T-test, ANCOVA, ANOVA, linear regression and logistic regression. Results: The levels of serum lipids and inflammatory markers in this study were similar in participants with and without microalbuminuria. In a linear regression model TG was the only lipid vi | P a g e parameter found to be associated with microalbuminuria (p = 0.018). Inflammatory markers were not associated with microalbuminuria. In a logistic regression model CRP and HDL-C showed negative association with microalbuminuria in men while in women no association was found. However men with a high CRP and a high TG were found to be more likely to have microalbuminuria (p = 0.007). Conclusion: A linear positive association was observed between microalbuminuria and TG in men and in women. The OR of having microalbuminuria was lower in participants with a high CRP, low HDL-C or in women with a high glucose. Women with a low HDL-C had higher OR of having MA and men with a high CRP and a high TG were found to be more likely to have microalbuminuria.

Despite best available care, uncontrolled chronic kidney disease (CKD) - a complex disease that impacts millions in the United States, will eventually progress to end stage renal disease which is associated with high morbidity and mortality. New evidence suggests management of earlier stages of CKD is effective in delaying disease progression. This project evaluated the impact of a CKD class, led by a nephrology nurse practitioner, on preventing disease progression in advanced CKD patients with diabetes and hypertension. The purpose of the class was to validate the need for the advanced practice nurse (APN) in the care continuum of CKD. CKD education is a quality improvement project based on the chronic illness trajectory nursing model by Corbin and Strauss. Using a case-control method and a simple descriptive statistic to compare the mean values, retrospective data from 52 patients were analyzed. Twelve non-participating patients had a mean 7% increase in serum creatinine levels at the 1-year mark. Forty participating patients saw a mean decrease of 30% serum creatinine. With significant evidence suggesting that disease progression is delayed and renal function is improved in all study markers for patients who participated in a CKD education class led by a nephrology nurse practitioner and who received usual care - an argument can be made for updating the APN role in the continuum of care for those with CKD. The results may contribute to social change by providing improved access to quality care that addresses the socioeconomic devastation of end stage renal disease.

To see if aggressive diuresis in first twenty four hours is associated with a comparable number of total days in the hospital as compared to non-aggressive diuresis. In this retrospective cohort study, we compared the length of hospital stay of consecutive patients admitted in one year based on their diuresis during the first twenty-four hours of hospitalization: aggressive diuresis (group 1) i.e. > 2400mL versus non-aggressive diuresis (group 2) i.e. ≤ 2400mL urine output. Patients were excluded if in cardiogenic shock, had creatinine level above 3 mg/dL on admission, or on dialysis. A total of 194 patients were enrolled (29 in group 1 and 165 in group 2 respectively). The Kaplan-Meier estimate of the median cumulative proportion of patients still hospitalized for the group 1 was 4 days and in group 2 was 5 days (log-rank test; P=0.67). In univariate analysis, Cox PH regression showed unadjusted hazard rate of discharge from hospital was slightly higher in group 1 than group 2 but was statistically non-significant (HR=1.08; P=0.70). In multivariate Cox model analysis, creatinine at the time of admission when greater than 1.6mg/dL (P=0.75), LVEF (P= 0.14), total twenty-four hours dose of intravenous Furosemide given (P=0.98) and interaction between Furosemide dose and Creatinine level (P=0.79) were not significant predictor of hospital discharge. Adjusted hazard rate for discharge from hospital was 12% higher in group 1 than group 2 but still statistically non-significant (HR=1.12; P=0.60). Since the length of hospital stay is similar between two groups, we suggest the goal of diuresis to be less than 2400mL in first twenty-four hours to prevent excessive dehydration.

Chronic kidney disease (CKD) affects more than 30 million adults in the U.S. and is strongly associated with cardiovascular events and mortality. Venous thromboembolism (VTE) is the third leading vascular disease, affects up to 900,000 Americans each year and contributes to as many as 100,000 deaths annually. The relationship of CKD and VTE has been described in patients receiving dialysis, kidney transplants recipients and in nephrotic syndrome, however, data supporting the association of VTE in mild to moderate CKD is conflicted. The overall goal of this research was to study the association of CKD and VTE and to understand the mechanisms of this association. To accomplish this goal we studied participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study, a nationally representative cohort of 30,239 blacks and whites in the U.S.. The first chapter provides a review of the state-of-the science on CKD and VTE and potential mechanisms for this association. We focus on factor VIII as a potential mediator of VTE risk in CKD by reviewing the biochemistry and epidemiology linking factor VIII and CKD. In Chapter 2, we use a cohort study design and a competing risk analysis to determine the risk of VTE with albuminuria (ACR) and with various equations for estimated glomerular filtration rate (eGFR). There was no association of ACR and VTE and the risk of VTE was similar among eGFR equations. Compared to a normal eGFR (>90 ml/min/1.73m2), eGFR < 45 ml/min/1.73m2 was associated with a two-fold risk of VTE. The association of eGFR and unprovoked VTE was similar to the association with provoked VTE. The population attributable fraction of CKD (eGFR<60 ml/min/1.73m2) was modest at 5%. In Chapter 3, we utilize a case-cohort study to determine if biomarkers of inflammation (C-reactive protein) and procoagulation (Factor VIII and D-dimer) attenuate the risk of VTE in CKD. These biomarkers were higher in lower kidney function and were also strongly associated with VTE. Adjustment for factor VIII fully attenuated the risk of VTE in CKD, thus factor VIII is a potential mediator of the association of CKD and VTE. We assessed whether lifestyle factors and medications mitigate the risk of VTE in those with and without CKD. Exercise frequency and use of statins were associated with reduced risk of VTE in the presence and absence of CKD, but normal BMI was associated with reduced VTE risk only in those without CKD. We conclude that CKD is a risk factor for VTE, and findings shed light on the mechanisms of this association. Interventions that might lower VTE risk in CKD patients include exercise and statin therapy, but not weight loss. Factor VIII is a potential mediator of VTE in CKD and deserves further study. We suggest several avenues for future research to explore the relationship of Factor VIII and CKD.

Chronic kidney disease (CKD) is a global health problem and efforts are needed to improve the care of individuals affected by the disease. A recent strategy for improving care within the healthcare system is patient engagement. Nurses and other health care clinicians can apply patient engagement into their clinical practice to improve the care they provide to their patients. Therefore, the purpose of this project was to increase the knowledge and awareness of patient engagement among clinicians who work with CKD patients. This quality improvement project used Lewin's force field analysis to analyze driving and restraining forces to help develop and implement strategies to develop an e-learning module. The project used practice-focused questions to determine if knowledge about patient engagement and the Shared End-Stage Renal Patients - Decision Making Tool could improve staff knowledge and awareness about patient engagement. A quantitative pretest, posttest approach was used to compare pretest scores to posttest scores after the e-learning module was viewed. Nine clinicians participated in the project study. Results showed that clinicians' knowledge and awareness about patient engagement increased from a mean pretest score of 5.22 to a mean posttest score of 6.22, (p = 0.08617). The sample of only 9 participants may have contributed to the lack of statistical significance after viewing the educational presentation. The e-learning module will provide positive social change as staff and students of renal programs learn about and apply the principles of patient engagement to their clinical practice.