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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.
161

Avaliação dos eventos envolvidos na evolução crônica da lesão renal aguda pós isquêmica em ratos com deficiência de vitamina D / Assessment of the events involved in chronic evolution of acute kidney injury in a murine ischemia/reperfusion model after vitamin D deficiency

Janaína Garcia Gonçalves 08 August 2014 (has links)
Na maioria dos países, a incidência e prevalência da doença renal crônica (DRC) vem aumentando ao longo dos anos. Embora tenha havido uma melhora significativa no manejo da DRC com os inibidores do sistema renina-angiotensina-aldosterona, a doença ainda é progressiva, levando a necessidade do surgimento de novas estratégias protetoras. A fibrose renal progressiva está presente na DRC e envolve a participação de várias citocinas, com destaque para o fator Transforming growth factor- beta1 (TGF-beta1). Tem sido demonstrado que a mortalidade de pacientes com DRC está diretamente relacionada à função renal e está associada a riscos tradicionais como cardiovasculares e infecções. Entretanto, esses riscos tradicionais explicam apenas metade das causas de mortalidade nesses pacientes. Evidências crescentes mostram que o status de vitamina D pode ser um fator de risco não tradicional para a evolução da DRC. Tendo em vista o importante papel da vitamina D na manutenção das funções fisiológicas essenciais e a observação da queda dos níveis deste hormônio na DRC, torna-se relevante o estudo da deficiência de vitamina D nos eventos envolvidos na evolução crônica da lesão renal aguda em modelo experimental de isquemia/reperfusão renal. Ratos Wistar foram divididos em quatro grupos: controle, animais que receberam dieta padrão; dVD, animais que receberam dieta depletada em vitamina D; Isq, animais que receberam dieta padrão e foram submetidos ao insulto de isquemia/reperfusão renal bilateral no 28º dia; Isq+dVD, animais que receberam dieta depletada em vitamina D e foram submetidos ao insulto de isquemia/reperfusão bilateral no 28º dia. Ao final dos 90 dias do protocolo, os animais foram submetidos à eutanásia, amostras de sangue, urina e o tecido renal foram coletados para a análise dos mecanismos de lesão renal. Os animais submetidos ao insulto de isquemia/reperfusão renal apresentaram hipertrofia renal, aumento dos níveis de pressão arterial média, colesterol e de PTH plasmático. Além disso, foi observada expansão da área intersticial, aumento do infiltrado de macrófagos/monócitos, da expressão de colágeno IV, fibronectina, vimentina e alfa-actina e redução da expressão da proteína Klotho. A deficiência de vitamina D contribuiu para a elevação dos níveis plasmáticos de PTH e aumento da proteinúria assim como para as alterações túbulo-intersticiais crônicas importantes (fibrose e infiltrado inflamatório do interstício, dilatação e atrofia tubular), aumento da expressão da citocina TGF-beta1 expressão do receptor de vitamina D (VDR) e da proteína Klotho, observados nos animais deficientes em vitamina D submetidos ao insulto de isquemia/reperfusão renal. Portanto, através de vias inflamatórias e com participação do fator de crescimento TGF-beta1 ê um fator agravante para o dano túbulo-intersticial e formação de fibrose intersticial nesse modelo experimental de isquemia/reperfusão renal / In most countries, the incidence and prevalence of chronic kidney disease (CKD) has been increasing over the years. Although there was a significant improvement in the management of CKD with renin-angiotensin-system inhibitors, the disease is still progressive, leading to the need of emergence of new protective strategies. The progressive renal fibrosis is present in CKD and involves the participation of several cytokines, especially the Transforming growth factor-beta1 (TGF-beta1). It has been shown that the mortality of patients with CKD is directly related to renal function, which is associated to traditional risk factors such as cardiovascular diseases and infections. However, these traditional risk factors explain only half of the causes of mortality in these patients. Growing evidence shows that vitamin D status may be a non-traditional risk factor for the progression of CKD. Considering the important role of vitamin D in the maintenance of essential physiological functions and the observation of low levels of this hormone in CKD, the study of vitamin D deficiency in the events involved in chronic evolution of acute kidney injury in an experimental model of ischemia/reperfusion becomes relevant. Wistar rats were divided into four groups : control, animals received a standard diet ; dVD, animals received a vitamin D-depleted diet ; Isq, animals received a standard diet and were subjected to bilateral renal ischemia/reperfusion injury on day 28; Isq +dVD, animals received a vitamin D-depleted diet and were subjected to bilateral renal ischemia/reperfusion injury on day 28 . At the end of the 90 days of the protocol, the animals were euthanized and samples of blood, urine and kidney tissue were collected for analysis of the mechanisms of renal injury. The animals subjected to the insult of ischemia/ reperfusion showed renal hypertrophy, increased levels of mean blood pressure, cholesterol and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of macrophages/monocytes, increased expression of collagen IV, fibronectin, vimentin and alpha-actin, and reduced expression of Klotho protein were observed. The vitamin D deficiency contributed to the elevation of plasma PTH levels and increased proteinuria as well as for important chronic tubulo-interstitial changes (fibrosis and inflammatory infiltration of the interstitium, tubular dilation and atrophy), increased expression of cytokine TGF-beta1 vitamin D receptor (VDR) and Klotho protein observed in vitamin D-deficient animals subjected to the insult of renal ischemia/reperfusion. Therefore, through inflammatory pathways and involvement of TGF-beta1 w y aggravating factor in tubulointerstitial damage and formation of interstitial fibrosis in this experimental model of renal ischemia/reperfusion
162

Hémodialyse quotidienne en France : caractéristiques, trajectoires, accès à la greffe et survie des patients / Daily hemodialysis in France : characteristics, trajectories, access to renal transplantion and patients' survival

Pladys, Adélaïde 05 December 2016 (has links)
L’augmentation de la fréquence hebdomadaire des séances d’Hémodialyse (HD) serait la technique qui se rapprocherait le plus du rôle physiologique des reins. L’Hémodialyse quotidienne (HDQ) a été développée afin d’améliorer la qualité de vie des patients ainsi que l’épuration sanguine. Néanmoins, son association avec la survie reste controversée et son lien avec l’accès à la greffe rénale n’avait jusqu’alors jamais été étudié. Par ailleurs, les connaissances en termes de pratiques en France étaient jusqu’à aujourd’hui très faibles. Dans ce contexte, cette thèse vise à caractériser les patients français en HDQ et leurs trajectoires en plus d’analyser l’association entre l’HDQ et la transplantation rénale et la survie des patients. Une étude épidémiologique a été menée à partir du Réseau en Epidémiologie et Information en Néphrologie (REIN) où ont été inclus tous les patients âgés ≥18 ans et qui ont démarré une séance d’HDQ entre 2003 et 2012 en France. L’extraction d’un certain nombre de données biocliniques de REIN a permis de montrer que les patients français en HDQ étaient caractérisés pour présenter des profils très hétérogènes. En effet, en fonction de l’âge médian (64 ans) deux sous-groupes de patients ont pu être comparés : les âgés (moyenne d’âge : 76,6 ± 6,9 ans) en mauvaises conditions médicales et qui décédaient rapidement ; les jeunes (moyenne d’âge : 47,2 ± 12 ans) qui étaient en HDQ avant d’accéder à la greffe. Par ailleurs, en fonction des trajectoires initiales, deux sous-groupes ont également pu être comparés : patients démarrant directement par HDQ (dHDQ, n=257) ; patients démarrant par un autre traitement (cHDQ, n=496). Ensuite, cette thèse a permis de montrer qu’en France, après l’inscription sur la liste, les patients en HDQ avaient une moindre probabilité d’accéder à la greffe que les patients en HD 3x/semaine (SHR=0,74 ; IC 95%: 0,58-0,95). Par ailleurs, après ajustement sur l’âge, le sexe et les comorbidités, l’HDQ était associée avec un sur-risque de décès (HR=1,58 ; IC 95%: 1,4-1,8) en comparaison avec l’HD 3x/semaine. Ce travail de thèse a permis d’élucider nos connaissances en termes de pratiques associées avec l’HDQ bien que les raisons pour lesquelles les patients démarrent une HDQ ne sont pas connues. Nous émettons l’hypothèse que les indications pour l’HDQ en France sont probablement différentes de celles appliquées dans d’autres pays, ceci pourrait expliquer nos résultats en termes de mortalité. / An increase frequency of weekly sessions of Hemodialysis (HD) should be more physiological than a conventional HD 3x/week. Daily Hemodialysis (DHD) was developed in order to enhance patients’ quality of life in addition to blood purification. Nevertheless, its effect on survival remains controversial and the association between DHD and the access to renal transplantation has never been evaluated. Moreover, knowledges about DHD practices in France were until today very poor. In this context, the aims of this thesis was firstly, to describe profiles of French patients on DHD and their initial trajectories; secondly to analyze the association between DHD and renal transplantation, then survival in comparison with conventional HD 3x/week. An epidemiologic study has been conducted based on Renal Epidemiology and Information in Nephrology (REIN) registry. Were included all patients aged ≥18 years who initiated a DHD between 2003 and 2012 in France. Bio-clinical data analyses showed that French patients were characterized to present various profiles. Indeed, according to the median age (64 years), two sub-groups were distinguished and compared: old (mean age: 76.6 ± 6.9 years) in bad medical conditions who died rapidly; young (mean age: 47.2 ± 12 years) waiting for renal transplantation. Moreover, according to the initial trajectories, two sub-groups were also constructed: patients starting directly with DHD (dDHD, n=257); patients starting with another dialysis before switching for DHD (cDHD, n=496). Then, this thesis allowed showing that in France and after being waitlisting, patients on DHD had lower probability of being renal transplanted (SHR=0.74; 95%CI: 0.58-0.95). Then, after the adjustment on sex, age and comorbidities, DHD was associated with a higher risk of death compared to conventional HD 3sessions/week. Reasons why a patient started a DHD are unknown, but this work allows us to enhance our knowledges in terms of medical practices associated with DHD. We hypothesized that DHD indications in France might be different from other countries which could explain our results in terms of mortality.
163

Economic evaluation of a new genetic risk score to prevent nephropathies in type-2 diabetic patients

Guinan, Kimberly 12 1900 (has links)
Un score de risque polygénique (SRP) a été mis au point pour permettre une prédiction précoce du risque de néphropathie chez les patients atteints de diabète de type-2 (DT2). Le but de cette étude était d’évaluer l’impact économique de l’implantation du SRP pour la prévention de la néphropathie chez les patients atteints du DT2, par rapport aux méthodes de dépistage habituelles au Canada. Tout d’abord, une revue systématique de la littérature a été effectuée pour examiner les évaluations économiques publiées sur le DT2 et la néphropathie. Les principales techniques de modélisation observées dans cette revue ont été utilisées pour réaliser une analyse coût-utilité à l’aide d’un modèle de Markov. Les états de santé du modèle étaient la pré-insuffisance rénale (pré-IR), l’IR et le décès. Les paramètres d’efficacité du modèle ont été basés sur les résultats de l’étude ADVANCE. Les analyses ont été menées selon une perspective du système de soins et une perspective sociétale. Sur un horizon temporel de la vie entière du patient, le SRP était une stratégie dominante par rapport aux méthodes de dépistage habituelles, selon les deux perspectives choisies. En effet, le SRP était moins coûteux et plus efficace en termes d’années de vie ajustée en fonction de la qualité, par rapport aux techniques de dépistage usuelles. Les analyses de sensibilité déterministe et probabiliste ont démontré que les résultats demeurent dominants dans la majorité des simulations. Cette évaluation économique démontre que l’adoption du SRP permettrait de réduire les coûts et d’améliorer la qualité de vie des patients. / The current screening method for diabetic nephropathy (DN) is based upon the detection of urinary albumin and the decline of estimated glomerular filtration rate, which occurs relatively late in the course of the disease. A polygenic risk score (PRS) was developed for early prediction of the risk for type 2 diabetes (T2D) patients who experience DN. The aim of this study was to assess the economic impact of the implementation of the PRS for the prevention of DN in T2D patients, compared to usual screening methods in Canada. First, a systematic literature review was conducted to examine all published economic evaluations in T2D and DN. The main trends in modelling technics obtained from this review were used to conduct a cost-utility analysis using a Markov model. Health states include pre-end-stage renal disease (Pre-ESRD), ESRD and death. Model efficacy parameters were based on prediction of outcome data by polygenic-risk testing of the ADVANCE trial. Analyses were conducted from Canadian healthcare and societal perspectives. Over a lifetime horizon, the PRS was a dominant strategy compared to usual screening methods, from both a healthcare system and societal perspective. In other words, the PRS was less expensive and more effective in terms of quality-adjusted life years compared to usual screening technics. Deterministic and probabilistic sensitivity analyses showed that results remained dominant in the majority of simulations. This economic evaluation demonstrates that the adoption of the PRS would not only be cost saving but would also help prevent ESRD and improve patients’ quality of life.
164

Sexual Dimorphism of Glomerular Capillary Morphology in Rats

Coker, Zackarias 01 May 2023 (has links) (PDF)
Chronic kidney disease (CKD) progresses faster in males than females; however, the underlying mechanisms remain poorly understood. Sex differences in glomerular capillary morphology has been hypothesized to contribute, in part, to the increased susceptibility to hypertension-induced renal injury and CKD progression in males, but this has not been investigated. The goal of the present study was to assess glomerular capillary morphology in male vs. female rats with intact kidneys and after uninephrectomy (UNX). We hypothesized that glomerular capillary radii (RCAP) and length (LCAP) would be greater in male rats. Male (n=4) and female (n=4) with intact kidneys and UNX (n=4 males, n=4 females) provided a 0.4% NaCl diet and water ad libitum. Kidneys were perfusion-fixed, the left kidney was excised, and a 3 mm transverse section through the midline of the kidney was selected for further processing. Multiple 1 mm3 cubes were randomly excised from the left, middle, and right regions of the outer cortex, embedded in EPONTM, sectioned (1 μm), and stained with toluidine blue. Four glomeruli from each region were randomly selected for stereological analysis. Glomerular tuft volume (VG), RCAP, and LCAP were assessed. In rats with intact kidneys, no significant sex differences were observed in VG, RCAP, or LCAP. VG, RCAP, and LCAP were significant greater in both male and female rats with UNX vs. respective rats with intact kidneys. In rats with UNX, males exhibited a significantly greater VG and LCAP, but not RCAP, as compared to females despite no significant differences in relative kidney weight. These data indicate that males exhibit greater compensatory increases in LCAP following UNX. The greater capillary length may lead to reduced podocyte density, a well-known mechanism that increases the susceptibility to CKD progression.
165

Fluid dynamic assessments of spiral flow induced by vascular grafts

Kokkalis, Efstratios January 2014 (has links)
Peripheral vascular grafts are used for the treatment of peripheral arterial disease and arteriovenous grafts for vascular access in end stage renal disease. The development of neo-intimal hyperplasia and thrombosis in the distal anastomosis remains the main reason for occlusion in that region. The local haemodynamics produced by a graft in the host vessel is believed to significantly affect endothelial function. Single spiral flow is a normal feature in medium and large sized vessels and it is induced by the anatomical structure and physiological function of the cardiovascular system. Grafts designed to generate a single spiral flow in the distal anastomosis have been introduced in clinical practice and are known as spiral grafts. In this work, spiral peripheral vascular and arteriovenous grafts were compared with conventional grafts using ultrasound and computational methods to identify their haemodynamic differences. Vascular-graft flow phantoms were developed to house the grafts in different surgical configurations. Mimicking components, with appropriate acoustic properties, were chosen to minimise ultrasound beam refraction and distortion. A dual-beam two-dimensional vector Doppler technique was developed to visualise and quantify vortical structures downstream of each graft outflow in the cross-flow direction. Vorticity mapping and measurements of circulation were acquired based on the vector Doppler data. The flow within the vascular-graft models was simulated with computed tomography based image-guided modelling for further understanding of secondary flow motions and comparison with the experimental results. The computational assessments provided a three-dimensional velocity field in the lumen of the models allowing a range of fluid dynamic parameters to be predicted. Single- or double-spiral flow patterns consisting of a dominant and a smaller vortex were detected in the outflow of the spiral grafts. A double- triple- or tetra-spiral flow pattern was found in the outflow of the conventional graft, depending on model configuration and Reynolds number. These multiple-spiral patterns were associated with increased flow stagnation, separation and instability, which are known to be detrimental for endothelial behaviour. Increased in-plane mixing and wall shear stress, which are considered atheroprotective in normal vessels, were found in the outflow of the spiral devices. The results from the experimental approach were in agreement with those from the computational approach. This study applied ultrasound and computational methods to vascular-graft phantoms in order to characterise the flow field induced by spiral and conventional peripheral vascular and arteriovenous grafts. The results suggest that spiral grafts are associated with advanced local haemodynamics that may protect endothelial function and thereby may prevent their outflow anastomosis from neo-intimal hyperplasia and thrombosis. Consequently this work supports the hypothesis that spiral grafts may decrease outflow stenosis and hence improve patency rates in patients.
166

BIRTHWEIGHT AND SUSCEPTIBILITY TO CHRONIC DISEASE

Issa Al Salmi Unknown Date (has links)
The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.
167

BIRTHWEIGHT AND SUSCEPTIBILITY TO CHRONIC DISEASE

Issa Al Salmi Unknown Date (has links)
The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.
168

BIRTHWEIGHT AND SUSCEPTIBILITY TO CHRONIC DISEASE

Issa Al Salmi Unknown Date (has links)
The thesis examines the relationship of birthweight to risk factors and markers, such as proteinuria and glomerular filtration rate, for chronic disease in postnatal life. It made use of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). The AusDiab study is a cross sectional study where baseline data on 11,247 participants were collected in 1999-2000. Participants were recruited from a stratified sample of Australians aged ≥ 25 years, residing in 42 randomly selected urban and non-urban areas (Census Collector Districts) of the six states of Australia and the Northern Territory. The AusDiab study collected an enormous amount of clinical and laboratory data. During the 2004-05 follow-up AusDiab survey, questions about birthweight were included. Participants were asked to state their birthweight, the likely accuracy of the stated birthweight and the source of their stated birthweight. Four hundred and twelve chronic kidney disease (CKD) patients were approached, and 339 agreed to participate in the study. The patients completed the same questionnaire. Medical records were reviewed to check the diagnoses, causes of kidney trouble and SCr levels. Two control subjects, matched for gender and age, were selected for each CKD patient from participants in the AusDiab study who reported their birthweight. Among 7,157 AusDiab participants who responded to the questionnaire, 4,502 reported their birthweights, with a mean (standard deviation) of 3.4 (0.7) kg. The benefit and disadvantages of these data are discussed in chapter three. The data were analysed for the relationship between birthweight and adult body size and composition, disorders of glucose regulation, blood pressure, lipid abnormalities, cardiovascular diseases and glomerular filtration rate. Low birthweight was associated with smaller body build and lower lean mass and total body water in both females and males. In addition low birthweight was associated with central obesity and higher body fat percentage in females, even after taking into account current physical activity and socioeconomic status. Fasting plasma glucose, post load glucose and glycosylated haemoglobin were strongly and inversely correlated with birthweight. In those with low birthweight (< 2.5 kg), the risks for having impaired fasting glucose, impaired glucose tolerance, diabetes and all abnormalities combined were increased by 1.75, 2.22, 2.76 and 2.28 for females and by 1.40, 1.32, 1.98 and 1.49 for males compared to those with normal birthweight (≥ 2.5 kg), respectively. Low birthweight individuals were at higher risk for having high blood pressure ≥ 140/90 mmHg and ≥ 130/85 mmHg compared to those with normal birthweight. People with low birthweight showed a trend towards increased risk for high cholesterol (≥ 5.5 mmol/l) compared to those of normal birthweight. Females with low birthweight had increased risk for high low density lipoprotein cholesterol (≥ 3.5 mmol/l) and triglyceride levels (≥ 1.7 mmol/l) when compared to those with normal birthweight. Males with low birthweight exhibited increased risk for low levels of high density lipoprotein cholesterol (<0.9 mmol/l) than those with normal birthweight. Females with low birthweight were at least 1.39, 1.40, 2.30 and 1.47 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases respectively, compared to those ≥ 2.5 kg. Similarly, males with low birthweight were 1.76, 1.48, 3.34 and 1.70 times more likely to have angina, coronary artery disease, stroke and overall cardiovascular diseases compared to those ≥ 2.5 kg, respectively. The estimated glomerular filtration rate was strongly and positively associated with birthweight, with a predicted increase of 2.6 ml/min (CI 2.1, 3.2) and 3.8 (3.0, 4.5) for each kg of birthweight for females and males, respectively. The odd ratio (95% confidence interval) for low glomerular filtration rate (<61.0 ml/min for female and < 87.4 male) in people of low birthweight compared with those of normal birthweight was 2.04 (1.45, 2.88) for female and 3.4 (2.11, 5.36) for male. One hundred and eighty-nineCKD patients reported their birthweight; 106 were male. Their age was 60.3(15) years. Their birthweight was 3.27 (0.62) kg, vs 3.46 (0.6) kg for their AusDiab controls, p<0.001 and the proportions with birthweight<2.5 kg were 12.17% and 4.44%, p<0.001. Among CKD patients, 22.8%, 21.7%, 18% and 37.6% were in CKD stages 2, 3, 4 and 5 respectively. Birthweights by CKD stage and their AusDiab controls were as follows: 3.38 (0.52) vs 3.49 (0.52), p=0.251 for CKD2; 3.28 (0.54) vs 3.44 (0.54), p=0.121 for CKD3; 3.19 (0.72) vs 3.43 (0.56), p= 0.112 for CKD4 and 3.09 (0.65) vs 3.47 (0.67), p<0.001 for CKD5. The results demonstrate that in an affluent Western country with a good adult health profile, low birthweight people were predisposed to higher rates of glycaemic dysregulation, high blood pressure, dyslipidaemia, cardiovascular diseases and lower glomerular filtration rate in adult life. In all instances it would be prudent to adopt policies of intensified whole of life surveillance of lower birthweight people, anticipating this risk. The general public awareness of the effect of low birthweight on development of chronic diseases in later life is of vital importance. The general public, in addition to the awareness of people in medical practice of the role of low birthweight, will lead to a better management of this group of our population that is increasingly surviving into adulthood.

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