Background. The kidney is one of the major organs involved in whole-body homeostasis and it is well understood that chronic renal impairment is further complicated with deranged carbohydrate metabolism, dyslipidemia, altered abdominal fat distribution and the activation of renin-angiotensin system (RAS). Recently, RAS blockades of angiotensinconverting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) have been noticed for their potential effects on improve glucose and lipid metabolisms and lowering the risk of new-onset diabetes. However, underlying cellular and molecular mechanisms are not fully established. / Conclusions. (1) UNX induces progressive renal impairment and dysregulation of pancreatic and renal RAS in rats. (2) Pancreatic RAS activation leads to intra-islet fibrosis, insulin-secreting beta-cell deficit and insulin secretory deficiency. (3) Renal cortex RAS dysregulation induces ectopic adipocyte differentiation and lipid infiltration, in combination with lipodystrophy and lipid peroxidation, results to insulin resistance. (4) Pancreatic insulin-secretion deficit and insulin resistance contribute to the development of glucose intolerance and hyperglycemia. (5) Kidney impacting on glucose and lipid metabolism by affecting pancreatic islet and adipocyte, suggesting an essential role of the kidney in maintaining the whole-body homeostasis. (6) RAS blockade with ACEI or ARB may prevent the development of chronic renal impairment and glucose and lipid dysmetabolisms in UNX rats. (7) Common pathways modulating blood pressure, glucose and lipid metabolism warrant future studies for the better management of the global epidemic of metabolic syndrome. / Materials and methods. Chronic renal impairment and RAS disturbance were induced by unilateral nephrectomy (UNX) in adult Sprague-Dawley rats undergoing as long as 10 months of observation. Three-month old male rats were randomized into 4 groups: (1) sham operated control rats (n=10), (2) untreated UNX model rats (n=10), (3) ACEI---lisinopril treated UNX rats (n=10), and (4) ARB-olmesartan treated UNX rats (n=10). Blood glucose levels during fasting and oral glucose tolerance test (OGTT) conditions, lipids, insulin and renal function were measured at 3, 6, 8 and 10 months after operation. Histological changes of kidney, pancreas, liver, and adipose tissue were examined at 10 months post-operation. / Objectives. (1) To set up a rat model with persistent chronic renal impairment and RAS activation. (2) To examine changes of fasting blood glucose, glucose tolerance, blood lipids and insulin sensitivity. (3) To examine changes of pancreatic islets and the factors contributing to pancreatic islet damage such as RAS, transforming growth factor (TGF)-beta and alpha-smooth muscle actin (SMA). (4) To examine changes of systemic and renal adipose tissue and the factors contributing to adipopathy such as RAS, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and hydroxy-3-methylglutary coenzyme A reductase (HMGCR). (5) To investigate preventive effect of RAS blockades by the ACEI-lisinopril (4 mg/kg body weight) and ARB-olmesartan (4 mg/kg body weight) on the rat model of progressive renal deficiency. / Results. (1) UNX rats developed time-dependent progressive renal functional impairment and marked glomerulosclerosis and tubulointerstitial lesions. (2) UNX rats showed fasting hyperglycemia, progressive glucose intolerance, hyperlipidemia and insulin resistance. (3) UNX rats demonstrated insulin secretory deficiency in parallel to pancreatic islet fibrosis, beta-cell deficit, and overexpression of RAS components, TGF-beta, and alpha-SMA. (4) UNX rats displayed adipopathy evidenced by shifts the subcutaneous and visceral fats to the ectopic fat with lipid accumulation, lipofuscin pigmentation and adipocytes transformation. The adipopathy associated with down-regulation of AT1R and over-expression of angiotensin, AT2R, PPAR-gamma and HMGCR in the remnant kidney. (5) Treatment with lisinopril and olmesartan significantly attenuated the development of chronic renal impairment, RAS dysregulation and aberrant proteins expression, islet damage, adipose redistribution, and glucose and lipid dysmetabolism. / Sui, Yi. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3422. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 195-220). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Les acides aristolochiques (AA) présents dans les aristoloches sont impliqués dans le développement d’une insuffisance rénale progressive chez l’homme, appelée néphropathie aux plantes chinoises (CHN). Elle se caractérise par une atrophie tubulaire sévère et une fibrose interstitielle associée à une fréquence élevée de cancers urothéliaux. L’observation en clinique d’une protéinurie tubulaire a suggéré que le tubule proximal était la cible des AA.<p><p>\ / Doctorat en sciences biomédicales / info:eu-repo/semantics/nonPublished

Growth failure is a major problem in children with chronic renal failure (CRF). A number of factors have been suggested as explanations for this impaired growth including renal osteodystrophy, age of onset of chronic renal failure, degree of azotemia and nutritional status. As children with CRF are frequently unable to maintain sufficient nutrient intakes for optimal growth, the nutritional status of these individuals must obviously have a major, if as yet poorly understood, role in the observed growth failure. Therefore, a nutritional, physical and biochemical study was conducted to assess the nutritional status of seven children undergoing maintenance hemodialysis. To evaluate the adequacy of dietary intake, fourteen day food records were obtained from each of the participants and average nutrient intakes were compared to the recommended daily nutrient intake of the Canadian Dietary Standard (CDS) (1975). To assess the physical status of the children, height, height velocity, weight, per cent body fat, and bone age were determined. As abnormalities of taste sensitivity are known to influence dietary patterns, salivary flow rates, salivary urea concentrations, and taste detection and recognition thresholds for sweet, sour, salt and bitter were determined pre and post dialysis. Biochemical investigations included the determination of pre and post dialysis plasma amino acid concentrations following a standardized fast of five hours, and the quantification of the amounts of amino acids lost into dialysate during a complete hemodialysis treatment. The mean caloric intake of 54% ±11 of the CDS is inadequate for optimal growth. The mean protein intake was 1.09 ±.16 grams of protein per kilogram of body weight. The first and second limiting amino acids were histidine and threonine, respectively. Nutritional deficiencies of certain water soluble vitamins (riboflavin, niacin and pyridoxine) existed for some of the children. The mean zinc, magnesium and copper intakes were 45% ±8, 51% ±19 and 54% ±32 of the CDS, respectively. Growth (as measured by body height and weight) was found to be retarded one to two standard deviations from normal in the children studied. Per cent body fat estimations were within normal limits, but bone age was frequently below chronological age. Taste sensitivity was impaired as shown by elevated pre dialysis sweet and bitter recognition thresholds (p<.01). This reduced taste acuity was improved post dialysis (p<.005), but did not reach normal values. Pre and post dialysis, salivary flow rates were reduced (p<.0005) and salivary urea concentrations elevated (p<.0005) when compared to normal. Pre dialysis, plasma concentrations of taurine, a-amino-butyric acid, valine, cystine, leucine, tyrosine and tryptophan were decreased from normal levels (p<.025), and aspartic acid, proline, glycine, citrulline, ornithine, histidine, arginine, asparagine, 3-methylhistidine and hydroxyproline were elevated above normal (p<.005). The presence of subclinical protein calorie malnutrition (PCM) was indicated by a depressed plasma essential to nonessential amino acid ratio, a depressed plasma valine to glycine ratio, and an elevated plasma phenylalanine to tyrosine ratio as compared to normal. The detection of 3-methylhistidine and hydroxyproline in plasma provides additional indications of PCM. The mean amount of total amino acid lost into dialysate was 4.7 ±.9 grams. Histidine, threonine, lysine and valine were the essential amino acids lost in the largest amounts. In conclusion, growth is retarded in children with CRF and may be due to the accumulation of metabolic end products which depress appetite and/or delay the natural rate of growth events Suboptimal nutriture, as evidenced by the presence of PCM, is a major factor in the growth retardation of these individuals. / Land and Food Systems, Faculty of / Graduate

Indiana University-Purdue University Indianapolis (IUPUI) / FGF23 is the central regulator for phosphate homeostasis. Both FGF23 and phosphate dysregulation are highly related with the progression of chronic kidney disease (CKD), which is a global health problem. In previous studies, FGF23 was found to be produced in bone and targeting the kidneys to regulate phosphate reabsorption and excretion. In the FGF23 signaling axis, it binds a receptor complex (αKlotho and FGFRs) in the distal convoluted tubules (DCT) and causes its biological effects in the proximal tubules (PT). The mechanism of how the signals passing on from DCT to PT is not clear. In my research, experiments were focused on the FGF23 signaling pathway within the kidney to study the communication steps between tubular cells. HBEGF treatment was given to FGF23 signaling impaired mouse models resulting in significant change of genes regulated by FGF23, indicating that HBEGF was important in the FGF23 signaling axis. Then high quality rabbit anti-mouse HBEGF antibodies were made to better study HBEGF activity in vivo and in vitro. A new cell model was characterized to test FGF23 effects on HBEGF signaling using Western blots and immunofluorescence. Lastly, the location of HBEGF activity was examined in the kidney in vivo. Immunostaining suggested that HBEGF activated the mitogen activated protein kinase (MAPK) pathway. This mapping may provide important information for the molecular relationships between FGF23 and HBEGF.

Luk, Pik Shan Yvonne. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 134-146). / Abstracts in English and Chinese ; some text in appendix also in Chinese. / Abstract (English version) --- p.ii-iii / Abstract (Chinese version) --- p.iv / Acknowledgement --- p.v / List of Table --- p.vi / Appendices --- p.vii / Chapter 1 --- Introduction --- p.1-5 / Chapter 2 --- Literature Review / Introduction --- p.6-7 / Psychological Distress --- p.7-13 / Health-related Quality of Life --- p.13-25 / Marital Relationship --- p.26-31 / Summary --- p.31-34 / Chapter 3 --- Aims & Methodology / Aims & Objectives --- p.35-37 / Operational Definition --- p.37-38 / Research Design --- p.38-39 / Setting & Sample --- p.39-40 / Instrument / Psychological Distress --- p.41-43 / Health-related Quality of Life --- p.43.44 / Marital Relationship --- p.44-46 / Demographic Data --- p.47 / Data Collection Procedure --- p.4748 / Ethical Consideration --- p.48-50 / Data Analysis --- p.50-51 / Pilot Study --- p.51-52 / Chapter 4 --- Findings / Introduction --- p.53-54 / Sociodemographic Characteristics --- p.54-56 / Psychological Distress --- p.57-58 / Health-related Quality of Life --- p.59-61 / Marital Relationship --- p.62-65 / Normality of the Outcome Variables --- p.65-66 / Relationships between the Study Outcomes and Sociodemographic Data --- p.66-68 / "Relationships between Anxiety, Depression, Health-Related Quality of Life and Marital Relationship" --- p.68-76 / Summary --- p.16-78 / Chapter 5 --- Discussion / Introduction --- p.79 / Socio-demographic and Clinical Characteristics of CAPD patients --- p.79-84 / Psychological Distress of CAPD Patients --- p.84-85 / Components of Psychological Distress: Anxiety --- p.85-86 / Components of Psychological Distress: Depression --- p.86-88 / Gender differences of the Levels of Anxiety and Depression among CAPD Patients --- p.88-89 / Cultural Difference of Anxiety and Depression among CAPD Patients --- p.89-90 / Health-related Quality of Life among CAPD Patients / Health-related Quality of Life of CAPD Patients Affected by Renal Symptoms --- p.90-91 / Health-related Quality of Life of CAPD Patients Affected by the effects of Kidney Disease --- p.91-93 / Health-related Quality of Life of CAPD Patients Affected by the burden of / Having Kidney Disease --- p.93-94 / Health-related Quality of Life of CAPD Patients Affected by the General Physical Health --- p.94-96 / Health-related Quality of Life of CAPD Patients Affected by the General Mental Health --- p.96-97 / Gender differences of the Levels of Health-related Quality of Life among CAPD Patients --- p.97-98 / Cultural Difference of Health-related Quality of Life among CAPD Patients --- p.98-99 / Sexual Issues and Marital Relationship of CAPD Patients / Sexual Issues of CA PD Patients --- p.100-102 / CAPD Patients' Perception of the Marital Relationship --- p.102-104 / Gender Differences in Perception of the Marital Relationship among CAPD Patients --- p.104 / Cultural Difference in Perception of the Marital Relationship among CAPD Patients --- p.105-106 / "Relationships between Participants' Characteristics and Psychological Distress," / HRQoL and Marital Relationship / "Relationships of Income with Anxiety, Depression and General Mental Health" --- p.107-108 / Relationship between Duration of Receiving Dialysis and Health-related Quality of Life --- p.108-109 / Relationship between Occupational Status and General Mental Health --- p.199.110 / "Relationships among Anxiety, Depression, HRQoL and Marital Relationship" / The Relationship between Anxiety and Depression --- p.110-111 / "The Relationship between Anxiety, Depression and HRQoL" --- p.112 / "The Relationship between Anxiety, Depression and Marital Relationship" --- p.112-113 / The Relationships among Domains of Health-related Quality of Life --- p.113-114 / The Relationship between Health-related Quality of Life and Marital Relationship --- p.114-115 / Predictors of Health-related Quality of Life among CAPD Patients / Anxiety and Depression as Predictors of Health-related Quality of Life --- p.116-118 / Marital Relationship as Predictors of Health-related Quality of Life --- p.118-119 / Summary --- p.119-121 / Chapter 6 --- Conclusion / Limitations / Validity of Participants' Responses --- p.122-123 / Generalization of the Study's Findings --- p.123-124 / Psychometric Property of the Chinese Version of KDQOL-36 --- p.124-125 / The Sexual Items ofKDQOL-SF --- p.125 / Appropriateness of Using HADS and Multiple Correlations --- p.126 / Implications of the Study Findings / Implications for nursing knowledge --- p.126-128 / Implications on the Nursing Practice --- p.128-130 / Recommendations for Further Research --- p.130-132 / Conclusion --- p.132-133 / Chapter 7 --- Reference --- p.134-146 / Chapter 8 --- Appendix --- p.147-179

Indiana University-Purdue University Indianapolis (IUPUI) / Advancements in human genomics have simultaneously enhanced our basic understanding of the human body and ability to combat debilitating diseases. Historically, research has shown that there have been many hindrances to realizing this medicinal revolution. One hindrance, with particular regard to the kidney, has been our inability to effectively and routinely delivery genes to various loci, without inducing significant injury. However, we have recently developed a method using hydrodynamic fluid delivery that has shown substantial promise in addressing aforesaid issues. We optimized our approach and designed a method that utilizes retrograde renal vein injections to facilitate widespread and persistent plasmid and adenoviral based transgene expression in rat kidneys. Exogenous gene expression extended throughout the cortex and medulla, lasting over 1 month within comparable expression profiles, in various renal cell types without considerably impacting normal organ function. As a proof of its utility we by attempted to prevent ischemic acute kidney injury (AKI), which is a leading cause of morbidity and mortality across among global populations, by altering the mitochondrial proteome. Specifically, our hydrodynamic delivery process facilitated an upregulated expression of mitochondrial enzymes that have been suggested to provide mediation from renal ischemic injury. Remarkably, this protein upregulation significantly enhanced mitochondrial membrane potential activity, comparable to that observed from ischemic preconditioning, and provided protection against moderate ischemia-reperfusion injury, based on serum creatinine and histology analyses. Strikingly, we also determined that hydrodynamic delivery of isotonic fluid alone, given as long as 24 hours after AKI is induced, is similarly capable of blunting the extent of injury. Altogether, these results indicate the development of novel and exciting platform for the future study and management of renal injury.

Text in English with abstracts in English and isiZulu / Poor adherence to their prescribed diet, medications and treatment contributes to increased mortality and morbidity in patients with end-stage renal disease. These patients must change their diet when receiving dialysis treatment, but cultural beliefs and practices can affect their adherence to the prescribed diet. The purpose of this qualitative, descriptive, exploratory study was to improve health education on prescribed diet adherence to patients living on haemodialysis at a haemodialysis unit in eThekwini Municipality. Data from a sample of 20 patients was collected using semi-structured interviews and analysed using qualitative content analysis. The findings revealed that haemodialysis patients’ prescribed diet adherence was influenced by cultural and religious views, and by family support. Food availability, patients’ geographical location and patients’ financial means hindered their adherence to their prescribed diet. A multi-disciplinary health care team including nurses, should be sensitive to patients’ different cultural beliefs and practices when providing health education. / Ukungabambeleli endleleni emisiwe yokudla, amakhambi nasekwelashweni kunomthelela ekwandiseni izimpawu zesifo sezinso esingapheli (ESRD) futhi kwandisa isibalo sabantu ababulawa yilesisifo. Iziguli ezinalesisifo zidinga ukushitsha indlela yokuphila, iziphuzo kanye nokulandela indlela emisiwe yokudla kakhulukazi mabe ngaphansi kokwelashwa ngokuhlanzwa kwegazi ngomshini (dialysis). Izinkolelo zamasiko nendlela zokuphila ezihambisana namasiko kwenze imfundiso nge ezempilo maqondana nendlela emisiwe yokudla yaba lukhuni. Inhloso yalolucwaningo bekuwukwandisa ulwazi nemfundiso ngezempilo mayelana nokulandela indlela emisiwe yokudla kwiziguli izithola ukulashwa ngokuhlanzwa kwegazi ngomshini (haemodialysis) esikhungweni esikuMasipala weTheku. Kusetshenziwe indlela yokwenza ucwaningo esezingeni elifanele, Imininingwano eqoqiwe eqembini (sample) leziguli ezingamashumi amabili (20) ezithola ukwelashwange haemodialyisis. Imininigwane iqoqwe kusetshenziswa izingxoxo ezihleliwe. Imigomo elawula ukuhlaziya ilandeliwe yonke ngenkathi kwenziwe lolucwaningo. Lolucwaningo luveze ukuthi indlela yokudla emisiwe yeziguli ezikwi dialysis iphazanyiswa imobono yamasiko, inkolo kanye nokusekelwa nokuzimbandakanya kwamalungu omndeni. Izinselelo ezinjengokutholakala, indawo isiguli esihlala kuyo nezinkinga zemali zivimbela ukubambelela endleleni emisiwe yokudla. Abasebenzi bezempilo kumele banakekele indima edlalwa izinkolelo namasiko uma befundisa ngezempilo ezigulini eziphethwe izinso. / Nursing Science / M.A. (Nursing Science)

La néphropathie aux plantes chinoises (CHN) est une maladie rénale grave qui a été décrite pour la première fois en 1993 chez des patientes ayant suivi un régime amaigrissant à base d’extraits de plantes chinoises (Aristolochia fangchi) contenant des acides aristolochiques (AA). Cette néphropathie se caractérise par une atrophie tubulaire et une fibrose interstitielle aboutissant à l’urémie terminale et se complique fréquemment de cancers des voies urinaires. Au moment d’initier ce travail, il subsistait toujours un large débat quant au rôle étiologique réel des acides aristolochiques dans la genèse de cette maladie. En effet, les gélules à visée amaigrissante contenaient d’autres substances potentiellement néphrotoxiques. Mais surtout, il n’existait aucune preuve expérimentale que les AA pouvaient induire une fibrose rénale interstitielle.<p>Dans la première partie de ce travail, nous démontrons que l’injection par voie sous-cutanée d’AA à la dose de 10 mg/Kg/jour à des rats Wistar mâles en déplétion sodée entraîne l’apparition au 35ème jour d’une atrophie tubulaire, d’une fibrose interstitielle et d’une insuffisance rénale, reproduisant ainsi les anomalies caractéristiques de la CHN. Nous avons ensuite montré que la dexfenfluramine, substance anorexigène à action de type sérotoninergique prise concomitamment par les patientes atteintes de CHN, ne potentialise pas la toxicité rénale des AA. Enfin, la stimulation du système rénine angiotensine (SRA) par la déplétion sodée ou l’inhibition de celui-ci par un traitement pharmacologique ne modifie pas la fibrose interstitielle ni l’insuffisance rénale induite par les AA.<p>En conclusion, nous avons réussi à développer un modèle in vivo de fibrose rénale interstitielle induite par les AA. Dès lors nous avons apporté la preuve expérimentale de l’implication des AA dans le développement de la CHN. Ce modèle a permis de démontrer que les autres éléments potentiellement néphrotoxiques contenues dans la cure d’amaigrissement (dexfenfluramine, diurétique, laxatif) n’influençaient pas l’évolution de la fibrose interstitielle, ce qui confirme que la prise isolée d’AA suffit à expliquer le développement de la CHN. Cette confirmation à d’importantes implications en santé publique dans la mesure où des plantes contenant des acides aristolochiques font toujours partie des phytothérapies traditionnelles. De plus, il est apparu que, dans ce modèle, les mécanismes de la fibrose rénale interstitielle pouvaient être largement indépendants du SRA. Enfin, de par sa durée limitée et sa grande reproductibilité, ce modèle constitue un outil expérimental d’avenir pour l’étude des mécanismes physiopathologiques de la fibrose rénale interstitielle en général.<p> / Doctorat en sciences médicales / info:eu-repo/semantics/nonPublished