Tang, Walfred. / "November 2011." / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 151-165). / Abstracts in English and Chinese. / Title Page --- p.i / Thesis/Assessment Committee (English) --- p.ii / Acknowledgements --- p.iii / Table of Content --- p.iv / List of Figures --- p.ix / List of Graphs --- p.xi / List of Tables --- p.xiv / Abbreviations --- p.xviii / Abstract (English) --- p.xx / Abstract (Chinese) --- p.xxii / Chapter Chapter 1: --- General Introduction / Chapter 1.1 --- Renal Development --- p.2 / Chapter 1.1.1 --- The three embryonic excretory systems --- p.2 / Chapter 1.1.1.1 --- Pronephros and mesonephros --- p.2 / Chapter 1.1.1.2 --- Metanephros --- p.4 / Chapter 1.1.2 --- Renal malformations --- p.6 / Chapter 1.1.2.1 --- Causes of renal malformations --- p.8 / Chapter 1.1.2.1.1 --- Physical obstruction --- p.9 / Chapter 1.1.2.1.2 --- Mutation --- p.9 / Chapter 1.1.2.1.3 --- Environmental insults --- p.10 / Chapter 1.2 --- Retinoic Acid --- p.11 / Chapter 1.2.1 --- "Retinoic acid synthesis, signaling and degradation in the Embryo" --- p.12 / Chapter 1.2.2 --- Retinoic acid and embryonic development --- p.14 / Chapter 1.2.2.1 --- Retinoic acid and renal development --- p.15 / Chapter 1.2.3 --- Retinoic acid teratogenicity --- p.17 / Chapter 1.2.3.1 --- Retinoic acid teratogenic mechanism --- p.18 / Chapter 1.2.3.2 --- Retinoic acid-induced renal agenesis mouse model --- p.21 / Chapter 1.2.4 --- Induction of RA deficiency --- p.24 / Chapter 1.3 --- Strategy of the Thesis --- p.28 / Chapter Chapter 2: --- General Materials and Methods / Chapter 2.1 --- Mouse Maintenance and Mating Method --- p.31 / Chapter 2.2 --- Bisdiamine Preparation --- p.32 / Chapter 2.3 --- All-trans Retinoic Acid Preparation --- p.32 / Chapter 2.4 --- Embryo Dissection --- p.32 / Chapter 2.5 --- Real-time Quantitative Reverse Transcription- Polymerase Chain Reaction (RT-PCR) --- p.33 / Chapter 2.5.1 --- Sample collection --- p.33 / Chapter 2.5.2 --- Total RNA extraction --- p.33 / Chapter 2.5.3 --- Reverse transcription --- p.34 / Chapter 2.5.4 --- Polymerase chain reaction --- p.35 / Chapter 2.5.5 --- Preparation of DNA standards --- p.36 / Chapter 2.6 --- Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick-end Labeling (TUNEL) Staining --- p.38 / Chapter 2.6.1 --- "Fixation, dehydration and embedding" --- p.38 / Chapter 2.6.2 --- Microtome sectioning --- p.39 / Chapter 2.6.3 --- TUNEL staining --- p.39 / Chapter Chapter 3: --- Induction of Renal Malformations by Bisdiamine via RA Deficien --- p.cy / Chapter 3.1 --- Introduction --- p.43 / Chapter 3.1.1 --- Time and dose responses to bisdiamine-induced renal malformations --- p.43 / Chapter 3.1.2 --- Methods to detect endogenous RA in embryonic tissues --- p.44 / Chapter 3.2 --- Experimental Design --- p.46 / Chapter 3.3 --- Materials and Methods --- p.48 / Chapter 3.3.1 --- Time and dose responses to bisdiamine administration --- p.48 / Chapter 3.3.2 --- Quantification of RA and retinol content in whole embryo by high pressure liquid chromatography (HPLC) --- p.49 / Chapter 3.3.2.1 --- Bisdiamine injection and sample collection --- p.49 / Chapter 3.3.2.2 --- Chromatographic system --- p.50 / Chapter 3.3.2.3 --- Preparation of standards --- p.50 / Chapter 3.3.2.4 --- Extraction of embryo samples --- p.51 / Chapter 3.3.2.5 --- Conditions of HPLC --- p.52 / Chapter 3.3.2.6 --- Recovery of sample --- p.53 / Chapter 3.3.2.7 --- Bradford protein assay --- p.53 / Chapter 3.3.3 --- X-gal staining of RARE-hsp-lacZ embryos --- p.54 / Chapter 3.3.4 --- Quantification of RA content in metanephroi by the RA-responsive cell line --- p.55 / Chapter 3.3.4.1 --- Bisdiamine injection and sample collection --- p.55 / Chapter 3.3.4.2 --- Maintenance of the RA-responsive cell line --- p.56 / Chapter 3.3.4.3 --- Seeding of cells and addition of samples --- p.57 / Chapter 3.3.4.4 --- X-gal staining --- p.58 / Chapter 3.3.5 --- TUNEL staining --- p.59 / Chapter 3.3.6 --- Real-time quantitative RT-PCR --- p.60 / Chapter 3.3.7 --- Statistical analysis --- p.61 / Chapter 3.4 --- Results --- p.63 / Chapter 3.4.1 --- Time response to bisdiamine treatment --- p.63 / Chapter 3.4.1.1 --- Bisdiamine administration increased resorption and affected various growth parameters of the fetuses --- p.64 / Chapter 3.4.1.2 --- Bisdiamine administration resulted in renal malformations --- p.68 / Chapter 3.4.1.3 --- Bisdiamine administration resulted in non-renal malformations --- p.71 / Chapter 3.4.2 --- Dose response to bisdiamine treatment --- p.76 / Chapter 3.4.2.1 --- Dose response of resorption and various growth parameters --- p.77 / Chapter 3.4.2.2 --- Dose response to bisdiamine in inducing renal malformations --- p.80 / Chapter 3.4.2.3 --- Dose response to non-renal malformations --- p.83 / Chapter 3.4.3 --- RA deficiency induced by bisdiamine --- p.88 / Chapter 3.4.3.1 --- Comparison of endogenous RA and retinol levels in control and bisdiamine-treated whole embryos at different time points after treatment --- p.88 / Chapter 3.4.3.2 --- Comparison of RA signaling patterns in control and bisdiamine-treated embryos at different time points after treatment --- p.90 / Chapter 3.4.3.3 --- Comparison of endogenous RA levels in control and bisdiamine-treated metanephroi at different time points after treatment --- p.93 / Chapter 3.4.4 --- Increase in the number of apoptotic nuclei in the metanephros after bisdiamine treatment --- p.95 / Chapter 3.4.5 --- Alteration of genes expression in the metanephros after bisdiamine treatment --- p.96 / Chapter 3.5 --- Discussion --- p.99 / Figures / Graphs / Chapter Chapter 4: --- Rescuing Bisdiamine-treated Metanephroi by In Vitro Supplementation with Low Concentrations of RA / Chapter 4.1 --- Introduction --- p.107 / Chapter 4.1.1 --- Embryonic kidney culture --- p.107 / Chapter 4.1.2 --- In vitro culture of the RA-treated metanephros --- p.108 / Chapter 4.1.3 --- Effect of exogenous retinoic acid on in vitro development of metanephros --- p.109 / Chapter 4.2 --- Experimental Design --- p.111 / Chapter 4.3 --- Materials and Methods --- p.113 / Chapter 4.3.1 --- Supplementation of low concentrations of RA to metanephric explant culture --- p.113 / Chapter 4.3.1.1 --- Preparation of culture medium supplemented with low concentrations of RA --- p.113 / Chapter 4.3.1.2 --- Metanephric explant culture --- p.114 / Chapter 4.3.2 --- Whole-mount immunohistochemical staining of ureteric epithelium and nephric tubules in metanephric explants --- p.115 / Chapter 4.3.3 --- TUNEL staining of metanephric explants --- p.116 / Chapter 4.3.4 --- Real-time quantitative RT-PCR --- p.117 / Chapter 4.3.5 --- Statistical analysis --- p.117 / Chapter 4.4 --- Results --- p.119 / Chapter 4.4.1 --- Rescue of bisdiamine-treated metanephric explants by in vitro culture in medium supplemented with low concentrations of RA --- p.119 / Chapter 4.4.1.1 --- Assessment of metanephric development under various concentrations of RA by morphological grading of UB tips at different day of culture --- p.119 / Chapter 4.4.1.2 --- Effect of various concentrations of RA on the number of UB tips and nephric tubules in metanephric explants at day 6 of culture --- p.126 / Chapter 4.4.2 --- Effect of RA supplementation on apoptosis in bisdiamine-treated metanephric explants --- p.131 / Chapter 4.4.3 --- Effect of RA supplementation on genes expression in bisdiamine-treated metanephric explants --- p.133 / Chapter 4.5 --- Discussion --- p.136 / Figures / Graphs / Chapter Chapter 5: --- Conclusion and Future Perspectives --- p.141 / References --- p.150

Introdução: A prevalência de doença renal crônica na faixa etária pediátrica ainda é desconhecida. O tratamento de escolha é o transplante renal, independente da idade. Os principais objetivos do tratamento são a manutenção do desenvolvimento físico, neurológico e esquelético, prevenção da doença do metabolismo mineral e ósseo (DMMO), adequada maturação sexual e da função endócrina. O déficit de crescimento está relacionado com a idade de surgimento da insuficiência renal e ocorre devido à má-nutrição energético-calórica, DMMO e uso de corticoide, além dos efeitos deletérios da anemia, uremia e resistência ao hormônio do crescimento. Causas relacionadas ao paciente como retardo de crescimento intra-uterino e malformações congênitas também estão relacionadas. Objetivos: avaliar o desenvolvimento pondero-estatural dos pacientes pediátricos submetidos a transplante renal no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC FMRP-USP). Casuística: revisão dos prontuários dos pacientes pediátricos submetidos a transplante renal no HC FMRP-USP e análise do desenvolvimento pondero-estatural comparando os score-z altura para idade e índice de massa corporal (IMC) para idade durante o acompanhamento. As variáveis analisadas foram sexo, faixa etária, uso de Basiliximab, realização ou não de diálise, tipo de transplante realizado (doador falecido ou doador vivo relacionado), hipertensão arterial, dose de manutenção de prednisona. Resultados: foi possível avaliar os dados de 31 pacientes, 10 femininos e 21 masculinos. Ao longo do tempo houve ganho significativo em peso (p< 0,0001) e estatura (p< 0,0001) mas nenhuma das variáveis analisadas mostrou diferença estatisticamente significativa. Houve interação significativa do uso de Basiliximab e da faixa etária sobre o IMC e do uso de Basiliximab, faixa etária e dose de prednisona utilizada sobre a evolução da estatura. A estatura manteve abaixo da média padrão durante todo o acompanhamento e nenhum paciente atingiu a altura final esperada. O IMC estava abaixo da média padrão na ocasião do transplante mas a partir do primeiro ano recuperou e manteve estável em torno do percentil 0. Conclusões: a doença renal crônica na infância compromete o desenvolvimento ponderoestatural dos pacientes afetados. / Introduction: The prevalence of chronic kidney disease in the pediatric age range is still unknown. The treatment of choice is a renal transplant, regardless of age. The main objectives of treatment are the maintenance of physical, neurological and skeletal development, the prevention of renal osteodystrophy, and appropriate sexual and endocrine function maturation. The growth deficit is related to the age at onset of renal failure and is due to energy-calorie malnutrition, to renal osteodystrophy and to corticoid use, in addition to the deleterious effects of anemia, uremia and of resistance to growth hormone. Additional patient-related causes are intrauterine growth retardation and congenital malformations. Objectives: to assess the weight-height development of pediatric patients submitted to renal transplantation at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo (HC FMRP-USP). Patients: The medical records of pediatric patients submitted to renal transplantation at HC FMRP-USP were reviewed and weight-height development was analyzed by comparing the zscores for height for age and body mass index (BMI) for age during follow-up. The variables analyzed were: sex, age range, use of Basiliximab, having undergone dialysis or not, type of transplant performed (cadaver donor or related live donor), arterial hypertension, and maintenance dose of prednisone. Results: it was possible to assess the data of 31 patients, 10 girls and 21 boys. A significant weight gain (p<0.0001) and height (p<0.0001) occurred over time but none of the variables analyzed showed a statistically significant difference. There was a significant interaction between age range and BMI, between the use of Basiliximab and age range and between the prednisone dose used and height evolution. Height was below the standard mean value throughout follow-up and no patient reached the expected final height. BMI was below the standard mean value at the time of transplantation, but recovered after the first year and remained stable at a value of about 0. Conclusions: renal failure during childhood compromises the weight-height development of affected patients.

nÃo hà / O poliomavirus tipo BK tem sido associado à nefropatia nos pacientes transplantados renais com uma incidÃncia variando entre 3 - 4% e em 60% dos casos podendo levar à perda do enxerto. Diversos estudos tÃm demonstrado a importÃncia do achado da cÃlula decoy na urina destes pacientes como primeira triagem para a replicaÃÃo viral fazendo o diagnÃstico diferencial entre a rejeiÃÃo celular aguda e a nefropatia pelo BK vÃrus. Neste contexto, o presente estudo objetivou detectar a presenÃa do BKV atravÃs da observaÃÃo da cÃlula decoy na urina dos transplantados renais, correlacionando este achado com os nÃveis sÃricos de urÃia e creatinina e o aspecto histopatolÃgico atravÃs da biÃpsia renal. Para tanto, a urina de 50 pacientes transplantados renais (28 homens e 22 mulheres) atendidos em dois hospitais de Fortaleza (Hospital UniversitÃrio Walter CantÃdio e Hospital Geral de Fortaleza) foram analisadas quanto à presenÃa de cÃlulas decoy detectadas atravÃs da citologia urinÃria pela coloraÃÃo de Papanicolau. As citologias foram analisadas e classificadas em negativa e positiva (&#8805; 1 cÃlula decoy). Resultado: Das 50 citologias urinÃrias analisadas 28 pacientes eram do sexo masculino e 22 do sexo feminino, receptores de doador vivo (n = 43) ou cadavÃrico (n = 7) com positividade para cÃlula decoy de 24% (12 pacientes). NÃveis de creatinina e urÃia aumentados, isoladamente, nÃo foram Ãteis para suspeitar da nefropatia pelo BKV ou rejeiÃÃo do transplante (p > 0,05). A correlaÃÃo dos nÃveis alterados de urÃia e creatinina, com a presenÃa ou ausÃncia das cÃlulas decoy, foi estatisticamente significativa (p < 0,05). A biÃpsia revelou nefropatia pelo BKV em cinco (20%) dos pacientes com cÃlulas decoy na urina e os achados histolÃgicos mais freqÃentes foram fibrose e infiltrado inflamatÃrio mononuclear. A imunossupressÃo mais empregada nos pacientes em estudo foi o esquema 1 (50%) (ciclosporina / azatioprina / zenapx), seguidos por esquemas 2 (16%) (MMF/FK 506 / zanapax) 1 esquema 3 (16%) (ciclosporina / prednizona / azatioprina). ConclusÃo: A positividade para cÃlulas decoy neste estudo (24%) à coincidente com a literatura (8 -26%) sugerindo infecÃÃo ativa. A presenÃa das cÃlulas decoy na urina foi Ãtil para definir os grupos de pacientes com possÃvel nefropatia pelo BKV daqueles com nefropatia por rejeiÃÃo, pois a negatividade para cÃlulas decoy na urina afasta em 100% dos casos a nefropatia pelo BKV, e a sua presenÃa serve de guia para avanÃar na investigaÃÃo de nefropatia pelo BKV. A biÃpsia confirmou em 5 dos 12 casos com cÃlulas decoy positivas na urina (20%) a nefropatia pelo poliomavirus sendo que um deles veio a perder o enxerto. O esquema de imunossupressÃo utilizado pelos pacientes em estudo e a presenÃa de nefropatia pelo BKV nÃo foi o que mais se relaciona na literatura. TambÃm os pacientes com nefropatia pelo BKV que utilizaram esquemas menos associados a esta condiÃÃo tiveram evoluÃÃo pior. Estes Ãltimos resultados indicam a necessidade de novos estudos com maior nÃmero de pacientes, tempo de acompanhamento maior e estudo das cepas virais. / The polyomavirus type BK has been associated to the nephropathy in the patients transplanted renal with an incidence varying among 3 - 4% and in 60% of the cases could take to the loss of the graft. Several studies have been demonstrating the importance of the discovery of the decoy cells in these patients' urine as first selection for the viral replication making it diagnose differential between the sharp cellular rejection and the nephropathy for the BK virus. In this context, the present study aimed at to detect the presence of BKV through the observation of the decoy cells in the urine of the transplanted renal, correlating this discovery with the serum urea levels and creatinine and the histopathology features through the renal biopsy. For so much, the 50 transplanted patients' urine renal (28 men and 22 women) assisted at two hospitals of Fortaleza (Academical Hospital Walter CantÃdio and General Hospital of Fortaleza) they were analyzed as for the presence of decoy cells detected through the urinary cytology by the coloration of Papanicolau. Were the cytology analyzed and done classify in negative and positive (&#8805; 1 decoy cell). Result: Of the 50 cytology analyzed urinary 28 patients they were male and 22 female, alive donor's receivers (n = 43) or cadaverous (n = 7) with assertiveness for decoy cells of 24% (12 patient). Creatinine levels and increased urea, separately, they were not useful to suspect of the nephropathy for BKV or rejection of the transplant (p > 0,05). The correlation of the altered levels of urea and creatinine, with the presence or absence of the decoy cells, was significant for the statistics (p < 0,05). The biopsy revealed nephropathy for BKV in five (20%) of the patients with cells decoy in the urine and the more frequent histological discoveries were fibrose and infiltrated inflammatory mononuclear. The most employed immune suppression in the patients in study was the outline 1 (50%) (ciclosporina / azatioprina / zenapx), following for outlines 2 (16%) (MMF/FK 506/zanapax) 1 outline 3 (16%) (ciclosporina / prednizona / azatioprina). Conclusion: The assertiveness for decoy cells in this study (24%) it is coincident with the literature (8 -26%) suggesting active infection. The presence of the decoy cells in the urine was useful to define the patients' groups with possible nephropathy for BKV of those with nephropathy for rejection, because the negativity for decoy cells in the urine moves away in 100% of the cases the nephropathy for BKV, and his/her presence serves as guide to move forward in the nephropathy investigation for BKV. The biopsy confirmed in 5 of the 12 cases with decoy cells positive in the urine (20%) the nephropathy for the polyomavirus and one of them vein to lose the graft. The immunosuppressive outline used by the patients in study and the nephropathy presence for BKV was not it that more it links in the literature. Also the patients with nephropathy for BKV that used less associated outlines this condition had worse evolution. These last results indicate the need of new studies with larger number of patients, time of larger attendance and study of the stumps turn.

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.

Chronic Kidney Disease (CKD) is a progressive condition that in the majority of cases leads to End Stage Renal Failure (ESRD) and the need for dialysis, with the only cure being renal transplant. CKD affects both adults and children; however the underlying causes of the disease are different. CKD in adults is most commonly secondary to diabetes and/or hypertension while CKD in children is usually caused by congenital structural abnormalities that result directly in renal dysfunction. There have been numerous reports of inflammatory and immunological disturbances in adult CKD that involve both the cellular and humoral immune systems. Consequences of these include an increased rate of cardiovascular disease (CVD), decreased response to vaccinations, as well as increased rates of infection, anaemia and malnutrition. Children with CKD display many of the clinical complications seen in adult kidney disease that are associated with inflammatory and immunological changes. In adults however, many of the primary conditions associated with CKD are inherently pro-inflammatory; therefore it is not clear whether the inflammatory changes observed in adults with CKD are due to pre-existing inflammatory conditions, renal disease per se or a combination of both. The majority of CKD in children is caused by conditions that are not inflammatory in nature. This presents a unique opportunity to study the inflammatory consequences of CKD alone, without the added complication of underlying inflammatory disorders. Despite this, there has been little investigation of the inflammatory and immunological status of children with CKD. Some very recent studies have shown that children with CKD have an increased systemic inflammatory state[1-3], however the nature of these immunological and inflammatory changes remains poorly defined. Identification of the specific inflammatory processes that occur in CKD may provide new treatment targets and the opportunity to develop urgently needed new therapies. The purpose of this thesis is to investigate the presence of immunological changes associated with inflammation in children with CKD. This is the first study to include children with very mild disease, and the significant changes that are present in the early stages of the disease are of particular note. I have shown that CKD in children is an intrinsically inflammatory condition, with increased accumulation of markers of oxidative stress and production of pro-inflammatory cytokines. The inflammatory markers identified in this study may be applied as a foundation for more sensitive diagnostic markers of disease progression as well as provide a basis for novel treatment strategies in this group of patients. Early identification of increased inflammation is a prerequisite for the application of preventive strategies. In addition, a better understanding of the level and mechanisms of systemic inflammation in children with CKD may enable a more accurate assessment of their risk of other inflammatory conditions such as CVD, anaemia, muscle wasting, and malnutrition. Future research that specifically focuses on the reasons and mechanisms for different rates of disease progression may emerge as a result of this study. Importantly, the findings of this study may have implications in the long term treatment of disease and may allow identification of new treatment strategies to achieve better patient outcomes. The outcomes of the study are: • Better definition of inflammatory profiles in paediatric CKD and correlation with disease severity and progression, which should contribute to improved management strategies. • Identification of new treatment targets to reduce the damage caused by chronic systemic inflammation. • Mechanistic understanding of the relationship of the inflammatory profile in regard to source leucocytes or other contributing cell types. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1330366 / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

<p>Det finns lite forskning om livskvalitet hos patienter med kronisk njursvikt som ännu inte startat i dialysbehandling och det är viktigt att ha kunskap om hur livskvaliteten påverkas hos dessa patienter. Syftet med litteraturstudien var att belysa olika faktorers påverkan på livskvaliteten hos patienter med kronisk njursvikt som inte startat i dialys. I studien har 16 vetenskapliga artiklar granskats och analyserats. I resultatet framkom att Hb-nivå, nutrition, sjukdomens svårighetsgrad och komorbiditet var faktorer som kunde påverka livskvaliteten. Även patienters upplevelser av antal och svårighetsgrad av symtom var påverkande faktorer. Ålder, kön, civilstånd, utbildning och arbetsstatus visade sig också kunna påverka livskvaliteten. I faktorer som patienterna kunde påverka, framkom copingstrategier och egenvård. I livskvalitet relaterat till planerad vård och omvårdnad framkom vårdplanering och specialistsjuksköterske-mottagning som faktorer som kunde påverka livskvaliteten. Genom kunskap inom detta område kan sjuksköterskan ge information och stöd till patienter och närstående och via omvårdnadsåtgärder förebygga och lindra symtom för att förbättra patienternas livskvalitet. Undersökningar av livskvalitet hos patienter med njursvikt som inte startat i dialys kan vara av värde vid utvärdering av vård och omvårdnad. Mer kvalitativ forskning om livskvalitet, coping och egenvård inom detta område behövs och sjuksköterskor behöver mer utbildning inom dessa områden för att kunna förbättra omvårdnaden.</p> / <p>There is little research on quality of life in patients with chronic renal failure not undergoing dialysis and it is important to know how the quality of life is affected in these patients. The aim of this literature review was to illustrate the impact of different factors on the quality of life in patients with chronic renal failure not undergoing dialysis. This study has been reviewed 16 scientific articles and analyzed. The result showed that the Hb-level, nutrition, the severity of the disease and co-morbidity were factors that could affect the quality of life. Also patients' perceptions of the number and severity of symptoms were influencing factors. Age, sex, marital status, education and work status also appeared to affect the quality of life. Among factors that patients themselves could affect were coping strategies and self-care. Well planned care and care delivered by specialist nurses did also affect the quality of life. The patients‟ quality of life may improve by the acts of the nurse, for example by providing information and support to patients and relatives, and by different nursing interventions directed towards prevention or relief of symptoms. Studies of quality of life in patients with renal failure not started in dialysis may be useful in the evaluation of health care and nursing. There is a need for more qualitative research on quality of life, coping and self-care in this field and nurses need more training in these areas in order to improve the nursing care.</p>

<p>Att ge bort en del av sig själv för att förbättra livet för en annan människa, är att ge gåvan till liv. Levande njurdonatorers upplevelser kommer ofta i skymundan eftersom studier ofta fokuserat på mottagarens upple-velse av njurtransplantationen. Donationen beskrivs med både positiva och negativa upplevelser. De negati-va upplevelserna förknippas med fysiska och psykiska komplikationer efter donationen. De positiva upplevel-serna beskrivs som ökad livskvalitet och glädje inför att hjälpa en människa till ett bättre liv. Syftet med denna litteraturstudie var att beskriva levande donatorers upp-levelser av att donera en njure från beslutsfattandet till tiden efter donationen. Studien genomfördes som en lit-teraturstudie, där 13 artiklar granskades och analysera-des. Resultatet visar att det finns flera faktorer, såsom oro inför mottagarens situation och oro inför sin egen framtid som påverkar donatorernas beslutsfattande. Det framkom även att både fysiska och psykiska upplevelser förekommer efter donationen. De fysiska upplevelserna var framförallt smärta, illamående samt ömhet och obe-hag runt operationssåret. Donatorns psykiska upplevel-ser efter donationen var vanligen oro inför mottagarens tillfrisknande, stress, depression samt nedstämdhet. Överlag upplevde donatorerna donationen positivt och var nöjda med sitt beslut. Mer forskning kring levande njurdonatorers upplevelser kan bidra till att sjuksköters-kor lättare kan stödja donatorer i donationsprocessen samt att blivande donatorer kan få en inblick i hur dona-tionen upplevs.</p>

<p>Bakgrund: Antalet patienter i behov av njurtransplantation per år är cirka 400-500, varav endast cirka 350 kommer att bli transplanterade. Bristen på organ är tydligt framträdande. I väntan på transplantation behöver patienten dialysbehandling, vilket ofta upplevs vara tidskrävande och utmattande. Sjuksköterskor bör ha kunskap om patienters upplevelser i samband med väntan på transplantation för att kunna utvecklas i sin roll som sjuksköterska och få en djupare förståelse för deras situation.</p><p>Syfte: Syftet var att beskriva kroniskt njursjuka patienters upplevelser av att leva med dialysbehandling och väntan på transplantation.</p><p>Metod: Studien är en litteratursammanställning av tio kvalitativa och kvantitativa vetenskapliga artiklar inom området, vilka har granskats, analyserats och sammanställts.</p><p>Resultat: I resultatet framkom flera olika upplevelser, så som längtan efter frihet, utmattning, höga förväntningar, frustration och rädsla inför framtiden i samband med dialysbehandlingen och väntan på transplantationen.</p><p>Slutsats: Kroniskt njursjuka patienters upplever sin situation som psykiskt, fysiskt och socialt påfrestande. En av sjuksköterskans viktigaste uppgifter i samband med bemötandet av patienter under dialysbehandling är att vara tillgänglig. Med en tillgänglig och öppen inställning till patienterna blir sjuksköterskan mer mottaglig för patienternas individuella behov.</p> / <p>Background: The number in need of kidney transplants per year is approximately 400-500, of which only about 350 will be transplanted. The shortage of organs is clearly prominent. In anticipation of the transplant patient needs dialysis, which is perceived to be time consuming and exhausting. Nurses should have knowledge of patients' experiences in connection with awaiting transplantation to be able to evolve in her role as a nurse and get a deeper understanding of the patients’ situation.</p><p>Aim: The aim of this study was to describe patients’ experiences of living with chronic kidney failure with dialysis and awaiting transplantation.</p><p>Method: The study is a literature compilation of ten qualitative and quantitative scientific articles in the field. The articles have been reviewed, analyzed and compiled. Results: The results revealed several different experiences, such as yearning for freedom, fatigue, high expectations, frustration and fear for the future in connection with the dialysis treatment and awaiting transplantation.</p><p>Conclusion: Chronic kidney disease patients perceive their situation as mentally, physically and socially stressful. One of the nurse's most important tasks in connection with the treatment of patients in dialysis is to be available. With an accessible and open approach to the patient in general, a nurse becomes more responsive to patient's individual needs.</p>

<p><strong>Objective</strong><em>:</em> Estimation of glomerular filtration rate (GFR) is an important tool in the diagnosis and management of chronic kidney disease. Today creatinine is the most frequently used marker for kidney function though several studies indicate that cystatin C is a superior marker. The purpose of this study was to validate Abbott Diagnostics turbidimetric cystatin C assay and enzymatic creatinine assay.</p><p><strong>Methods</strong><em>:</em> The validation was performed by studies of CV for the two methods and correlations between the two and other available methods for assessing GFR. The stability of cystatin C at room temperature was also evaluated.</p><p><strong>Results</strong><em>: </em>Both methods showed good precision. The Abbott cystatin C assay generally gave lower values and thereby higher estimated GFRs than the correlated Gentian method. The Abbott enzymatic creatinine assay gave higher values than the correlated Jaffe method. Those results are generally unexpected, but in this study the cause is an automatically applied negative intercept used together with the Jaffe method. Cystatin C showed high stability when stored at room temperature.</p><p><strong>Conclusions</strong><em>:</em> Estimated GFRs tend to differ depending on the choice of method for analyzing cystatin C or creatinine and this study gives an overview of the range of variation. The study also enlightens the need for an international calibrator for the cystatin C methods presented by different manufacturers.</p>

Det finns lite forskning om livskvalitet hos patienter med kronisk njursvikt som ännu inte startat i dialysbehandling och det är viktigt att ha kunskap om hur livskvaliteten påverkas hos dessa patienter. Syftet med litteraturstudien var att belysa olika faktorers påverkan på livskvaliteten hos patienter med kronisk njursvikt som inte startat i dialys. I studien har 16 vetenskapliga artiklar granskats och analyserats. I resultatet framkom att Hb-nivå, nutrition, sjukdomens svårighetsgrad och komorbiditet var faktorer som kunde påverka livskvaliteten. Även patienters upplevelser av antal och svårighetsgrad av symtom var påverkande faktorer. Ålder, kön, civilstånd, utbildning och arbetsstatus visade sig också kunna påverka livskvaliteten. I faktorer som patienterna kunde påverka, framkom copingstrategier och egenvård. I livskvalitet relaterat till planerad vård och omvårdnad framkom vårdplanering och specialistsjuksköterske-mottagning som faktorer som kunde påverka livskvaliteten. Genom kunskap inom detta område kan sjuksköterskan ge information och stöd till patienter och närstående och via omvårdnadsåtgärder förebygga och lindra symtom för att förbättra patienternas livskvalitet. Undersökningar av livskvalitet hos patienter med njursvikt som inte startat i dialys kan vara av värde vid utvärdering av vård och omvårdnad. Mer kvalitativ forskning om livskvalitet, coping och egenvård inom detta område behövs och sjuksköterskor behöver mer utbildning inom dessa områden för att kunna förbättra omvårdnaden. / There is little research on quality of life in patients with chronic renal failure not undergoing dialysis and it is important to know how the quality of life is affected in these patients. The aim of this literature review was to illustrate the impact of different factors on the quality of life in patients with chronic renal failure not undergoing dialysis. This study has been reviewed 16 scientific articles and analyzed. The result showed that the Hb-level, nutrition, the severity of the disease and co-morbidity were factors that could affect the quality of life. Also patients' perceptions of the number and severity of symptoms were influencing factors. Age, sex, marital status, education and work status also appeared to affect the quality of life. Among factors that patients themselves could affect were coping strategies and self-care. Well planned care and care delivered by specialist nurses did also affect the quality of life. The patients‟ quality of life may improve by the acts of the nurse, for example by providing information and support to patients and relatives, and by different nursing interventions directed towards prevention or relief of symptoms. Studies of quality of life in patients with renal failure not started in dialysis may be useful in the evaluation of health care and nursing. There is a need for more qualitative research on quality of life, coping and self-care in this field and nurses need more training in these areas in order to improve the nursing care.