La maladie rénale chronique (MRC) est un véritable problème de santé publique. Bien qu'elle puisse avoir plusieurs origines, celle-ci est caractérisée par le développement d'une inflammation chronique ainsi qu'une fibrose conduisant à une diminution progressive de la fonction rénale. Il est nécessaire de trouver de nouvelles cibles thérapeutiques pour arrêter la progression de cette pathologie. La protéine NOV/CCN3 a été identifiée comme étant une cible potentiellement intéressante. Dans cette étude, nous avons montré que dans un modèle in vivo de néphropathie obstructive, NOV avait un rôle proinflammatoire et profibrotique. Dans un autre modèle in vivo de néphropathie hypertensive, nous avons montré que NOV était régulée par l'Angiotensine II (AngII) et pouvait inhiber l'expression du récepteur AT1R de l'AngII et ainsi limiter les effets délétères de cette hormone. Bien que contradictoires, ces résultats montrent un rôle important de NOV au cours du développement des néphropathies indiquant que cette protéine peut avoir des effets opposés en fonction du contexte pathologique. Enfin, du fait de l'étroite relation entre NOV et l'AngII, nous avons montré que NOV était aussi régulée par cette hormone au niveau aortique et avait un effet proinflammatoire au niveau vasculaire dans des conditions d'hypertension. L'ensemble de nos résultats montrent un rôle important de NOV dans ces différents types de pathologies et que cette protéine pourrait être une cible intéressante pour traiter les néphropathies ou encore les pathologies cardiovasculaires. / Chronic kidney disease (CKD) is a major public health problem. Regardless of the primary cause, CKD is characterized by the development of chronic inflammation and fibrosis leading to progressive decline of renal function and eventually end-stage renal disease (ESRD). Actually, regular hemodialysis and renal transplantation are the only available therapies for ESRD patients. Therefore, there is an urgent need for new therapeutically targets against this incurable disease. Recently, the NOV/CNN3 protein was shown to be an interesting candidate. In this study we have shown that, in obstructive nephropathy in mice, NOV has profinflammatory and profibrotic effects. In addition, we have shown in a mouse model of hypertensive nephropathy, that NOV was regulated by Angiotensin II (AngII) and could inhibit AT1R receptor expression to limit the deleterious effects of this hormone. These results show an important role of NOV during the development of two different types of nephropathies and may indicate that this protein can have model specific effects. Finally, we have shown that NOV itself was also regulated by AngII in the aorta and has proinflammatory effects in hypertensive conditions. Taken together our results show an important role of NOV in these different types of pathologies and that this protein could be a key player in the development of CKD as well as vascular diseases. Nevertheless, further investigations are still required to better characterize the precise role of NOV in these pathological contexts.

Inledning: Som röntgensjuksköterska är det viktigt att ha en bred förståelse över eventuella risker och komplikationer som kan uppträda även efter att patienten har genomgått koronara interventioner. I denna yrkesroll ingår det att inför ingrepp där kontrastmedel ska administreras, ta hänsyn till patientens tillstånd, aktuella prover samt njurvärde. Det finns riskfaktorer där skada för patienten föreligger som bör uppmärksammas. Syfte: Med detta arbete var syftet att undersöka om det finns mindre kända riskfaktorer för kontrastmedelsinducerad njurskada efter koronarangiografi. Metod: Studien genomfördes som en litteraturöversikt där 10 stycken kvantitativa, vetenskapliga artiklar analyserades. Resultat: I denna studie kunde författarna urskilja fyra mindre kända riskfaktorer som inte nämns under nationella rekommendationer. Slutsats: Bakomliggande sjukdomar behöver inte alltid vara orsaken till utvecklad kontrastmedelsinducerad njurskada. Det kan finnas andra faktorer som även orsakar detta även om mer forskning inom området behövs. / Background: In the job as a radiographer it’s important to know of and have a good understanding of possible risks and complications which can occur to a patient after a completed coronary intervention. Working as a radiographer there will be administration of contrast media and consideration for the patient’s status, current blood tests and renal function is of utmost importance. There are risk factors where kidney injury is at hand and need to be observed. Purpose: Examine if there are risk factors for contrastmedia induced kidney injury which are not currently under national recommendations for administering contrast media. Method: This study was conducted as a literature review where 10 scientific articles of quantitative model were analyzed. Results: The authors of this study identified four risk factors not mentioned in the national recommendations. Conclusions: Underlying morbidity is not always a predictor of contrast media induced kidney injury. There can be other factors causing this pathologic state even though further research is required.

BK virus (BKV) is a ubiquitous polyomavirus known to asymptomatically reside in the renal tissues of up to 90% of the human population. BK virions reactivate during periods of intense immunosuppression and can cause disease in renal transplant recipients, such as BKV-associated nephropathy (BKVAN). BKVAN can lead to loss of the transplanted renal grafts. For this reason, the study of BKV biology is of importance to the transplant community. Previous studies have shown that BKV upregulates the pro-growth mTOR pathway in host cells, thereby increasing BKV replicative efficiency. Downstream effectors of the mTOR pathway, particularly p70S6 kinase, control the basal rate of protein translation, in part through regulation of ribosomal biogenesis. It was hypothesized that viral upregulation of the mTOR pathway is beneficial for viral replication due to an increase in the number of ribosomes available to translate viral proteins. Therefore, inhibition of the mTOR pathway could reduce viral replication. This study investigated whether host cell mTOR inhibition could reduce BK viral replication in an in vitro model. We utilized the dual PI3K/mTOR inhibitor NVP BEZ-235 (Novartis Pharmaceuticals), which potently downregulates expression of both upstream (PI3K) and central (mTOR) effectors of the mTOR pathway. Immortalized renal epithelial cells were exposed to varying concentrations of BEZ-235 for a period of 48 hours, infected with BK virus for three hours, and allowed to grow for a further 48 hours. Cell populations were then assayed via quantitative PCR (qPCR), Western blotting and fluorescent immunohistochemical staining to determine the effect of BEZ-235 on BK viral replication. Western blot experiments confirmed the effectiveness of BEZ-235's inhibition of the mTOR pathway in a renal epithelial cell culture model, as well as downregulation of the mTOR pathway during BK viral infection. Western blotting for the key BK replicative protein Large T antigen showed a dose-dependent decrease in expression, with increasing concentrations of BEZ-235. Fluorescent immunohistochemical staining showed a dose-dependent decrease in expression of Large T antigen staining in host cell nuclei. qPCR results were inconclusive, in that no clear pattern in the number of BKV genomes per cell population could be observed across the range of BEZ-235 concentrations tested. While results from our study indicate that BEZ-235 can reduce BKV replication in vitro, further in vitro experimentation, including repetition of approaches already carried out as well as novel approaches, will be needed to definitively confirm inhibition of the mTOR pathway as a viable antiviral strategy.

There is an epidemic of chronic kidney disease of unknown origin (CKDu) primarily affecting younger men in Central America, especially El Salvador and Nicaragua. The primary hypothesis has included heat stress and dehydration. Although medication usage is widely viewed as a likely contributor to kidney damage, the association with chronic kidney disease in Central America has not been fully explored. This study investigated medication usage, symptom presentation, and kidney function among 524 outdoor workers in agricultural and non-agricultural industries enrolled in the Mesoamerican Nephropathy Occupational Study (MANOS) led by Boston University researchers. An overview of the literature on the adverse effects of medication on renal function and thermoregulation, with a focus on medications considered in MANOS, was conducted. Medication usage and symptom presentation on both a short- and long-term timeframe were explored in relation to kidney function measured by estimated glomerular filtration rate. Long-term usage of NSAIDS and potassium supplements was significantly associated with kidney function. Neither short- or long-term uses of acetaminophen, the most commonly used medication, were associated with kidney function. While several self-reported health symptoms were significantly associated with lower kidney function in crude models, the associations’ significance levels lessened after adjusting for age, country, and industry. In contrast, symptoms of chistata (a local term for painful urination) and lower abdominal pain three months prior to data collection each significantly predicted higher kidney function. The results of this exploratory, cross-sectional study present an opportunity for further study on how medications and symptoms, related to both nephrotoxicity and heat stress, could be associated with kidney function.

Diese retrospektiv-deskriptive Analyse befasste sich mit dem Nephropathiespektrum des Universitätsklinikums Leipzig von 1983 bis 2010. Anders als in manch anderen Ländern existiert in Deutschland kein zentrales Register, welches bundesweit Daten zu Nephropathien sammelt und verwertet. Es wurden 467 Biopsien ausgewertet. Knapp 60% der Patienten waren männlich (n=278), 40% weiblich (n=186). Das mittlere Alter betrug 46 Jahre. Das Durchschnittsalter bei Männern betrug 47 Jahre, bei Frauen 45 Jahre. Insgesamt waren 293 primäre GN, 118 sekundäre GN und 17 INP vorhanden. Die häufigste Diagnose war die IgAN (17% der ges. NP), gefolgt von der RPGN (13 % der ges. NP), der HTNP (10%), der MCGN (9%) und der MGN (9%). Die IgAN war mit 28% aller prim. GN die häufigste primäre GN, gefolgt von der RPGN (21% der prim. GN), der MCGN (14%), der MGN (14%) und der FSGS (5%). Die HTNP war die häufigste sekundäre GN (38% der sek. GN), gefolgt von der Lupus-Nephritis (27%) und der DNP (15%). Die häufigste INP war die Calcineurin-Hemmer-NP (29% der INP), gefolgt von der TMA und der Sklerodermie-NP (jeweils 18%), der Oxalatkristall-NP und der Medikamententoxischen NP (jeweils 12%). Die mittlere Inzidenz der IgAN lag bei 0,8/100.000 Einwohner, der MesP bei 0,7/100.000 Einwohner, der MCGN bei 0,6/100.000 Einwohner, der MGN bei 0,5/100.000 Einwohner, der MPGN bei 0,3/100.000 Einwohner, der FSGS bei 1,0/100.000 Einwohner, der RPGN bei 0,7/100.000 Einwohner, der LNP bei 0,5/100.000 Einwohner, der HTNP bei 0,7/100.000 Einwohner und der DNP bei 0,4/100.000 Einwohner. Beim Vergleich des Zeitraums von 1983 bis 1990 mit dem von 1990 bis 2010 fiel eine Abnahme der IgAN von 29% auf 16%, eine Zunahme der FSGS von 0 auf 4% und der RPGN von 6% auf 14% auf. Auch die DNP nahm von 2% auf 4% zu. Unter den vom Pathologischen Institut des Uniklinikums Hamburg-Eppendorf befundeten Nierenbiopsien war die IgAN die häufigste NP, gefolgt von der RPGN. Dagegen war unter den vom Pathologischen Institut des Uniklinikums Erlangen befundeten Biopsien die FSGS die Häufigste, gefolgt von der RPGN. Der Erkrankungsgipfel lag bei der IgAN zwischen dem 29. und 48. Lebensjahr, bei der MCGN zwischen dem 28. und 58. Lebensjahr, bei der MGN zwischen dem 38. und 67. Lebensjahr und bei der FSGS zwischen dem 47. und 73. Lebensjahr. Die RPGN hatte ihren Erkrankungsgipfel zwischen der 4. und 6. Lebensdekade, die Lupus-Nephritis zwischen dem 22. und 40. Lebensjahr und die HTNP zwischen dem 41. und 61. Lebensjahr. Das mittlere Alter bei der DNP lag bei 57 Jahren. Insgesamt waren von 1983 bis 2010 Veränderungen im Nephropathiespektrum zu beobachten. Eine Zunahme der Inzidenz der FSGS, wie in außereuropäischen Ländern beschrieben, konnte festgestellt werden. Auch die Inzidenz der RPGN stieg über die letzten Jahre deutlich an und löste, gemeinsam mit der FSGS, die IgAN ab 2009 als die bis dahin häufigste Diagnose ab.

Orientador: Áureo Evangelista Santana / Resumo: A anemia é considerada um dos fatores para avaliar progressão da doença renal e diminuição da qualidade de vida do paciente. Conforme a doença renal progride, ocorre aumento gradativo na produção de toxinas urêmicas que reduz a meia vida dos eritrócitos circulantes por interferir na estabilidade da membrana eritrocitária. Para tanto, utiliza-se a contagem de reticulócitos para classificar a anemia como regenerativa ou não regenerativa. Objetivou-se neste estudo avaliar a resistência da membrana das hemácias, utilizando-se do teste de Fragilidade Osmótica Eritrocitária (FOE) em cães com doença renal crônica (DRC) e avaliação de reticulócitos. Foram avaliados 43 cães provenientes da rotina do Serviço de Nefrologia e Urologia do Hospital Veterinário Governador Laudo Natel da Faculdade de Ciências Agrárias e Veterinárias - UNESP - campus Jaboticabal. As referidas unidades experimentais foram distribuídas em três grupos, quais sejam, G0 (n=13), composto por cães hígidos e G1, DRC estádios 1 e 2 (n=14) e G2, DRC estádios 3 e 4 (n=16), classificados de acordo com o recomendado pela International Renal Interest Society. A fim de definir os critérios de inclusão dos cães foram feitos, além do exame físico, a avaliação de pressão arterial, hemograma, contagem de reticulócitos, exames bioquímicos, urinálise e relação proteína/creatinina urinária (UP/C). Para execução do teste de FOE as hemácias foram diluídas em concentrações decrescentes de cloreto de sódio e analisadas por citometria ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Anemia is considered one of the factors to assess the kidney disease progress and the decrease in patient's quality of life. As kidney disease progresses, there is a gradual increase in urinary toxin production that shortens the circulating erythrocyte half-life by interfering with erythrocyte membrane stability. To do this, use a reticulocyte count to classify anemia as regenerative or non-regenerative. The objectives of this study were to evaluate the resistance of the red blood cells, using the Erythrocyte Osmotic Fragility test in dogs with chronic kidney disease (CKD) and to evaluate reticulocytes. Forty-three dogs were charged, followed by the routine of the Nephrology and Urology Service of the Governor Laudo Natel Veterinary Hospital of the Faculty of Agricultural and Veterinary Sciences - UNESP - Campus Jaboticabal. The experimental units were divided into three groups, namely, G0 (n = 13), consisting of healthy dogs and G1, CKD stages 1 and 2 (n = 14) and G2, CKD stages 3 and 4 (n = 16), classification proposed by the International Renal Interest Society. In order to define the inclusion criteria of dogs made, in addition to physical examination, an assessment of blood pressure, blood count, reticulocyte count, biochemical tests, urinalysis, and urinary protein/creatinine ratio. To perform the erythrocyte osmotic fragility test, red blood cells were diluted in decreasing sodium chloride filters (0.9 to 0.0%) and analyzed by flow cytometry. As creatinine serum concen... (Complete abstract click electronic access below) / Mestre

京都大学 / 0048 / 新制・論文博士 / 博士(農学) / 乙第12973号 / 論農博第2823号 / 新制||農||1037(附属図書館) / 学位論文||H28||N4955(農学部図書室) / 32411 / 新制||農||1037 / (主査)教授 久米 新一, 教授 今井 裕, 教授 松井 徹 / 学位規則第4条第2項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19396号 / 医博第4047号 / 新制||医||1012(附属図書館) / 32421 / 京都大学大学院医学研究科医学専攻 / (主査)教授 長船 健二, 教授 野田 亮, 教授 萩原 正敏 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

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京都大学 / 新制・課程博士 / 博士(社会健康医学) / 甲第24536号 / 社医博第128号 / 新制||社医||12(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 近藤 尚己, 教授 西浦 博, 教授 柳田 素子 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM