Orientador: André Luis Balbi / Banca: Jacqueline Teixeira Caramori / Banca: Pedro Alejandro Gordan / Resumo: A Insuficiência Renal Aguda apresenta uma alta incidência em pacientes internados em hospitais terciários, principalmente em Unidades de Terapia Intensiva, estando associada a elevada mortalidade. Este trabalho tem como objetivos descrever a população de pacientes internados no Hospital das Clínicas de Faculdade de Medicina de Botucatu - UNESP com diagnóstico de Insuficiência Renal Aguda atendidos pelo Grupo de Interconsultas do Serviço de Nefrologia e avaliar os fatores de risco associados ao óbito nestes pacientes. Foram acompanhados 946 pacientes no período de abril de 2002 a dezembro de 2006, todos maiores de 12 anos, com diagnóstico de Necrose Tubular Aguda e internados nas diferentes enfermarias e Unidades de Terapia Intensiva do Hospital das Clínicas, exceto na Pediatria e Nefrologia. Insuficiência Renal Aguda foi definida como um aumento de creatinina sérica de pelo menos 30% de seu valor basal em período mínimo de 48 horas. A média de idade foi de 61,8 ± 16,7 anos, com predomínio do sexo masculino (61,9%). Pacientes provenientes de enfermarias clínicas foram mais freqüentes (62,1%), sendo que 15,9% estavam internados na cardiologia e 15,2% na clínica médica geral, enquanto 13,3% estavam internados na enfermaria de gastroenterologia cirúrgica. 46,1% estavam internados em Unidades de Terapia Intensiva e a sepse esteve presente em 9,7% dos casos. Isquemia (51,2%) foi a etiologia mais freqüente e o tempo de acompanhamento nefrológico apresentou mediana de 7,5 dias, com intervalo interquartílico de 4 a 14 dias. / Abstract: Acute Renal Failure (ARF) present a high incidence in critically ill patients taken into tertiary care hospitais, mostly in the Intensive Care Unit (ICU) patients, were also associate with great mortality rate. The objective of this work was to describe the population of patients hospitalized in the School Medicine, Botucatu- UNESP with diagnosis of ARF, attended by Group of - Interconsults of Service Nephrology and to evaluate the risk factors associate with death in this patients. This was a cohort study which evaluated 946 patients with ARF, from April 2002 to December 2006, was included patients older than 12 years, with diagnosis of ARF due to Acute Tubular Necrosis (ATN) and hospitalized in wards and ICU of HC- FMBUNESP (except in the Pediatrics and Nephroloy wards). ARF was defined as serum creatinine at least 30% above basal value from 48 hours at minimum. The average of age was 61,8 ± 16,7 years, with predominantly masculine gender (61,9%). 15,9% were hospitalized in the cardiology and 15,2% in the clinical medical, while 13,3% were hospitalized in the gastroenterology surgical ward. 46,1% of patients were hospitalized in ICU and the sepsis was present in 9,7% of the cases. Ischemia was the etiology more frequent (51,2%) and the time of accompaniment nephrologic presented an median of 7,5 days (4 - 14). / Mestre

The critical function of the kidney is to regulate the body’s extracellular fluid volume to maintain homeostasis. When insults to the kidney occur, as in the case of kidney ischemia, the function of the kidney to filter metabolic wastes and reabsorb essential solutes is compromised, leading to a variety of clinical manifestations. Current metrics of kidney function are measured by the rise of a single analyte, the serum creatinine, which implies injury of the kidney tubule and its epithelial cells and is encapsulated by the term Acute Kidney Injury (AKI). Yet, creatinine does not specify the etiology, the cell type, or the molecular pathways that are affected by the acute decreases in kidney excretory function. During my thesis work, I hypothesized that there is a pathogenetic heterogeneity of kidney injury and a specificity of location, timing, and molecular mechanisms, unique to each of these three injury models: kidney ischemia, volume depletion, and urinary tract infection. Using genetic mouse models, RNA-sequencing, and a range of molecular biology techniques, I have found (1) kidney ischemia activates inflammatory responses, signal transduction pathways, and epithelial repair and reprogramming, that are not activated in volume depletion, (2) which in contrast, is a transient metabolic condition, inducing genes regulating energy metabolism that were reversible upon rehydration. Lastly, (3) I have found that urinary tract infection, particularly one that invades the kidney, involves a novel heme transport system in the collecting duct of the kidney, that may contribute to nutritional defenses against bacterial pathogens. Each of these findings is explored in specific aims and experiments, which I detail here in my thesis.

According to traditional Chinese medicine , Cordyceps sinensis (CS) can prevent subjects from renal failure. The aim of this study was to investigate the protective effect of CS preconditioning on ischemic renal acute failure in rats and to assess its mechanism. The animal model of ischemic acute renal failure was performed by left nephrectomy and clamping right renal vessel for 45 mins in S-D rats. Cordyceps group had been pretreated with two-day 600 mg/kg CS before I/R injury. Rats were sacrificed at 1, 3, 6, 16, 48 and 120 h after reperfusion for evaluation of renal function and histopathological PASD staining. The immunohistochemistry and Western blotting of SDF-1£\, CXCR4 and Ki67 were also performed. £E-galactosidase activity was detected with the senescence staining. The results showed that the level of creatinine in Cordyceps group were significant lower after 48 hours I/R injury (p =0.04). PSAD staining in Cordyceps group revealed less tubular necrosis, tubular dilatation, and cast formation at 6 and 16 hour than in control group. Immunohistochemistry of SDF-1£\ in Cordyceps group demonstrated staining in the distal tubules and collecting ducts at 1, 3, 6, and 16 h. The CXCR4 signal of control group had gradually intensified from 1 to 6 hr after I/R . In Cordyceps group, the CXCR4 expression had been stabilized until 16 h after I/R. The £]-galactosidase activity was higher in control group at 1, 3 and 6 hours. However, the senescence was presented at 1 and 3 hours in Cordyceps group. The nuclear staining of repair enzyme Ki67 in Cordyceps group showed higher density than in control group. Pathologic morphology indicated CS may protect subjects from ischemic acute renal failure. CS also induced SDF-1£\ expression in early stage of I/R injury, and maintained the stable CXCR4 expression. CS can not only reduce the activity of senescence-related £]-galactosidase, but also regulate the expression of repair enzyme Ki67, indicating that CS may alleviate the ischemic-induced senescence and enhance renal repair.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Renal failure in patients undergoing Aortic surgery is associated with a poor outcome. The shortcomings of serum creatinine for measuring renal function are well documented. We examined the value of alternative markers in diagnosing and predicting renal damage in patients undergoing abdominal aortic surgery and those exposed to intravascular contrast media. Cystatin C lacks some of the reservations associated with serum creatinine when used as a marker of glomerular filtration rate. The protease inhibitor alpha-glutathione Stransferase (a-GST) is recovered in urine after injury to proximal tubular cells. Urine microalbumin is a marker of glomerular permeability. Together we used all four assays to detect and characterize the nature of renal injury after surgery and contrast exposure. Cystatin C had a marginally better sensitivity than serum creatinine at detecting baseline renal impairment. It also showed earlier changes in individual patients whose renal dysfunction deteriorated over time. The urinary markers showed an earlier significant rise after the onset of surgery when compared to serum markers, but only a-GST rose significantly after contrast exposure. Patients undergoing a supra-renal cross-clamp showed significantly higher a-GST levels (and not the other three markers) when compared to the infra-renal group. Cystatin C appears to have better sensitivity and specificity for predicting the need for dialysis in patients undergoing surgery. Peak serum creatinine and cystatin C after contrast exposure show good correlation with peak values after surgery. Cystatin C is equivalent to and may be better than serum creatinine in detecting preexisting and deteriorating renal impairment. Although the urinary assays are earlier markers of renal injury, their clinical significance needs to be determined. Elevation in creatinine and cystatin C after contrast exposure parallel those after surgical intervention and may be helpful in selecting out high-risk patients prior to surgery. / Thesis (M.Med.Sc.)-University of Natal, 2003.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaves 263-321) Also available in print.

Made available in DSpace on 2014-06-11T19:32:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-12-07Bitstream added on 2014-06-13T20:24:25Z : No. of bitstreams: 1 nascimento_gvr_dr_botfm.pdf: 431185 bytes, checksum: 6bbeed7f487bb4cbad5e3143bf450b76 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Evidências apontam que o momento de início da diálise pode influenciar diretamente a evolução de pacientes portadores de Insuficiência Renal Aguda (IRA). Assim, a diálise precoce surge como meio adicional para reduzir a mortalidade nestes pacientes. Porém, os parâmetros utilizados para o início da terapia substitutiva renal (TSR) nestes casos ainda não estão estabelecidos. Objetivo: avaliar se pacientes com IRA por Necrose Tubular Aguda (NTA) submetidos a diálise com níveis baixos de uréia (inferior aos atualmente preconizados) apresentam menor mortalidade e maior recuperação renal comparados aqueles submetidos a TSR com uréia elevada. Métodos: corte retrospectiva de pacientes com IRA por NTA submetidos a diálise no período de marco de 2001 a maio de 2006 no HCUNESP. Os pacientes foram alocados em 2 grupos de acordo com os valores de uréia no momento da indicação da diálise: GI: 150 e GII:>150 mg/dl. IRA foi definida como um aumento de creatinina sérica > 30% do valor basal, excluídas causas pré-renais e pós-renais. Foram avaliados pacientes >18 anos, em diálise por mais de 48 h e com ATN-ISS < 0,9 e acompanhados até óbito, recuperação da função renal ou tempo em diálise > 30 dias. Estatística: Teste T e Mann-Whitney (comparação entre grupos) e Qui-quadrado, Exato de Fisher e Goodman (proporções). Nível de significância de 5%. Resultados: Foram analisados 1561 pacientes, sendo excluídos 861 por não apresentarem IRA por NTA. Dos 700 restantes, 333 (47,5%) foram submetidos a diálise, sendo excluídos 247. Os 86 pacientes restantes foram alocados em 2 grupos, sendo 23 em GI e 63 em GII. / There is evidence that the timing of dialysis initiation can influence the evolution of patients with acute renal failure (ARF). Also early dialysis seems to reduce mortality in these patients. However the parameters used at the start of renal replacement therapy (RRT) still are not established in these cases. Objective: to evaluate whether patients with ARF due to acute tubular necrosis (ATN), starting dialysis with low urea levels (lower than current recommendations) present less mortality and higher renal recuperation than those submitted to RRT with elevated urea. Patients and Methods: a retrospective cohort of patients with ARF due to ATN submitted to dialysis, from March 2001 to May 2006 at HC-UNESP. Patients were allocated into two groups according to urea values at time of RRT indication: GI.150 and GII>150 mg/dl. ARF was defined as serum creatinine >30% above basal value; pre and post renal causes were excluded. Patients were >18 years old, in dialysis for >48h, and with ATN-ISS <0.9; they were accompanied until death, renal function recovery, or RRT>30 days. Statistics: T and Mann-Whitney tests (comparison between groups) and Chi squared; Exact Fisher, and Goodman tests (proportions); significance level 5%. Results: From 1561 patients analyzed, 861 were excluded for not presenting ARF due to ATN. From the remaining 700, 333 (47.5%) were submitted to RRT, of these, 247 were excluded, leaving 86 patients (23 in GI and 63 in GII). Groups had similar median ages (GI: 61 and GII: 63 years); prognosis index: ATN-ISS (0.61and 0.67) and APACHE II (21 and 28); percentage of patients with prior end-stage renal disease (21.7% and 46%); in clinical wards (43.5% and 66.7%), and ICU (69.6% and 77.8%); number of RRT sessions (9 and 8); type of dialysis (hemodialysis: 43,5% and 20,7%) and dialysis dose received (Kt/V: 0.62}0.16 and 0.54}0.11). GI patients presented higher renal function recuperation (GI: 43.5%, GII 11.1%; p=0.

Made available in DSpace on 2014-06-11T19:27:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-12-13Bitstream added on 2014-06-13T19:35:39Z : No. of bitstreams: 1 galvao_sfv_me_botfm_prot.pdf: 503261 bytes, checksum: 325320966be17182448387b64650477c (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A Insuficiência Renal Aguda apresenta uma alta incidência em pacientes internados em hospitais terciários, principalmente em Unidades de Terapia Intensiva, estando associada a elevada mortalidade. Este trabalho tem como objetivos descrever a população de pacientes internados no Hospital das Clínicas de Faculdade de Medicina de Botucatu - UNESP com diagnóstico de Insuficiência Renal Aguda atendidos pelo Grupo de Interconsultas do Serviço de Nefrologia e avaliar os fatores de risco associados ao óbito nestes pacientes. Foram acompanhados 946 pacientes no período de abril de 2002 a dezembro de 2006, todos maiores de 12 anos, com diagnóstico de Necrose Tubular Aguda e internados nas diferentes enfermarias e Unidades de Terapia Intensiva do Hospital das Clínicas, exceto na Pediatria e Nefrologia. Insuficiência Renal Aguda foi definida como um aumento de creatinina sérica de pelo menos 30% de seu valor basal em período mínimo de 48 horas. A média de idade foi de 61,8 ± 16,7 anos, com predomínio do sexo masculino (61,9%). Pacientes provenientes de enfermarias clínicas foram mais freqüentes (62,1%), sendo que 15,9% estavam internados na cardiologia e 15,2% na clínica médica geral, enquanto 13,3% estavam internados na enfermaria de gastroenterologia cirúrgica. 46,1% estavam internados em Unidades de Terapia Intensiva e a sepse esteve presente em 9,7% dos casos. Isquemia (51,2%) foi a etiologia mais freqüente e o tempo de acompanhamento nefrológico apresentou mediana de 7,5 dias, com intervalo interquartílico de 4 a 14 dias. / Acute Renal Failure (ARF) present a high incidence in critically ill patients taken into tertiary care hospitais, mostly in the Intensive Care Unit (ICU) patients, were also associate with great mortality rate. The objective of this work was to describe the population of patients hospitalized in the School Medicine, Botucatu- UNESP with diagnosis of ARF, attended by Group of - Interconsults of Service Nephrology and to evaluate the risk factors associate with death in this patients. This was a cohort study which evaluated 946 patients with ARF, from April 2002 to December 2006, was included patients older than 12 years, with diagnosis of ARF due to Acute Tubular Necrosis (ATN) and hospitalized in wards and ICU of HC- FMBUNESP (except in the Pediatrics and Nephroloy wards). ARF was defined as serum creatinine at least 30% above basal value from 48 hours at minimum. The average of age was 61,8 ± 16,7 years, with predominantly masculine gender (61,9%). 15,9% were hospitalized in the cardiology and 15,2% in the clinical medical, while 13,3% were hospitalized in the gastroenterology surgical ward. 46,1% of patients were hospitalized in ICU and the sepsis was present in 9,7% of the cases. Ischemia was the etiology more frequent (51,2%) and the time of accompaniment nephrologic presented an median of 7,5 days (4 - 14).

Orientador: André Luís Balbi / Banca: Emmanuel de A. Burdemann / Banca: Domingos D'ávila / Banca: Regina Abdulkader / Banca: Pasqual Barreti / Resumo: Evidências apontam que o momento de início da diálise pode influenciar diretamente a evolução de pacientes portadores de Insuficiência Renal Aguda (IRA). Assim, a diálise precoce surge como meio adicional para reduzir a mortalidade nestes pacientes. Porém, os parâmetros utilizados para o início da terapia substitutiva renal (TSR) nestes casos ainda não estão estabelecidos. Objetivo: avaliar se pacientes com IRA por Necrose Tubular Aguda (NTA) submetidos a diálise com níveis baixos de uréia (inferior aos atualmente preconizados) apresentam menor mortalidade e maior recuperação renal comparados aqueles submetidos a TSR com uréia elevada. Métodos: corte retrospectiva de pacientes com IRA por NTA submetidos a diálise no período de marco de 2001 a maio de 2006 no HCUNESP. Os pacientes foram alocados em 2 grupos de acordo com os valores de uréia no momento da indicação da diálise: GI: 150 e GII:>150 mg/dl. IRA foi definida como um aumento de creatinina sérica > 30% do valor basal, excluídas causas pré-renais e pós-renais. Foram avaliados pacientes >18 anos, em diálise por mais de 48 h e com ATN-ISS < 0,9 e acompanhados até óbito, recuperação da função renal ou tempo em diálise > 30 dias. Estatística: Teste T e Mann-Whitney (comparação entre grupos) e Qui-quadrado, Exato de Fisher e Goodman (proporções). Nível de significância de 5%. Resultados: Foram analisados 1561 pacientes, sendo excluídos 861 por não apresentarem IRA por NTA. Dos 700 restantes, 333 (47,5%) foram submetidos a diálise, sendo excluídos 247. Os 86 pacientes restantes foram alocados em 2 grupos, sendo 23 em GI e 63 em GII. / Abstract: There is evidence that the timing of dialysis initiation can influence the evolution of patients with acute renal failure (ARF). Also early dialysis seems to reduce mortality in these patients. However the parameters used at the start of renal replacement therapy (RRT) still are not established in these cases. Objective: to evaluate whether patients with ARF due to acute tubular necrosis (ATN), starting dialysis with low urea levels (lower than current recommendations) present less mortality and higher renal recuperation than those submitted to RRT with elevated urea. Patients and Methods: a retrospective cohort of patients with ARF due to ATN submitted to dialysis, from March 2001 to May 2006 at HC-UNESP. Patients were allocated into two groups according to urea values at time of RRT indication: GI.150 and GII>150 mg/dl. ARF was defined as serum creatinine >30% above basal value; pre and post renal causes were excluded. Patients were >18 years old, in dialysis for >48h, and with ATN-ISS <0.9; they were accompanied until death, renal function recovery, or RRT>30 days. Statistics: T and Mann-Whitney tests (comparison between groups) and Chi squared; Exact Fisher, and Goodman tests (proportions); significance level 5%. Results: From 1561 patients analyzed, 861 were excluded for not presenting ARF due to ATN. From the remaining 700, 333 (47.5%) were submitted to RRT, of these, 247 were excluded, leaving 86 patients (23 in GI and 63 in GII). Groups had similar median ages (GI: 61 and GII: 63 years); prognosis index: ATN-ISS (0.61and 0.67) and APACHE II (21 and 28); percentage of patients with prior end-stage renal disease (21.7% and 46%); in clinical wards (43.5% and 66.7%), and ICU (69.6% and 77.8%); number of RRT sessions (9 and 8); type of dialysis (hemodialysis: 43,5% and 20,7%) and dialysis dose received (Kt/V: 0.62}0.16 and 0.54}0.11). GI patients presented higher renal function recuperation (GI: 43.5%, GII 11.1%; p=0. / Doutor

Orientador: Antonio Sérgio Martins / Banca: Antonio Sérgio Martins / Banca: Luis Cuadrado Martin / Banca: Marcos Augusto Moraes Silva / Banca: Noedir Antonio / Banca: Groppo Stolf / Resumo: A insuficiência renal aguda (IRA) no pós-operatório de cirurgia cardiovascular é causa de maior morbidade e mortalidade. A disfunção renal caracterizada pelo aumento da creatinina sérica deternina maior número de complicações operatórias e diminuição da sobrevida. Fatores de risco genéticos e no pré-operatório foram determinados, contudo, a influência dos fatores de risco intra-operatórios, a circulação extracorpórea e suas variáveis também devem ser considerados. A cirurgia de revascularização do miocárdio sem circulação extracorpórea tem sido utilizada para diminuir a morbidade. A hemodiluição durante a CEC tem sido relacionada ao aumento da IRA no pós-operatório de cirurgia cardiovascular. O ateroembolismo, a isquemia-reperfusão e a resposta inflamatória são mecanismos envolvidos na lesão renal em cirurgia cardiovascular. Os fatores relacionados à circulação extracorpórea devem ser monitorados no intra-operatório para a diminuir o risco de IRA em cirurgia cardiovascular. O objetivo desta revisão é avaliar os diferentes fatores de risco, com enfâse naqueles relacionados à circulação extracorpórea e à hemodiluição / Abstract: Acute renal failure after cardiovascular surgery is a risk factor for morbidity and mortality. Increase in serum creatinine is related to kidney dysfunction which determines augmentation of postoperative complications and affects long term-survival. Genetic and pre-operatory risk factors have been identified, however, cardiopulmonary bypass and its variables might be considered. Myocardial revascularization without cardiopulmonary bypass is being used to attenuates morbidity. Hemodilution during cardiopulmonary bypass has been related in the increase of acute renal failure following cardiopulmonary bypass. Although a diversity of mechanisms exist by which the kidneys may be damaged during cardiac surgery, atheroembolism, ischemia-reperfusion, and inflammation are believed to be primary contributors to perioperative renal insult. Variables related to cardiopulmonary bypass are easily monitored in the operating room and might be treated to attenuate kidney dysfunction. The objective of this revision is to evaluate risk factors, specially those related to cardiopulmonary bypass and hemodilution / Doutor