Made available in DSpace on 2014-06-11T19:25:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-21Bitstream added on 2014-06-13T20:14:15Z : No. of bitstreams: 1 pinto_mpr_me_botfm.pdf: 313356 bytes, checksum: 0e7af8768f28717e8fc720462d87afa7 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / É consenso na literatura que a desnutrição é freqüente em pacientes hospitalizados, devido principalmente a patologias que aumentam o risco nutricional, tais como a Injúria Renal Aguda (IRA). Sendo assim, a avaliação do estado nutricional nessa condição clínica torna-se uma ferramenta fundamental para a identificação de possíveis distúrbios nutricionais. Os objetivos deste trabalho foram realizar avaliação nutricional inicial e identificar, a partir desta, marcadores clínicos e nutricionais associados ao óbito em pacientes com IRA. Tratou-se de estudo prospectivo transversal realizado no Hospital das Clínicas da Faculdade de Medicina de Botucatu – UNESP no período de março de 2008 até março de 2010. Logo após a primeira avaliação nefrológica, foi realizada uma avaliação nutricional composta por dados clínicos, inquérito alimentar, balanço nitrogenado, antropometria, bioimpedância, Avaliação Subjetiva Global (ASG) e exames laboratoriais, tendo como desfecho o óbito. Foram avaliados 278 pacientes, com predomínio do sexo masculino e maiores de 60 anos, com mortalidade de 39,9%. Na análise multivariada, sepse, oligúria e necessidade de diálise estiveram associados a maior mortalidade. Quanto às características nutricionais e antropométricas, maior metabolismo basal, uso de dieta oral comparada ao jejum e maior ângulo de fase foram variáveis associadas a menor mortalidade, enquanto o uso de dieta parenteral comparada ao jejum, maiores valores de uréia e fósforo e menores valores de creatinina e albumina estiveram associados a maior mortalidade. Em conclusão, a partir da avaliação nutricional inicial, este estudo identificou variáveis associadas ao óbito que podem ser úteis no acompanhamento nefrológico de pacientes com IRA / There is consensus in the literature that malnutrition is frequent in hospitalized patients, mainly due to the presence of pathologies that increase the nutritional risk, such as Acute Kidney Injury (AKI), and thus the assessment of nutritional status in that clinical condition makes a fundamental tool for the identification of possible nutritional disorders. The objectives of this research were to realize initial nutritional assessment and identify, from this, clinical and nutritional markers associated with death in these patients. This was a transversal prospective study with patients with AKI, admitted to the HC-FMBUNESP of March 2008 until March 2010. Immediately after the first nephrology evaluation, was applied a nutritional assessment composed of clinical data, food investigation, nitrogen balance (NB), anthropometry, bioelectrical impedance, Subjective Global Assessment (SGA) and laboratory values, taking death as outcome. Were evaluated 278 patients, with predominance of males with a mortality of 39.9%. In the multivariate analysis, sepsis, oliguria and requirement dialysis were associated with greater mortality. As regards the nutritional and anthropometric characteristics, negative NB was present in 69.2% of the population. The other multivariate analyzes showed that greater basal metabolism, use of oral diet compared to fasting and greater phase angle were variables associated with lower mortality, while the use of diet parenteral compared to fasting, higher values of urea and phosphorus and lower creatinine and albumin were associated with greater mortality. In conclusion, from the initial nutritional assessment of patients with AKI, this study identified nutritional variables related to death, which must be assessed together with clinical variables, by nephrologist

Made available in DSpace on 2014-06-11T19:35:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-24Bitstream added on 2014-06-13T19:05:31Z : No. of bitstreams: 1 carraretto_ar_dr_botfm.pdf: 822756 bytes, checksum: d39d7bb3ab7eed1fb356cccaf87705ec (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A hiperglicemia aumenta a lesão renal na isquemiareperfusão em ratos anestesiados com isoflurano (Iso). Este efeito é desconhecido com o uso do propofol (Prop). O objetivo desse estudo é avaliar o efeito do isoflurano (Iso) e do propofol na lesão renal de isquemia-reperfusão na presença de hiperglicemia transitória.Utilizou-se 36 ratos Wistar machos, distribuídos de modo aleatório em seis grupos de seis animais, designados: PHS (Prop + Hiperglicemia - Sham); IHS (Iso + Hiperglicemia - Sham); PHI (Prop + Hiperglicemia + Isquemia); IHI (Iso + Hiperglicemia + Isquemia); PI (Prop + Isquemia) e II (Iso + Isquemia). A anestesia foi mantida com isoflurano (1,5 a 2%) (IHS, IHI e II) ou propofol (1 mg.kg-1.min-1) (PHS, PHI e PI). A pressão arterial média (PAM) foi medida para o controle da anestesia. A hiperglicemia foi induzida com a injeção de 2,5 g.kg-1 de solução de glicose por via intraperitoneal. Todos os animais foram submetidos à nefrectomia direita. Os dois grupos “sham” foram submetidos à hiperglicemia. Os demais grupos foram submetidos à isquemia renal por 25 minutos. Os valores plasmáticos da glicose e da creatinina foram determinados no início (M1), no final do experimento (M2) e 24 horas após o final do experimento (M3), quando os animais retornaram ao laboratório e foram anestesiados com isoflurano para coleta de uma nova amostra sanguínea e nefrectomia esquerda, para análise histológica, com o uso de uma escala para avaliação da necrose tubular (0 a 5 = lesão máxima), e avaliação por citometria de fluxo, para determinação dos percentuais da apoptose inicial (APTi) e de células viáveis (VC). Houve tratamento estatístico para os valores da PAM, glicose e creatinina plasmáticas escore de lesão histológica e avaliação da citometria de fluxo,sendo as diferenças consideradas significantes quando <0,05.A glicemia (mg.dL-1) em M2 foi maior nos grupos... / The hyperglycemia augments the renal ischemic-reperfusion injury (IRI) in rats anesthetized with isoflurane (Iso). This effect with propofol (Prop) is unknown. The purpose of this investigation was to examine the effect of isoflurane and propofol in renal ischemia/reperfusion injury (IRI) during transient hyperglycemia.Rats were randomly assigned in six groups of six animals, groups: PHS (Prop + Hyperglycemia - Sham); IHS (Iso + Hyperglycemia - Sham); PHI (Prop + Hyperglycemia + Ischemia); IHI (Iso + Hyperglycemia + Ischemia); PI (Prop + Ischemia) and II (Iso + Ischemia). Propofol in a dose of 1 mg.kg-1.min-1 (PHS, PHI and PI) or saline was infused (IHS, IHI and II). Mean arterial pressure (MAP) was monitored for anesthesia control. Hyperglycemia was induced with the injection of 2.5 g.kg-1 of glucose solution. All animals underwent to right nephrectomy. The two sham groups underwent to hyperglycemia with ischemia. The others groups were submitted to a left renal ischemia for 25 minutes. Serum creatinine and glucose values were determined in the beginning (M1) and at the end of experiment (M2) and 24 hours after the experiment (M3) rats were anesthetized with isoflurane and blood sample was collected and the left kidney removed for histological analysis, using a scale for tubular necrosis (0-5 = injury maximum). In addition to a histological study, cells from the left kidney were evaluated for apoptosis by flow cytometry (FCM) as a % of initial apoptosis (APTi) and viable cell (VC). Statistical analysis were applied to the values of MAP, serum creatinine and glucose, histological score injury and FCM and statistical differences were considered when p<0.05.Serum glucose at M2 was higher in PHS (351.8±141.0) and IHI (348.3±52.3) in relation to groups PI (147.0±62.4) and II (162.7±40.2). Groups IHS (302.5±80.0) and PHI (308.5±74.5) showedintermediary values. Serum creatinine... (Complete abstract click electronic access below)

Introduction: Patients with acute kidney injury (AKI) in developing countries are described in a profile of young age, with less comorbidities, with unifactorial, and with a lower mortality compared to patients in developed countries. Objective: To assess mortality in patients with acute kidney injury undergoing hemodialysis (HD) and its associated factors in a developing country setting. Methods: Retrospective study. Demographic, clinical, and mortality variables were collected from patients who presented AKI and underwent HD between January 2014 and December 2015 at a national reference hospital in Lima, Peru. Risk ratios (RR) and 95% confidence intervals (95%CI) were estimated through Poisson regressions. Results: Data from 72 patients with AKI that underwent HD were analyzed, 66.7% of them were < 64 years old, and 40.2% of all patients died undergoing HD. Crude analysis showed higher mortality among those who used vasopressors, but lower mortality among those with creatinine values > 8.9 mg/ dL. The adjusted analysis showed that having had a creatinine level of > 8.9 mg/ dL, compared to a creatinine level of < 5.2 mg/dL at the time of initiating HD, was associated with 74% less probability of death. Conclusion: Four out of every ten AKI patients undergoing HD die. Higher levels of creatinine were associated with lower probability of mortality.

INTRODUCTION: The worldwide incidence of acute kidney injury is 18% and the overall hospital mortality can rise above 50%. In Peru, there are few series about mortality of acute kidney injury in hemodialysis patients. OBJECTIVES: To identify risk factors associated to hospital mortality of acute kidney injury in hemodialysis patients. METHODS: This is a retrospective cohort of patients with acute kidney injury in hemodialysis of Hospital Nacional Edgardo Rebagliati Martins gathered between January 2013 and December 2015. The sample size was 154 patients which allowed a power of 80% and a CI of 95%. ICD-10 codes were used to identify medical records of patients with acute kidney injury (N.17) and hemodialysis (Z.49). The independent variable was oliguria, and the primary outcome was hospital mortality. Poisson regression was used for multivariate analysis. RESULTS: We identified a total of 285 patients; 212 medical records were analyzed and 44 were excluded. Out of the 168 medical records, 129 belonged to living patients and 39 to deceased ones. The overall mortality incidence was 17.2%. The principal etiologies of acute kidney injury while in hemodialysis were sepsis (39.2%), and severe dehydration (10.8%). In the adjusted model, the risk factors associated to hospital mortality of acute kidney injury while in hemodialysis were elevated serum lactate (RR 1.09), elevated serum potassium (RR 0.93), and mean arterial pressure (RR 0.97). CONCLUSIONS: Lactate is an objective parameter that can predict prognosis and contributes to a better management of acute kidney injury in hemodialysis patients. INTRODUCCIÓN: La incidencia de insuficiencia renal aguda a nivel mundial es 18% y la mortalidad intrahospitalaria puede alcanzar más del 50%. En Perú, existen escasos estudios acerca de la mortalidad en pacientes con insuficiencia renal aguda en hemodiálisis. OBJETIVOS: Identificar los factores de riesgo asociados a mortalidad intrahospitalaria en pacientes con insuficiencia renal aguda en hemodiálisis. MÉTODOS: Es una cohorte retrospectiva, en la cual se estudió a los pacientes con insuficiencia renal aguda en hemodiálisis en el Hospital Nacional Edgardo Rebagliati Martins entre enero de 2013 y diciembre de 2015. Se halló un tamaño de muestra de 154 pacientes con una potencia de 80%, y un intervalo de confianza de 95%. Se utilizaron los códigos de la Clasificación Internacional de Enfermedades-10 para identificar las historias clínicas de pacientes con insuficiencia renal aguda (N.17) y hemodiálisis (Z.49). La variable independiente fue oliguria y la variable dependiente fue mortalidad intrahospitalaria. Para el análisis multivariado, se utilizó regresión de Poisson. RESULTADOS: El universo fue de 285 pacientes. Se revisaron 212 historias clínicas y se excluyeron 44. De las 168 historias clínicas estudiadas, 129 pertenecían a pacientes vivos y 39 a fallecidos. La incidencia de mortalidad fue de 17,2%. Las principales causas de insuficiencia renal aguda en hemodiálisis fueron sepsis (39,2%) y deshidratación severa (10,8%). En el modelo ajustado, los factores de riesgo asociados a mortalidad intrahospitalaria de insuficiencia renal aguda en hemodiálisis fueron lactato (riesgo relativo 1,09), potasio (riesgo relativo 0,93), y presión arterial media (riesgo relativo 0,97). CONCLUSIONES: El lactato es un parámetro objetivo que permite predecir el pronóstico y contribuye a un mejor manejo de los pacientes con insuficiencia renal aguda en hemodiálisis.

Acute kidney injury (AKI) induced by renal ischaemia reperfusion injury (IRI) is characterised by renal failure, acute tubular necrosis (ATN), inflammation and microvascular congestion. Apoptotic cell administration reduces inflammation in experimental models of acute inflammation in the lung, joints and peritoneum. Preliminary data suggested that administration of 20x106 apoptotic thymocytes to mice 24-hours prior to renal IRI ameliorated renal function without affecting ATN 24-hours following IRI. This thesis attempted to validate these finding and explore underlying hypothetical mechanisms. These studies examined if functional protection was conferred by apoptotic cell modulation of (a) circulating IgM antibodies or (b) coagulation status leading to improved intrarenal microvascular blood flow. Pathogenic IgM antibodies bind ischaemic cardiac or skeletal muscle and the intestine leading to complement activation and worse injury. We examined IgM binding to human renal (HK-2) cells by flow cytometry and to ischaemic murine kidney tissue. H2O2 or Antimycin A treated HK-2 cells incubated with human serum (IgM source) exhibited no IgM binding. Medullary IgM deposition assessed by immunofluorescence was minimal following IRI. We also assessed IgM deposition by immunohistochemistry following hepatic IRI and discovered dramatic deposition. These data suggest that IgM antibodies exhibit differential binding to injured tissues and are not directly involved in renal IRI, but may have a role in hepatic IRI. To support our second hypothesis we studied apoptotic cell modulation of coagulation. A thrombin generation assay revealed that early apoptotic cell-treated mice exhibited delayed thrombin generation. Furthermore, in vitro studies confirmed direct apoptotic cell-platelet binding. To replicate apoptotic cell derived functional protection Balb/c mice underwent 20, 24 or 25-minutes of ischaemia to induce mild, moderate or severe kidney dysfunction. Renal function and injury was determined 24-hours following IRI by plasma creatinine measurement and ATN scoring. Unexpectedly, intravenous pretreatment of mice with apoptotic thymocytes conferred no protection. Indeed, apoptotic thymocytes further impaired renal function depending upon injury severity. Impairment of renal function was not secondary to increased microvascular congestion, inferred by fibrin and platelet deposition, neither increased ATN nor inflammation, assessed by neutrophil infiltration. These data indicate that apoptotic cell administration does not protect from subsequent renal IRI and that apoptotic cells are thus not inherently anti-inflammatory in all models of acute inflammation. Unable to replicate apoptotic cell derived functional protection we explored the binding of IgM antibodies to apoptotic cells which acts to facilitate dead cell clearance. We characterised IgM binding to non-apoptotic and apoptotic murine thymocytes and human Jurkat cells using flow cytometry, confocal and electron microscopy. We demonstrated specific IgM binding to a subset of late apoptotic cells. Electron microscopy indicated that IgM+ apoptotic cells exhibited marked plasma membrane disruption, suggesting that access to intracellular epitopes was required for IgM binding. Binding of IgM to permeabilised non-apoptotic and apoptotic cells suggested that IgM bound epitopes are ‘apoptosis independent’ such that IgM may bind any cell with profound plasma membrane disruption. Interestingly, permeabilised erythrocytes exhibited significant IgM binding thus supporting the importance of cell membrane epitopes. These data suggest that IgM may recognise and tag damaged nucleated cells or erythrocytes that exhibit significant cell membrane disruption.

Acute kidney injury (AKI), characterized by an abrupt loss of kidney function with retention of nitrogenous waste products, is common in the months to years following kidney transplantation and is associated with an increased risk of transplant failure (graft loss). Kidney transplant patients who experience graft loss and return to dialysis have an increased mortality risk and a lower quality of life. Research involving kidney transplant patients can prove challenging, as they are relatively small in number. To increase statistical power, researchers may utilize administrative databases. However, these databases are not designed primarily for research, and knowledge of their limitations is needed, as significant bias can occur. When using administrative databases to study AKI in kidney transplantation, the method used to define AKI should be carefully considered. The power of a study may be greatly increased if AKI can be accurately defined using administrative diagnostic codes because data on AKI will be universally available for all patients in the database. However, the methods by which diagnostic codes are assigned to a patient allow for error to be introduced. We confirmed that, when compared to the gold standard definition for AKI of a rise in serum creatinine, the diagnostic code for AKI has low sensitivity but high specificity in the kidney transplant population (the best performing coding algorithm had a sensitivity of 42.9% (95% CI 29.7, 56.8) and specificity of 89.3% (95% CI 86.2, 91.8) (Chapter 3). We therefore determined that for the study outlined in Chapter 4, defining AKI using diagnostic codes would significantly under-­capture AKI and misclassify patients. We decided to define AKI using only serum creatinine criteria even though this would limit our sample size (creatinine data was only available for a subset of patients in the administrative databases). In Chapter 4, we derived an index score to predict the risk of graft loss in kidney transplant patients following an admission to hospital with AKI. The index includes six readily available, objective clinical variables that increased the risk of graft loss: increasing age, increased severity of AKI (as defined by the AKIN staging system), failure to recover from AKI, lower baseline estimated glomerular filtration rate, increased time from kidney transplant to AKI admission, and deceased donor. The derived index requires validation in order to assess its utility in the clinical realm.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13330号 / 論医博第2198号 / 新制||医||1044(附属図書館) / 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 羽賀 博典, 教授 山下 潤 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Ľubica Múčková Supervisor: Prof. MUDr. Jaroslav Dršata, CSc. Consultant: Ing. Jana Netriová, PhD. Title of diploma thesis: Laboratory diagnostics of kidney injury in patients with diabetes mellitus I and II Diabetes mellitus is a chronic metabolic disease. This disease leads to develompement of both microvascular and macrovascular complications. In this work we examined a microvascular complication - diabetic nephropathy - and its laboratory diagnostics. We focussed on parameters cystatin C and creatinine. We estimated a glomerular filtration with Grubb, Stevens and MDRD equations. The Grubb and Stevens equations use cystatin C to determine the glomerular fitrlation rate (GFR), MDRD equations use creatinine, albumin and urea. For the asessment of kidney function we evaluated albumin and total protein waste in urine samples collected for 24 hours. The parameters were measured in file of 183 patients. Number of pacients with diabetes I.type was 49 and with diabetes II.type was 134. The main intention of this work was to evaluate equations used for determination of GFR, to compare their pros and cons and put them in contrast with albumin and total proteins waste. In case of the patients...

Background and Aim: Acute kidney injury (AKI) is used as a marker of severity in Clostridium difficile infection (CDI) patients. We estimated the true effect of AKI in inpatient mortality of CDI patients, as there are no large-scale, population-based, propensity-matched studies evaluating AKI's effect in this patient cohort. Methods: A retrospective observational study utilizing the National Inpatient Sample from years 2003 to 2012, including all adults with CDI, excluding cases missing data on age, inpatient mortality or gender. Trends and CDI-related complications as mortality predictors were assessed using survey-weighted multivariable regression. We estimated AKI's independent effect by propensity-matching, post-stratifying by chronic kidney disease status, allowing for multiple comorbidity adjustment. Results: A total of 2 859 599 patients with CDI were included, of which 896 122 (31.3%) had principal diagnosis of CDI. AKI prevalence was 22%. Mortality rate was 8.4%, while among AKI patients was higher (18.2%). In multivariable regression, AKI was associated with higher mortality (odds ratio [OR] = 3.16, 95% confidence interval [CI]: 3.02–3.30; P < 0.001), while after propensity matching, AKI increased mortality by 86% (OR = 1.86, 95% CI: 1.79–1.94; P < 0.001). CDI incidence increased by 1.8, together with the rate of AKI (12.6% in 2003 to 28.8% in 2012, P-trend < 0.001). Despite increasing hospitalizations, mortality over the study period decreased to 7.2% (2012) from 9.0% (2003); P-trend < 0.001. Conclusion: Hospital admissions of patients with CDI and concomitant AKI are increasing, but their inpatient mortality has improved over the study period. AKI is a significant contributor to mortality, independently of other comorbidities, complications, and hospital characteristics, emphasizing the need for early diagnosis and aggressive management in such patients.

Indiana University-Purdue University Indianapolis (IUPUI) / Acute kidney injury (AKI) affects millions of patients worldwide yet has few treatment options. There is a critical need to identify novel interventions for AKI, especially approaches targeting cell types that are central to the disease, such as neutrophils. Neutrophils are professional phagocytic cells that respond early to tissue injury. In rodent models of severe ischemic-reperfusion-injury AKI, neutrophils transiently infiltrate the injured kidney, appearing within 6 hours, and are gone by 72 hours. These infiltrating neutrophils are considered proinflammatory and harmful to tissue repair and recovery of kidney function. However, neutrophils can exhibit atypical activity such as antigen presentation and have a central role in recovery from myocardial ischemic injury. Furthermore, little is known of neutrophil polarization, atypical activity, or neutrophil diversity in AKI. Lastly, the kidney generated and renal-protective immunomodulatory protein uromodulin (Tamm-Horsfall Protein, THP) regulates granulopoiesis. In the absence of uromodulin, there is a systemic increase in neutrophils and mouse kidneys are sensitive to injury in AKI. To elucidate neutrophil diversity in AKI and their sensitivity to uromodulin, I performed a series of single-cell sequencing experiments to generate transcriptional profiles of neutrophils from the blood and kidneys of wild-type and THPknockout mice after renal ischemic-reperfusion-injury (IRI). Neutrophil diversity was detected following IRI of the mouse kidney in the blood and kidney. The distribution of subpopulations was sensitive to the kidney milieu. Within the kidney, this diversity and the transcriptional programs of neutrophil subpopulations was sensitive to the severity of ischemic injury. Lastly, Cxcl3 was uniquely upregulated in specific neutrophils after severe ischemic injury. Using single-cell sequencing of uromodulin knock-out mice, I detected the upregulation of toll-like receptor pathways and complement cascades across neutrophil subpopulations in a THP sensitive manner. Furthermore, CXCR2 ligand expression was a combination of moderate and severe injury in wild-type mice. This confirmed previously reported cytokine dysregulation in the uromodulin knock-out mouse after IRI and uncovers a novel role for Cxcl3. Thus, upon revisiting the well-studied neutrophil, I have uncovered novel neutrophil diversity that correlates with recovery of kidney function in AKI and suggests new roles for an old player.