Made available in DSpace on 2014-06-11T19:30:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-12-12Bitstream added on 2014-06-13T21:00:59Z : No. of bitstreams: 1 taniguchi_fp_dr_botfm.pdf: 574800 bytes, checksum: 10af142c1ac5d57d2fa2fe16744a2f5b (MD5) / 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. / 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.

Objectives: To assess national trends of AP (acute pancreatitis) admissions, outcomes, prevalence of AKI (acute kidney injury) in AP, and impact of AKI on inpatient mortality. Methods: We queried the Nationwide Inpatient Sample database from 2003 to 2012 to identify AP admissions using ICD-9-CM codes. After excluding patients with missing information on age, gender, and inpatient mortality, we used ICD-9-CM codes to identify complications of AP, specifically AKI. We examined trends with survey-weighted multivariable regressions and analyzed predictors of AKI and inpatient mortality by multivariate logistic regression. Additionally, both AKI and non-AKI groups were propensity-matched and regressed against mortality. Results: A total of 3,466,493 patients (1.13% of all discharges) were hospitalized with AP, of which 7.9% had AKI. AP admissions increased (1.02%→1.26%) with rise in concomitant AKI cases (4.1%→11.7%) from year 2003–2012. Mortality rate decreased (1.8%→1.1%) in the AP patients with a substantial decline noted in AKI subgroup (17.4%→6.4%) during study period. Length of stay (LOS) and cost of hospitalization decreased (6.1→5.2 days and $13,654 to $10,895, respectively) in AKI subgroup. Complications such as AKI (OR: 6.08, p < 0.001), septic shock (OR: 46.52, p < 0.001), and acute respiratory failure (OR: 22.72, p < 0.001) were associated with higher mortality. AKI, after propensity matching, was linked to 3-fold increased mortality (propensity-matched OR: 3.20, P < 0.001). Conclusion: Mortality, LOS, and cost of hospitalization in AP has decreased during the study period, although hospitalization and AKI prevalence has increased. AKI is independently associated with higher mortality.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / The young field of gene therapy offers the promises of significant progress towards the treatment of many different types of human diseases. Gene therapy has been proposed as an innovative way to treat Acute Kidney Injury (AKI). Through proteomic analysis, the upregulation of two enzymes, IDH2 and SULT1C2, within the mitochondrial fraction has been identified following ischemic preconditioning, a treatment by which rat kidneys are protected from ischemia. Using the hydrodynamic fluid gene delivery technique, we were able to upregulate the expression of IDH2 and SULT1C2 in the kidney. We found that the delivery of IDH2 plasmid through hydrodynamic fluid delivery to the kidney resulted in increased mitochondrial oxygen respiration compared with injured kidneys without gene delivery. We also found that renal ischemic preconditioning altered the membrane fluidity of mitochondria. In conclusion, our study supports the idea that upregulated expression of IDH2 in mitochondria can protect the kidney against AKI, while the protective function of upregulated SULT1C2 needs to be further studied.

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

Background: Dialysis is an intervention that involves the use of fairly advanced technology and is fairly expensive. Patients and health care funders are increasingly demanding evidence for the effectiveness for such high technology high cost interventions. While dialysis therapy has improved immediate prognosis in patients with kidney failure, the long-term survival of patients on chronic renal replacement therapy (dialysis or renal transplantation) is much lower than that of the general population and the mortality rates remain high for patients with acute renal failure needing dialysis. There are considerable variations between different countries and even between the dialysis centres within the same country with regards to the selection of the primary type of dialysis (haemodialysis or peritoneal dialysis) and in the different methods or equipment used to perform the various components of these various modalities. It is possible that variations in clinical practice are associated with variations in clinical outcomes such as mortality and morbidity. It is then important to identify the best practices from the various variations in current use and implementing these best practices may reduce morbidity and mortality of these patients. Methods: Systematic reviews, identifying and including only randomised trials, focusing on key clinical policy decision points in the dialysis process were undertaken. The review of literature was done in a systematic way according to a detailed scientific methodology. For all of the systematic reviews, a detailed protocol was written and agreed to by the authors of the review. The protocol detailed the clinical question, the types of studies, participants, interventions and outcomes to be included, search strategy and the statistical methods to be employed. Relevant randomised studies were then identified by systematically searching the electronic medical databases and reference lists of published studies; data relevant to predetermined outcome measures were extracted and where appropriate summary statistics were derived from meta-analysis. Recommendations and implications for clinical practice and future research studies were made following each review. The areas of dialysis policy reviewed were (1) Comparison of high-flux versus low-flux haemodialysis (HD) membranes for patients with end-stage renal disease (ESRD), (2) Comparison of extracorporeal renal replacement therapy technologies for patients with ESRD, (3) Comparison of intermittent (IRRT) and continuous renal replacement therapy (CRRT) for acute renal failure (ARF) in adults, (4) Comparison of antimicrobial interventions for the prevention of HD catheter related infections, (5) Comparison of continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) for patients with ESRD, and (6) Comparison of treatment measures for depression in dialysis patients. Conclusions: As the currently available evidence has not demonstrated superiority with high-flux membranes with respect to important clinical outcomes such as mortality, quality of life and hospitalisation, it is not possible to recommend the use of these membranes in preference to low-flux membranes. It has not been possible at present to demonstrate with the current evidence available that convective modalities (HF, HDF or AFB) have significant advantages over HD with regard to clinically important outcomes of mortality, dialysis-related hypotension and hospitalisation. It is not therefore possible to recommend the use of one modality in preference to the other. In ARF patients who are haemodynamically stable, the RRT modality does not appear to influence important patient outcomes, and therefore the preference for CRRT over IRRT in such patients does not appear justified in the light of available evidence. CRRT was shown to achieve better haemodynamic parameters such as MAP. APD appears to be more beneficial than CAPD, in terms of reducing peritonitis rates and with respect to certain social issues that impact on patients' quality of life. Further, adequately powered trials are required to confirm the benefits for APD found in this review and detect differences with respect to other clinically important outcomes that may have been missed by the trials included in this review due to their small size and short follow-up periods. APD may however be considered advantageous in select group of patients such as in the younger PD population and those in employment or education due to its psychosocial advantages. Firm conclusions on the efficacy of treatment measures for depression in chronic dialysis patients cannot be made as we identified only one small RCT that was of short duration. Current screening tools for depression are recognised to have poor specificity in the medically ill due to overlap of somatic symptoms of the medical illness. The development of a valid diagnostic tool would be helpful. The systematic reviews in general highlighted the paucity of large-scale randomised trials in nephrology even on topics of great practical relevance such as depression in dialysis. In many of the areas assessed adequate conclusions could not be reached as there was a lack of large-scale well designed randomised controlled trials raising the possibility that important clinical differences between the interventions assessed may have been missed due to Type 2 statistical error. We identified numerous RCTs which were small in size looking at surrogate end-points such as molecular markers of inflammation, especially in the areas of membrane flux and extracorporeal RRT technologies. Unfortunately benefits with surrogate end-points do not necessarily translate to better clinical outcomes. The urgent need of the hour is to conduct well-designed large scale RCTs in major areas of clinical importance such as the use of extracorporeal renal replacement therapy technologies looking at hard clinical end-points such as mortality, hospitalisation and quality of life.

A prevalência de LRA no pós-operatório (PO) de cirurgia cardíaca varia em torno de 5% a 31%, dependendo da população estudada e do critério adotado para sua definição. Os objetivos deste estudo foram classificar a função renal de pacientes em pós-operatório de cirurgia cardíaca, utilizando o sistema classificador RIFLE (R="risk", I="injury", F="failure", L= ‘loss" e E="end-stage") e avaliar o desempenho discriminatório de um marcador de taxa de filtração glomerular, a Cistatina C (CC). A amostra compôs-se de 121 pacientes, sem história de lesão renal prévia, acompanhados nas 24 , 48 e 72 horas. Os desfechos considerados foram alta ou óbito no PO. O RIFLE foi utilizado para comparação com demais variáveis, bem como dois de seus componentes, a creatinina plasmática e o clearance de creatinina. As categorias “R", “I" e “F" do RIFLE foram consideradas como LRA. A idade média dos pacientes foi de 50 anos, com 61,2% de sexo masculino, 38,8% de sexo feminino e predomínio da raça branca (92%). A cirurgia valvar foi a mais realizada (48,8%), seguida de 43,8% de revascularização do miocárdio e 7,4% de cirurgias combinadas, sendo que em 78% dos pacientes foi adotada a circulação extracorpórea com duração máxima de 120 minutos. A grande maioria (97,5%) dos pacientes obteve alta hospitalar. A LRA ocorreu em 78,5% pelo critério RIFLE. Quanto à CC, constatou-se relação de seus níveis com a piora da função renal vista pelo RIFLE nos períodos estudados. A CC apresentou maior sensibilidade e especificidade do que a Creatinina (Cr) para sinalização de piora da função renal com área sob a curva (0,67 vs 0,62). O estudo confirmou melhor desempenho da CC para detecção de LRA do que a Cr em PO da cirurgia cardíaca / The prevalence of acute kidney injury (AKI) in the postoperative period of cardiac surgery ranges from 5 to 31%, depending on the population studied and the criteria used for its definition. The objectives of this study were to classify the renal function of the patients in the postoperative period of cardiac surgery according to the RIFLE classification (Risk, injury, Failure, Loss and End-stage) and to assess the discriminating power of a glomerular filtration rate marker, the Cystatin C (CC). The sample was composed by 121 patients, with no kidney failure history, who were followed up 24, 48 and 72 hours after surgery. The outcome considered were hospital discharge or death. RIFLE was used as basis to compare the other variables, as well as two of its components: the Serum Creatinine (Cr) and the Creatinine Clearance. Patients classified as “R", “I" and “F" were considered with AKI. The mean age of the patients was 50 years, with 61.2% of males, 38.8% of females and a preponderance of Caucasians (92%). The valve surgery was the most performed surgery (48.8%), followed by 43.8% of myocardial revascularization and 7.4% of combined surgery. In 78% of the cases, a coronary artery bypass grafting was adopted and lasted 120 minutes time or less. The great majority (97.5%) of the patients were discharged from hospital. The AKI occurred in 78.5% of the sample using the RIFLE criteria. Regarding the CC, it was noticed a relationship between its levels and the worsening of the renal function, according to RIFLE, in the studied period. The CC presented a higher sensibility and specificity than Cr to signal the worsening of the renal function (area under the curve 0.67 vs. 0,62). The study confirmed a better performance of the CC than the Cr marker to detect AKI in the postoperative period of cardiac surgery

A lesão de isquemia e reperfusão (IRI) continua a ser um problema clínico e o estresse do retículo endoplasmático (ERS) parece ser um importante mediador desse processo. A presença da heme oxigenase-1 (HO-1) ou do monóxido de carbono (CO), parece proteger da IRI. O objetivo do nosso trabalho foi avaliar a papel da HO-1 e CO na IRI renal. A indução da HO-1 em camundongos promoveu uma proteção na IRI renal, com melhora da função renal, menos inflamação e atenuação do ERS. Ao avaliarmos o papel do CO, verificamos que há também uma proteção, mediada por p38, vias purinérgicas, estabilização de HIF-1a e eritropoietina. Há ainda uma melhora do metabolismo energético celular após o tratamento com CO. Enfim, podemos concluir que, na presença da HO-1 ou do CO, há uma melhora da lesão isquêmica, através de uma maior ativação de vias citoprotetoras, com atenuação do ERS, redução da inflamação e consequente melhora da função renal. / Ischemia-reperfusion injury (IRI) remains a clinical problem and endoplasmic reticulum stress (ERS) seems to be an important mediator of this process. The presence of heme oxygenase-1 (HO-1) or carbon monoxide (CO) appears to protect from IRI. The aim of our study was to evaluate the role of HO-1 and CO in renal IRI. The induction of HO-1 in mice promoted protection in renal IRI with improved renal function, less inflammation and attenuation of ERS. When evaluating the role of CO, we found that there is also a protection mediated by p38, purinergic signaling, HIF-1a stabilization and erythropoietin. There is still an improvement of cellular energy metabolism after treatment with CO. Finally, we conclude that, in the presence of HO-1 or CO, there is an improvement of the ischemic lesion, through greater activation of cytoprotective pathways, with reduced ERS, reducing inflammation and consequent improvement in renal function.

The possibility that changes in membrane transport systems may contribute to the pathophysiology of the uraeraic syndrome has not been extensively studied. This thesis presents a study of eight erythrocyte membrane transport systems, namely the Na/K pump, the amino acid systems y⁺, ASC, gly, L and T, the nucleoside and choline transporters. The results indicate that, compared to normal controls, K⁺ flux through the Na/K pump was reduced in chronic renal failure patients (CRF), on haemodialysis (HD), and on continuous ambulatory peritoneal dialysis (CAPD), but was normal in functional transplant (FT) patients' erythrocytes. The number of Na/K pumps per erythrocyte was decreased in CRF and CAPD but showed no differences between HD, FT and Normal controls. The mean turnover rate per pump site was reduced in patients on HD, whereas other groups were not significantly different from controls. Cross-incubation experiments suggest that the lowered pump flux seen in the HD group was due to plasma factors since reversibility of the defect was achieved when those cells were incubated in normal plasma. The defect was completely reversed with a successful transplant. Erythrocytes from haemodialysis patients exhibited an increased uptake of L-lysine through the y⁺ system. The uptake of L-serine was decreased and the affinity of the ASC system for L-serine was increased in these patients compared with controls. The glycine transporter showed a significant increase in affinity for glycine. The flux of L-leucine and L-tryptophan showed no differences from control cells. Erythrocyte membrane transport of uridine was similar in normal control cells and in those obtained from uraemic patients. Choline influx rates were significantly increased and affinity of the transporter for choline reduced in dialysis patients' erythrocytes. Renal transplant and CRF patients showed variable influx rates which gave a significant negative correlation with creatinine clearance. These results show that there are selective abnormalities in some membrane transport system of the erythrocyte in patients with renal failure. The mechanism and possible significance of these changes are discussed.

Thematic Paper (M.C.T.M. (Clinical Tropical Medicine))--Mahidol University, 2008. / LICL has E-Thesis 0038 ; please contact computer services. LIRV has E-Thesis 0038 ; please contact circulation services.