Les maladies rénales chroniques (MRC) et l'insuffisance rénale aiguë (IRA) sont des problèmes essentiels de santé publique en raison de l'augmentation continue de leur fréquence et du manque de solutions thérapeutiques contre ces maladies. L'acide lysophosphatidique (LPA) est un lysophospholipide bioactif qui induit un large éventail de réponses cellulaires par le biais de récepteurs membranaires spécifiques (LPA1 à LPA6) couplés aux protéines G. Dans ce travail, nous nous sommes intéressés aux effets biologiques et au métabolisme du LPA dans les MRC et l'IRA. Des travaux antérieurs de l'équipe avaient montré que le LPA contribuait, via le récepteur LPA1, au développement de la fibrose tubulointerstitio (TIF) dans un modèle de MRC chez la souris : l'obstruction urétérale. Dans la première partie de la thèse nous avons étudié l'implication du LPA dans un modèle plus avancé de MRC: la néphrectomie subtotale (SNX) chez la souris. Nos travaux ont montré que 5 mois après chirurgie les souris (SNX) développaient une albuminurie massive associée à une TIF sévère et à une hypertrophie glomérulaire. Chez ces souris la concentration en LPA mesurée par chromatographie liquide en spectrométrie de masse en tandem était augmentée dans l'urine et étroitement corrélée à l'albuminurie et à la TIF. En parallèle, nous avons observé une diminution de l'expression rénale des Lipid-Phosphate Phosphatases (LPP 1, 2 et 3) responsables de l'inactivation du LPA. Nous avons également observé que l'expression rénale des récepteurs LPA1, 2, 3 et 4 était diminuée chez les souris Snx. Nous avons conclu que les effets délétères éventuels du LPA dans le développement de la MRC chez les souris SNX était vraisemblablement lié à une augmentation de sa production rénale plutôt qu'à une sensibilité accrue du rein au LPA. Des travaux antérieurs avaient montré que l'injection de LPA protégeait contre l'apparition des lésions rénales induites par ischémie/reperfusion chez la souris. Une autre étude avait montré que le LPA permettait d'atténuer l'inflammation systémique et les dommages aux organes induits par un choc septique. Dans la deuxième partie de la thèse, nous avons étudié l'influence du LPA sur l'IRA induite par une endotoxémie au LPS (lipopolysaccharide) chez la souris. Nous avons observé que l'injection de LPA permettait d'atténuer l'élévation d'urée et de créatinine plasmatiques, ainsi que l'augmentation d'expression rénale de cytokines inflammatoires (IL-6, TNFa, MCP-1) induites par le LPS. Le LPA a également empêché la baisse d'expression rénale du facteur PGC1a ainsi que les altérations ultra-structurales des mitochondries rénales induites par le LPS. In vitro, le LPA atténue l'augmentation d'expression des cytokines pro-inflammatoires (TNFa et MCP-1) induite par le LPS dans les macrophages RAW264. Enfin, nos travaux ont montré que l'endotoxémie au LPS chez la souris entrainait une réduction de la concentration urinaire de LPA associée à une réduction des enzymes anaboliques LPA (autotaxine et acylglycérol kinase) et une élévation de l'expression de de LPP2, dans le cortex rénal. Nous en avons conclu que l'IRA associée à l'endotoxémie pourrait être liée, au moins en partie, à une réduction de la production rénale de LPA et, par voix de conséquence, de ses effets anti-inflammatoires protecteurs de la fonction rénale. En conclusion, notre travail montre que les variations de production rénale de LPA pourraient jouer un rôle important dans le développement des maladies rénales. L'augmentation du LPA dans les MRC favoriserait ses effets délétères (fibrose, inflammation). Sa réduction dans l'IRA réduirait ses effets anti-inflammatoires. Cibler le catabolisme LPA pourrait donc être une approche intéressante dans le traitement des maladies rénales. / Both chronic kidney diseases (CKD) with consecutive development of end stage renal disease (ESRD) and acute kidney injury (AKI) represent worrying problems for healthcare system due to its increased frequency and the lack of efficient treatments. Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that elicits a wide range of cell responses (proliferation, migration, transformation, contraction etc.) through the activation of specific G protein-coupled receptors (LPA1 to LPA6). In this work we were interested in involvement of the LPA and changes in its metabolism in CKD and AKI. Previous works showed that LPA exerts pro-fibrotic activity and contributes to development of tubulointerstitioal fibrosis (TIF) after ureteral obstruction through activation of LPA1 receptors. In the first part of the thesis we were interested whether LPA signalization is involved in more advanced model of the disease. We found that 5 months after subtotal nephrectomy (SNX) mice develop massive albuminuria, TIF and glomerular hypertrophy compared to control animals. LPA concentration measured by liquid chromatography tandem mass spectrometry was increased in urine but not in plasma of animals. That increase in LPA significantly correlated with albuminuria and TIF. In addition we found a decreased renal expression of lipid phosphate phosphatases (LPP1, 2 and 3) that are responsible for the degradation of LPA by dephosphorylation. Moreover, the expression of LPA1-LPA4 receptors is down-regulated, whereas LPA5 and LPA6 are unchanged. We concluded here that the possible deleterious effect of LPA in the development of CKD in SNX mice was likely related to its increased production rather than an increased sensitivity of the kidney to LPA. Since LPA was reported previously to protect kidney damage in the course of ischemia/reperfusion injury, and that it was able to mitigate the systemic inflammation and organ damage in sepsis, we were interested in second part of the thesis to determine whether exogenous and/or endogenous LPA might protect against sepsis-associated AKI. C57BL/6 mice were treated with exogenous LPA 18:1 1 hour before being injected with the lipopolysaccharide (LPS) and AKI was analyzed after 24h. LPA pre-treatment significantly mitigated the LPS-induced elevation of plasma urea and creatinine, lessened the up-regulation of inflammatory cytokines (IL-6, TNFa, MCP-1) and completely prevented the down-regulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1a) in kidney. LPA also prevented LPS-mediated alterations of renal mitochondria ultrastructure. In vitro, pre-treatment with LPA 18:1 (10 µM) significantly attenuated LPS-induced up-regulation of the pro-inflammatory cytokines (TNFa and MCP-1) in RAW264 macrophages. In addition we found that LPS led to the reduction of urinary LPA concentration that was associated with a reduction in LPA anabolic enzymes (autotaxin and acylglycerol kinase), and an elevation in LPA catabolic enzyme (lipid phosphate phosphatase 2) expression in kidney cortex. We concluded hereby that exogenous LPA exerts protection against endotoxemia-induced kidney injury. Moreover, the observation that LPS reduces the renal production of LPA suggests that sepsis-associated AKI could be mediated, at least in part, by alleviation of the protective action of endogenous LPA. In general our work shows that LPA local metabolism is altered in both forms of kidney diseases. In course of sepsis-induced AKI LPS leads to increased local catabolism of LPA leading to low availability of the phospholipid and alleviating its protective effect whereas in advanced CKD the local catabolism of the phospholipid is decreased with subsequent increase of urine LPA that favors development of the disease. Targeting LPA catabolism can be an interesting approach in treatment of kidney diseases.

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Hintergrund: Die regionale Citrat-Antikoagulation im Rahmen der Nierenersatztherapie hat bei interdisziplinären Intensivpatienten in den letzten Jahren zunehmend an Bedeutung gewonnen. Für Schwerbrandverletzte existieren bislang kaum Untersuchungen zu diesem Verfahren. Ziel dieser Arbeit war es, die kontinuierliche Nierenersatztherapie mit Citrat-Antikoagulation bei Intensivpatienten mit akutem Nierenversagen nach schwerem Verbrennungstrauma im Hinblick auf Praktikabilität, Effektivität und Komplikationshäufigkeit sowie die Stabilität von Elektrolyt- und Säure-Basen-Haushalt und Gerinnung zu untersuchen. Daneben sollten Aussagen zur Prävalenz des akuten Nierenversagens in dieser Patientengruppe und zu dessen Einfluss auf die Letalität getroffen werden. Methode: Im Rahmen einer retrospektiven Untersuchung wurden unter Verwendung von Patientenakten und Patientendatenmanagementsystem (PDMS) Daten von 27 Schwerbrandverletzten (VKOF ≥ 20% oder ABSI ≥ 8) mit akutem Nierenversagen ausgewertet, die zwischen Januar 2004 und Dezember 2009 im Verbrennungszentrum des Klinikums Sankt Georg Leipzig mit einer kontinuierlichen Nierenersatztherapie behandelt wurden. Bei allen Patienten kam ein Dialysegerät Prisma CFM (Gambro Hospal GmbH, Deutschland) mit einer Polyacrylnitril-Filtermembran (AN 69, Filterset M 100) der gleichen Firma zum Einsatz. Standardverfahren war eine kontinuierliche veno-venöse Hämodiafiltration (CVVHDF) im Prädilutionsmodus. Bei 18 Patienten wurde eine regionale Citrat-Antikoagulation als Antikoagulationsverfahren eingesetzt, bei 7 Patienten eine systemische Heparin-Antikoagulation, bei 2 Patienten kamen alternierend beide Verfahren zum Einsatz. Für die 18 Patienten unter regionaler Citrat-Antikoagulation erfolgte eine detaillierte Analyse des akuten Nierenversagens unter Einbeziehung des klinischen Verlaufes, der Laborparameter und der Behandlungsdaten des Nierenersatzverfahrens. Ergebnisse: Die Prävalenz eines akuten Nierenversagens mit Notwendigkeit zur Nierenersatztherapie bei Schwerbrandverletzten betrug 15,5%. Die Sterblichkeitsrate war in der Patientengruppe mit Nierenversagen etwa fünffach erhöht (25,9 vs. 4,8%). Die Letalitätsrate bei den Patienten unter systemischer Heparin-Antikoagulation war bei vergleichbarem Verbrennungsausmaß etwa fünfmal höher als unter regionaler Citrat-Antikoagulation (57,1 vs. 11.1%). Die Nierenersatztherapie wurde im Median nach 6 Tagen begonnen, die mediane Behandlungsdauer pro Patient betrug 7 Tage. Bei Start der CVVHDF wiesen 94,4% der Patienten einen Schockzustand mit Notwendigkeit einer Vasopressortherapie auf, 83,3% zeigten schwere Dysfunktionen in mindestens 3 Organsystemen, der SOFA-score lag im Median bei 14. Bei einer mittleren Citratkonzentration von 3,6 mmol/l Blut im Extrakorporalkreiskauf konnte eine mediane effektive Filterlaufzeit von 67 Stunden erreicht werden. Hypocalcämien (<0,9 mmol/l) fanden sich in 1,1%, Hypercalcämien (>1,3 mmol/l) in 0,4%. Hypernatriämien (<150 mmol) waren mit 0,4% ebenso selten wie metabolische Alkalosen (pH >7,50 und BE >4) mit 0,2%. Im Gesamtdialysezeitraum von 3790 Stunden gab es nur ein Blutungsereignis, die Gerinnungsparameter zeigten bis auf einen passageren Abfall der Thrombozytenzahl keine signifikanten Veränderungen. Die erzielte mittlere Dialysedosis war mit 35,1 ml/kg Körpergewicht/h ausreichend hoch. Neben einer Reduktion der Nierenretentionsparameter Serum-Creatinin und Serum-Harnstoff fanden sich unter dem Nierenersatzverfahren verbesserte Oxygenierungsindices und sinkende SOFA-scores. Keiner der überlebenden Patienten war zum Zeitpunkt der Entlassung dialysepflichtig. Zusammenfassung: Die CVVHDF unter regionaler Citrat-Antikoagulation ist bei Schwerbrandverletzten ein effektives und in Bezug auf Säure-Basen-Haushalt, Elektrolyte und Gerinnung sicheres Verfahren. Neben einer effektiven Elimination harnpflichtiger Substanzen konnten eine exzellente Stabilität von Elektrolyten und metabolischen Parametern sowie eine suffiziente Antikoagulation im Extrakorporalkreislauf mit niedrigem Blutungsrisiko und konstant langen Filterlaufzeiten nachgewiesen werden. Die Prävalenz des akuten Nierenversagens bei Schwerbrandverletzten ist hoch, die Letalität bei Vorliegen des Organversagens vier-bis fünffach erhöht.

Contexte: la survenue d’IRA chez les patients ayant subi un traumatisme est une problématique qui a été peu étudiée jusqu’à ce jour. La présence de cette atteinte rénale a été démontrée comme étant associée à un risque accru de morbidités et de mortalité chez les sujets atteints. Objectifs: identifier les facteurs prédictifs d’insuffisance rénale ou plus récemment appelée atteinte rénale dans cette population particulière et tenter de trouver des facteurs qui peuvent être mesurés dans les premières heures de la prise en charge du patient. Aussi, nous avons cherché à savoir si l’injection de produit de contraste est associée à un risque accru d’insuffisance rénale aiguë dans cette population. Méthodes et résultats: la recherche a eu lieu à l’Hôpital du Sacré-Coeur de Montréal, un centre de traumatologie tertiaire en milieu urbain. Nous avons utilisé le registre des patients hospitalisés en traumatologie dans notre centre hospitalier entre 2002 et mars 2007 de même que les banques de données de laboratoire et de radiologie pour obtenir les données sur la créatinine et les examens avec produits de contraste. Finalement, une revue de dossiers structurée fut conduite pour recueillir le reste de l’information requise. L’incidence d’IRA dans la population étudiée est estimée à environ 5 %. Une analyse cas témoins fut conduite pour identifier les facteurs prédictifs d’IRA. Quarante-neuf cas d’IRA diagnostiqués par le médecin traitant et 101 témoins sélectionnés au hasard ont été analysés. Les facteurs prédictifs suivants ont été identifiés à l’analyse univariée : la première valeur de créatinine obtenue (p<0,001), l’instabilité hémodynamique (p<0,001), les antécédents d’insuffisance rénale chronique tels que notés dans le dossier par le médecin traitant (p=0,009), une maladie cardiaque (p=0,007), une chirurgie dans les 48 premières heures suivant le traumatisme (p=0,053), le niveau de gravité du traumatisme (Injury Severity Score) (p=0,046) et l’injection de produit de contraste au cours des 48 heures suivant le trauma (p=0,077). Parmi ces facteurs, deux ont été identifiés comme prédicteurs indépendants d’IRA à l’analyse multivariée. Une des valeurs était la première valeur de créatinine obtenue RC = 6,17 (p<0,001, IC95 % 2,81 – 13,53) pour chaque augmentation de 0.5mg/dL de créatinine. L’autre facteur était la présence d’instabilité hémodynamique RC 11,61 (p<0,001, IC95 % 3,71 – 36,29). Conclusion: des informations obtenues tôt dans la prise en charge du patient permettent de prédire le risque d’IRA chez ces patients. L’administration de contraste (intraveineuse ou intra-artérielle) ne s’est pas avérée un facteur indépendant de prédiction d’insuffisance rénale aiguë dans cette population dans le modèle multivarié. / Background: acute kidney injury (AKI) has important mortality and morbidity complications. Few studies have looked at predictors of acute renal failure in a trauma patient population. Objectives: we sought to identify factors associated with AKI that can be assessed in the early hospital stay of trauma patients. We also specifically assessed if the administration of radiological contrast was a predictor of AKI. Methods: we conducted a nested case-control study from the trauma registry of an urban Level I trauma center which includes data on more than 6 000 subjects. The cases consisted of 49 patients with a diagnosis of AKI by their treating physician in the first 7 days following their trauma between 2002 and 2007 (March 2007). The controls were randomly selected for a 1:2 case to control ratio. Data were retrieved from the prospective trauma registry database. Additional data were also obtained via the hospital laboratory and radiology databases. Finally, a structured chart review was conducted to obtain the remaining information. Univariate analyses were conducted. Elements with a significance level of <0.1 were included in a multivariate logistic regression model. Results: predictors identified in the univariate analysis were: the first creatinine value obtained (p<0,001), hemodynamic instability (p<0,001), history of coronary artery disease (p=0,007), history of chronic renal insufficiency as per physician’s diagnosis in the chart (p=0,009), surgery in the 48 hours following the trauma (p=0,053), and, injection of contrast in the 48 hours following the trauma (p=0,077). In the final multivariate model, two factors were statistically significant. One factor was the first creatinine value p<0,001, OR 6,17 CI95 % (2,81 – 13,53) for each increase of creatinine by 0,5mg/dL. The other factor was the presence of hemodynamic instability p<0,001 OR 11,61 CI95 % (3,71 – 36,29). Conclusion: easily obtained information in the emergency department can aid in predicting the risk of AKI in a trauma population. Early administration of radiological contrast was not an independant predictor of AKI in this population.

Sepsis and septic shock remain major cause of mortality in non-coronary intenisve care units. Prognosis of septic patiens worsens further in case of concomitant acute kidney injury. Pathophysiological pathways leading to renal dysfunction in sepsis remain unclear despite of enormous experimental and clinical research. Similarly, the role of extracorporeal blood purification techniques as an adjunctive treatment in sepsis is highly controversial. The aim of our study was to dynamically assess renal haemodynamic, microvascular and metabolic responses in a porcine clinically relevant model of septic shock. The same experimental model was used in experiments elucidating potential benefit effects of two distinct haemopurification methods on different biological responses to infectious insult.

The purpose of the dissertation Continuous Elimination Methods in Intensive Care in Prospective of Hospital Nurse is to inform about acute kidney injury and chronic kidney disease. These are major reason to use elimination methods at intensive care units and anesthesiological resuscitation departments. We further determine elimination issues. Continuous elimination methods in intensive care medicine are important medical treatment at acute kidney injury and chronic kidney disease. Particularly, acute kidney injury belongs to frequent complications at critically diseased patients, therefore will be properly discussed. It is afraid, because decreased renal function leads to incapability to excrete waste products of metabolism and sustain homeostasis. Mortality at acute kidney injury is higher than at chronic kidney disease so support or renal replacement therapy, in order to save life, is the only accepted method of choice at present time. The techniques of renal support or replacement therapy are integral part of instensive care medicine. The aim of this thesis is to elaborate latest accessible findings and specialized nursing care at continuous elimination methods. Ve have tried to create integrated, comprehensible summary of knowledge of this topic. We expect these findings are fundamental to high-quality nursing at patients with this disorder. The dissertation was conducted as a method of review and synthesis. As long as this part is purely theoretical-based, it gathers informations from czech and also foreign sources. The data was acquired from scientific publications, technical papers, monographs and web. The outcome of this work can be used for further research of this topic or contribute to resource information for paramedical staff. In the thesis we analyze acute kidney injury, briefly chronic kidney disease, then we proceed through the history of dialysis and its specifications. These are closely explained. We focus on technical aspect of various elimination methods, the division, indication to initation, advantage and disadvantage, vascular access will also be described. The possibilities of anticoagulation have been defined, the types of membrane hemofiltrates and dialysators, substitutional and dialysing solutions have been characterized, the need of dietary measures has been emphasized. The complications that can happen during the use of elimination method have not been left out of consideration. We describe the intensive care units, nurse competencies, their work, monitoration, patients' and elimination unit preparation and vascular access care.

Submitted by CIBELE TAÍS PUATO DE ALMEIDA null (ctpdalmeida@alunos.fmb.unesp.br) on 2016-04-01T18:34:01Z No. of bitstreams: 1 Tese Cibele Tais Puato de Almeida.pdf: 839793 bytes, checksum: 01a41de5a6976ff81d2d379acd327e1f (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-04-05T18:47:49Z (GMT) No. of bitstreams: 1 almeida_ctp_dr_bot.pdf: 839793 bytes, checksum: 01a41de5a6976ff81d2d379acd327e1f (MD5) / Made available in DSpace on 2016-04-05T18:47:49Z (GMT). No. of bitstreams: 1 almeida_ctp_dr_bot.pdf: 839793 bytes, checksum: 01a41de5a6976ff81d2d379acd327e1f (MD5) Previous issue date: 2016-02-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A Diálise Peritoneal Contínua (DPC) e a Hemodiálise (HD) diária são opções para o tratamento de pacientes com Lesão Renal Aguda (LRA). A DPC pode causar alterações na função respiratória principalmente relacionadas ao aumento da Pressão Intra-Abdominal (PIA) e a HD pode levar a hipoxemia pelo contato do sangue com o circuito extracorpóreo e pela disfusão do CO2 no dialisato. No entanto, ambos os métodos podem melhorar a mecânica respiratória e a oxigenação pela retirada de líquidos e consequentemente redução do edema pulmonar. O objetivo principal deste estudo foi comparar os efeitos da DPC e da HD diária na mecânica ventilatória e oxigenação de pacientes com LRA sob Ventilação Mecânica Invasiva (VMI). Metodologia: Estudo tipo coorte prospectivo que avaliou 154 pacientes, sendo 37 em DPC e 94 em HD. Foram avaliados, por até 3 dias, os parâmetros de mecânica respiratória como Complacência Estática (Cest) e Resistência do Sistema Respiratório (Rsr) e também o Índice de Oxigenação (IO). Os pacientes foram avaliados nos momentos 1, 2 e 3 (pré-diálise) e 1, 2 e 3 (pós-diálise) em relação a Cest e Rsr e nos momentos 1, 2 e 3 em relação ao IO. Para comparação entre as características clínicas iniciais dos pacientes foram utilizados os testes t de student, qui-quadrado e exato de fisher. Para comparação das variáveis Cest, Rsr e IO no tempo foi utilizado o modelo Anova de medidas repetidas, seguido do teste de comparações múltiplas de Wald ou Tukey. Foi considerado um nível de significância de 5%. Resultados: Na comparação dos parâmetros clínicos iníciais entre os dois grupos, todas as características foram iguais, exceto a idade que foi maior entre aqueles em DPC (70,8±11,6 Vs 60±15,8 - p<0,0001). Nos dois grupos a Cest aumentou significativamente, sem difereça entre os grupos – Pré-Diálise (DPC: 40±17,4, 42,8±17,2,48±19; HD: 39,1±21,3, 39,5±18,9, 45,2±21) Pós-Diálise (DPC: 42,8±17,2, 48±19, 57,1±18,3; HD: 42±19, 45±18,5, 56±24,8). A Rsr permaneceu estável entre os pacientes em DPC (Pré-Diálise: 10,4±5,1, 13,3±7,7, 13,5±10,3; Pós-Diálise: 13,3±7,7, 13,5±10,3, 11,1±5,9) e diminuiu entre os pacientes em HD (Pré-Diálise: 10,4±5,1, 10,4±5,1, 10,4±5,1; Pós-Diálise: 10,5±6,8, 10±4,9, 8,9±4,2). Houve diferença estatística na Rsr entre os grupos, no pós-diálise 1 e 2 (p=0,03). O IO aumentou nos dois grupos (DPC: 260,7±119, 252,7±87,1, 287,3±88,4; HD: 228±85, 257±84, 312,1±111,5), sem diferença estatística entre eles. Conclusão: Os resultados obtidos no presente trabalho sugerem que pacientes com LRA, sob VMI, submetidos tanto a DPC quanto a HD Diária apresentam melhora da mecânica ventilatória e da oxigenação, sem diferença entre os grupos. / The Continuous Peritoneal Dialysis (CPD) and daily Hemodialysis (HD) are options for the treatment of Acute Kidney Injury (AKI) patients. The CPD can cause changes in respiratory function mainly related to increase Intra-Abdominal Pressure (IAP) and HD can lead to hypoxemia due to blood contact with the extracorporeal circuit and the diffusion of CO2 in the dialysate. However, both methods can improve respiratory mechanics and oxygenation due to the fluid removal and consequently reduced pulmonary edema. The aim of this study was to compare the effects of the CPD and daily HD on respiratory mechanics and oxygenation of AKI patients undergoing Invasive Mechanical Ventilation (IMV). Methodology: A prospective cohort study evaluated 154 patients, 37 on CPD and 94 on HD. The respiratory mechanics parameters such as Static Compliance (Cest) and Resistance of the Respiratory System (Rsr) and Oxygenation Index (OI) were assessed for three days. Patients were evaluated at moments 1, 2 and 3 (pre-dialysis) and 1, 2 and 3 (post-dialysis) in relation to Cest and Rsr and at times 1, 2 and 3 in relation to the IO. The student t test, chi-square and fisher exact were used to compare the baseline patients characteristics. ANOVA model for repeated measures was used to compare the variables Cest, Rsr and OI, followed by the multiple comparison Tukey or Wald Test. Significance level was 5%. Results: Comparing the initial clinical parameters between the two groups, all characteristics were similar except that the age that was higher among those on CPD (70.8 ± 11.6 vs 60 ± 15.8 - p <0.0001). In both groups, Cest increased significantly, with no difference between the two groups – Pre-Dialysis (CPD: 40 ± 17.4, 42.8 ± 17.2, 48 ± 19; HD: 39.1 ± 21.3, 39. 5 ± 18.9, 45.2 ± 21) Post-Dialysis (CPD: 42.8 ± 17.2, 48 ± 19, 57.1 ± 18.3; HD: 42 ± 19, 45 ± 18.5, 56 ± 24.8). The Rsr remained stable among patients on CPD (Pre-Dialysis: 10.4 ± 5.1, 13.3 ± 7.7, 13.5 ± 10.3, Post-Dialysis: 13.3 ± 7.7, 13.5 ± 10.3, 11.1 ± 5.9) and decreased among HD patients (Pre-Dialysis: 10.4 ± 5.1, 10.4 ± 5.1, 10.4 ± 5, 1, Post-Dialysis: 10.5 ± 6.8, 10 ± 4.9, 8.9 ± 4.2) There was significant statistically difference in Rsr between the two groups at the post-dialysis moments 1 and 2 (p = 0.03). OI increased in both groups (CPD: 260.7 ± 119, 252.7 ± 87.1, 287.3 ± 88.4; HD: 228 ± 85, 257 ± 84, 312.1 ± 111.5), although there was not significant statistically difference between them. Conclusion: This study showed that AKI patients undergoing IMV and daily HD or CPD had improvement in the mechanical ventilation and oxygenation, with no difference between the two groups.

Submitted by CARISTON RODRIGO BENICHEL null (c.benichel@hotmail.com) on 2017-04-10T14:24:49Z No. of bitstreams: 1 Dissertação_Mestrado_Cariston_Benichel.pdf: 2521475 bytes, checksum: fc0e6d77bc2fc94383f1d4527314f0d0 (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-04-17T17:25:37Z (GMT) No. of bitstreams: 1 bernichel_cr_me_bot.pdf: 2521475 bytes, checksum: fc0e6d77bc2fc94383f1d4527314f0d0 (MD5) / Made available in DSpace on 2017-04-17T17:25:37Z (GMT). No. of bitstreams: 1 bernichel_cr_me_bot.pdf: 2521475 bytes, checksum: fc0e6d77bc2fc94383f1d4527314f0d0 (MD5) Previous issue date: 2017-02-23 / Introdução: Lesão renal aguda (LRA) é um problema de saúde que repercute diretamente nos índices de morbimortalidade de pacientes graves. Objetivo: Identificar os fatores associados à LRA em pacientes clínicos e cirúrgicos durante a hospitalização em Unidade de Terapia Intensiva (UTI). Método: Foi realizado um estudo tipo caso-controle em uma UTI geral de hospital privado do interior paulista, mediante levantamento dos registros de prontuário dos pacientes internados, no período de 2014 e 2015. Para tanto, os participantes foram divididos em quatro grupos, sendo: dois casos, constituído de pacientes clínicos e cirúrgicos que desenvolveram LRA durante hospitalização na UTI e dois controles com o mesmo perfil, mas que não desenvolveram LRA durante o período do estudo. Considerou-se LRA um aumento de 0,3 mg/dl sobre o valor basal de creatinina sérica nas primeiras 48hs de internação na UTI, conforme definição adotada na classificação AKIN (Acute Kidney Injury Network), pelo critério de creatinina. As variáveis analisadas foram: sexo, idade, raça, estado civil, dias de internação, desdobramento da hospitalização, uso de ventilação mecânica, diagnóstico de entrada, fatores de risco cardiovascular e outras comorbidades, fatores de risco nefrológicos), procedimentos realizados (vascular e contrastado), medicamentos nefrológicos/utilização de antibióticos e exames laboratoriais. Inicialmente, todas as variáveis foram analisadas descritivamente. As variáveis quantitativas foram apresentadas em termos de médias e desvios-padrão e as variáveis classificatórias em tabelas contendo frequências absolutas (n) e relativas (%). Foi realizada análise univariada de cada exposição sobre a LRA, incluindo no modelo de regressão logística múltipla as exposições que nesta etapa mais se associaram com a LRA. Na sequência realizou-se o teste de interações duplas entre as exposições incluídas no modelo múltiplo, e o modelo final foi composto somente com os principais efeitos de cada exposição, gerando assim odds ratio da LRA entre pacientes clínicos e cirúrgicos. Valores de p < 0,05 foram considerados estatisticamente significantes. Resultados: Participaram deste estudo 656 pacientes, sendo 205 do grupo clínico, 123 do cirúrgico e o mesmo número de controle, para ambos os grupos (328). O tempo de internação dos clínicos foi maior, média de 10 dias, a prevalência da LRA foi estimada em 12%. Praticamente a mesma proporção de homens e mulheres foram acometidos pela LRA. Na análise univariada foram identificados como fatores associados à LRA para o grupo de pacientes clínicos: dias de internação (p<0.0001), óbito (p<0.0001), ventilação mecânica (p<0.0001), diagnóstico respiratório (p=0.0178) e cardiovascular (p=0.0008), diabetes (p=0.0347), hipertensão arterial (p=0.0009), sepse (p<0.0001), parada cardiorrespiratória (p=0.0326), hipovolemia (p=0.0002), insuficiência cardíaca (p<0.0001), procedimento contrastado (p=0.0046), quimioterapia (p=0.0180), droga vasoativa (p<0.0001), antibiótico e antibiótico simultâneo (p<0.0001), associação > três fatores (p<0.0001). Para o grupo de cirúrgicos destacaram-se: ter companheiro (p=0.0085), dias de internação (p<0.0001), óbito (p<0.0001), ventilação mecânica (p<0.0001), diagnóstico gastrointestinal (p=0.0094) e neurológico (p=0.0349), doença tromboembólica (p=0.0442), sepse (p=0.0006), PCR (p=0.0442), hipovolemia (p=0.0199), arritmia (p=0.0099), neoplasia renal (p=0.0442), doença obstrutiva renal (p=0.0242), furosemida (p=0.0031), droga vasoativa (p<0.0001), antibiótico simultâneo (p<0.0001), associação > três fatores (p<0.0001). Na análise multivariada foram identificados como fatores associados à LRA para o grupo de pacientes clínicos: hipertensão (p=0.0349; OR=1.9615), hipovolemia (p=0.0060, OR=5.607), insuficiência cardíaca (p=0.0032; OR=5.3123), noradrenalina (p<0.0001; OR 9.4912), dopamina (p=0.0009; OR 3.5212), dobutamina (p=0.0131; OR 5.2612) antibiótico simultâneo (p<0.0001; OR=3.4821), e associação > três fatores (p<0.0001; OR=5.0074). Nesta análise, para os cirúrgicos os fatores associados à LRA foram: hipovolemia (p=0.0260; OR=3.2778), furosemida (p=0.0032; OR=2.3701), noradrenalina (p=0.0060; OR=4.8851), glico/polipeptídeo (p=0.0009; OR=22.9281) e associação > três fatores (p<0.0001; OR=1.2682). Conclusão: A LRA em pacientes clínicos e cirúrgicos é um evento multifatorial, que ocorreu notadamente em pacientes com idade avançada, com maior tempo de internação e predispões ao óbito. Associou-se a etiologias cardiovasculares, complicações decorrentes da gravidade dos participantes e utilização de medicamentos com potencial nefrotóxico. O estudo também mostrou que a concomitância de mais de três fatores de risco contribuiu para a LRA. Produto da dissertação: Elaborado software para classificação do risco e presença de LRA entre pacientes clínicos e cirúrgicos hospitalizados na UTI adulto, o qual foi incluído na plataforma institucional do prontuário eletrônico. Este material aborda duas etapas de avaliação: a primeira integra os fatores associados com a disfunção renal e eventual emissão de alerta amarelo via sistema de prescrição médica e evolução multiprofissional; e a segunda, com a detecção da LRA utilizando o critério de AKIN (e eventual emissão de alerta vermelho via sistema de prescrição médica e evolução multiprofissional). As avaliações serão realizadas na admissão e a cada 48 horas de hospitalização na UTI. / Introduction: Acute kidney injury (AKI) is a health problem that directly affects the morbidity and mortality rates of critically ill patients. Object: Identify the factors associated with AKI in clinical and surgical patients during hospitalization in the Intensive Care Unit (ICU). Method: A case-control study was carried out at a general ICU of a private hospital in the interior of São Paulo, by means of a survey of the records of hospitalized patients, in the period of 2014 and 2015. Participants were divided into four groups. : Two cases, consisting of clinical and surgical patients who developed AKI during ICU hospitalization and two controls with the same profile but who did not develop AKI during the study period. An increase of 0.3 mg / dL over the baseline serum creatinine in the first 48 hours of ICU admission was considered, according to the definition adopted by the Acute Kidney Injury Network (AKIN), by the creatinine criterion. The variables analyzed were: gender, age, color, marital status, days of hospitalization, hospitalization, use of mechanical ventilation, diagnosis of entry, cardiovascular risk factors and other comorbidities, nephrological risk factors), vascular and Nephrological drugs / use of antibiotics and laboratory tests. Initially, all variables were analyzed descriptively. The quantitative variables were presented in terms of means and standard deviations and the classificatory variables in tables containing absolute (n) and relative (%) frequencies. Univariate analysis of each exposure on AKI was performed, including in the multiple logistic regression model the exposures that were most associated with AKI at this stage. The double interactions test was performed between the exposures included in the multiple model, and the final model was composed only with the main effects of each exposure, thus generating the odds ratio of AKI between clinical and surgical patients. Values of p <0.05 were considered statistically significant. Results: 656 patients participated in this study, 205 of the clinical group, 123 of the surgical group and the same number of controls, for both groups (328). Clinical hospitalization time was longer, mean of 10 days, the prevalence of AKI was estimated at 12%. Almost the same proportion of men and women were affected by the AKI. In the univariate analysis, the following factors were identified for the clinical group: hospitalization (p <0.0001), death (p <0.0001), mechanical ventilation (p <0.0001), respiratory (p = 0.0178) and cardiovascular (P = 0.0008), hypertension (p = 0.0008), hypertension (p = 0.0009), sepsis (p <0.0001), cardiorespiratory arrest (p = 0.0326), hypovolemia (P <0.0180), vasoactive drug (p <0.0001), antibiotic and simultaneous antibiotic (p <0.0001), association> three factors (p <0.0001). For the surgical group, the following were the most important: companion (p = 0.0085), days of hospitalization (p <0.0001), death (p <0.0001), mechanical ventilation (p <0.0001), gastrointestinal (p = 0.0094) and neurological (P = 0.0449), thromboembolic disease (p = 0.0442), sepsis (p = 0.0006), CRP (p = 0.0442), hypovolaemia (p = 0.0199), arrhythmia (p = 0.0099), renal neoplasia (P = 0.0242), furosemide (p = 0.0031), vasoactive drug (p <0.0001), concurrent antibiotic (p <0.0001), association> three factors (p <0.0001). In the multivariate analysis, hypertension (p = 0.0349, OR = 1.9615), hypovolemia (p = 0.0060, OR = 5.607), heart failure (p = 0.0032, OR = 5.3123) (P <0.0001; OR 9.4912), dopamine (p = 0.0009, OR 3.5212), and dobutamine (p = 0.0131; OR 5.2612) 0.0001; OR = 5.0074). In this analysis, the factors associated with AKI were hypovolemia (p = 0.0260, OR = 3.2778), furosemide (p = 0.0032, OR = 2.3701), noradrenaline (p = 0.0060, OR = 4.8851), glycol / polypeptide P = 0.0009; OR = 22.9281) and association> three factors (p <0.0001; OR = 1.2682). Conclusion: The LRA in clinical and surgical patients is a multifactorial event that occurred notably in patients with advanced age, with longer hospitalization and predispositions to death. It was associated with cardiovascular etiologies, complications due to the severity of the participants and use of drugs with nephrotoxic potential. The study also showed that the concomitance of more than three risk factors contributed to AKI. Product of the dissertation: Elaborated software for risk classification and presence of AKI among clinical and surgical patients hospitalized in the adult ICU, which was included in the electronic medical records institutional platform. This material addresses two stages of evaluation: the first integrates the factors associated with renal dysfunction and eventual issuance of yellow alert via the medical prescription system and multiprofessional evolution; And the second, with the detection of AKI using the AKIN criterion (and possible red alert issuance via a medical prescription system and multiprofessional evolution). The evaluations will be performed at admission and every 48 hours of ICU hospitalization.

Introdução: A lesão renal aguda (LRA) ocorre em unidades de terapia intensiva (UTI), com incidência de 30%, enquanto que a incidência hospitalar é 3-5%. A mortalidade nestes pacientes, inalterada nas últimas décadas, varia entre 50 e 70%. O padrão clínico para diagnóstico da LRA é a dosagem da creatinina sérica, que é um método pouco sensível, tardio e incapaz de discriminar a gravidade da lesão. Esse fato compromete o uso de terapias efetivas em tempo hábil e não permite vislumbrar a evolução pós LRA. O reconhecimento da lesão renal precoce contribui para a prevenção de danos renais maiores. O NGAL, proteína presente no sangue e na urina proveniente da lesão de células tubulares renais, é capaz de detectar a LRA antes do aumento da creatinina, estabelece medidas de prevenção e tratamento logo após o insulto, indica o grau de severidade da lesão e sugere o início da terapia de substituição renal (TSR). Objetivo: Esse estudo visa caracterizar a evolução da função renal de pacientes com LRA baseados na classificação AKIN (Acute Kidney Injury Network) e no NGAL. Material e método: Estudo de coorte prospectivo consistindo de 83 pacientes internados em UTI, avaliados em relação ao fluxo urinário, creatinina plasmática e NGAL. Resultados: Um total de 65 pacientes desenvolveram LRA, 28 a adquiriram durante a internação na UTI e 37 já apresentavam LRA na admissão. Dos pacientes com LRA, trinta e três (50,8%) apresentaram AKIN estágio 1, treze (20,0%) apresentaram AKIN estágio 2 e dezenove (29,2%) AKIN estágio 3. Os pacientes classificados em AKIN estágio 3 apresentaram valor significativamente maior de NGAL do que o grupo com AKIN estágio 1. Níveis de NGAL significativamente menores (p< 0,05) foram encontrados em pacientes que não desenvolveram LRA. Dentre os fatores associados ao óbito, destacamos a presença de doença de Chagas, LRA e Sepse; a baixa fração de ejeção (FE); o uso de drogas vasoativas (DVA), ventilação mecânica (VM) e balão intra-aórtico (BIA); maior pontuação no escore SOFA; necessidade de hemodiálise; redução da diurese e elevações da creatinina e NGAL. Observamos que somente as variáveis: presença de BIA (p=0,013), balanço hídrico positivo positivo (p< 0,001) e necessidade de hemodiálise (p< 0,001) foram preditores de óbito. Somente a presença de sepse, distúrbios do sódio e fluxo urinário foram preditores de diálise Conclusão: Níveis de NGAL colhidos nas primeiras 24 horas de admissão na UTI contribuíram para predizer o desenvolvimento da LRA além de corresponder ao aumento da severidade da LRA. / Introduction: The incidence of AKI varies from 3-5% in hospitalized patients to 30% in patients in intensive care units (ICU). Over the last decades, mortality rates have remained unchanged for adult patients, at 50-70%. The clinical standard for AKI diagnosis is the serum creatinine levels, which have low sensitivity, are incapable of differentiating the lesions severity, and lead to the late diagnosis in the injury process. These facts compromise the timely use of effective therapies and the assessing of the lesions evolution. NGAL, a protein present in the blood, in the urine and provenient from kidney tubule cells damage, is capable of detecting AKI before serum cretinine levels rise, allowing treatmen to be undertaken right after the injury; it also reflects injury severity and may forecast the need of renal replacement therapy. Objective: this study aims to assess the evolution of kidney function of AKI patients, based on the AKIN (Acute Kidney Injury Network) classification and on NGAL levels. Material and methods: Coorte prospective study consisting of 83 intensive care patients, who had their serum creatinine, NGAL and urine output evaluated. Results: a total of 65 patients developed AKI, 28 developed it during their hospital stay, and 37 already demonstrated it at ICU admission. Of the AKI patients, 33 (50,8%) were classified as AKIN stage 1, 13 (20,0%) as AKIN stage 2 and 19 (29,2%), as AKIN stage 3. The AKIN stage 3 patients showed to have significantly higher NGAL levels than AKIN stage 1 patients. Significantly lower NGAL levels (p<0,05) were found in patients that have not developed AKI. Among the factors associated to mortality, we highlight Chagas disease, AKI and sepsis, low ejection fraction, the use of vasoative drugs, mechanical ventilation, intra-aortic balloon pump use, higher SOFA score, need of renal replacement therapy, reduction in urine output, higher NGAL and serum creatinine levels. Only positive hydric balance (p>0,001), the use of intra-aortic balloon pump, and the need of renal replacement therapy were able to predict death. Also, only the urine output, the presence of sepsis or sodium disturbances were able to predict the need of renal replacement therapy. Conclusion: NGAL levels obtained in the fist 24 hours after admission to the intensive care unit contributed to the prediction of AKI development, and they were indicative of the injurys severity.