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.

In dieser Dissertation wurden am Ferkelmodell (8-15 kg, drei Gruppen: „Kontrolle“ n=7, „Herz-Lungen-Maschine (HLM)“ n=10, „(-)-Epigallocatechin-3-Gallat (EGCG)“ n=6, die Kontrollgruppe wurde thorakotomiert, die HLM- und die EGCG-Gruppe wurden thorakotomiert und für 90 Minuten an eine HLM angeschlossen, die EGCG-Gruppe erhielt vor und nach der HLM-Zeit EGCG) drei Fragestellungen behandelt: Erstens wurde untersucht, ob die Verwendung einer HLM während eines kardiochirurgischen Eingriffes unter hypothermen Bedingungen mit nicht-pulsatilem Blutfluss und Kardioplegie die Niere schädigte. Dafür wurden Paraffinschnitte der Niere aus der Kontroll- und der HLM-Gruppe mit Hämatoxylin-Eosin (HE) angefärbt und unterschiedliche Strukturen betrachtet, wobei histopathologische Veränderungen in der HLM-Gruppe auffielen. Paraklinisch fanden sich erhöhte nierenspezifische Blutwerte (Serumkreatinin und -harnstoff) in der HLM-Gruppe. Diese Ergebnisse waren hinweisend für eine funktionell relevante Schädigung der Niere durch die HLM. Unterstützend kam ein Absinken des Gesamteiweißes im Serum der HLM-Gruppe hinzu, was auf eine generelle Schädigung des Organismus durch die HLM hindeutete. Zweitens wurde betrachtet, ob die gesetzten Schäden die Merkmale eines Ischämie-Reperfusionsschadens aufwiesen. Hierzu wurden Paraffinschnitte der Niere aus der Kontroll- und der HLM-Gruppe immunhistochemisch (Hypoxie-induzierter-Faktor-1-alpha-Tyramide- Signal-Amplification (HIF-1-alpha-TSA)-, Nitrotyrosin-3-Amino-9-Ethylcarbazol (Nitrotyrosin-AEC)- und Apoptose-induzierender-Faktor-Tyramide-Signal-Amplification (AIF-TSA)-Färbung) angefärbt. Dabei zeigte sich, dass sich die HLM-Gruppe in einer hypoxischen Situation befand (HIF-1-alpha Akkumulation in den Zellkernen), nitrosativem Stress ausgesetzt war (Nitrotyrosin in den Tubuli) und dass sie teilweise so stark geschädigt wurde, dass Apoptose induziert wurde (AIF in Zellkernen) – alle drei Färbungsergebnisse waren hinweisend für einen ischämischen Zustand, in dem sich die HLM-Gruppe befunden hat. Auch die Ergebnisse der durchgeführten renalen Reversed Phase High Performance Liquid Chromatography (RP-HPLC) deuteten auf ebendies hin. Unterstützend wirkten die Ergebnisse des arteriellen Laktats – die HLM-Gruppe zeigte eine Hyperlaktämie – und die Tatsache, dass einige der histologischen Merkmale für eine frühe Schockniere (welche ischämischen Ursprungs sein kann) in der HLM-Gruppe gefunden wurden. Dies alles zeigte, dass der HLM-assoziierte Nierenschaden vorrangig die Natur eines Ischämie-Reperfusionsschadens aufwies. Drittens wurde untersucht, ob EGCG diese HLM-assoziierte Schädigung abmildern konnte. Dafür wurden bei der EGCG-Gruppe alle oben genannten Untersuchungen durchgeführt. Die Ergebnisse zeigten, dass EGCG in der Dosierung 10 mg/kg eine renoprotektive Wirkung gegen die HLM-assoziierten Schäden hatte, und diese abmildern bzw. ihnen entgegenwirken konnte. Diese Ergebnisse sind für die pädiatrische Kardiochirurgie interessant, welche zum Beispiel bei der Korrektur angeborener Herzdefekte auf die Verwendung der HLM angewiesen ist. Komplikationen wie eine Nierenschädigung post operationem sind nicht selten und verkomplizieren den Verlauf. Die vorliegende Dissertation zeigt das renoprotektive Potential des in grünem Tee vorkommenden Katechins EGCG im Umfeld eines kardiochirurgischen Eingriffes mit Verwendung einer HLM. Die Wirksamkeit dieser Substanz ist wahrscheinlich darin begründet, dass sie mehr als ein Antioxidans ist. Neben seiner Radikalfänger- und Stickstoffmonoxidscavenger-Fähigkeiten ist EGCG außerdem antiapoptotisch wirksam. Derzeit wird die Kardiochirurgie mit Verwendung einer HLM in der Veterinärmedizin nur in wenigen Zentren angewendet. Es besteht für die Zukunft jedoch die Hoffnung, dass gerade für Kleintierbesitzer, die ihre Tiere als Familienmitglied betrachten, und auch für zoologische Einrichtungen bei der Diagnose eines Herzfehlers die Kardiochirurgie mit Verwendung einer HLM als Therapiemöglichkeit eine interessante und realistische Alternative zur bislang angewandten palliativen medikamentösen Therapie darstellen kann. / In this dissertation a piglet model (8-15 kg, three groups: “control” n=7, “extracorporeal circulation (EC)” n=10, “EGCG” n=6, the control-group was thoracotomized, the EC- and the EGCG-group were thoracotomized and underwent cardiopulmonary bypass (CPB) for 90 minutes, and the EGCG-group received EGCG before and after the CPB) is presented. Three questions were raised and answered: Firstly, it was investigated if the use of a CPB during cardiac surgery with hypothermia, non-pulsatile blood flow and cardioplegia caused damage to the kidney. In order to answer this question, paraffin slices of the kidney of the control- and the EC-group were stained with hematoxylin-eosin (HE), and different structures were evaluated – this staining showed histopathological changes in the EC-group. Paraclinical, the EC-group showed elevated kidney-specific blood parameters (serumcreatinine and -urea). These findings indicated a functionally relevant impairment of the kidney caused by the CPB. Supporting this, the EC-group also showed a decline of the total amount of proteins in the serum, which was suggestive of a generalized injury of the body by the CPB. Secondly, it was investigated whether the injury of the kidney might have been caused by an ischemia/reperfusion injury. Therefore, paraffin slices of the kidney of the control- and the EC-group were immunhistochemically stained (hypoxia-induced-factor-1-alpha-tyramidesignal-amplification (HIF-1-alpha-TSA)-, nitrotyrosine-3-amino-9-ethylcarbazole (nitrotyrosine-AEC)- and apoptosis-inducing-factor-tyramide-signal-amplification (AIF-TSA)-staining). These stainings revealed, that the EC-group had suffered from a hypoxemic situation (accumulation of HIF-1-alpha in the nuclei), from nitrosative stress (presence of nitrotyrosine in the tubuli), and that the kidney was partly damaged to the point of an induction of apoptosis (presence of AIF in the nuclei) – all three of these findings indicated, that the kidneys of the EC-group were put into an ischemic situation. The findings of the renal reversed phase high performance liquid chromatography (RP-HPLC) indicated the same thing. This was also supported by the blood parameter of lactate – the EC-group showed a hyperlactemia – and by some histological findings in the EC-group, which were characteristical for an early shock-kidney (which may be caused by ischemia). Taken together, these findings showed that the CPB-associated kidney injury was primarily caused by an ischemia/reperfusion injury. Thirdly, it was investigated, whether EGCG might attenuate the CPB-associated kidney injury. For that purpose, all of the investigation methods mentioned above were carried out with the samples of the EGCG-group. The findings showed that EGCG (dose: 10 mg/kg) had a protective effect on the kidney, protecting it against the damage caused by the CPB, and was able to partly attenuate this damage and partly even fully counteract it. These findings are of interest for pediatric cardiac surgery, which for example for the correction of innate heart defects depends on the use of CPB. Complications – like acute renal injury post operationem – occur frequently and complicate the recovery. This dissertation demonstrates the renoprotective potential of the natural compound EGCG in the setting of cardiac surgery with the use of CPB. The reason for the effectiveness of EGCG in this situation probably is that EGCG is more than an antioxidant. EGCG not only works as a radical- and nitric-oxide-scavenger, but also is antiapoptotic. In veterinary medicine cardiac surgery with CPB is done by few centers only. However for the future there is hope that people – especially pet owners who view their companion animals as family members, and zoos – become more and more willing to and interested in having an animal diagnosed with a heart defect treated with cardiac surgery including the use of an CPB, instead of – like its usually done nowadays – only giving palliative medication to the animal.

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.

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.

IntroduÃÃo: A prevenÃÃo da nefropatia induzida por contraste (NIC) à difÃcil nas situaÃÃes de emergÃncia tornando essenciais estudos sobre NIC em pacientes submetidos à angioplastia de urgÃncia. Objetivo: Determinar a incidÃncia e fatores associados à NIC em pacientes com infarto agudo do miocÃrdio (IAM) submetidos à angioplastia nas primeiras 12 horas apÃs inÃcio dos sintomas. MÃtodos: Foram estudados 201 casos consecutivos de IAM com supradesnivelamento do segmento ST com menos de 12 horas de evoluÃÃo. Todos os pacientes foram submetidos ao mesmo protocolo de angioplastia. A NIC foi definida como elevaÃÃo absoluta da creatinina de pelo menos 0,5 mg/dL e/ou aumento relativo da creatinina de 25% em relaÃÃo ao valor basal no perÃodo entre 48 e 72 horas apÃs a administraÃÃo do contraste. As variÃveis que diferiram entre os pacientes com e sem NIC na anÃlise univariada foram analisadas por regressÃo logÃstica. Resultados: A amostra foi formada por 135 (67,2%) homens e 66 (32,8%) mulheres com idade mÃdia de 66,6  11,7 anos. A incidÃncia de NIC foi de 23,8%. Na anÃlise univariada os pacientes com NIC eram mais idosos e com maior frequÃncia de fraÃÃo de ejeÃÃo do ventrÃculo esquerdo &#8804; 40% e da classificaÃÃo Killip &#8805; 2. Na anÃlise multivariada nÃo foram encontrados preditores independentes de NIC. ConclusÃo: A NIC acomete  dos pacientes com IAM submetidos à angioplastia sem variÃveis preditoras. Esse resultado ressalta a necessidade de medidas preventivas para NIC apÃs uso de contraste em angioplastia de urgÃncia. / Introduction: The prevention of contrast-induced nephropathy (CIN) is difficult in emergency situations, making it essential to study CIN in patients submitted to urgent angioplasty. Objective: To determine the incidence and associated factors to CIN in patients with myocardial infarction (MI) submitted to primary angioplasty in the first 12 hours after onset of symptoms. Methods: We studied 201 consecutive cases of MI with ST-segment elevation with less than 12 hours of evolution. All patients were submitted to the same angioplasty protocol. CIN was defined as an absolute increase of creatinine of at least 0.5 mg/dL and/or a relative increase of creatinine of 25% in relation to baseline in a period between 48 and 72 hours after contrast administration. The variables that differed between patients with and without CIN in univariate analysis were analyzed by logistic regression. Results: The sample was formed by 135 (67.2%) men and 66 (32.8%) women, with mean age of 66.6  11.7 years. The incidence of CIN was 23.8%. In univariate analysis the patients with CIN were older and had higher frequency of left ventricular ejection fraction &#8804; 40% and Killip classification &#8805; 2. In multivariate analysis, we did not find independent predictors of CIN. Conclusion: CIN occurred in  of the patients with MI submitted to angioplasty without predictor variables. This finding highlights the need for CIN preventive measures after contrast use in emergency angioplasty.

Os ácidos graxos de cadeia curta (AGCC) são produzidos pela microbiota intestinal e possuem papéis anti-inflamatórios e ação inibitória sobre histona deacetilases. A lesão renal aguda (LRA) é caracterizada por uma inflamação renal que influencia a função do rim. Este projeto avaliou se o tratamento com os AGCC impactaria nos desfechos inflamatórios da LRA em camundongos. Foi observado que o tratamento com AGCC, protege da LRA. Esta melhora foi associada a uma menor inflamação e menor taxa de apoptose. Além disso, o tratamento com acetato diminuiu a atividade de histona deacetilase. Administrando bactérias produtoras de acetato, também foi possível observar uma proteção da LRA, junto de uma menor inflamação sistêmica. Esta proteção do AGCC na LRA foi também observada em modelo de LRA secundária à sepse In vitro, o tratamento com AGCC modularam tanto células imunes como células renais sob estímulos inflamatórios e de hipóxia. AGCC modulam processos inflamatórios no rim via ações epigenéticas ou não, podendo ser uma promissora ferramenta na proteção da LRA. / Short-Chain Fatty Acids (SCFA) are produced by the intestinal microbiota and have anti-inflammatory and histone deacetylases inhibitors properties. Acute kidney injury (AKI) is characterized by renal inflammation that may impair kidney function. This project evaluated whether treatment with SCFA inflammatory impacts the outcomes of AKI in mice. It was observed that treatment with SCFA protected the AKI. This improvement was associated with less inflammation and lower apoptosis rate. In addition, treatment with acetate decreased the activity of histone deacetylase. Giving bacteria producing acetate, was also observed protection from AKI, along with a lower systemic inflammation. This protection of the AGCC in AKI was also observed in sepsis model. In vitro, SCFA treatment modulated both immune cells and renal cells under hypoxia and inflammatory stimuli. SCFA modulate inflammatory processes in the kidney via epigenetic actions or not, may be a promising tool in the protection of the AKI.

Tenofovir (TDF), um antirretroviral análogo nucleotídeo inibidor da transcriptase reversa, indicado para o tratamento da infecção pelo vírus da Hepatite B em indivíduos HBeAg reagentes, não cirróticos, tem sido implicado na ocorrência de Injúria renal aguda (IRA) e lesão do túbulo proximal renal (TPR), com características semelhantes à Síndrome de Fanconi, caracterizada por glicosúria, bicarbonatúria, fosfatúria, uricosúria e proteinúria de baixo peso molecular. Outros trabalhos sugerem que os pacientes em uso de TDF sofram toxicidade aos glomérulos, com uma pequena, porém significante redução da taxa de filtração glomerular. O tempo de uso da droga para que ocorra lesão renal é desconhecido. Entretanto, a maioria dos estudos de investigação de nefrotoxicidade do TDF foi realizada em pacientes portadores de infecção pelo HIV. Especula-se que a nefrotoxicidade desta droga possa ser exacerbada ou reduzida pelo uso de outras medicações, frequentemente usadas por pacientes com HIV, que competem com o transporte tubular ou com sua metabolização, aumentando o seu nível sérico. O objetivo geral deste trabalho é avaliar prospectivamente a incidência de lesão renal pelo uso de TDF em pacientes portadores de hepatite B. Os objetivos específicos deste trabalho são: (1) avaliar incidência de lesão do TPR através da avaliação da excreção urinária de ácido úrico, fósforo e da proteína de baixo peso molecular neutrophil gelatinase associated lipocalin (NGAL); (2) avaliar a incidência de redução aguda da taxa de filtração glomerular (LRA) ou redução crônica da mesma. Métodos: Foram incluídos 24 pacientes portadores de Hepatite B que tiveram indicação de iniciar o uso de TDF com idade superior a 18 anos ou inferior a 75 anos. Neste estudo prospectivo, foi realizado a coleta de dados clínicos (idade, gênero, etnia, tempo de doença, antecedentes pessoais, medicações concomitantes, fator de risco para contaminação do VHB, história familiar de infecção VHB) e a avaliação laboratorial foi feita através da coleta de sangue e urina feitas antes do início do uso do TDF e, posteriormente à sua introdução, semestralmente durante 2 anos. Ao final do seguimento foi avaliada a incidência de lesão renal pelo uso de TDF, através das seguintes dosagens: glicemia, fosfatemia, gasometria, creatinina e Cistatina C séricas, microalbuminúria, proteinúria, proteinúria de baixo peso molecular (NGAL), clearance de creatinina, fosfatúria, uricosúria e urina rotina. Foi feita análise estatística comparativa entre os pacientes que usaram o TDF pré tratamento e pós tratamento para detectar lesão do TPR ou redução da taxa de filtração glomerular ao longo do tempo. Resultados: Não foi identificado aumento significativo da creatinina no decorrer do estudo (p = 0,09; R = 2,4%), entretanto, foi observada uma queda significativa nos valores do clearance de creatinina em 24 horas (p < 0,01; R = 15,8%). Não foi observada tendência de queda da filtração glomerular através das fórmulas MDRD simplificada (p = 0,11), CKD-EPI (p=0,14), CKD-EPI cystatin C (p = 0,23). Em relação à cistatina C sérica também não foi observada sua elevação no decorrer do tempo (p=0,15; R = 2,4%). Não foi observado, utilizando-se modelo de regressão linear, aumento na excreção urinária de albumina no decorrer do estudo (p = 0,97; R = 0,00%), mas houve aumento significativo na proteinúria de 24h (p < 0,01). Foi observada também, redução da uricosúria com o passar do tempo (p = 0,01; R = 6,7%) e houve correlação positiva entre o clearance de creatinina dosado em urina de 24 horas e a excreção de ácido úrico em urina de 24 horas (p=0,01; r = + 0,60). A fração de excreção de fósforo (urina de 24h): não foi observada alteração no decorrer do tempo (p = 0,83; R = 0,5%), porém houve correlação negativa com entre o clearance de creatinina dosado em urina de 24 horas e a fração de excreção de fósforo (FePO4) dosada em urina de 24 horas (p = 0,05; r = - 0,25). A detecção de NGAL na urina foi feita pelo índice UNGAL/Ucreat e não foi observado aumento significativo de sua excreção no decorrer do tempo (p = 0,40, r = 0,8%). Conclusão: em conclusão no presente estudo observou-se desenvolvimento de lesão renal aguda em 10% dos pacientes em uso de tenofovir e redução significativa da filtração glomerular. A fosfatúria e proteinúria observados sugerem que a lesão tenha sido decorrente de tubulopatia proximal e os marcadores mais específicos de lesão renal, cistatina C e NGAL, não foram superiores aos biomarcadores disponíveis na prática clínica na detecção destas alterações. / Tenofovir (TDF) a nucleotide analog reverse transcriptase inhibitor antiretroviral indicated for the treatment of infection with the hepatitis B virus in reagents HBeAg individuals, non-cirrhotic patients, has been implicated in the occurrence of acute kidney Injury (AKI) and the proximal tubule injury kidney (TPR), with similar to Fanconi syndrome characterized by glucosuria, bicarbonatúria, phosphaturia, proteinuria, uricosuria and low molecular weight characteristics. Other studies suggest that patients using TDF toxicity suffer the glomeruli, with a small but significant reduction in glomerular filtration rate. The time of drug use for kidney damage that occurs is unknown. However, most of the research studies of nephrotoxicity TDF was performed in patients with HIV infection. It is speculated that the nephrotoxicity of this drug may be exacerbated or reduced by the use of other medications, often used by patients with HIV, which compete with the tubular transport or metabolism, increasing its serum level. The overall objective of this study is to prospectively evaluate the incidence of renal injury by the use of TDF in patients with hepatitis B. The specific objectives of this work are: (1) assess the incidence of injury TPR by assessment of urinary excretion of uric acid, phosphorus and protein of low molecular weight neutrophil gelatinase associated lipocalin (NGAL); (2) assess the incidence of acute reduction in glomerular filtration rate (IRA) or chronic reduction. Methods: 24 patients with hepatitis B who were advised to initiate the use of TDF over the age of 18 years or below 75 years were included. In this prospective study, the collection of clinical data (age, gender, ethnicity, duration of disease, personal history, concomitant medications, risk factor for HBV infection, family history of HBV infection) and laboratory evaluation was done by collect blood and urine samples taken before initiation of the use of TDF and after its introduction, semiannually for 2 years. At final follow-up the incidence of renal injury by the use of TDF was assessed through the following dosages: glucose, phosphatemia, gases, creatinine and serum cystatin C, microalbuminuria, proteinuria, low molecular weight proteinuria (NGAL), clearance creatinine, phosphaturia, uricosuria and urine routine. The comparative statistical analysis of patients using TDF pre-treatment and post treatment to detect the TPR injury or reduced glomerular filtration rate over time. Results: There was not significant increase in creatinine identified during the study (p = 0.09; R = 2.4%), however, a significant decrease was observed in the values of creatinine clearance at 24 hours (p <0.01; R = 15.8%). No downward trend was observed in glomerular filtration through the simplified MDRD formulas (p = 0.11), CKD-EPI (p = 0.14), CKD-EPI cystatin C (p = 0.23). Regarding the serum cystatin C its elevation was not observed over time (p = 0.15, R = 2.4%). Increased urinary albumin excretion during the study was not observed using a linear regression model (p = 0.97, R = 0.00%), but there was significant increase in 24-hour proteinuria (p <0, 01). And there was a positive correlation between creatinine clearance at 24 hour urine and the excretion of uric acid in 24 hour urine (p = 0.01, R = + 0.60), uricosuria reduction over time was also observed (p = 0.01, R = 6.7%). No change was observed over time in the fractional excretion of phosphorus (24 h urine), (p = 0.83; R = 0.5%), but there was a negative correlation between creatinine clearance urine dosed at 24 hours and fractional excretion of phosphorus (FePO4) measured in 24 hour urine (p = 0.05, r = - 0.25). The detection of NGAL in the urine was taken by UNGAL / Ucreat index and was not observed significant increase in excretion over time (p = 0.40, r = 0.8%). Conclusion: In conclusion at the present study we observed the development of acute kidney injury in 10% of patients using tenofovir and a significant reduction in glomerular filtration. The phosphaturia and proteinuria observed suggest that the injury has been caused by proximal tubulopathy and more specific markers of renal injury as cystatin C and NGAL were not greater than the available biomarkers in clinical practice for their detection.