Introdução: Pacientes com doença renal crônica (DRC) têm maior probabilidade de desenvolver complicações no pós-operatório. O efeito da N-acetilcisteína (NAC) na prevenção da lesão renal aguda (LRA) associada à cirurgia cardíaca é controvertido. As principais causas desta controvérsia residem na não uniformidade dos critérios para definir a LRA e nas doses da NAC empregadas. Objetivos: O objetivo primário foi avaliar o efeito renoprotetor da NAC em pacientes com DRC durante as primeiras 72 horas depois de cirurgia de revascularização miocárdica eletiva, recorrendo à classificação AKIN, um critério de diagnóstico internacionalmente validado, para definir a LRA e utilizando doses de máximas de NAC sancionadas para uso clínico. Os objetivos secundários foram verificar o impacto do tratamento sobre o estresse oxidativo, morbimortalidade, necessidade de diálise durante a internação e sobre outros marcadores envolvidos na fisiopatologia da LRA. Métodos: estudo prospectivo e duplo-cego em 70 pacientes com DRC estágios 3 e 4 submetidos à revascularização miocárdica cirúrgica eletiva aleatorizados para receber NAC 150 mg/kg IV (dose de ataque) iniciada 2 h antes da cirurgia, seguida por 50 mg/kg IV em 6 horas (grupo NAC) ou solução de NaCl 0,9% IV (grupo Controle). Resultados: A incidência da LRA foi reduzida no grupo NAC (57,1% versus 28,6%, p=0,016). O não uso da NAC (RR= 5,98 IC 95% -2,86 A -0,28, P= 0,015) e a circulação extracorpórea (CEC) (RR= 6,39, IC 95% -2,98 a -0,34, p= 0,012) foram preditores independentes da LRA. Em pacientes tratados com CEC a NAC reduziu o risco de LRA de 63% para 46%. Nos Controles o estresse oxidativo foi elevado (p= 0,01) nas 72 h de pós-operatório. No grupo NAC esta resposta foi abolida. Outros marcadores da LRA foram também mais elevados nos Controles: Cistatina C (p< 0,001) e Neutrophil Gelatinase Associated Lipocalin , NGAL (p= 0,002). Os níveis de proteína C reativa e a incidência da morbimortalidade foram semelhantes entre os grupos. Nenhum paciente necessitou de diálise. Conclusões: A NAC, empregada em doses máximas, reduz a incidência de LRA em pacientes com DRC submetidos à cirurgia de revascularização miocárdica, abole a resposta do estresse oxidativo associado à ocorrência da LRA e reduz o impacto negativo da CEC na função renal / Introduction: Post-operative complications are frequent among patients with chronic kidney disease (CKD). The renoprotective effect of N-acetylcysteine (NAC) in patient undergoing myocardial revascularization is controversial, mainly because of differences in the doses of NAC administered and to different criteria to define acute kidney injury (AKI). Objectives: The primary objective was to evaluate the renoprotective effect of NAC in patients with CKD, stages 3 or 4, undergoing elective coronary artery bypass graft (CABG), with or without cardiopulmonary bypass (CPB), during the first 72 h post-operative. We used a validated criterion to define AKI (AKIN classification) and a maximum IV dose of NAC sanctioned for clinical use. The secondary objectives were to assess the effect of NAC on oxidative stress and other surrogate markers of renal lesion (C Cystatin and Neutrophil Gelatinase Associated Lipocalin, NGAL) and on morbimortality and the need of post-operative dialysis during hospitalization. Methods: this was a prospective double-blind study in 70 stages 3 or 4 CKD patients undergoing CABG randomized to receive either NAC 150 mg/kg IV (induction) started 2 h before surgery, followed by 20 mg/kg IV for 6 h (group NAC) or 0.9 saline IV (group Control). Results: The incidence of AKI was reduced in the group NAC (57.1% versus 28.6%, p=0.016). Non use of NAC (RR= 5.98 95% IC -2.86 to -0.28, p= 0.015) e CPB (RR= 6.39, 95% IC -2.98 to -0.34, p= 0.012) were independent predictors of AKI. NAC also reduced the incidence of AKI from 63% to 46% in patients treated with CPB. Oxidative stress was increased in the Control group (p= 0.01) while it was abolished in patients receiving NAC. Circulating C Cystatin (p< 0.001) and NGAL (p= 0.002) were also reduced by NAC. C-reactive protein and the incidence of death and cardiovascular events were not influenced by NAC. No patient needed dialysis during hospitalization. Conclusions: Maximum IV doses of NAC reduces the incidence of AKI in patients with pre-existing CKD undergoing elective CABG, abolishes oxidative stress and mitigate the negative effect of CPB on renal function

A deficiência de vitamina D (dVD) aumenta o risco de morte em pacientes hospitalizados. A injúria de isquemia/reperfusão renal (Isq) ativa vias de necrose e/ou apoptose e proliferação celular. A injúria renal aguda (IRA) induz a ativação de inibidores do ciclo celular, incluindo a p21, uma inibidora de kinase dependente de ciclina, a qual possui efeito protetor na IRA. A p21 é um alvo genômico da 25-hidroxivitamina D [25 (OH) D], a qual, atuando através de receptores de vitamina D (VDRs), possui efeitos imunomoduladores potentes e antiproliferativos, sugerindo a participação deste hormônio na fisiopatologia da doença renal. Desta forma, o objetivo deste estudo foi verificar a participação da deficiência de vitamina D no modelo de isquemia/reperfusão renal em ratos. Foram utilizados ratos Wistar que foram divididos em quatro grupos: controle (C), animais que receberam dieta padrão por 30 dias; dVD, animais que receberam dieta livre de vitamina D por 30 dias; Isq, animais que receberam dieta padrão por 30 dias e no 28º dia foram submetidos ao insulto de isquemia/reperfusão em ambos os rins por 45 minutos; e dVD+Isq, animais que receberam dieta livre de vitamina D por 30 dias e no 28º dia foram submetidos ao insulto de isquemia/reperfusão em ambos os rins por 45 minutos. Ao final dos 30 dias e após 48 horas da realização da isquemia/reperfusão, os animais foram submetidos à eutanásia e amostras de sangue, urina e tecido renal foram coletados para o estudo dos mecanismos de lesão renal. A injúria renal aguda associada à deficiência de vitamina D levou a uma queda da filtração glomerular e aumento da proteinúria; aumento da relação peso renal/peso corporal, sugerindo maior proliferação e hipertrofia; induziu uma diminuição na ativação dos receptores de vitamina D e da expressão da proteína p21 e aumento da expressão de caspase-3; observou-se déficit de concentração urinária com diminuição da expressão da AQP2; e um maior dano morfológico caracterizado pela análise da área intersticial e presença de necrose tubular. Nossos dados mostraram que alterando os níveis da p21 na IRA isquêmica, a vitamina D, via VDRs, controla a inflamação renal, a proliferação e a lesão celular / Vitamin D deficiency (VDD) increases the risk of death in hospitalized patients. Ischemia/reperfusion injury activates pathways of necrosis and/or apoptosis and cell proliferation. Acute kidney injury (AKI) induces the activation of cell cycle inhibitors, including p21, an inhibitor of cyclin-dependent kinase, which has a protective effect on the IRA. The p21 is a genomic target of 25-hydroxyvitamin D [ 25 (OH) D], which, acting through vitamin D receptors (VDRs), has potent antiproliferative and immunomodulatory effects, suggesting the involvement of this hormone in the pathophysiology of renal disease. Thus, the aim of this study was to assess the role of vitamin D deficiency in rats submitted to renal ischemia/reperfusion. Wistar rats were divided into four groups: control (C), animals that received a standard diet for 30 days; VDD, animals that received vitamin D-free diet for 30 days; IRI, animals that received standard diet for 30 days and on day 28 were subjected to the ischemia/reperfusion insult (IRI) in both kidneys for 45 minutes; and VDD+IRI, animals that received vitamin D-free diet for 30 days and on day 28 were subjected to the IRI in both kidneys for 45 minutes. At the end of 30 days and 48 hours after the IRI insult, the animals were euthanized and samples of blood, urine and kidney tissue were collected to study the mechanisms of renal injury. Acute kidney injury associated with vitamin D deficiency led to a decrease in glomerular filtration rate and increased proteinuria; increased relative kidney weight/body weight, suggesting greater proliferation and hypertrophy; induced a decrease in the activation of vitamin D receptors and the p21 protein expression and, increased caspase-3 expression; renal concentration impairment with decreased AQP2 expression, as well as greater morphological damage characterized by interstitial area analysis and presence of tubular necrosis. Our data showed that altering the levels of p21 in ischemic-AKI, vitamin D via VDRs, controls kidney inflammation, proliferation and cell injury

Introdução: Injúria Renal Aguda (IRA) é uma patologia grave e com elevada incidência em pacientes críticos. Apesar do avanço no conhecimento fisiopatológico ocorrido nas últimas décadas, pouco desse conhecimento foi traduzido em terapia para IRA já instalada. Medidas preventivas para evitar a progressão da IRA em momentos iniciais da injúria continuam a ser o principal foco na terapia da IRA. Nesse contexto, o diagnóstico e determinação precoce da gravidade da injúria renal são fundamentais para evitar a progressão para estágios mais graves e diminuir a morbidade e a mortalidade associadas à síndrome. Objetivos: O objetivo principal deste estudo, foi avaliar se o padrão de elevação dos biomarcadores permite a detecção precoce do diagnóstico de IRA. E os objetivos secundários foram avaliar se os biomarcadores podem auxiliar na predição da gravidade da IRA, na necessidade de diálise e óbito. Métodos: Estudo prospectivo, unicêntrico, entre janeiro de 2012 e janeiro de 2015. Foram avaliados e incluídos pacientes com critérios de alto risco para IRA nas Unidades de Terapia Intensiva (UTI) clínicas e cirúrgicas. Características clínicas e demográficas foram avaliadas no início da internação e a evolução laboratorial e hemodinâmica dos pacientes foram acompanhadas durante as primeiras 48 horas de internação na UTI. Os biomarcadores precoces de injuria renal aguda séricos e urinários, assim como a bioquímica e microscopia urinária, foram analisados a cada 12 horas durante este período. IRA foi definida pelo critério da creatinina do KDIGO. Episódios de IRA com resolução em 3 dias foram definidos como transitória (IRAt) e episódios com duração maior que 3 dias como persistente (IRAp). Resultados: Durante o período estudado foram avaliados 376 pacientes, dos quais 70 preencheram os critérios de inclusão e 32 (46%) evoluiram com IRA. Noventa porcento dos pacientes incluídos no estudo foram pacientes em pós-operatorio. Não houve diferença nas características basais entre os grupos com IRA e sem IRA. A fração de excreção de sódio (FENa) foi maior no grupo com IRAp à admissão, entretanto foi menor que 1% em todos os grupos. O gradiente transtubular de potássio (TTKG) foi significativamente maior no 4º e 5º momentos no grupo com IRAp quando comparado aos outros grupos. Os níveis de Neutrophil Gelatinase-Associated Lipocalin (NGAL), tanto séricos como urinários foram significativamente maiores no grupo com IRAp em relação ao grupo IRAt e não IRA, assim como Liver-type Fatty Acid-Binding Protein (L-FABP) e o Kidney Injury Molecule-1 (KIM-1). Não se constatou diferença significativa entre os grupos em relação ao Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), alfa e pi-Glutathione-transferase (alfa- GST e pi-GST). Entre os pacientes com diagnóstico de IRA pela creatinina sérica nos primeiros 2 dias de UTI, o emprego do NGAL sérico e/ou urinário possibilitaram o diagnóstico mais precoce da IRA em relação à creatinina em 59,3 % e 27,6% dos pacientes, respectivamente. O NGAL sérico e urinário foram preditores independentes de mortalidade e de necessidade de terapia de substituição renal à análise multivariada. Conclusão: Na IRA persistente a bioquímica urinária apresentou diferenças em relação à FENa e ao TTKG. A performance do NGAL sérico e urinário nesta população conseguiu antecipar o diagnóstico da IRA em relação ao critério da creatinina. O NGAL sérico e urinário foram preditores independentes de necessidade de terapia de substituição renal e mortalidade / Background: Acute kidney injury (AKI) is a syndrome with high incidence in critical ill patients and associated with severe complications. Although important advances has been achieved in the understanding of its physiopathology, this knowledge have not resulted in improvements in therapy for AKI. Preventive measures to avoid AKI progress at the initial phases of injury are still the main goal of AKI therapy. Therefore, early diagnosis and assessment of disease severity are essential to prevent disease progression and to reduce morbidity and mortality. Objectives: The main goal of this study was to evaluate whether a panel of biomarkers would allow early detection of AKI. Secondary endpoints were to evaluate whether biomarkers can predict the severity of AKI, need for dialysis and mortality in high-risk critical ill patients. Methods: We performed a prospective study between January 2012 and 2015. We recruited patients admitted in intensive care unit (ICU) with high risk for AKI. Clinical and demographic characteristics were recorded. Urinary biomarkers and urine biochemistry were measured sequentially every 12 hours during the first two days of ICU stay. AKI was defined according to KDIGO creatinine criteria. Patients were classified as having transitory AKI (tAKI) or persistent AKI (pAKI). Results: Of the 376 patients initially evaluated, 70 met the inclusion criteria. Thirty-two patients (46 %) met KDIGO criteria for AKI. Ninety percent of the patients in this study were surgical. The baseline characteristics were similar among all groups. The fractional excretion of sodium (FENa) was higher in pAKI group, and it was < 1% in all groups. In patients who developed pAKI the transtubular potassium gradient (TTKG) was significantly higher at 36h and 48h. Plasma and urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Liver-type Fatty Acid-Binding Protein (L-FABP) and Kidney Injury Molecule-1 (KIM-1) were significantly higher in the pAKI group as compared to the t AKI and non AKI groups in different times of evaluation. There was no difference in levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), alfa and pi-Glutathione-transferase (alfa-GST and pi-GST) within the groups during the first 48 h of ICU admission. Based on the cutoff levels, plasma and urinary NGAL would determine earlier diagnosis in 59.3% and 27.6% patients in the first two days of ICU, respectively. In the multivariate analysis, plasma and urinary NGAL were independent predictors of need for dialysis and mortality. Conclusions: In this study population, persistent AKI have alterations in urinary physicochemical parameters such as FENa and TTKG. Plasma and urinary NGAL were early biomarkers for AKI diagnosis. Plasma and urinary NGAL were independent predictors of dialysis and mortality

Introdução: A injúria renal aguda vem se apresentando como uma complicação frequente na população no contexto intra-hospitalar, e as terapias de substituição renal são empregadas como método de tratamento. Neste cenário, o cateter temporário para hemodiálise tornou-se um dispositivo essencial à terapêutica. Todavia, as complicações mecânicas e infecciosas tornaram-se eventos associados à prestação de assistência à saúde, acarretando índices elevados de morbidade e mortalidade nos pacientes acometidos por injúria renal aguda em hemodiálise. Objetivos: avaliar os fatores associados à retirada do cateter temporário para hemodiálise, bem como os motivos relacionados à solicitação de hemocultura e os fatores associados à infecção da corrente sanguínea relacionada ao cateter temporário para hemodiálise. Pacientes e Métodos: trata-se de um estudo observacional retrospectivo, envolvendo pacientes internados em um hospital público universitário de alta complexidade especializado em Cardiologia e Pneumologia, da cidade de São Paulo, Brasil. O estudo foi realizado no período de 01de julho de 2009 - 31de dezembro de 2010, sendo aprovado pela Comissão de Ética para análise de Projetos de Pesquisa (CAPPesq) do HCFMUSP nº0342/11. Resultados: foram avaliados 1.140 pacientes, atendidos pelo serviço de Nefrologia da instituição, dos quais 723 pacientes foram excluídos por não atenderem aos critérios de inclusão e 417 pacientes compuseram a amostra; 657 cateteres temporários foram utilizados durante o período. Os cateteres apresentaram duração média de 13 dias. O fluxo sanguíneo insuficiente para manutenção da hemodiálise foi a principal complicação mecânica associada à retirada do cateter temporário (30,7%), enquanto os fatores relacionados à infecção foram responsáveis por 31,1% dos casos, sendo a febre o principal sinal flogístico. A análise de Kaplan-Meier demonstrou maior sobrevida dos cateteres relacionados aos fatores infecciosos. A infecção da corrente sanguínea (ICS) relacionada ao cateter temporário para hemodiálise foi diagnosticada em 5,5% da população, com taxa de infecção de 5,54/1.000 cateteres-dia. Patógenos Gram negativos foram responsáveis por 52% dos casos de ICS-laboratorial, com predomínio das bactérias da família Enterobacteriacea; seguidas por germes Gram positivos (26%), sendo o Sthapylococcus spp de maior incidência e os fungos representados pela Candida não albicans (22%). Conclusões: fluxo sanguíneo insuficiente foi a principal causa mecânica para a retirada do cateter temporário para hemodiálise. No que concerne aos aspectos infecciosos, demostrou-se a necessidade de vigilância epidemiológica permanente, tendo em vista as altas taxas de suspeita infecciosa. A infecção da corrente sanguínea relacionada ao cateter temporário para hemodiálise apresentou taxas superiores aos preconizados em diretrizes internacionais. Finalmente, o perfil microbiológico identificado sugere predomínio da rota endoluminal de contaminação / Introduction: Acute kidney injury is a frequent complication in hospitalized patients, in which renal replacement therapies are frequently required. In this scenario, temporary venous access catheters for hemodialysis have become an essential therapy device. However, mechanical and infectious complications have become morbid events associated with health care provision, resulting in high morbidity and mortality in these patients. Objectives: To evaluate the factors associated with the removal of temporary catheters for hemodialysis, reasons for the request of blood culture, and the factors associated with bloodstream infection related to temporary catheters for hemodialysis. Patients and Methods: it was performed a retrospective observational study involving patients admitted to a tertiary public hospital specialized in Cardiology and Pneumology in the city of São Paulo, Brazil. The study was conducted between 1st July 2009 - 31st December 2010, and approved by the Ethics Committee for Analysis of Research Projects (CAPPesq) HCFMUSP nº0342/11. Results: A total of 1140 patients were evaluated by the Nephrology attending physicians. From the total sample, 723 patients were excluded for not fulfilling the inclusion criteria, resulting in a final sample of 417 patients with 657 temporary catheters whose mean duration was 13 days. Insufficient blood flow was the main complication associated with mechanical removal of temporary catheters (30.7%) while the factors associated with infection accounted for 31.1%, in which fever was the main infectious signal. The Kaplan-Meier analysis showed higher survival for catheters associated with infectious factors. A bloodstream infection (BSI) related to temporary catheters for hemodialysis was diagnosed in 5.5% of the population with an infection rate of 5.54/1,000 catheter-days. Gram negative pathogens were responsible for 52% of laboratorial ICS, with predominance from Enterobacteriaceae bacteria; followed by Gram positive germs (26%), with predominance of Staphylococcus spp and fungi represented by Candida non-albicans (22%). Conclusions: insufficient blood flow was the main mechanical factor for the removal of temporary catheters for hemodialysis. Regarding the infectious aspects, it was demonstrated the need for rigorous surveillance because of the high rates of suspected infections. Bloodstream infections associated with temporary catheters for hemodialysis presented higher rates than those determined in international guidelines. Finally, the microbiological profile suggests the predominance of endoluminal route of contamination

INTRODUÇÃO: Em pacientes transplantados renais, a paratireoidectomia está associada à piora aguda da função renal. Os efeitos agudos e crônicos da paratireoidectomia sobre a filtração glomerular foram pouco estudados em Hiperparatireoidismo Primário (HPTP). MÉTODO E CASUÍSTICA: Neste estudo retrospectivo de coorte, foram estudados 494 pacientes submetidos a paratireoidectomia por HPTP, entre os anos de 2007 e 2016. Variações agudas da creatinina foram aferidas diariamente na internação, até o 4o pós-operatório, sendo classificados conforme os critérios de KDIGO para IRA. Dados bioquímicos incluíram dosagem sérica de creatinina, cálcio iônico e total, paratormônio (PTH) e 25-OH vitamina D. A taxa de filtração glomerular foi estimada a partir da equação CKD-EPI. Foram comparados dados de função renal pré e pós-operatórios até 5 anos de seguimento. RESULTADOS: Dos 494 pacientes, 391 (79,1%) eram mulheres e 422 (85,4%) de cor branca. A causa mais comum de HPTP foi adenoma de paratireóide (351, 71,1%) e a mediana de idade foi de 58 anos. As medianas (Q1-Q3) de creatinina, PTH e cálcio total séricos foram de: 0,81 mg/dL (0,68-1,01), 154,5 pg/mL (106-238,5) e 10,9 mg/dL (10,3-11,5) respectivamente. A mediana de eGFR préoperatória foi de 86 mL/min x 1,73m2. No período agudo, houve redução mediana de 26 mL/min x 1,73m2 na eGFR (p < 0,0001), que representou -27,44% (±19,12%) de variação aguda da eGFR. De acordo com os critérios de IRA, 41,1% dos pacientes tiveram IRA estágio 1, 5,9% estágio 2 e 1,8% estágio 3. Outros 223 pacientes (45,1%) tiveram elevação da creatinina porém não preencheram critérios de IRA. Na análise univariada foram observadas correlações fracas, porém significativas, entre o percentual de variação aguda de eGFR e os seguintes fatores pré-operatórios: idade, PTH, cálcio e creatinina. Uma redução definitiva da eGFR foi observada em 60,7% dos pacientes, após 12 meses de seguimento. CONCLUSÃO: Houve significativa redução aguda da função renal após paratireoidectomia por HPTP, sendo que quase metade dos pacientes preencheram critérios de IRA. Observou-se importante recuperação da eGFR no primeiro mês de pós-operatório, podendo ocorrer algum grau de perda definitva de função renal / INTRODUCTION: In kidney transplant patients, parathyroidectomy is associated with acute decrease in renal function. Acute and chronic effects of parathyroidectomy on renal function have not been as extensively studied in primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: Retrospective cohort study of 494 patients undergoing parathyroidectomy for PHPT. Acute renal changes were evaluated daily until day 4 post parathyroidectomy, and stratified according to acute kidney injury (AKI) criteria. Biochemical assessment included serum creatinine, total and ionized calcium, PTH, and 25-hydroxyvitamin D (25OHD). EGFR were calculated using the CKD-EPI equation. We compared preoperative and postoperative renal function up to 5 years of follow-up. RESULTS: 391 (79.1%) patients were female and 422 (85.4%) were non-African American. Median age was 58 years old. Median (interquartile range) preoperative serum creatinine, PTH and total calcium were 0.81 mg/dL (0.68- 1.01), 154.5 pg/mL (106-238.5), and 10.9 mg/dL (10.3-11.5) respectively. Median (interquartile range) preoperative eGFR was 86 mL/min/1.73m2 (65-101.3). After surgery the median acute decrease in eGFR was 26 mL/min/1.73m2 (p < 0.0001). Acutely, 41.1% patients developed AKI stage 1, 5.9% AKI stage 2 and 1.8% AKI stage 3. Acute eGFR decrease (%) correlated with age, PTH, calcium and preoperative creatinine, in univariate analysis. Permanent reduction in eGFR occurred in 60.7 % of the patients, after acute episode. CONCLUSION: There is a significant acute impairment in renal function after parathyroidectomy for PHPT and almost half of patients meet the criteria for AKI. Significant eGFR recovery was observed during first month after surgery, but a small permanent reduction may occur

La circulation extracorporelle compte parmi les progrès techniques majeurs associés à la chirurgie cardiaque. Elle constitue aussi l’une des causes de complications principales car responsable d’une réponse inflammatoire généralisée qui résulte de la conjugaison des effets du stress oxydant et des cytokines libérés, contribuerait à la dysfonction multi-organe aboutissant aux complications myocardiques et rénales survenant au cours des périodes per- et postopératoires. La première partie de notre travail avait pour objectif d’explorer l’évolution des taux circulants du GDF-15, cytokine associée au stress oxydant et à l’inflammation, dans ce contexte de chirurgie cardiaque. Notre étude prospective a démontré pour la première fois que cette procédure est accompagnée de l’augmentation du GDF-15 dont les taux plasmatiques sont associés aux lésions postopératoires cardiaques et rénales.L’évaluation du risque opératoire repose sur un ensemble de scores dont le calcul est basé essentiellement sur des caractéristiques cliniques. Ces scores présentent toutefois un certaines limitations. Chez les patients « médicaux » atteints de pathologies cardiovasculaires la stratification du risque est définie en associant des caractéristiques cliniques à l’évaluation des taux circulants de biomarqueurs. L’objectif de cette seconde partie a donc été de mettre en évidence le pouvoir prédictif du GDF-15 en tant que biomarqueur circulant dans la survenue de complications rénales au cours de la chirurgie cardiaque sous CEC. Nous avons mis en évidence que les patients présentant des taux préopératoires élevés de GDF-15 sont à risque de développer une insuffisance rénale aigue postopératoire. / Ischemic cardiac diseases are the most frequent and deleterious pathologies leading to important cardiovascular-related mortality worldwide. One of the alternative therapies consists to treat these patients using cardiac surgery. Cardiopulmonary bypass was developed to greatly improve this surgical procedure. However, some adverse effects can occur during cardiac surgery associated with cardiopulmonary bypass due to the inflammatory response. This phenomenon is the result of various mechanisms including oxidative stress and inflammatory cytokines which lead to multi-organ failure and then to myocardial and renal injuries occurring during the peri- and post-operative periods.The first part of this work was designed to evaluate in the context of cardiac surgery the kinetics of plasma GDF-15 levels, an oxidative stress and inflammation related cytokine. Our prospective study demonstrated for the first time the kinetic increase in plasma GDF-15 levels which were associated to postoperative cardiac and renal injuries.Currently, operative risk evaluation is based on score calculation including clinical criteria. These risk scores present some limitations. Concerning other cardiac patients out of surgical fields, the risk assessment is defined using clinical parameters and biomarkers evaluation (cardiac troponin, BNP, Nt-proBNP). Thus, we aimed to determine whether pre-operative GDF-15 as plasma biomarker could help to identify patients at high risk of renal injuries. We found that patients with the highest pre-operative plasma GDF-15 levels are at risk for post-operative acute kidney injury.

<p>Hronična bolest bubrega (HBB) je zdravstveni problem koji se javlja &scaron;irom sveta i povezana je sa visokim kardiovaskularnim komorbiditetom i smrtno&scaron;ću. Veliki porast broja bolesnika koji imaju terminalnu bubrežnu slabo&scaron;ću (TBS) nastaje kao posledica eksponencijalnog porasta broja bolesnika čija je slabost bubrega posledica hipertenzije i dijabetesa, kao i porasta broja starih sa TBS. Zbog toga vi&scaron;e od 50% bolesnika sa HBB umire zbog kardiovaskularnih bolesti i pre započinjanja lečenja metodama za zamenu funkcije bubrega. Utvrditi kliničke karakteristike bolesnika sa i bez kontrastom indukovane nefropatije (pre svega varijable bubrežne funkcije definasane pomoću AKIN i RIFLE kriterijuma) podvrgnutih kardiohirur&scaron;kim operacijama, potom utvrditi postojanje razlike u mortalitetu i postoperativnom morbiditetu između bolesnika sa i bez kontrastom indukovane nefropatije, a koji se podvrgavaju kardiohirur&scaron;koj operaciji i takođe utvrditi prediktore mortaliteta i morbiditeta kod bolesnika sa prethodnom kontrastom indukovanom nefropatijom koji se podvrgavaju kardiohirur&scaron;koj operaciji. Studija je koncipirana kao retroprospektivna opservaciona studija u ukupnom trajanju od pet godina retrospektivnog perioda i pola godine prospektivnog perioda kojim su obuhvaćene dve grupe bolesnika: I grupa - pacijenti sa kontrastom indukovanom nefropatijom (CIN) i II grupa - pacijenti bez CIN; koji su podvrgnuti kardiohirur&scaron;kim operacijama (koronarna, valvularna, kombinovana hirurgija i ostale) na Institutu za kardiovaskularne bolesti Vojvodine u Sremskoj Kamenici. Od ukupnog broja operisanih pacijenata u ovom perioda (oko 5000 bolesnika) u ovu studiju je uključeno 1269 bolesnika. U na&scaron;oj studiji ukupno je analizirano 1269 bolesnika koji su svrstani u dve grupe. Prvu grupu je činilo 59 (4,6%) pacijenata koji su koronarografisani (dijagnostička, terapijska) i razvili CIN te su upućeni u istoj hospitalizaciji po indikaciji konzilijuma na koronarnu, valvularnu i kombinovanu hirurgiju. Drugu grupu je činilo 1210 (95,4%) bolesnika kod kojih nakon koronarografije nije razvijena kontrastom indukovana nefropatija, a takođe su tokom iste hospitalizacije operisani. Kriterijumi za uključivanje pacijenata u studiju su svi punoletni bolesnici koji su upućeni na kardiohirur&scaron;ke operacije (koronarna, valvularna, kombinovana i ostale). CIN je definisan kao porast vrednosti kreatinina unutar pet dana nakon koronarografije za 25% u odnosu na vrednost kreatina pre koronarografije. Praćene su preoperativne, operativne i postoperativne karakteristike bolesnika sa CIN i bolesnika bez CIN. U disertaciji su kori&scaron;ćene mere deskriptivne statistike: aritmetička sredina, standardna devijacija, medijana, kvartili, frekvence i procenti. Za poređenje srednjih vrednosti varijabli dve populacije primenjen je test za nezavisne uzorke i Man-Vitnijev test. Povezanost kategorijskih varijabli ispitana je pomoću Hi-kvadrat testa za tabele kontigencije ili pomoću Fi&scaron;erovog testa. Određivanje uticaja promenljivih na ishod lečenja izvr&scaron;en je primenom univarijantne i multivarijantne binarne logističke regresije, koja je poslužila i za pravljenje nove varijable (modela) za procenu ishoda lečenja. Prediktivni kvalitet varijabli na ishod ocenjen je pomoću ROC krivih. Za određivanje dužine preživljavanja primenjena je Kaplan-Meier analiza preživljavanja. Uticaj varijabli na preživljavanje izvr&scaron;en je na osnovu Coxove regresione analize. Za statistički značajnu testa uzeta je vrednost p&lt;0,05. Statistička obrada podataka izvedena je primenom statističkog paketa SPSS 17. Dokazana je statistička značajnost u ispitivanim grupama u pogledu akutizacije bubrežne insuficijencije (p=0,007). Broj bolesnika sa akutizacijom bubrežne insuficijencije u grupi CIN je bio 3 (5,1%), a u grupi bez CIN je 6 (0,5%). Dokazana je statistička značajnost u ispitivanim grupama na osnovu perikardnog izliva (p=0,046). Statističku značajnost treba uslovno prihvatiti jer je broj bolesnika sa perikardnim izlivom u grupi sa CIN bio samo 1 (1,7%). Dokazana je statistička značajnost u ispitivanim grupama na osnovu mortaliteta (p&lt;0,0005). Broj umrlih u grupi pacijenata sa CIN je 8 (13,6%), a u grupi pacijenata bez CIN je 23 (1,9%). Dokazana je statistička značajnost u ispitivanim grupama na osnovu AKIN kriterijuma (p&lt;0,0005). Broj bolesnika bez AKIN kriterijuma u grupi sa CIN bio je 29 (49,2%), a u grupi pacijenata bez CIN je 1210 (100,0%). U Stadijumu 1 AKIN kriterijuma broj bolesnika u grupi sa CIN bio je 26 (44,1%), a u grupi bolesnika bez CIN je 0 (0,0%). U Stadijumu 2 AKIN kriterijuma broj bolesnika u grupi sa CIN bio je 1 (1,7%), a u grupi bolesnika bez CIN bio je 0 (0,0%). U Stadijumu 3 AKIN kriterijuma broj bolesnika u grupi sa CIN bio je 3 (5,1%), a u grupi bolesnika bez CIN bio je 0 (0,0%). Dokazana je statistička značajnost u ispitivanim grupama na osnovu RIFLE kriterijuma (p&lt;0,0005). Broj bolesnika bez RIFLE kriterijuma u grupi sa CIN bio je 0 (0,0%), a u grupi pacijenata bez CIN bio je 1169 (96,6%). U riziku (Risc) RIFLE kriterijuma broj bolesnika u grupi sa CIN bio je 51 (86,4%), a u grupi bolesnika bez CIN bio je 41 (3,4%). U o&scaron;tećenju (Injury) RIFLE kriterijuma broj bolesnika u grupi sa CIN bio je 5 (8,5%), a u grupi bolesnika bez CIN bio je 0 (0,0%). U stabost (Failure) RIFLE kriterijuma broj bolesnika u grupi sa CIN bio je 3 (5,1%), a u grupi bolesnika bez CIN bio je 0 (0,0%). Dokazana je statistička značajnost u ispitivanim grupama na osnovu broja komplikacija (p&lt;0,0005). Broj bolesnika bez komplijacija u grupi sa CIN bio je 39 (66,1%), a u grupi pacijenata bez CIN bio je 1027 (84,9%). Broj bolesnika sa 1 komplijacijom u grupi sa CIN bio je 12 (20,3%), a u grupi pacijenata bez CIN bio je 146 (12,1%). Broj bolesnika sa 2 komplijacije u grupi sa CIN bio je 6 (10,2%), a u grupi pacijenata bez CIN bio je 20 (1,7%). Broj bolesnika sa 3 komplijacije u grupi sa CIN bio je 1 (1,7%), a u grupi pacijenata bez CIN bio je 11 (0,9%). Broj bolesnika sa 4 komplijacije u grupi sa CIN bio je 1 (1,7%), a u grupi pacijenata bez kontrastom indukovane nefropatije bio je 6 (0,5%). Dokazana je statistička značajnost u ispitivanim grupama na osnovu MACE komplikacija (p&lt;0,0005). Broj bolesnika sa MACE komplikacijama u grupi sa CIN bio je 20 (33,9%), a u grupi pacijenata bez CIN bio je 183 (15,1%). Akutna bubrežna slabost je relativno česta komplikacija kardiohirur&scaron;kih operacija. Posebno su ugroženi bolesnici sa visokim preoperativnim rizikom, u na&scaron;oj studiji pacijenti sa prethodnim CIN-om, kod kojih je akutizacija bubrežne slabosti znatno učestalija. Kardiohirur&scaron;ki bolesnici kod kojih nastane akutna bubrežna slabost imaju, kao i u na&scaron;oj studiji, vi&scaron;e postoperativnih komplikacija, produžen boravak u jednici intenzivne nege, kao i rizik za nastanak hronične bubrežne bolesti.</p> / <p>Chronic kidney disease (CKD) is a healthcare problem that occurs worldwide and is associated with high cardiovascular comorbidity and mortality. A large increase in the number of patients with terminal renal failure (TRF) occurs as a result of an exponential increase in the number of patients whose renal failure is due to hypertension and diabetes, as well as an increase in the number of elderly with TRF. As a result, more than 50% of patients with CKD die from cardiovascular disease even before starting treatment with kidney replacement therapy. To determine the clinical characteristics of patients with and without contrast-induced nephropathy (CIN) (renal function parameters defined by AKIN and RIFLE criteria) undergoing cardiac surgery, to determine the difference in mortality and postoperative morbidity between patients with and without CIN who are submitted to cardiac surgery and also to determine predictors of mortality and morbidity in patients with CIN undergoing cardiac surgery. The study was conceived as a retroprospective observational study with a total duration of five years of retrospective period and half a year of prospective period which included two groups of patients: Group I - patients with contrast-induced nephropathy (CIN) and Group II - patients without CIN; who underwent cardiac surgery (coronary, valvular, combined surgery and other) at the Institute for Cardiovascular Diseases of Vojvodina in Sremska Kamenica. Out of the total number of operated patients in this period (about 5000 patients), 1269 patients were included in this study. In our study, a total of 1269 patients were analyzed, which were classified into two groups. The first group consisted of 59 (4.6%) patients who underwent coronary angiography (diagnostic, therapeutic) and developed CIN and were submitted to surgery in the same hospitalization as indicated by heart team. The second group consisted of 1210 (95.4%) patients who did not develop CIN after coronary angiography but were also operated on during the same hospitalization. Criteria for inclusion of patients in the study are: all adult patients who are referred for cardiac surgery (coronary, valvular, combined and other). CIN was defined as a at least 25% increase in creatinine value within five days after coronary angiography compared to creatine value before coronary angiography. Preoperative, operative and postoperative characteristics of patients with CIN and patients without CIN were analyzed. Statistical analyses included measures of descriptive statistics: arithmetic mean, standard deviation, median, quartiles, frequencies and percentages. To compare the mean values of the variables of the two populations, t-test for independent samples and the Mann-Whitney test were applied. The correlation of categorical variables was examined using the Chi-square test for contingency tables or using the Fisher test. The influence of variables on the treatment outcome was determined by applying univariate and multivariate binary logistic regression, which also served to create a new variable (model) for assessing the treatment outcome. The predictive quality of outcome variables was assessed using ROC curves. Kaplan-Meier survival analysis was used to determine survival length. The influence of variables on survival was performed based on Cox regression analysis. For a statistically significant test, the value of p &lt;0.05 was taken. Statistical data processing was performed using the statistical package SPSS 17. Statistical significance was observed in the examined groups regarding the acutization of renal failure (p = 0.007). The number of patients with acute renal failure in the CIN group was 3 (5.1%), and in the group without CIN it was 6 (0.5%). Statistical significance was observed between the examined groups based on pericardial effusion (p = 0.046). Statistical significance should be conditionally accepted because the number of patients with pericardial effusion in the group with CIN was only 1 (1.7%). Statistical significance was demonstrated in the examined groups based on mortality (p &lt;0.0005). The number of deaths in the group of patients with CIN was 8 (13.6%), and in the group of patients without CIN it was 23 (1.9%). Statistical significance was demonstrated in the examined groups based on the AKIN criteria (p &lt;0.0005). The number of patients without AKIN criteria in the group with CIN was 29 (49.2%), and in the group of patients without CIN it was 1210 (100.0%). In Stage 1 of the AKIN criterion, the number of patients in the group with CIN was 26 (44.1%), and in the group of patients without CIN it was 0 (0.0%). In Stage 2 of the AKIN criterion, the number of patients in the group with CIN was 1 (1.7%), and in the group of patients without CIN it was 0 (0.0%). In Stage 3 of the AKIN criterion, the number of patients in the group with CIN was 3 (5.1%), and in the group of patients without CIN it was 0 (0.0%). Statistical significance was demonstrated between the examined groups based on the RIFLE criteria (p &lt;0.0005). The number of patients without RIFLE criteria in the group with CIN was 0 (0.0%), and in the group of patients without CIN it was 1169 (96.6%). In the Risk of the RIFLE criterion, the number of patients in the group with CIN was 51 (86.4%), and in the group of patients without CIN it was 41 (3.4%). In the Injury of the RIFLE criterion, the number of patients in the group with CIN was 5 (8.5%), and in the group of patients without CIN it was 0 (0.0%). In the Failure of the RIFLE criterion, the number of patients in the group with CIN was 3 (5.1%), and in the group of patients without CIN it was 0 (0.0%). Statistical significance was demonstrated in the examined groups based on the number of complications (p &lt;0.0005). The number of patients without complications in the group with CIN was 39 (66.1%), and in the group of patients without CIN it was 1027 (84.9%). The number of patients with 1 complication in the group with CIN was 12 (20.3%), and in the group of patients without CIN it was 146 (12.1%). The number of patients with 2 complications in the group with CIN was 6 (10.2%), and in the group of patients without CIN it was 20 (1.7%). The number of patients with 3 complications in the group with CIN was 1 (1.7%), and in the group of patients without CIN it was 11 (0.9%). The number of patients with 4 complications in the group with CIN was 1 (1.7%), and in the group of patients without contrast-induced nephropathy it was 6 (0.5%). Statistical significance was demonstrated between the examined groups based on MACE complications (p &lt;0.0005). The number of patients with MACE complications in the group with CIN was 20 (33.9%), and in the group of patients without CIN it was 183 (15.1%). Acute renal failure is a relatively common complication of cardiac surgery. Vulnerable patients are particularly at risk, in our study patients with previous CIN, in whom the acutazation of renal failure is significantly more frequent. Cardiac surgery patients who develop acute renal failure have, as demonstrated in our study, more postoperative complications, prolonged stay in the intensive care unit, as well as the risk of developing chronic kidney disease.</p>

Introduction to the issue: Stay in an intensive care unit or anaesthesiology and resuscitation department has a demonstrable effect on the quality of life, whether mental, physical, or mental. A large percentage of patients experience post intensive care syndrome. The huge challenge for nursing care is to reduce this percentage and enable patients to recover in the best possible way and return to normal life of the same quality as before the hospitalization Methodology: The aim of this work is to find out how the quality of life of patients is affected after hospitalization in the intensive care unit or anaesthesiology and resuscitation department, with a proportion of acute renal failure and the need for continuous renal replacement. First, patients were evaluated with APACHE II score, SOFA and TISS 2. Next, questionnaires in which they responded to the period before hospitalization (SF 36, DEMMI, ADL, IADL) were filled, when released from ARO they went through the test of physical capability, (30s sit-up test, 6-minute walk test), further measurements when released from ICU took place (HADS, MAF, DEMMI, ADL, 30s sit-p test, 6-minute walk test), and after three months (SF 36, HADS, MAF, DEMMI, IADL, ADL 30s sit-up test, 6-minute walk test and a week of wearing a Garmin vivofit bracelet). Main...

Disease subtyping has been a critical aim of precision and personalized medicine. With the potential to improve patient outcomes, unsupervised and semi-supervised methods for determining phenotypes of subtypes have emerged with a recent focus on matrix and tensor factorization. However, interpretability of proposed models is debatable. Principal component analysis (PCA), a traditional method of dimensionality reduction, does not impose non-negativity constraints. Thus coefficients of the principal components are, in cases, difficult to translate to real physical units. Non-negative matrix factorization (NMF) constrains the factorization to positive numbers such that representative types resulting from the factorization are additive. Archetypal analysis (AA) extends this idea and seeks to identify pure types, archetypes, at the extremes of the data from which all other data can be expressed as a convex combination, or by proportion, of the archetypes. Using AA, this study sought to evaluate the sufficiency of AKI staging criteria through unsupervised subtyping. Archetype analysis failed to find a direct 1:1 mapping of archetypes to physician staging and also did not provide additional insight into patient outcomes. Several factors of the analysis such as quality of the data source and the difficulty in selecting features contributed to the outcome. Additionally, after performing feature selection with lasso across data subsets, it was determined that current staging criteria is sufficient to determine patient phenotype with serum creatinine at time of diagnosis to be a necessary factor.

<p>Uvod: Učestalost akutne renalne insuficijencije, odnosno akutnog bubrežnog o&scaron;tećenja u jedinicama intenzivnog lečenja se kreće od 36 do 66 %. Akutno bubrežno o&scaron;tećenje povi&scaron;ava smrtnost, trajanje hospitalizacije i ukupne tro&scaron;kove lečenja. Ranije prepoznavanje prediktivnih faktora za nastanak akutnog bubrežnog o&scaron;tećenja može da ima značajan uticaj na pravovremeno započinjanje terapijskih mera i smanjivanje mortaliteta kod kritično obolelih. Cilj istraživanja: Utvrditi incidencu akutnog bubrežnog o&scaron;tećenja na Odeljenju reanimacije Urgentnog centra Kliničkog centra Vojvodine tokom 2011.godine, učestalost sepse kao etiolo&scaron;kog faktora i značajne prediktivne faktore za nastanak akutnog bubrežnog o&scaron;tećenja koji se javljaju u toku prvih 24 časa lečenja na odeljenju intenzivnog lečenja. Metodologija: Retrospektivno-prospektivna opservaciona studija uključila je uzorak od 251 ispitanika koji su se lečili na dva odeljenja intenzivnog lečenja u Kliničkom centru Vojvodine tokom 2010, 2011, i prvih 6 meseci 2012.godine. Iz medicinske dokumentacije (istorije bolesti, dnevne terapijske liste i liste vitalnih i laboratorijskih parametara) za svakog ispitanika je verifikovano prisutvo ili odsustvo potencijalnog prediktivnog faktora. Zatim je zabeležena pojava akutnog bubrežnog o&scaron;tećenja prema RIFLE kriterijumima. Statistička analiza je izvr&scaron;ena pomoću statističkog paketa IBM SPSS 20 Statistics. Podaci su predstavljeni tabelarno i grafički, a statistička značajnost određivana je na nivou p&lt; 0,05. Prikupljeni podaci su obrađeni standardnim statističkim testovima. Za izvođenje modela predviđanja primenjena je multivarijatna logistička regresija. Određene su granične tačke na osnovu ROC analize za dobijene značajne prediktore iz multivarijacione logističke regresije i izračunati su pridruženi bodovi koji bi činili skoring sistem za utvrđivanje rizika od nastanka akutnog bubrežnog o&scaron;tećenja. Rezultati: Incidenca akutnog bubrežnog o&scaron;tećenja na Odeljenju reanimacije Urgentnog centra Kliničkog centra Vojvodine u Novom Sadu kod bolesnika koji su hospitalizovani najkraće 48 časova u toku 2011.godine je 32 %. Rezna tačka (cut off value) zapremine provocirane diureze jedan čas nakon intravenskog davanja bolusa furosemida od 0,165 ml/kg telesne mase/čas/po miligramu datog furosemida ima najvi&scaron;u senzitivnost (82,3 %) i specifičnost (67,5 %) u diferenciranju bolesnika koji će razviti ABO. Konačni model predloženog skoring sistema sa ulogom predikcije nastanka ABO nakon 24 časa lečenja bolesnika na odeljenju intenzivnog lečenja sadrži sledeće varijable: starost vi&scaron;u od 53 godine, vrednost APACHE skora vi&scaron;u od 16, prosečnu diurezu prvih 6 časova hospitalizacije nižu od 0,875 ml/kg/h, primenu vazopresora, kalijemiju vi&scaron;u od 4,5 mmol/l i koncentraciju laktata iznad 2 mmol/l. Zaključak: Incidenca akutnog bubrežnog o&scaron;tećenja na Odeljenju reanimacije Urgentnog centra Kliničkog centra Vojvodine je slična literaturnim podacima. Bolesnici koji su stariji, imaju vi&scaron;e vrednosti APACHE II skora, nižu prosečnu zapreminu diureze u toku prvih 6 časova po prijemu, koji primaju vazopresorne medikamente, imaju vi&scaron;u koncentraciju kalijuma i vi&scaron;e koncentracije laktata u toku prvih 24 časa lečenja imaju veću &scaron;ansu da razviju akutno bubrežno o&scaron;tećenje.</p> / <p>Introduction: The incidence of acute renal insufficiency (acute kidney injury) in intensive care unit is between 36 and 66 %. Acute kidney injury is responsible for higher mortality, longer hospitalization and higher costs. Earlier recognition of acute kidney injury predictive factors could have important impact on right timing of therapeutic measures and lower mortality in critically ill patients. Aims: investigate the incidence of acute kidney injury during 2011. in patients who are hospitalized at Department of reanimation of Emergency centre, Clinical centre of Vojvodina, incidence of acute kidney injury caused by sepsis in the same period and detect acute kidney injury occurrence predicitive factors Methodology: This retrospective-prospective observational study investigated 251 critically ill patients-study subjects who were treated at two intensive care departments in Clinical centre of Vojvodina during 2010, 2011 and first six months of 2012. Potential predictive factors were identified out of medical records (patient history, daily therapeutic lists, vital parameters and laboratory values lists); the occurrence of acute kidney injury was noted according to RIFLE criteria. IBM SPSS version 20 was used for statistical analysis, standard statystical test were applied. The results were presented in tables and graphs, statystical significance was set at p value of less than 0,05. Multivariate logistic regression model was used for potential predictive factors. Statystically important factors were identified and their best sensitivity and specificity cut-off values were found using ROC curve analysis.; These cut-off values were used for creating a scoring system that determines the risk for acute kidney injury occurrence. Results: The incidence of acute kidney injury at Department of reanimation, Clinical centre of Vojvodina in patients who were hospitalized at least 48 hours was 32 % during 2011. The cut off value of provoked hourly urine output during first hour after furosemide intravenous bolus of 0.165 ml/kg body weight/h/miligram of administered furosemide has the highest sensitivity (82.3 %) and specifity (67.5 %) in differentiation of patients who would develop acute kidney injury and those who would not. The final suggested model of scoring system with the role of acute kidney injury prediction after 24 hours of treatment contains the next variables: age higher than 53 years, APACHE II score higher than 16, avarage hourly urine output during first 6 hours after ICU admission less than 0,875 ml/kg BW/h, vasopressor medication administration, blood potassium concentration higher than 4,5 mmol/l, lactates higher than 2 mmol/l after 24 hours of treatment. Conclusion: The incidence of acute kidney injury at Department of reanimation of Emergency centre, Clinical centre of Vojvodina is similar to world literature references. Critically ill patients who are more likely to develop acute kidney injury are older, have higher APACHE II score values, lower avarage urine output in the first 6 hours after ICU admission, are administered vasopressor medication, have higher blood potassium and lactate concentration in the first 24 hours of their treatment.</p>