O excesso de adenina na dieta (ADE) promove precipitação intrabular de cristais, levando a uma nefrite intersticial progressiva com perda de função renal. Estudo recente demonstrou que esse processo requer ativação do sistema NF-kB. No presente estudo investigamos o possível envolvimento de outros componentes da imunidade inata, além do NF-kB. Verificamos também a hipótese de que a nefropatia associada aos cristais continua a progredir mesmo depois de cessada a sobrecarga de adenina. Foram estudados ratos Munich-Wistar machos e adultos sem tratamento (C) ou recebendo 0.5% de ADE na dieta. Após 1 semana, a ADE foi removida da dieta e os animais foram seguidos por 4 ou 24 semanas. A administração de ADE por 1 semana promoveu uma inflamação intersticial aguda, com perda de função renal, alteração da pressão caudal, sem alterações glomerulares. Os mediadores da imunidade inata, como TLR2, TLR4, inflamassoma NLRP3, IL1beta e IL-6, apresentaram-se ativados sem, no entanto, ativar o sistema NF-kB. Após cessada a sobrecarga de ADE, a inflamação persistiu, com infiltração por macrófagos, expressão elevada de AngII, deposição progressiva de colágeno e, na fase mais tardia, glomeruloesclerose, caracterizando um processo inflamatório crônico, autônomo, que não contou com a participação do eixo NLR/IL1beta. Em contraste, o sistema NF-kB foi ativado, sendo um dos possíveis estímulos a produção intra-renal de AngII. Dois mecanismos patogênicos podem ser identificados neste estudo: 1) agudo, associado à ativação do eixo NLR-IL1beta; 2) crônico, associado à produção de AngII renal e à ativação do sistema NF-kB / Excess adenine in the diet (ADE) promotes intratubular crystal precipitation, leading to progressive interstitial nephritis and loss of renal function. A recent study has shown that this process requires activation of the NF-kB system. In the present study we investigated the possible involvement of other components of innate immunity, in addition to NF-kB, as well as whether nephropathy associated with excess adenine continues to progress even after dietary cessation. Male Munich-Wistar rats without treatment (C) or receiving 0.5% of ADE in the diet were studied. After 1 week, ADE was removed from the diet and the animals were followed for 4 or 24 weeks. Administration of ADE for 1 week promote acute interstitial inflammation, with loss of renal function, alteration of caudal pressure, without glomerular changes. Mediators of innate immunity, such as TLR2, TLR4, NLRP3 inflamassome, IL1beta and IL-6 , were shown to be activated, with no apparent activation of the NF-kB system. In the late phases of the model, the inflammation persisted, with significant infiltration by macrophages, high expression of AngII, progressive collagen deposition and glomerulosclerosis, characterizing a chronic, autonomic inflammatory process that did not involve the participation of the NLR/IL1beta axis. By contrast, the NF-kB system was activated, with intra-renal AngII production as a possible stimulus. Two mechanisms operated this study: 1) an acute one, associated with activation of the NLR-IL1beta axis; 2) a chronic one, associated with intrarenal AngII production and NF-kB activation

A gordura pericárdica (GP), um componente do tecido adiposo visceral, tem sido consistentemente relacionada com aterosclerose coronária na população geral. Este estudo avaliou a associação entre GP e a calcificação arterial coronária (CAC) em pacientes com doença renal crônica (DRC) não dialítica. Este é um estudo transversal post-hoc da linha de base de coorte prospectiva de 117 pacientes com DRC em seguimento ambulatorial sem doença coronária manifesta (idade, 56,8 ± 11 anos; 64% do sexo masculino; 95,1% hipertensos; 25,2% diabéticos; 15,5% com história prévia de tabagismo; e estágios 2 a 5 da DRC e ritmo de filtração glomerular estimado de 36,8 ± 18,1 ml/min). O escore de CAC, volume de GP e gordura visceral abdominal (GVA) foram medidos por tomografia computadorizada. A associação da GP, como variável contínua, com a presença de CAC foi analisada por regressão logística multivariada. CAC (escore de cálcio>0) esteve presente em 59,2% dos pacientes. Na comparação com os pacientes sem CAC, aqueles com CAC eram 10 anos mais velhos, apresentaram maior proporção de homens (78,7% versus 42,9%, p < 0.001), tiveram maior circunferência de abdominal (95,9 ± 10,7 versus 90,2 ± 13,2 centímetros, p=0,02), maior volume de GP (224,8 ± 107,6 versus 139,1 ± 85,0 cm³, p < 0,01), e maior área de GVA (109,2 ± 81,5 versus 70,2 ± 62,9 cm², p=0,01). Em análise multivariada ajustada para idade, sexo, diabetes, história de tabagismo, história de tabagismo, e hipertrofia ventricular concêntrica; GP esteve significantemente associada com a presença de CAC (OR: 1,88 95% IC: 1,03-3,43 por desvio padrão, p=0,04). GP permaneceu associada com CAC mesmo após ajuste adicional para ritmo de filtração glomerular e fósforo sérico (OR: 1,85 95% IC: 1,00 - 3,42, p=0,05). A GP está independentemente associada com CAC em pacientes com DRC não dialítica. / Pericardial fat (PF), a component of visceral adipose tissue has been consistently related to coronary atherosclerosis in the general population. This study evaluated the association between PF and coronary artery calcification (CAC) in non-dialysis dependent chronic kidney disease (CKD) patients. This is a post-hoc cross sectional analysis of the baseline of a prospective cohort of 117 outward CKD patients without manifest coronary artery disease (age, 56.9 ± 11.0 years, 64,1% males, 95.1% hypertensive, 25.2% diabetics, 15.5% ever smokers, CKD stage 2 to 5 with estimated glomerular filtration rate 36.8 ± 18.1 ml/min). CAC scores, PF volume and abdominal visceral fat (AVF) areas were measured by computed tomography. The association of PF as a continuous variable with the presence of CAC was analyzed by multivariate logistic regression. CAC (calcium score >0) was present in 59.2% patients. On the comparison with patients with no CAC, those with CAC were 10 years older on average, had a higher proportion of male gender (78.7% vs. 42.9%, p < 0.001), and had higher values of waist circumference (95.9 ± 10.7 versus 90.2 ± 13.2 cm, p=0.02), PF volumes (224.8±107.6 versus 139.1±85.0 cm³, p < 0.01) and AVF areas (109.2 ± 81.5 versus 70.2 ± 62.9 cm², p=0.01). In the multivariate analysis, adjusting for age, gender, diabetes, smoking and, left ventricular concentric hypertrophy, PF was significantly associated with the presence of CAC (OR: 1.88 95% CI: 1.03-3.43 per standard deviation, p=0.04). PF remained associated with CAC even after additional adjustments for estimated glomerular filtration rate or serum phosphorus (OR: 1.85 95% CI: 1.00-3.42, p=0.05). PF is independently associated with CAC in non-dialysis dependent CKD patients

INTRODUÇÃO: A calcificação vascular (CV) é uma condição comum na doença renal crônica (DRC) e está associada a um maior risco de mortalidade, eventos cardiovasculares e outras comorbidades. A dieta pode ser importante na fisiopatologia da CV e um alvo em potencial para medidas terapêuticas, mas o seu papel ainda não é claro. Assim, o objetivo deste estudo foi avaliar a associação entre o consumo de energia, macro e micronutrientes e CV em pacientes com DRC em tratamento conservador. MÉTODOS: Foram analisados os dados da linha de base de 454 participantes do estudo PROGREDIR. O consumo alimentar foi avaliado por meio de um questionário de frequência alimentar e a ingestão de nutrientes foi ajustada pela energia pelo método dos resíduos. A calcificação arterial coronária (CAC) foi mensurada por tomografia computadorizada sem contraste e apresentada pelo escore de cálcio de Agatston. Após a exclusão dos participantes que utilizavam stent coronário, as análises foram realizadas em 373 pacientes. Inicialmente, considerando-se a distribuição assimétrica da CAC e a não independência entre a ingestão de nutrientes, a associação entre a CAC e o consumo alimentar foi avaliada modelos lineares generalizados mistos. Devido à colinearidade entre os nutrientes, em seguida foi utilizada a regressão de LASSO para identificar os nutrientes mais relacionados à variabilidade da CAC. RESULTADOS: A mediana da idade e da CAC foi de 68 (60, 76) anos e 165 (8, 785), respectivamente. O maior tercil de CAC se associou diretamente à ingestão de fósforo, cálcio e magnésio. Houve um maior consumo de vitamina A, ácido pantotênico e potássio no segundo tercil. Após ajustes para variáveis de confusão (idade, sexo, diabetes mellitus e tabagismo como efeitos fixos e o indivíduo como efeito aleatório), a ingestão de ácido pantotênico (? = 0,48; IC95% 0,22, 0,75; p < 0,001), fósforo (beta = 0,38; IC95% 0,10, 0,65; p = 0,01), cálcio (beta = 0,0008; IC95% 0,0001, 0,0017; p = 0,04) e potássio (beta = 0,0005; IC95% 0,0001, 0,009; p = 0,02) permaneceram associadas à CAC nos modelos lineares generalizados mistos. Devido à colinearidade entre esses nutrientes, foi utilizada a regressão de LASSO para avaliar os nutrientes mais associados à variabilidade da CAC. Nessa abordagem, os nutrientes que mais explicaram a variância da CAC foram o fósforo (beta = 0,25), o cálcio (beta = 0,09) e o potássio (beta = 0,06). CONCLUSÕES: Houve associação entre a CAC e o consumo de fósforo, cálcio e potássio em uma população com DRC. Estudos futuros são necessários para confirmar esses resultados e avaliar o papel de intervenções sobre a prevenção e progressão da CAC baseadas nesses micronutrientes / BACKGROUND: Vascular calcification (VC) is a widespread condition in chronic kidney disease (CKD) and is associated with a higher risk of mortality, cardiovascular events, and other comorbidities. Diet may play an important role in VC and is a potential target for therapeutic measures, but this role is not clear. Thus, the aim of this study was to evaluate the association between energy, macro-and micronutrient intakes and VC in non-dialysis CKD patients. METHODS: We analyzed the baseline data from 454 participants of PROGREDIR study. Dietary intake was evaluated by a validated food frequency questionnaire and nutrient intakes were adjusted for energy by residual method. Coronary artery calcification (CAC) was measured by non-contrast computed tomography and was presented by Agatston calcium score. After exclusion of participants with coronary stent, 373 people remained for the analyses. Initially, taking into account the asymmetrical distribution of CAC and the non-independence between nutrient intakes, we evaluated the association between CAC and dietary intake by generalized linear models and generalized linear mixed models. To address the collinearity between nutrients, we next evaluated the nutrients mostly related to CAC variability by LASSO regression. RESULTS: Median age and CAC were 68 (60, 76) years old and 165 (8, 785), respectively. The highest tertile of CAC was directly associated with the intake of phosphorus, calcium and magnesium. There was a higher intake of vitamin A, pantothenic acid and potassium in the second tertile. After adjustment for confounding variables (age, gender, diabetes mellitus and tobacco use as fixed effects and individual as random effect), the intake of pantothenic acid (? = 0.48; CI95% 0.22, 0.75; p < 0.001), phosphorus (beta = 0.38; CI95% 0.10, 0.65; p = 0.01), calcium (beta = 0.0008; CI95% 0.0001, 0.0017; p = 0.04) and potassium (beta = 0.0005; CI95% 0.0001, 0.009; p = 0.02) remained associated with CAC in the generalized linear mixed models. In order to handle the collinearity between these nutrients, we used the LASSO regression to evaluate the nutrients associated with CAC variability. In this approach, the nutrients that most explained the variance of CAC were phosphorus (beta = 0.25), calcium (beta = 0.09) and potassium (beta = 0.06). CONCLUSIONS: We found an association between CAC and the intake of phosphorus, calcium and potassium in a CKD population. Future studies are needed to confirm these findings and assess the role of interventions on these micronutrients on CAC prevention and progression

Dados clínicos e histológicos referentes a biópsias pulmonares cirúrgicas de 63 pacientes adultos, com infiltrado difuso, a maior parte em insuficiência respiratória, foram analisados. A severidade de cada alteração histopatológica foi avaliada semiquantiativamente segundo um sistema histológico de escores. "Índices" agudo e crônico foram estabelecidos. Associação estatiscamente significante ocorreu entre a sobrevida e idade, dano alveolar difuso, comorbidade e "índice crônico". A análise histológica detalhada de espécimes pulmonares mostrou-se mais informativa do que o simples diagnóstico nosológico. Maiores estudos prospectivos com adequada casualização poderão confirmar esta conclusão / Clinical and histological data concerning open lung biopsy from 63 adult patients, with diffuse infiltrates, most of them with respiratory failure, from 1982 to 2003, were analyzed. Severity of each pathological alteration was semiquantitatively rated following an histological score system. "Acute" and "chronic" indices were then established. Statistically significant association occurred between survival and increasing age, diffuse alveolar damage, comorbidity and the "chronic score". Detailed histological analysis of lung specimens was proven to provide more than nosological diagnosis. Greater studies in a randomized and prospective trial could finalize and confirm this conclusion

O hiperparatireoidismo secundário à doença renal crônica (HPS) acomete inúmeros pacientes. Não existe consenso sobre qual tipo de paratireoidectomia (PTx) se associa com melhores resultados. Na PTx total com autoimplante (PTx-AI) especula-se se o número de fragmentos implantados melhora desfechos clínicos. Trinta e seis (36) pacientes com HPS foram randomizados para PTx-AI com 45 ou 90 fragmentos de paratireoide. Prospectivamente, avaliamos os fatores clínicos, bioquímicos e anatomopatológicos que influenciaram a função do AI. No início do estudo (t0), o Grupo-45 (N = 28) e Grupo-90 (N = 8) eram semelhantes, com exceção dos níveis séricos de fosfato. Após 12 meses (t12), os níveis séricos de PTH do enxerto e sistêmico correlacionaram-se com o cálcio iônico (Cai)-t0 (r2 = 0,442, p = 0,016; r2= 0,450, p = 0,008, respectivamente). A duração da fome óssea correlacionou-se com fosfatase alcalina (FA)-t0 (r2 = 0,593, p = 0,001). Nas células paratireoideanas, a expressão de PCNA correlacionou-se com o tempo em hemodiálise (r2 = 0,437, p = 0,016); a expressão do receptor-1 do fator de crescimento de fibroblastos (FGFR1) com FA-t0 (r2 = -0,758; p = 0,0001); o receptor de vitamina-D (VDR) com Cai-t0 (r2 = -0,464, p = 0,007) e carga cumulativa de Ca elemento (r2 = - 0,359, p = 0,04); o receptor sensível ao Ca (CaSR) com menor uso de calcitriol (r2 = -0,445, p = 0,049); e o Klotho com a dose de vitamina D pré- PTx (r2 = 0,811, p = 0,027) e com fosfato-t0 (r2= -0,528, p = 0,017). Houve progressão do escore de calcificação vascular [0,53 (0 - 4) vs. 1,1 (0 - 8); p = 0,04], que se correlacionou com a carga cumulativa de Ca elemento (r2 = 0,605, p = 0,006) e com o fosfato-t0 (r2 = 0,503; p = 0,028). Em conclusão, a PTx independentemente do número de AI controlou o HPS; porém parece piorar a calcificação vascular. Os níveis séricos de PTH pós-PTx ou evolução para hipo- ou normoparatireoidismo não foram influenciados pelo número de AI, nem por outros parâmetros bioquímicos e tão pouco pela densidade de expressão de PCNA, CaSR, VDR, FGFR1 ou Klotho nas células paratireoideanas / Hyperparathyroidism secondary to chronic kidney disease (SHP) affects many patients. There is no consensus about what kind of parathyroidectomy (PTx) is associated with better results. In total PTx with auto transplant (PTx- AT) it is speculated that the number of implanted fragments improves clinical outcomes. Third six (36) patients with refractory SHP were randomized to PTx-AT with 45 or 90 parathyroid fragments. We prospectively evaluated the clinical, biochemical and pathological factors influencing AT function. At baseline (t0) Group-45 (N = 28) and Group-90 (N = 8) were similar, except for serum phosphate levels. After 12 months (t12), PTH levels of graft and systemic correlated with ionic calcium (Cai) t0 (r2 = 0.442, p = 0.016; r2 = 0.450, p = 0.008, respectively). The duration of hungry bone syndrome correlated with alkaline phosphatase (AP) -t0 (r2 = 0.593, p = 0.001). In parathyroid cells, PCNA expression correlated with time on hemodialysis (r2 = 0.437, p = 0.016), expression of receptor-1 of fibroblast growth factor (FGFR1) with AP-t0 (r2 = -0.758; p = 0.0001), vitamin D receptor (VDR) with Cai t0 (r2 = -0.464, p = 0.007) and cumulative elemental Ca load (r2 = -0.359, p = 0.04), Ca sensing receptor (CaSR) with less use of calcitriol (r2 = -0.445, p = 0.049), and Klotho with the dose of vitamin D pre-PTx (r2 = 0.811, p = 0.027) and phophate-t0 (r2 = -0.528, p = 0.017). There was progression of vascular calcification score [0.53 (0 to 4) vs. 1.1 (0 to 8); p = 0.04] which correlated with cumulative elemental Ca load (r2 = 0.605, p = 0.006) and with phosphate-t0 (r2 = 0.503; p = 0.028). In conclusion, PTx controlled refractory SHP regardless of the number of AT; however, it seems to worsening vascular calcification. Serum levels of PTH or post-PTx evolution of hypo- or normoparathyroidism were not influenced by the number of AT or other biochemical parameters, nor by the density of PCNA expression, CaSR, VDR, FGFR1 or Klotho in parathyroid cells

Der septische Schock geht bis heute mit einer hohen Mortalität einher und stellt für die Intensivmedizin ein schwer beherrschbares Krankheitsbild dar. Er ist die häufigste Todesursache auf nicht kardiologischen Intensivstationen und es wird davon ausgegangen, dass der Anteil septischer Patienten relativ wie absolut zunehmen wird. Das Ziel der vorliegenden Arbeit war, den Einfluss von Hydrokortison auf die Schockdauer und die Wirkung von Hydrokortison in Abhängigkeit der Nebennierenrindenfunktion sowie den Einfluss auf die Morbidität, gemessen am SOFA-Score zu untersuchen. Es wurden 41 Patienten mit frühem septischem Schock in eine doppelblinde, placebokontrollierte, randomisierte Studie eingeschlossen. Zur Beurteilung der Nebennierenfunktion wurde vor Beginn der Studie ein ACTH-Test durchgeführt und je nach Anstieg wurden die Patienten in „Non-Responder“ und „Responder“ unterteilt. Es zeigte sich, dass Hydrokortison zu einer signifikanten Verkürzung der Schockdauer führte. Die Frage nach dem unterschiedlichen Effekt von Hydrokortison bei „Respondern“ und „Non-Respondern“ konnte nicht abschließend geklärt werden; es zeigte sich bei den „Respondern“ und „Non-Respondern“, die Hydrokortison erhalten hatten, ein Trend zu einer kürzeren Schockdauer, der aber keine statistische Signifikanz erreichte, vermutlich weil die Gruppengröße durch die Aufteilung zu klein wurde. Die vorliegenden Ergebnisse sind insofern mit anderen Studien kongruent, bedürfen aber noch der weiteren Abklärung in Studien mit größeren Patientenkollektiven. Der SOFA-Score war unter Hydrokortison in den ersten 48 Stunden signifikant reduziert. In anderen Studien war dies mit einer geringeren Mortalität assoziiert. Die Behandlung mit Hydrokortison reduziert also die Schockdauer und stellt eine wichtige Therapierationale zur Vorbeugung des sepsis-induzierten Organversagens dar. / Up to the present day septic shock is often accompanied with high mortality. For the medical intensive care field it is a hardly controllable disease pattern. Septic shock is the most frequent cause of death at non-cardiological intensive care units. It is believed that the number of septic patients will increase relatively as well as absolutely. The aim of this paper was to examine the influence of hydrocortisone on shock duration, the effect of hydrocortisone dependent on the adrenal function and the influence on morbidity, measured with SOFA score. 41 patients with early septic shock participated in a double-blind, placebo-controlled, randomised study. In the beginning of the study an ACTH-test was conducted in order to assess the adrenal function. Dependent on the increase of ACTH, the patients were classified into "non-responder" and "responder". It became apparent that hydrocortisone leads to a significant reduction of shock duration. The question about the different effect of hydrocortisone on “responder“ and “non-responder“ could not cleared up conclusively. “Responder“ and „non-responder“ who received hydrocortisone showed a trend towards shorter shock duration. There was, however, no statistic significance, probably because the groups became too small because of the division. The present results are insofar congruent with other studies, but they need further clarification through studies with bigger patient groups. For those using hydrocortisone the SOFA score was significantly reduced during the first 48 hours. In other studies this fact was associated with less mortality. The treatment with hydrocortisone therefore reduces the shock duration and is an important therapy rationale for the prevention of septic induced multi-organ failure.

Es wurden Studien zur biochemischen Evaluierung des akuten Koronarsyndroms unter drei Aspekten unternommen: (1) Die klinische Anwendung der biochemischen Marker zur Diagnosesicherung und Risikostratifizierung bei Patienten mit akutem Koronarsyndrom, (2) die Bedeutung kardialer Troponine unter besonderen physiologischen und pathophysiologischen Bedingungen und (3) die tierexperimentelle Evaluierung passagerer Ischämie mit der Fragestellung, ob eine Erhöhung kardialer Troponine im Plasma bei reversibler Myokardschädigung auftreten kann. Die klinische Anwendung der kardialen Marker kann zuverlässig nach aktuellen Richtlinien erfolgen und sollte immer auch die Messung eines kardialen Troponins beinhalten. Troponin-Testsysteme sollten in klinischen Studien hinsichtlich des diagnostischen und prognostischen Nutzens evaluiert worden sein. Die in dieser Arbeit untersuchten Systeme wiesen nachweisbare Unterschiede auf, die jedoch für den klinischen Einsatz nicht bedeutsam sind. Geringe Troponin T-Erhöhungen bei Patienten mit akutem Koronarsyndrom und eher geringer oder atypischer Symptomatik haben eine eindeutige prognostische Aussagekraft und ergänzen damit signifikant die klinische Einschätzung und das EKG. Kardiale Troponine können bei herzgesunden Probanden unter extremer körperlicher Leistung gering erhöht sein. Die prognostische Bedeutung dieser Befunde ist unklar. Kardiales Troponin kann bei kardial asymptomatischen Patienten mit Niereninsuffizienz ohne sichere prognostische Bedeutung erhöht sein. Tierexperimentell ergeben sich Hinweise darauf, daß es bei reversibler Ischämie im Sinne eines "continuous release" zur Freisetzung von kardialem Troponin bzw. zumindest von Degradationsprodukten desselben kommen kann. Die zukünftige Entwicklung von Richtlinien zum Einsatz biochemischer Marker wird entscheidend davon abhängen, ob auf den erhobenen Befunden therapeutische Strategien mit nachgewiesenem Nutzen im Sinne einer "evidence based medicine" aufbauen. / Three studies with respect to the biochemical evaluation of acute coronary syndromes were undertaken : (1) The clinical application of biochemical markers for diagnosis and risk stratification in patients with acute coronary syndroms. (2) The value of cardiac troponins under different physiological and pathophysiological conditions. (3) Experimental transient myocardial ischemia in an animal model with respect to the question, whether elevation of cardiac troponins in plasma perhaps occur after reversible myocardial damage. The clinical appilication of cardiac markers is sufficiently possible following actual guidelines and should include cardiac troponin measurement. The troponin test-system has to be evaluated in clinical studies with respect to its diagnostic and prognostic properties. In this study significant differences between two cardiac troponin I test-systems could be shown. The differences were below clinical relevance. Mild to moderate elevations of cardiac troponin T in patients with acute coronary syndromes and low grade Braunwald class angina are of prognostic value and add on information obtained by history and ECG. Cardiac troponins may be found elevated in apparently healthy athletes after exhaustive exercise. The prognostic significance of these findings remains unclear. Cardiac troponins are frequently elevated in renal insufficiency patients without cardiac symptoms. These elevations had no prognostic value in our study. The experimental data suggest that troponins are released in reversible myocardial damage during transient ischemia. This adds evidence on the continuous release hypothesis of cardiac troponins and degradation products. The future development of guidelines for the use of cardiac markers in daily routine will strictly depend on therapeutic consequences which base on the analytical results in the sense of evidence based medicine.

Altas concentrações de glicose podem ativar a sinalização celular TLR4/NF-kB, desencadeando a produção de mediadores proinflamatórios. Nós investigamos se o sistema NF-kB está envolvido na patogênese e na progressão da doença renal diabética (DRD) experimental, em um modelo de diabetes mellitus (DM) tipo 1 de longa duração. Ratos Munich-Wistar foram tornados diabéticos por uma única injeção de estreptozotocina e foram mantidos moderadamente hiperglicêmicos por meio de injeções diárias de insulina. Após 12 meses, dois subgrupos - progressores e não-progressores - puderam ser formados com base no grau de glomeruloesclerose dos animais diabéticos. Apenas os ratos progressores exibiram ativação renal da via TLR4/NF-kB/IL-6. A ativação dessa via mostrou-se já presente em ratos com DM de curta duração (dois meses), quando a albuminúria e a glomeruloesclerose ainda não são detectáveis. O tratamento crônico com um inibidor do NF-kB, o ditiocarbamato de pirrolidina (PDTC), inibiu a ativação renal da via TLR4/NF-kB/IL-6 nos animais diabéticos, sem interferir em seus níveis glicêmicos. O PDTC preveniu o aumento progressivo da albuminúria, o desenvolvimento de lesões glomerulares/inflamação e o estresse oxidativo renal. A proteína p65, um componente do sistema NF-kB, foi detectada em glomérulos escleróticos e em áreas intersticiais inflamadas de biópsias de pacientes com nefropatia por diabetes tipo 1. Essas observações sugerem que o sistema NF-kB renal desempenha um papel chave no desenvolvimento e na progressão da DRD experimental e pode se tornar um importante alvo terapêutico no esforço para prevenir a progressão da DRD humana / High glucose concentration can activate the TLR4/NF-kB axis, triggering the production of proinflammatory mediators. We investigated whether the NF-kB pathway is involved in the pathogenesis and progression of experimental diabetic kidney disease (DKD) in a model of long-term type 1 diabetes mellitus (DM). Munich-Wistar rats underwent DM by a single streptozotocin injection, and were kept moderately hyperglycemic by daily insulin injections. After 12 months, two subgroups - progressors and nonprogressors - could be formed based on the degree of glomerulosclerosis. Only the progressors exhibited renal TLR4/NF-kB/IL-6 activation. This scenario was already present in rats with short-term DM (two months), at a time when no albuminuria or overt glomerulosclerosis can be detected. Chronic treatment with the NF-kB inhibitor, pyrrolidine dithiocarbamate (PDTC), prevented the renal TLR4/NF-kB/IL-6 activation, while exerting no interference on blood glucose. PDTC abrogated the increase in albuminuria, prevented the development of glomerular injury/inflammation and oxidative stress in DM rats. In addition, the NF-kB p65 component was detected in sclerotic glomeruli and inflamed interstitial areas in biopsy material from patients with type 1 DM. These observations indicate that the renal NF-kB pathway plays a key role in the development and progression of experimental DKD, and can become an important therapeutic target in the quest to prevent the progression of human DKD

Hepatite fulminante (HF) é uma doença grave caracterizada pela perda da função hepática em indivíduos previamente saudáveis. Apenas 20% dos pacientes com HF apresentam recuperação espontânea da doença, para o restante a única opção de tratamento é o transplante de fígado (TF). Os critérios existentes para indicação de TF em pacientes com HF não avaliam com exatidão a gravidade e a chance de sobrevida, identificando casos que se beneficiariam com o transplante precoce ou casos de maior gravidade, que já não apresentam condições clínicas para o transplante. O objetivo do estudo foi avaliar a sobrevida de pacientes com diagnóstico de HF e indicação de TF, identificando fatores prognósticos durante o tempo de priorização, no período imediato após o TF e relacionando os dados dos pacientes com os dos doadores. Foram analisados retrospectivamente pacientes com diagnóstico de HF, priorizados para TF. Foram coletados dados demográficos, clínicos e laboratoriais dos 156 pacientes incluídos no estudo, sendo 107 transplantados (grupo Tx) e 49 não transplantados (grupo não-Tx). Todos os pacientes do grupo não-Tx tiveram óbito. Na análise do período de priorização, os pacientes do grupo não-Tx apresentaram encefalopatia grave (82% x 61%, p=0,018), taxa de insuficiência renal (80% x 46,1%, p < 0,001), incidência de etiologia criptogênica (42,9% x 19,9%, p=0,010), níveis de creatinina (2,35 ± 2,02 x 1,50 ± 1,44, p=0,001), lactato (67 ± 42 x 43 ± 27, p=0,001) e escores MELD (42 ± 9 x 36 ± 9, p < 0,001) e BiLE (14 ± 5 x 10 ± 4, p < 0,001) significantemente maiores em relação ao grupo Tx. O grupo Tx apresentou incidência significantemente maior de etiologia autoimune (17,8% x 4,1%, p=0,022) e pH arterial (7,40 ± 0,08 x 7,35 ± 0,14, p < 0,046) em relação ao grupo não-Tx. A análise de regressão logística múltipla identificou insuficiência renal (p=0,045) como fator prognóstico independente para óbito antes do TF. Na análise do período pós-TF, dos pacientes transplantados (grupo Tx), 61 tiveram sobrevida de 30 dias (grupo vivo-pós-Tx) e 46 tiveram óbito em 30 dias (grupo óbito-pós-Tx). Os pacientes do grupo óbito-pós-Tx apresentaram presença de encefalopatia grave (72,1% x 47,8%, p=0,016) e insuficiência renal (56,1% x 33,3%, p=0,028), significantemente maiores em relação ao grupo vivo-pós-Tx. O grupo vivo-pós-Tx apresentou pH arterial (7,40 ± 0,07 x 7,35 ± 0,09, p < 0,016) significantemente maior em relação ao grupo óbito-pós-Tx. Na avaliação de sobrevida pós-TF com os dados dos doadores, o grupo vivo-pós-Tx apresentou incidência significantemente maior de órgãos provenientes de doadores de etnia parda (33,3% x 8,7%, p=0,037) em relação ao grupo óbito-pós-Tx. A análise de Cox múltipla identificou: lactato > 48mg/dL (p=0,035) e pH arterial < 7,329 (p=0,002) do receptor e IMC > 26,2kg/m2 (p=0,012) do doador como fatores independentes de mortalidade 30 dias após o TF. Concluímos que insuficiência renal durante a priorização é indicador independente de óbito antes do TF e, lactato e pH arterial do receptor e IMC do doador são indicadores independentes de sobrevida 30 dias pós-TF / Fulminant hepatitis (FH) is a serious disease characterized by impairment of liver function in previously healthy individuals. Only 20% of patients with FH present spontaneous recovery of hepatic function. In about 80% of cases, the only treatment option is the liver transplantation (LT). The existing criteria for indication of LT in patients with FH do not accurately assess the severity and the chance of survival, then is not always possible to separate cases that could benefit by an early transplantation from those cases of greater severity that no longer present clinical condition for transplantation. The aim of this study was to survival of these patients diagnosed with FH, identifying prognostic factors during prioritization period and immediately after LT. The patients diagnosed with FH and prioritized for LT were analyzed retrospectively. Demographic, clinical and laboratory data were collected from the 156 patients included in the study, where 107 transplanted (Tx group) and 49 non-transplanted (non-Tx group). All patients in the non-Tx group died. In the analysis of the prioritization, patients from non-Tx group presented severe encephalopathy (82% x 61%, p=0.018), renal failure (80% x 46%, p < 0.001), cryptogenic etiology (42.9% x 19.9%, p=0.010), creatinine (2.35 ± 2.02 x 1.50 ± 1.44, p=0.001), lactate (67 ± 42 x 43 ± 27, p=0.001) and MELD (42 ± 9 x 36 ± 9, p < 0.001) and BiLE (14 ± 5 x 10 ± 4, p < 0.001) scores greater than Tx group. Tx group presented significantly higher incidence autoimune etiology (17.8% x 4.1%, p=0.022) and arterial pH level (7.40 ± 0.08 x 7.35 ± 0.14, p < 0.046) compared to non-Tx group. The multiple logistic regression analysis identified renal failure (p=0.045) as independent prognostic factor for death in the transplantation waiting-list. In the analysis of the post-TF period, of transplant patients (Tx group), 61 had a 30-day survival (live-post-Tx group) and 46 died within 30 days (death-post-Tx group). The patients of death-after-Tx group presented severe encephalopathy (72.1% x 47.8%, p=0.016), renal failure level (56.1% x 33.3%, p=0.028) greater than alive-after-Tx group. The alive-post-Tx group presented arterial pH (7.40 ± 0.07 x 7.35 ± 0.09, p < 0.016) greater than death-after-Tx group. The evaluation of survival rate after LT related to donor\'s data the alive-after-Tx group presented significantly greater incidence of mixed ethnicity (33.3% x 8.7%, p=0.037) compared to death-after-Tx group. Cox multiple analysis identified: lactate > 48mg/dL (p=0.035) and arterial pH < 7.329 (p=0.002) of receptor and BMI > 26.2kg/m2 (p=0.012) of donor as independent factors for mortality up to 30 days after LT. In conclusion renal failure is independent indicator of death during prioritization period and lactate and arterial pH of receptor and BMI of donor are also independent indicators of survival rate after 30 days after LT

Bakgrund:Dialysbehandling är en livslång behandling och kräver att patienten följer upp behandlingsrytmen för att kunna uppnå högsta möjliga livskvalitet. Olika livsförändringar uppstår i samband med uppkomsten av njurinsufficiens och påbörjad dialysbehandling. Livet med dialys innebär ofta ett helt nytt liv för patienterna. Syfte: Att beskriva upplevelser av dialysbehandling hos vuxna patienter med njurinsufficiens. Metod:En litteraturöversikt har använts som metod för att besvara arbetets syfte. Tretton vetenskapliga artiklar har analyserats med hjälp av fem olika steg framtagna av Fribergs analysmetod.  Huvudresultat:patienterna upplevde brist på information, behov av egen kontroll, förlust av aktiviteter och sociala relationer. Ibland upplevde patienterna behandlingen som påfrestande och hade svårt att anpassa livet efter det. Rädsla upplevdes också av de flesta patienterna, men däremot kunde säkerhet och trygghet upplevas när patienterna fick sin behandling av vårdpersonal som hade tillräckligt med kunskap och erfarenhet och när de hade familjen och vänner runt om sig. Slutsats:Patienterna hade både positiva och negativa upplevelser i samband med dialysbehandlingen. Vårdpersonalen och familjen spelade en viktig roll i patienterna liv och deras existens gjorde en inverkan i hur patienterna upplevde sin dialysbehandling. / Background:Dialysis treatment is a lifelong treatment and requires the patient to follow up on the treatment rhythm in order to achieve the highest possible quality of life. Different life changes occur in connection with the onset of renal insufficiency and initiated dialysis treatment. Life with dialysis often means a completely new life for patients. Aim:To describe the experiences of dialysis treatment in adult patients with renal insufficiency. Method:A literature review has been used as method for answering the purpose of this work. Thirteen scientific articles have been analyzed using five different steps developed by Friberg’s analysis method. Results:Patients experienced a lack of information, a need of own control, loss of activities and social relations. Sometimes patients experienced the treatment as stressful and had difficulty adjusting life after that. Fear was also experienced by most patients, but on the other hand, safety and security could be experienced when patients received their treatment by healthcare professionals who had enough knowledge and experience and also when they had family and friends around them.Conclusion: The patients had both positive and negative experiences in connection to the dialysis treatment. The healthcare staff and the family had an important role in the patients' lives and their existence made an impact on how the patients experienced their dialysis treatment.