Cyanidin-3-O-glucoside plays a protective role against renal ischemia/ reperfusion injury via the JAK/STAT pathway

Purpose: To investigate the role of cyanidin-3-O-glucoside (C3G) in renal ischemia/reperfusion (I/R) injury and the potential mechanisms. Methods: Mouse models were established by clamping the left renal vessels, and in vitro cellular models were established by hypoxic reoxygenation. Results: Renal dysfunction and tissue structural damage were significantly higher in the I/R group. After treatment with different concentrations of C3G, the levels of renal dysfunction and tissue structural damage decreased at different levels. And its protective effect was most pronounced at 200 mg/kg. The use of C3G reduced apoptosis as well as the expression of endoplasmic reticulum stress (ERS)-related proteins. Hypoxia/reoxygenation (H/R)-induced apoptosis and ERS are dependent on oxidative stress in vitro. In addition, both AG490 and C3G inhibited the activation of JAK/STAT pathway and attenuated oxidative stress, ischemia-induced apoptosis and ERS. Conclusions: The results demonstrated that C3G blocked renal apoptosis and ERS protein expression by preventing reactive oxygen species (ROS) production after I/R via the JAK/STAT pathway, suggesting that C3G may be a potential therapeutic agent for renal I/R injury.

Des-resucitación en la sobrecarga de fluidos asociada a la lesión renal aguda / Des-resuscitation in the overload of fluids associated with acute kidney injury

Los resultados generales del tratamiento de la lesión renal aguda en los últimos años han mejorado casi de manera constante, aunque sin una comprensión completa de su fisiopatología. La respuesta a este interrogante radicaría en la comprensión del rol proactivo en lo que hace a la administración / remoción de los fluidos, abarcando todo el proceso de reanimación de los pacientes críticos, es decir no limitándose a la administración sino también al momento oportuno de la remoción de los mismos, buscando como principal objetivo mejorar la perfusión tisular. Se discute entre otros el papel clave que ejerce la integridad vascular en la sobrecarga de fluidos, haciendo hincapié en el papel del glicocálix endotelial. Las maniobras de des-resucitación activa con diuréticos o con terapias de soporte renal, podrían ser instrumentos cada vez más reconocidos en la aplicación de la sobrecarga de fluidos, en particular en aquellos pacientes con lesión renal aguda.

In the last few years the general results in the treatment of acute kidney injury has improved constantly, without a complete comprehension of its pathophysiology. With this paradigm in mind, in these last few years we have seen an evolving comprehension of the possible answers that may be based on recognizing the more proactive role of fluid management in the resuscitation of critical patients, not limited only to the delivery of fluids, but also to their active removal, having as the principal objective the improvement of tissue perfusion. The key role of vascular integrity in fluid overload is discussed, emphasizing the role of the endothelial glycocalyx. Active des-resuscitation maneuvers with diuretics or with renal support therapies could be increasingly recognized instruments in the management of fluid overload, particularly in those patients with acute kidney injury.

Consenso de lesión renal aguda en el recién nacido / Acute kidney injury in the newborn: a consensus statement

La lesión renal aguda constituye un factor de riesgo independiente de la morbimortalidad en el recién nacido. Dentro de este grupo etario, presentan aún más susceptibilidad los recién nacidos prematuros en los cuales la nefrogénesis no se ha completado y los recién nacidos de bajo peso que presentan menor masa nefronal. Todo esto hace que el recién nacido deba ser evaluado y manejado de modo diferente al paciente pediátrico. En el presente consenso, se presentan las nuevas definiciones de lesión renal aguda y se revisan las diferentes etiologías, los métodos de diagnóstico y los tratamientos recomendados.

Acute kidney Injury is recognized as an independent risk factor of morbidity and mortality in neonates. Additionally, in this age group, there are other aggravating factors, such as incomplete nephrogenesis in premature infants and lower nephron mass in low birth weight neonates. All this means that the newborn must be evaluated and managed differently from the pediatric patient. In the present consensus, we review the new definitions of acute kidney injury, etiologies, diagnostic methods and recommended treatments.

Acute Kidney Injury by SARS-CoV-2 virus in patients with COVID-19: an integrative review / Lesión Renal Aguda por virus de SARS-CoV-2 en pacientes con COVID-19: revisión integrativa / Lesão renal aguda pelo vírus SARS-COV-2 em pacientes com COVID-19: revisão integrativa

ABSTRACT Objective: to assess scientific evidence on SARS-CoV-2 Acute Kidney Injury in patients with COVID-19. Methods: an integrative review, with adoption of PICO strategy and classification of the level of evidence, carried out on April 10, 2020 in the PubMed database, of articles available between December 2019 and April 2020. Results: the sample consisted of six original, five observational and one experimental articles. Observational studies addressed the clinical findings of patients with COVID-19 and association between kidney damage, infection, and morbidity-mortality. Conclusion: the studies addressed the mechanism of intracellular infection of SARS-CoV-2, its cytopathic effects on kidney cells and incidence of acute kidney injury in patients infected with SARS-CoV-2. Acute kidney injury is associated with increased mortality and morbidity in these patients. This review realizes the need for new research that can mention kidney care to patients with COVID-19.

RESUMEN Objetivo: evaluar la evidencia científica sobre la lesión renal aguda por SARS-CoV-2 en pacientes con COVID-19. Métodos: revisión integradora, con la adopción de la estrategia PICO y clasificación del nivel de evidencia, realizada el 10 de abril de 2020 en la base de datos PubMed, de artículos disponibles entre diciembre de 2019 y abril de 2020. Resultados: la muestra estuvo compuesta por seis artículos originales, cinco de los cuales son de observación y uno experimental. Los estudios de observación abordaron los hallazgos clínicos de pacientes con COVID-19, la asociación entre daño renal, la infección y la morbilidad y mortalidad. Conclusión: los estudios abordaron el mecanismo de infección intracelular del SARS-CoV-2, sus efectos citopáticos en las células renales y la incidencia de lesión renal aguda en pacientes infectados con el SARS-CoV-2. La Lesión Renal Aguda se asocia con una mayor mortalidad y morbilidad en estos pacientes. Esta revisión resalta la necesidad de más investigación que pueda aludir la atención renal a pacientes con COVID-19.

RESUMO Objetivo: avaliar as evidências científicas sobre Lesão Renal Aguda pela SARS-CoV-2 em pacientes com COVID-19. Métodos: revisão integrativa, com adoção da estratégia PICO e classificação do nível de evidência, realizada em 10 de abril de 2020 na base de dados PubMed, de artigos disponíveis entre dezembro de 2019 e abril de 2020. Resultados: a amostra foi composta por seis artigos originais, sendo cinco observacionais e um experimental. Os estudos observacionais abordaram os achados clínicos dos pacientes com COVID-19, associação entre os danos renais, infecção e morbimortalidade. Conclusão: os estudos abordaram o mecanismo de infecção intracelular da SARS-CoV-2, seus efeitos citopáticos nas células renais e a incidência de Lesão Renal Aguda nos pacientes infectados pela SARS-CoV-2. A Lesão Renal Aguda está associada ao aumento da mortalidade e morbidade nestes pacientes. Esta revisão concretiza a necessidade de novas pesquisas que possam aludir a atenção renal ao paciente com COVID-19.

Un enfoque actual para el diagnóstico precoz y tratamiento de la insuficiencia renal aguda / A current view on the early diagnosis and treatment of acute kidney failure

La insuficiencia renal aguda es el síndrome caracterizado por una disminución brusca, sostenida y potencialmente reversible de la velocidad de filtración glomerular y de las funciones tubulares, afectando de forma global la función renal. Comprende una serie de eventos que se inician con la presencia de factores de riesgo que conducen hacia las fases de progresión de la insuficiencia renal aguda (estrés, lesión e insuficiencia renal), que culmina con la necesidad de terapias de reemplazo renal o muerte. Actualmente, el uso de biomarcadores que diferencien entre un daño funcional temprano o daño estructural de inicio tardío del riñón, le permite al médico realizar un diagnóstico y manejo oportuno antes de que se establezcan las fases previas a la insuficiencia renal, mejorando así la sobrevida de estos pacientes. Esta revisión busca integrar evidencia científica disponible que describe las fases previas de la insuficiencia renal aguda, revisando sus posibles causas, clasificaciones y métodos actuales de diagnóstico, junto con las principales recomendaciones vigentes para su manejo.

Acute kidney injury is a syndrome characterized by a sudden, sustained, and potentially reversible decrease in glomerular filtration rate and tubular function, which globally impacts renal function. It comprises of a series of events starting with the presence of risk factors, then evolving towards acute kidney injury progression, characterized by stress, injury, and renal failure, culminating with either the use of renal replacement therapy or death. Currently, the use of biomarkers that differentiate between the initial functional deterioration and late-onset structural damage of the kidney enables the clinician to perform an early diagnosis and indicate treatment before the stages of acute kidney injury progression are established, thus increasing survival rates.

Clinical assessment and pathophysiology of Bothrops venom-related acute kidney injury: a scoping review

Bothrops are one of the most common medically important snakes found in Latin America. Its venom is predominantly hemotoxic and proteolytic, which means that local lesion (edema and redness) and hemorrhagic symptoms are recurrent in envenoming by this snake. Although hemorrhage is usually the major cause of death, snakebite-related acute kidney injury is another potentially fatal clinical complication that may lead to chronic kidney disease. The present review highlights the main studies on Bothrops venom-related acute kidney injury, including observational, cross-sectional, case-control and cohort human studies available up to December 2019. The following descriptors were used according to Medical Subject Headings (MeSH): on Medline/Pubmed and Google Scholar "acute kidney injury" or "kidney disease" and "Bothrops"; on Lilacs and SciELO "kidney disease" or "acute kidney injury" and "Bothrops". Newcastle-Ottawa quality assessment scale was used to appraise the quality of the cross-sectional and cohort studies included. The selection of more severe patients who looked for health care units and tertiary centers is a risk of bias. Due to the methodological heterogeneity of the studies, a critical analysis of the results was performed based on the hypothesis that the design of the included studies influences the incidence of acute kidney injury. Fifteen human studies (total participants 4624) were included according to stablished criteria. The coagulation abnormalities (hemorrhagic symptoms, abnormal fibrinogen and activated partial thromboplastin time) were associated with acute kidney injury in the most recent studies reported. The findings observed in this review provide up-to-date evidence about the acute kidney injury pathogenesis following Bothrops syndrome. Studies pointed out that coagulation abnormalities comprise the major pathway for acute kidney injury development. This review may improve patient management by primary healthcare providers, allowing earlier diagnosis and treatment of Bothrops venom-related acute kidney injury.(AU)

Renal changes and acute kidney injury in covid-19: a systematic review

SUMMARY OBJECTIVE We aimed to present a review of renal changes in patients with COVID-19. METHODS We performed a systematic review of the literature to identify original articles regarding clinical, laboratory, and anatomopathological kidney changes in patients infected with SARS-CoV-2 published until May 7, 2020. The search was carried out across PubMed, Scopus, and Embase using the keywords "COVID-19", "coronavirus", "SARS-CoV-2", "kidney injury" and "kidney disease". Fifteen studies presented clinical and laboratory renal changes in patients with COVID-19, and three addressed anatomopathological changes. DISCUSSION Acute kidney injury (AKI) was a relevant finding in patients with COVID-19. There were also significant changes in laboratory tests that indicated kidney injury, such as increased serum creatinine and blood urea nitrogen (BUN), proteinuria, and hematuria. The presence of laboratory abnormalities and AKI were significant in severely ill patients. There was a considerable prevalence of AKI among groups of patients who died of COVID-19. Histopathological analysis of the kidney tissue of patients infected with SARS-CoV-2 suggested that the virus may directly affect the kidneys. CONCLUSION Although COVID-19 affects mainly the lungs, it can also impact the kidneys. Increased serum creatinine and BUN, hematuria, proteinuria, and AKI were frequent findings in patients with severe COVID-19 and were related to an increased mortality rate. Further studies focusing on renal changes and their implications for the clinical condition of patients infected with the novel coronavirus are needed.

RESUMO OBJETIVO Apresentar uma revisão sobre as alterações renais nos pacientes com COVID-19. MÉTODOS Foi realizada uma revisão sistemática de literatura para buscar estudos referentes a pacientes com alterações renais clínicas, laboratoriais e anatomopatológicas durante a infecção por SARS-CoV-2. A busca foi realizada nas bases de dados eletrônicos PubMed, Scopus e Embase, com as palavras-chaves: "COVID-19", "coronavirus", "Sars-CoV-2", "kidney injury" e "kidney disease", para identificar artigos originais publicados na literatura até 07 de maio de 2020. Quinze estudos trouxeram alterações renais clínicas e laboratoriais dos pacientes com COVID-19, e três abordaram análises anatomopatológicas. DISCUSSÃO A Lesão renal aguda (LRA) foi um achado relevante nos pacientes com COVID-19. Houve também alterações significativas nos exames laboratoriais que indicam lesão renal, como o nível de creatinina e ureia séricas, proteinúria e hematúria. As alterações laboratoriais e a LRA foram importantes nos pacientes que desenvolveram o quadro grave da doença. Há considerável prevalência de LRA nos grupos de pacientes que vieram a óbito. Na análise histopatológica de pacientes com SARS-CoV-2 foram encontrados achados renais sugestivos que o vírus poderia ter efeitos diretos sobre o rim. CONCLUSÃO A COVID-19 é uma doença que, apesar de acometer principalmente os pulmões, também acomete os rins. Aumento das escórias nitrogenadas, hematúria, proteinúria e LRA foram achados frequentes em pacientes com quadros graves da COVID-19. Esses achados foram relacionados a maior mortalidade. É necessária a realização de mais estudos com enfoque nas alterações renais e suas implicações no quadro clínico causadas pelo novo coronavírus.

Reserva funcional renal: concepto y aplicabilidad potencial en la práctica clínica / Renal functional reserve: concept and potential application in clinical practice

Renal functional reserve (RFR) is the capacity of the kidney to increase its glomerular filtration rate (GFR) in response to physiological or pathological stimuli. The most commonly used stimuli to assess this reserve are an oral load of proteins of animal origin, amino acid infusions, dopamine, glucagon or combinations of them. RFR is calculated as the difference between stimulated and baseline GFR. Vegetarians have lower baseline GFR than the general population and an increased RFR. Subjects with only one kidney and those suffering from chronic nephropathies usually have a reduced or absent RFR despite having normal basal GFR. Quantification of RFR may be useful to detect subclinical renal damage, physiological conditions that reduce baseline GFR, evaluation of potential donors for kidney transplantation, suspected hyperfiltration, detection of renal lability against acute injuries or pregnancy and the evaluation after an acute renal injury when renal function seems to be recovered and residual subclinical damage is suspected.

Preoperative proteinuria is associated with increased rates of acute kidney injury after partial nephrectomy

ABSTRACT Purpose We investigated the association between preoperative proteinuria and early postoperative renal function after robotic partial nephrectomy (RPN). Patients and Methods We retrospectively reviewed 1121 consecutive RPN cases at a single academic center from 2006 to 2016. Patients without pre-existing CKD (eGFR≥60 mL/min/1.73m2) who had a urinalysis within 1-month prior to RPN were included. The cohort was categorized by the presence or absence of preoperative proteinuria (trace or greater (≥1+) urine dipstick), and groups were compared in terms of clinical and functional outcomes. The incidence of acute kidney injury (AKI) was assessed using RIFLE criteria. Univariate and multivariable models were used to identify factors associated with postoperative AKI. Results Of 947 patients, 97 (10.5%) had preoperative proteinuria. Characteristics associated with preoperative proteinuria included non-white race (p<0.01), preoperative diabetes (p<0.01) and hypertension (HTN) (p<0.01), higher ASA (p<0.01), higher BMI (p<0.01), and higher Charlson score (p<0.01). The incidence of AKI was higher in patients with preoperative proteinuria (10.3% vs. 4.6%, p=0.01). The median eGFR preservation measured within one month after surgery was lower (83.6% vs. 91%, p=0.04) in those with proteinuria; however, there were no significant differences by 3 months after surgery or last follow-up visit. Independent predictors of AKI were high BMI (p<0.01), longer ischemia time (p<0.01), and preoperative proteinuria (p=0.04). Conclusion Preoperative proteinuria by urine dipstick is an independent predictor of postoperative AKI after RPN. This test may be used to identify patients, especially those without overt CKD, who are at increased risk for developing AKI after RPN.

TLR7 mediates increased vulnerability to ischemic acute kidney injury in diabetes

SUMMARY OBJECTIVE Diabetes is a risk factor for acute kidney injury (AKI). However, its mechanism of pathogenesis has not been elucidated. The aim of the study was to investigate the role of inflammation and the toll-like receptor 7 (TLR7) in ischemic AKI for diabetes. METHODS A high glucose hypoxia-reoxygenation model of human renal tubular epithelial (HK-2) cells was used to generate AKI induced by ischemia-reperfusion in diabetes. The activity of cells was measured by CCK-8 assay and LDH activity. Inflammatory cytokines were assessed by ELISA. TLR7, MyD88, and NF-κB expressions were examined by western blotting. Apoptosis was evaluated by flow cytometry. RESULTS The high glucose group and low glucose group were subjected to hypoxia-reoxygenation. The low glucose group developed only mild cell damage, apoptosis, and inflammatory response. In contrast, an equivalent hypoxia-reoxygenation injury provoked severe cell damage, apoptosis, and inflammatory response in the high glucose group. Expression of TLR7 and its related proteins were measured in the high glucose group before and after hypoxia-reoxygenation. The high glucose group exhibited more significant increases in TLR7 expression following hypoxia-reoxygenation than the low glucose group. In addition, the expression of TLR7 and its related proteins after hypoxia-reoxygenation were higher in the high glucose group than in the low glucose group. Inhibition of TLR7 provides significant protection against ischemic injury in diabetes. CONCLUSION Our results suggest that diabetes increases the vulnerability to ischemia-induced renal injury. This increased vulnerability originates from a heightened inflammatory response involving the TLR7 signal transduction pathway.

RESUMO OBJETIVO O diabetes é um fator de risco para a lesão renal aguda (LRA). No entanto, seu mecanismo de patogênese não foi elucidado. O objetivo do estudo foi investigar o papel da inflamação e do receptor Toll-like 7 (TLR7) na LRA isquêmica no diabetes. MÉTODOS Um modelo de hipóxia-reoxigenação de células epiteliais tubulares renais humanas (HK-2) na presença de concentrações altas de glicose foi utilizado para gerar LRA induzida por isquemia-reperfusão em diabetes. A atividade das células foi medida pelo ensaio Cell Counting Kit-8 (CCK-8) e pela atividade da lactato desidrogenase (LDH). As citocinas inflamatórias foram avaliadas por ensaio imunoenzimático (Elisa). A expressão de TLR7, do fator de diferenciação mieloide 88 (MyD88) e do fator de transcrição nuclear-κB (NF-κB) foi examinada por Western blotting. A apoptose foi avaliada por citometria de fluxo. RESULTADOS Os grupos glicose alta e glicose baixa foram submetidos à hipóxia-reoxigenação. O grupo de baixa glicose desenvolveu apenas danos celulares ligeiros, apoptose e uma resposta inflamatória. Em contraste, no grupo de alta glicose, uma lesão equivalente de hipóxia-reoxigenação provocou danos celulares graves, apoptose e uma resposta inflamatória. A expressão de TLR7 e suas proteínas relacionadas foi medida no grupo de alta glicose antes e após a hipóxia-reoxigenação. O grupo de alta glicose exibiu maiores aumentos na expressão de TLR7 após hipóxia-reoxigenação do que o grupo de baixa glicose. Além disso, a expressão de TLR7 e suas proteínas relacionadas após a hipóxia-reoxigenação foi maior no grupo com alto nível de glicose do que no grupo com baixo nível de glicose. A inibição do TLR7 fornece proteção significativa contra a lesão isquêmica no diabetes. CONCLUSÃO Nossos resultados sugerem que o diabetes aumenta a vulnerabilidade à lesão renal induzida por isquemia. Essa vulnerabilidade acrescida tem por origem uma resposta inflamatória aumentada envolvendo a via de transdução de sinal do TLR7.

Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs / Aspectos fisiopatológicos da nefropatia por anti-inflamatórios não esteroidais

Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used medications associated with nephrotoxicity, especially when used chronically. Factors such as advanced age and comorbidities, which in themselves already lead to a decrease in glomerular filtration rate, increase the risk of NSAID-related nephrotoxicity. The main mechanism of NSAID action is cyclooxygenase (COX) enzyme inhibition, interfering on arachidonic acid conversion into E2 prostaglandins E2, prostacyclins and thromboxanes. Within the kidneys, prostaglandins act as vasodilators, increasing renal perfusion. This vasodilatation is a counter regulation of mechanisms, such as the renin-angiotensin-aldosterone system works and that of the sympathetic nervous system, culminating with compensation to ensure adequate flow to the organ. NSAIDs inhibit this mechanism and can lead to acute kidney injury (AKI). High doses of NSAIDs have been implicated as causes of AKI, especially in the elderly. The main form of AKI by NSAIDs is hemodynamically mediated. The second form of NSAID-induced AKI is acute interstitial nephritis, which may manifest as nephrotic proteinuria. Long-term NSAID use can lead to chronic kidney disease (CKD). In patients without renal diseases, young and without comorbidities, NSAIDs are not greatly harmful. However, because of its dose-dependent effect, caution should be exercised in chronic use, since it increases the risk of developing nephrotoxicity.

Resumo Os anti-inflamatórios não esteroidais (AINEs) são medicamentos comumente utilizados, associados à nefrotoxicidade, sobretudo quando utilizados cronicamente. Fatores como idade avançada e comorbidades, que por si só já levam à diminuição da taxa de filtração glomerular, aumentam o risco de nefrotoxicidade dos AINEs. O principal mecanismo de ação dos AINEs é a inibição da enzima ciclooxigenase (COX), interferindo na conversão do ácido araquidônico em prostaglandinas E2, prostaciclinas e tromboxanos. Nos rins, as prostaglandinas atuam como vasodilatadoras, aumentando a perfusão renal. Essa vasodilatação atua como uma contrarregulação de mecanismos, como a atuação do sistema renina-angiotensina-aldosterona e do sistema nervoso simpático, culminando com uma compensação para assegurar o fluxo adequado ao órgão. O uso de AINEs inibe esse mecanismo, podendo causar lesão renal aguda (LRA). Altas doses de AINEs têm sido implicadas como causas de LRA, especialmente em idosos. A principal forma de LRA por AINEs é a hemodinamicamente mediada. A segunda forma de apresentação da LRA induzida por AINES é a nefrite intersticial aguda, que pode se manifestar com proteinúria nefrótica. O uso de AINEs em longo prazo pode ocasionar doença renal crônica (DRC). Nos pacientes sem doenças renais, jovens e sem comorbidades, os AINEs não apresentam grandes malefícios. Entretanto, por seu efeito dose-dependente, deve-se ter grande cautela no uso crônico, por aumentar risco de desenvolver nefrotoxicidade.

Análisis función ventricular derecha, función renal y fluidos tras resucitación en pacientes con ventilación mecánica / Right ventricular, renal function, and fluids balance analysis after resuscitation in patients on mechanical ventilation

INTRODUCTION: Hemodynamic optimization is a main goal in the management of critically ill patients. Right ventricular function, renal failure and fluid balance are part of this process. Our goal is to analysis those, after the initial resuscitation. MATERIAL AND METHODS: A prospective, observational study was performed with all the patients admitted to a Medical Service of Intensive Care of a Tertiary, University Hospital. All patients analyzed required mechanical ventilation as a support for their underling pathology. All consecutive patients admitted to the unit under mechanical ventilation were collected, in the absence of shock, with the expectation of remaining under mechanical ventilation for at least 24 more hours after data collection. The incidence of right ventricular failure according to the defined parameters, renal failure, and fluid balance were described. We had described its association with mechanical ventilation and mortality. RESULTS: A total of 30 patients were selected. Right ventricular failure was observed in 16.6% of patients (5/30). There was no statistically significant association with the need of tracheotomy, renal failure or mortality. It was not associated with longer average stay, days of mechanical ventilation or higher severity scores. 40% of the patients presented acute renal failure. Renal failure was not associated statistically significant with the need of tracheotomy or failure in scheduled extubation, however, it was associated with higher mortality. Patients requiring mechanical ventilation with normal creatinine values ​​after initial resuscitation, had a mortality rate of 28.5% in comparison to patients who had altered values in which the mortality rate was 77.7%, (p < 0.018). Regarding the post-resuscitation net fluid balance, no statistically significant differences were found in the comparison of means between survivors and non survivors, with renal failure or right ventricular failure. No even was it associated with higher mortality. CONCLUSIONS: Right ventricular failure, despite not being associated with mortality, days of mechanical ventilation or failure in extubation in a statistically significant way, presents an incidence of 16.6% in patients connected to mechanical ventilation admitted to a polyvalent icu. Acute renal failure is associated in a statistically significant way with mortality in our sample. We had not found association between fluid overload and renal failure in our sample.

INTRODUCCIÓN: La optimización hemodinámica es piedra angular en el manejo del enfermo crítico. La función ventricular derecha, el fallo renal y el balance hídrico son parte de este proceso. Nuestro objetivo es su análisis tras la resucitación inicial. MATERIAL Y MÉTODOS: Se realiza un estudio prospectivo, observacional, con todos los enfermos que ingresan en un Servicio médico de Medicina Intensiva de un Hospital Terciario y Universitario. Todos los enfermos analizados precisan ventilación mecánica como soporte de su patología. Se recogen todos los enfermos consecutivos ingresados en la unidad bajo ventilación mecánica, en ausencia de shock, con previsión de permanecer bajo ventilación mecánica al menos 24 horas más tras la recogida de datos. Se describe la incidencia de fallo ventricular derecho según los parámetros definidos, fallo renal, balance. Describiremos también su asociación con ventilación mecánica, mortalidad. RESULTADOS: Se seleccionaron un total de 30 pacientes. Se objetivó fallo ventricular derecho en el 16,6% de los pacientes (5/30). No se asoció de forma estadísticamente significativa a la necesidad de traqueotomía, fallo renal o mortalidad. Tampoco se asoció a mayor estancia media, días de ventilación mecánica o índices de gravedad mayores. El 40% de los pacientes presentaron fallo renal agudo. El fallo renal no se asocia de forma estadísticamente significativa con la necesidad de traqueotomía ni fracaso en la extubación, sin embargo, se asocia a mayor mortalidad. Los pacientes que precisan ventilación mecánica y presentan valores de creatinina normales tras resucitación inicial, cuentan con una tasa de mortalidad del 28,5% en comparación con aquellos pacientes que presentan cifras alteradas en las cuales la tasa de mortalidad es del 77,7%, (p < 0,018). Con respecto al balance hídrico neto post resucitación, no se encontraron diferencias estadísticamente significativas en la comparación de medias de los supervivientes, con fallo renal o fallo en ventrículo derecho. Tampoco se asoció a mayor mortalidad. CONCLUSIONES: El fallo ventricular derecho, pese a no asociarse a la mortalidad, días de ventilación mecánica o fallo en la extubación de forma estadísticamente significativa, presenta una incidencia del 16,6% en los enfermos conectados a ventilación mecánica ingresados en una uci polivalente. El fallo renal agudo sí se asocia de forma estadísticamente significativa a la mortalidad en nuestra muestra. No hemos encontrado asociación entre sobrecarga hídrica y fallo renal en nuestro estudio.

Near-infrared spectroscopy parameters in patients undergoing continuous venovenous hemodiafiltration / Espectroscopia no infravermelho próximo em pacientes sob hemodiafiltração venovenosa contínua

ABSTRACT Objective To investigate the impacts of continuous venovenous hemodiafiltration on the microcirculation in patients with acute kidney injury. Methods A prospective observational pilot study conducted in a 40-bed, open clinical-surgical intensive care unit of a private tertiary care hospital located in the city of São Paulo (SP), Brazil. Microcirculation was assessed using near-infrared spectroscopy by means of a 15mm probe placed over the thenar eminence. Vascular occlusion test was performed on the forearm to be submitted to near-infrared spectroscopy by inflation of a sphygmomanometer cuff to 30mmHg higher than the systolic arterial pressure. The primary endpoint was the assessment of near-infrared spectroscopy-derived parameters immediately before, 1, 4 and 24 hours after the initiation of continuous venovenous hemodiafiltration. Results Nine patients were included in this pilot study over a period of 2 months. Minimum tissue oxygen saturation measured during the vascular occlusion test was the only near-infrared spectroscopy-derived parameter to differed over the time (decrease compared to baseline values up to 24 hours after initiation of continuous venovenous hemodiafiltration). Conclusion The impacts of microcirculatory dysfunction on clinical outcomes of patients undergoing to continuous venovenous hemodiafiltration need to be further investigated.

RESUMO Objetivo Avaliar o impacto da hemodiafiltração venovenosa contínua na microcirculação de pacientes com lesão renal aguda. Métodos Estudo piloto, prospectivo e observacional conduzido em uma unidade de terapia intensiva clínico-cirúrgica aberta, com 40 leitos, localizada em um hospital terciário, privado, na cidade de São Paulo (SP), Brasil. A microcirculação foi avaliada empregando-se a espectroscopia no infravermelho próximo, por meio de uma sonda de 15mm posicionada sobre a eminência tenar. O teste de oclusão vascular foi realizado no antebraço a ser submetido à espectroscopia no infravermelho próximo, inflando-se o manguito de um esfigmomanômetro a um valor 30mmHg acima da pressão arterial sistólica. O desfecho primário foi a avaliação dos parâmetros derivados por espectroscopia no infravermelho próximo imediatamente antes, 1, 4 e 24 horas após o início da hemodiafiltração venovenosa contínua. Resultados Foram incluídos nove pacientes neste estudo piloto ao longo de 2 meses. A saturação de oxigênio tecidual mínima mensurada durante o teste de oclusão vascular foi o único parâmetro derivado por espectroscopia no infravermelho próximo que diferiu ao longo do tempo, com queda em relação aos valores iniciais nas primeiras 24 horas após o início da hemodiafiltração venovenosa contínua. Conclusão A influência da disfunção microcirculatória sobre os desfechos clínicos de pacientes submetidos à hemodiafiltração venovenosa contínua precisa ser melhor investigada.

Fatores prognósticos em pacientes graves com meningite bacteriana adquirida na comunidade e lesão renal aguda / Prognostic factors among critically ill patients with community-acquired acute bacterial meningitis and acute kidney injury

RESUMO Objetivo: Investigar os fatores prognósticos em pacientes graves com meningite bacteriana adquirida na comunidade e lesão renal aguda. Métodos: Estudo retrospectivo com inclusão de pacientes em um hospital terciário dedicado a doenças infecciosas localizado em Fortaleza (CE), com diagnóstico de meningite bacteriana adquirida na comunidade complicada por lesão renal aguda. Investigaram-se os fatores associados a óbito, ventilação mecânica e uso de vasopressores. Resultados: Incluíram-se 41 pacientes, com média de idade de 41,6 ± 15,5 anos, 56% dos quais do sexo masculino. O tempo médio entre a admissão à unidade de terapia intensiva e o diagnóstico de lesão renal aguda foi de 5,8 ± 10,6 dias. A mortalidade global foi de 53,7%. Segundo os critérios KDIGO, 10 pacientes foram classificados como estágio 1 (24,4%), 18 como estágio 2 (43,9%) e 13 como estágio 3 (31,7%). A classificação em estágio KDIGO 3 aumentou de forma significante a mortalidade (OR = 6,67; IC95% = 1,23 - 36,23; p = 0,028). A presença de trombocitopenia não se associou com aumento da mortalidade, porém foi um fator de risco para a ocorrência da classificação KDIGO 3 (OR = 5,67; IC95% = 1,25 - 25,61; p = 0,024) e para necessidade de utilizar ventilação mecânica (OR = 6,25; IC95% = 1,33 - 29,37; p = 0,02). Os pacientes que necessitaram de ventilação mecânica 48 horas após o diagnóstico de lesão renal aguda tiveram níveis mais elevados de ureia (44,6 versus 74mg/dL; p = 0,039) e sódio (138,6 versus 144,1mEq/L; p = 0,036). Conclusão: A mortalidade de pacientes graves com meningite bacteriana adquirida na comunidade e lesão renal aguda é alta. A severidade da lesão renal aguda se associou com mortalidade ainda mais elevada. A presença de trombocitopenia se associou com lesão renal aguda mais grave. Níveis mais elevados de ureia podem prever mais precocemente a ocorrência de lesão renal aguda de maior gravidade.

ABSTRACT Objective: To investigate prognostic factors among critically ill patients with community-acquired bacterial meningitis and acute kidney injury. Methods: A retrospective study including patients admitted to a tertiary infectious disease hospital in Fortaleza, Brazil diagnosed with community-acquired bacterial meningitis complicated with acute kidney injury. Factors associated with death, mechanical ventilation and use of vasopressors were investigated. Results: Forty-one patients were included, with a mean age of 41.6 ± 15.5 years; 56% were males. Mean time between intensive care unit admission and acute kidney injury diagnosis was 5.8 ± 10.6 days. Overall mortality was 53.7%. According to KDIGO criteria, 10 patients were classified as stage 1 (24.4%), 18 as stage 2 (43.9%) and 13 as stage 3 (31.7%). KDIGO 3 significantly increased mortality (OR = 6.67; 95%CI = 1.23 - 36.23; p = 0.028). Thrombocytopenia was not associated with higher mortality, but it was a risk factor for KDIGO 3 (OR = 5.67; 95%CI = 1.25 - 25.61; p = 0.024) and for mechanical ventilation (OR = 6.25; 95%CI = 1.33 - 29.37; p = 0.02). Patients who needed mechanical ventilation by 48 hours from acute kidney injury diagnosis had higher urea (44.6 versus 74mg/dL, p = 0.039) and sodium (138.6 versus 144.1mEq/L; p = 0.036). Conclusion: Mortality among critically ill patients with community-acquired bacterial meningitis and acute kidney injury is high. Acute kidney injury severity was associated with even higher mortality. Thrombocytopenia was associated with severer acute kidney injury. Higher urea was an earlier predictor of severer acute kidney injury than was creatinine.

Complement activation in atypical hemolytic uremic syndrome and scleroderma renal crisis: a critical analysis of pathophysiology / Ativação de complemento em síndrome urêmica hemolítica atípica e crise renal por esclerodermia: uma análise crítica da fisiopatologia

ABSTRACT Scleroderma is an autoimmune disease that affects multiple systems. While pathophysiologic mechanisms governing the development of scleroderma are relatively poorly understood, advances in our understanding of the complement system are clarifying the role of complement pathways in the development of atypical hemolytic uremic syndrome and scleroderma renal crisis. The abundant similarities in their presentation as well as the clinical course are raising the possibility of a common underlying pathogenesis. Recent reports are emphasizing that complement pathways appear to be the unifying link. This article reviews the role of complement system in the development of atypical hemolytic uremic syndrome and scleroderma renal crisis, and calls for heightened awareness to the development of thrombotic angiopathy in patients with scleroderma.

RESUMO A esclerodermia é uma doença autoimune que afeta múltiplos sistemas. Embora os mecanismos fisiopatológicos que regem o desenvolvimento da esclerodermia sejam relativamente pouco compreendidos, os avanços em nossa compreensão do sistema do complemento estão esclarecendo o papel das vias do complemento no desenvolvimento da síndrome urêmica hemolítica atípica e da crise renal da esclerodermia. As abundantes semelhanças em sua apresentação, bem como o curso clínico, estão aumentando a possibilidade de uma patogênese subjacente comum. Relatórios recentes estão enfatizando que as vias de complemento parecem ser o link unificador. Este artigo analisa o papel do sistema do complemento no desenvolvimento da síndrome urêmica hemolítica atípica e da crise renal na esclerodermia, e exige maior conscientização para com o desenvolvimento da angiopatia trombótica em pacientes com esclerodermia.

Risk for acute kidney injury in primary health care / Riesgo de lesión renal aguda en la atención primaria de salu / Risco para lesão renal aguda na atenção primária à saúde

ABSTRACT Objective: To identify hypertensive and diabetic patients at risk for developing acute kidney injury in the primary health care setting. Method: Observational, longitudinal, prospective study. Sample of 56 diabetic and hypertensive individuals. A semi-structured questionnaire was adopted for data collection. For the description of results, were calculated dispersion measures and the Spearman test was used for statistical analysis. The result was considered significant when p <0.05. Results: Of the total sample, 23.2% of users evolved with renal impairment, of which 19.6% with risk for renal injury, and 3.6% with kidney injury itself. Age and body mass index were associated with worsening of renal function (p = 0.0001; p = 0.0003), respectively. Conclusion: A quarter of the health system users, hypertensive and diabetic, evolved with impaired renal function, more specifically to stages of risk for renal injury and kidney injury according to the RIFLE classification.

RESUMEN Objetivo: Identificar los pacientes hipertensos y diabéticos con riesgo para desarrollar lesión renal aguda en el escenario de la atención primaria de salud. Método: Estudio observacional, longitudinal y prospectivo. Casuística compuesta de 56 individuos diabéticos e hipertensos. Un cuestionario semiestructurado fue adoptado para la recolección de datos. Para la descripción de los resultados, se calcularon medidas de dispersión, y para el análisis estadístico se usó la prueba de Spearman. El resultado se consideró significativo cuando p < 0,05. Resultados: Del total de la muestra, el 23,2% de los usuarios evolucionaron con deterioro renal, siendo el 19,6% con riesgo para lesión renal y el 3,6% con lesión renal. La edad y el índice de masa corporal tuvieron asociación con el empeoramiento de la función renal (p = 0,0001; p = 0,0003), respectivamente. Conclusión: Se identificó que un cuarto de los usuarios del sistema de salud, hipertensos y diabéticos, evolucionaron con alteración de la función renal, más específicamente en las etapas de riesgo y de lesión renal según la clasificación RIFLE.

RESUMO Objetivo: Identificar pacientes hipertensos e diabéticos com risco para desenvolver lesão renal aguda no cenário da atenção primária à saúde. Método: Estudo observacional, longitudinal, prospectivo. Casuística composta de 56 indivíduos diabéticos e hipertensos. Adotou-se questionário semiestruturado para coleta de dados. Para descrição dos resultados foram calculadas medidas de dispersão e o teste de Spearman para análise estatística. O resultado foi considerado significativo quando p < 0,05. Resultados: Do total, 23,2% dos usuários evoluíram com comprometimento renal, sendo 19,6% com risco para lesão renal e 3,6% com lesão renal, propriamente dita. A idade e o índice de massa corporal mostraram associação com a piora da função renal (p=0,0001; p=0,0003), respectivamente. Conclusão: Identificou-se que um quarto dos usuários do sistema de saúde, hipertensos e diabéticos evoluíram com comprometimento da função renal, mais especificamente nos estágios de risco e de lesão renal segundo a classificação RIFLE.

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.