A pilot study identifying a set of microRNAs as precise diagnostic biomarkers of acute kidney injury

In the last decade, Acute Kidney Injury (AKI) diagnosis and therapy have not notably improved probably due to delay in the diagnosis, among other issues. Precocity and accuracy should be critical parameters in novel AKI biomarker discovery. microRNAs are key regulators of cell responses to many stimuli and they can be secreted to the extracellular environment. Therefore, they can be detected in body fluids and are emerging as novel disease biomarkers. We aimed to identify and validate serum miRNAs useful for AKI diagnosis and management. Using qRT-PCR arrays in serum samples, we determined miRNAs differentially expressed between AKI patients and healthy controls. Statistical and target prediction analysis allowed us to identify a panel of 10 serum miRNAs. This set was further validated, by qRT-PCR, in two independent cohorts of patients with relevant morbi-mortality related to AKI: Intensive Care Units (ICU) and Cardiac Surgery (CS). Statistical correlations with patient clinical parameter were performed. Our results demonstrated that the 10 selected miRNAs (miR-101-3p, miR-127-3p, miR-210-3p, miR-126-3p, miR-26b-5p, miR-29a-3p, miR-146a-5p, miR-27a-3p, miR-93-3p and miR-10a-5p) were diagnostic biomarkers of AKI in ICU patients, exhibiting areas under the curve close to 1 in ROC analysis. Outstandingly, serum miRNAs estimated before CS predicted AKI development later on, thus becoming biomarkers to predict AKI predisposition. Moreover, after surgery, the expression of the miRNAs was modulated days before serum creatinine increased, demonstrating early diagnostic value. In summary, we have identified a set of serum miRNAs as AKI biomarkers useful in clinical practice, since they demonstrate early detection and high diagnostic value and they recognize patients at risk.

Duração do período de molhamento foliar em pomares de macieira em céu aberto e sob tela antigranizo, em Vacaria-RS

A duração do período de molhamento foliar (DPM) é um importante parâmetro para a determinação do risco de doenças da macieira, especialmente a sarna, principal doença da cultura. O clima regional e as características de implantação e manejo de pomares são fatores determinantes da ocorrência do molhamento foliar. Em função do microclima do dossel, é necessário conhecer a posição com maior DPM, para dar suporte a modelos de previsão de doenças. Poucos trabalhos avaliaram a DPM em pomares de macieira, sendo que inexistem estudos nas condições de cultivo do Sul do Brasil, em particular na região produtora de Vacaria, Rio Grande do Sul. Este trabalho objetivou caracterizar a variação espacial da DPM em dosséis de macieiras em céu aberto e sob tela antigranizo, na região de Vacaria. O experimento foi desenvolvido em pomares de macieiras 'Royal Gala', conduzidos em líder central com apoio (espaçamento de 1m x 3m), sendo um coberto por tela antigranizo e o outro em céu aberto. A DPM foi monitorada nos estratos superior, médio e inferior dos dosséis de macieira. A duração do molhamento foliar foi superior no estrato inferior do dossel, tanto em céu aberto quanto sob tela antigranizo. Houve tendência de mais alta DPM no pomar coberto para todos os estratos do dossel, com diferença significativa entre ambientes nos estratos superior e médio. Os valores de DPM foram mais similares entre os estratos no dossel coberto por tela antigranizo do que no dossel a céu aberto.

Modelos para estimativa da área foliar da mangueira utilizando medidas lineares

Objetivou-se determinar os modelos que melhor descrevem a relação entre as dimensões lineares e a área foliar da mangueira, cultivar Tommy Atkins, além de estabelecer o fator de correção. A pesquisa foi conduzida na Fazenda Experimental da Universidade Federal Rural da Amazônia, na vila de Cuiarana, município de Salinópolis. Foram analisadas de 90 a 150 folhas, em 11 árvores de um campo experimental, determinando-se o comprimento e a largura máxima das folhas. A área foliar real foi determinada usando o integrador de área foliar "Area Meter" (AM 300). O fator de correção foi obtido pela divisão da área foliar real pela área foliar calculada. A área foliar foi também estimada por meio de modelos linear e não linear. Os modelos gerados apresentaram ótimo desempenho, com valores de R² entre 90 e 97%. O fator de correção de 0,71 pode ser utilizado para estimar a área foliar real da mangueira, multiplicado pelas medidas lineares. Os modelos que utilizaram o produto das dimensões como variável independente apresentaram valores de R² superiores aos que utilizaram apenas uma das dimensões, sendo o tipo cúbico o mais preciso.

Estimativa de temperaturas basais e exigência térmica em mangueiras no nordeste do estado do Pará

O objetivo deste trabalho foi estimar as temperaturas basais e a exigência térmica da mangueira, na região nordeste do Estado do Pará. Um experimento foi realizado em um pomar de mangueiras de 25 hectares, durante as safras de 2010/2011 e 2011/2012, sendo acompanhadas diariamente a fenologia e as condições meteorológicas desde a floração até a colheita. As duas safras experimentaram diferentes condições meteorológicas, e, por isso, a duração do ciclo e a exigência térmica diferiram significativamente. As temperaturas basal inferior e superior para a cultura da mangueira foram de 13 °C e 32 °C, respectivamente, a exigência térmica média encontrada para a mangueira atingir o ponto de colheita comercial foi de 1.024,23 °C dia-1 a 1.157,99 °C dia-1 e a duração média do ciclo da mangueira foi de 110 a 112 dias.

1C.06: Ambulatory pulse pressure is negatively associated with excretions of urinary caffeine and its metabolites

OBJECTIVE: Systolic blood pressure (BP) has been associated with urinary caffeine and its metabolites such as paraxanthine and theophylline. Caffeine and caffeine metabolites could influence arterial pulse pressure (PP) via sympathomimetic effects, smooth muscle relaxation, and phosphodiesterase inhibition. The purpose of this analysis was to explore the association of ambulatory PP with urinary caffeine and its related metabolites in a large population-based sample. DESIGN AND METHOD: Families were randomly selected from the general population of three Swiss cities (2009-2013). Ambulatory BP monitoring was conducted using validated Diasys Integra devices. PP was defined as the difference between the systolic and diastolic ambulatory BP. Urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured in 24 h urine using ultra-high performance liquid chromatography tandem mass spectrometry. Urinary excretions were log-transformed to satisfy regression assumptions. We used linear mixed models to explore the associations of urinary caffeine and caffeine metabolite excretions with 24-hour, day- and night-time PP while adjusting for major confounders. RESULTS: The 836 participants (48.9% men) included in this analysis had mean (±SD) age of 47.8 (±17.5), and mean 24-hour systolic and diastolic BP of 120.1 mmHg (±13.9) and 78.0 (±8.6). Except theobromine, log transformed urinary caffeine and caffeine metabolite excretions were associated negatively with 24-hour, daytime and night-time ambulatory PP. 24-hour, daytime, and night-time ambulatory PP decreased by -0.804 mmHg (SE, 0.209), -0.749 (0.215), and -0.968 (0.243) (all P values <0.005), for each doubling excretion of caffeine. Strong negative associations with night-time ambulatory PP were observed for paraxanthine and theophylline.(Figure is included in full-text article.) CONCLUSIONS: : The negative associations of PP with caffeine, paraxanthine, and theophylline excretions suggest that caffeine and its metabolites do lower BP, possibly by modifying arterial stiffness.

5C.09: Heritability of renal function parameters and electrolyte levels in the Swiss population

OBJECTIVE: Electrolytes handling by the kidney is essential for volume and blood pressure (BP) homeostasis but their distribution and heritability are not well described. We estimated the heritability of kidney function as well as of serum and urine concentrations, renal clearances and fractional excretions for sodium, chloride, potassium, calcium, phosphate and magnesium in a Swiss population-based study. DESIGN AND METHOD: Nuclear families were randomly selected from the general population in Switzerland. We estimated glomerular filtration rate (eGFR) using the CKD-EPI and MDRD equations. Urine was collected separately during day and night over 24-hour. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including as covariates in the model: age, sex, body mass index and study center. RESULTS: The 1128 participants (537 men and 591 women from 273 families), had mean (sd) age of 47.4(17.5) years, body mass index of 25.0 (4.5) kg/m2 and CKD-EPI of 98.0(18.5) mL/min/1.73 m2. Heritability estimates (SE) were 46.0% (0.06), 48.0% (0.06) and 18.0% (0.06) for CKD-EPI, MDRD and 24-hour creatinine clearance (P < 0.05), respectively. Heritability [SE] of serum concentration was highest for calcium (37%[0.06]) and lowest for sodium (13%[0.05]). Heritabilities [SE] of 24-h urine concentrations and excretions, and of fractional excretions were highest for calcium (51%[0.06], 44%[0.06] and 51%[0.06], respectively) and lowest for potassium (11%[0.05], 10%[0.05] and 16%[0.06], respectively). All results were statistically different from zero.(Figure is included in full-text article.) CONCLUSIONS: : Serum and urine levels, urinary excretions and renal handling of electrolytes, particularly calcium, are heritable in the general adult population. Identifying genetic variants involved in electrolytes homeostasis may provide useful insight into the pathophysiological mechanisms involved in common chronic diseases such as kidney diseases, hypertension and diabetes.

4B.05: Plasma Lasma copeptin is associated with insulin resistance in a Swiss population-based study

OBJECTIVE: Previous studies suggest that arginine vasopressin may have a role in metabolic syndrome (MetS) and diabetes by altering liver glycogenolysis, insulin, and glucagon secretion and pituitary ACTH release. We tested whether plasma copeptin, the stable C-terminal fragment of arginine vasopressin prohormone, was associated with insulin resistance and MetS in a Swiss population-based study. DESIGN AND METHOD: We analyzed data from the population-based Swiss Kidney Project on Genes in Hypertension. Copeptin was assessed by an immunoluminometric assay. Insulin resistance was derived from the HOMA model and calculated as follows: (FPI x FPG)/22.5, where FPI is fasting plasma insulin concentration (mU/L) and FPG fasting plasma glucose (mmol/L). Subjects were classified as having the MetS according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Mixed multivariate linear regression models were built to explore the association of insulin resistance with copeptin. In addition, multivariate logistic regression models were built to explore the association between MetS and copeptin. In the two analyses, adjustment was done for age, gender, center, tobacco and alcohol consumption, socioeconomic status, physical activity, intake of fruits and vegetables and 24 h urine flow rate. Copeptin was log-transformed for the analyses. RESULTS: Among the 1,089 subjects included in this analysis, 47% were male. Mean (SD) age and body mass index were 47.4 (17.6) years 25.0 (4.5) kg/m2. The prevalence of MetS was 10.5%. HOMA-IR was higher in men (median 1.3, IQR 0.7-2.1) than in women (median 1.0, IQR 0.5-1.6,P < 0.0001). Plasma copeptin was higher in men (median 5.2, IQR 3.7-7.8 pmol/L) than in women (median 3.0, IQR 2.2-4.3 pmol/L), P < 0.0001. HOMA-IR was positively associated with log-copeptin after full adjustment (β (95% CI) 0.19 (0.09-0.29), P < 0.001). MetS was not associated with copeptin after full adjustment (P = 0.92). CONCLUSIONS: Insulin resistance, but not MetS, was associated with higher copeptin levels. Further studies should examine whether modifying pharmacologically the arginine vasopressin system might improve insulin resistance, thereby providing insight into the causal nature of this association.

1D.03: Inactive matrix GLA protein is associated with renal resistive index in a population-based study

OBJECTIVE: Renal resistive index (RRI) varies directly with renal vascular stiffness and pulse pressure. RRI correlates positively with arteriolosclerosis in damaged kidneys and predicts progressive renal dysfunction. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular (CV) markers, CV outcomes and mortality. In this study we hypothesize that increased RRI is associated with high levels of dp-ucMGP. DESIGN AND METHOD: We recruited participants via a multi-center family-based cross-sectional study in Switzerland exploring the role of genes and kidney hemodynamics in blood pressure regulation. Dp-ucMGP was quantified in plasma samples by sandwich ELISA. Renal doppler sonography was performed using a standardized protocol to measure RRIs on 3 segmental arteries in each kidney. The mean of the 6 measures was reported. Multiple regression analysis was performed to estimate associations between RRI and dp-ucMGP adjusting for sex, age, pulse pressure, mean pressure, renal function and other CV risk factors. RESULTS: We included 1035 participants in our analyses. Mean values were 0.64 ± 0.06 for RRI and 0.44 ± 0.21 (nmol/L) for dp-ucMGP. RRI was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, pulse pressure, mean pressure, heart rate, renal function, low and high density lipoprotein, smoking status, diabetes, blood pressure and cholesterol lowering drugs, and history of CV disease (P < 0.001). CONCLUSIONS: RRI is independently and positively associated with high levels of dp-ucMGP after adjustment for pulse pressure and common CV risk factors. Further studies are needed to determine if vitamin K supplementation can have a positive effect on renal vascular stiffness and kidney function.

Inactive Matrix Gla-Protein is associated with arterial stiffness in an adult population-based study

Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, height, systolic and diastolic blood pressure (BP), heart rate, renal function, low- and high-density lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol lowering drugs, and history of cardiovascular disease (P≤0.01). In conclusion, high levels of dp-ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors, renal function, and age. Experimental studies are needed to determine whether vitamin K supplementation slows arterial stiffening by increasing MGP carboxylation.

FERRUGEM DO PESSEGUEIRO:REAÇÃO DE CULTIVARES EM SISTEMA DE PRODUÇÃO INTEGRADA

RESUMOA ferrugem do pessegueiro, causada pelo fungo Tranzschelia discolor, é a principal doença foliar da cultura. O objetivo deste trabalho foi avaliar e comparar a intensidade da ferrugem em onze cultivares de pessegueiro (Aurora 1, Chimarrita, Chiripá, Coral, Eldorado, Granada, Leonense, Maciel, Marli, Premier e Vanguarda) em pomar manejado de acordo com as normas da produção integrada, no município da Lapa-PR, no período de novembro e abril. O experimento foi composto de três blocos contendo três plantas por cultivar em cada bloco. Na planta central de cada cultivar, avaliaram-se a incidência e a severidade da ferrugem do pessegueiro em folhas de oito ramos mistos previamente marcados, a cada 15 dias. A incidência da ferrugem nas folhas de todas as cultivares variou de 25,4% (Eldorado) a 82,6% (Chimarrita) na primeira safra e de 15,3% (Eldorado) a 49,3% (Granada) na segunda safra. O modelo logístico foi ajustado aos dados de incidência ao longo do tempo. Os valores estimados de inóculo inicial e taxa de progresso não diferiram entre as cultivares. A severidade foi baixa (<1 %), para a maioria das cultivares, nas duas safras, e a área abaixo da curva de progresso da severidade das cultivares Chimarrita e Granada diferenciou-se das demais somente na primeira safra. Não foi observada desfolha provocada pela doença. A cultivar Eldorado apresentou menor intensidade da ferrugem, e Chimarrita e Granada maior intensidade dentre as cultivares avaliadas.

Tratamento endovascular da oclusão das artérias ilíacas

A oclusão das artérias ilíacas é uma patologia freqüente. Várias opções cirúrgicas existem para o seu tratamento, como a ponte aorto-bifemoral, a ponte femoro-femoral cruzada, o implante de endoprótese e outros. A ponte aorto-bifemoral é considerada o tratamento com melhores resultados. O tratamento endovascular da oclusão das artérias apresenta alta taxa de sucesso e baixo índice de complicações. Realizamos este tratamento em 24 pacientes, com idade média de 61 anos, variando de 39 a 82 anos. A indicação foi claudicação intermitente em 19 pacientes e isquemia crítica em cinco. O fator de risco mais freqüente foi tabagismo em 19 pacientes. A taxa de sucesso técnico na ultrapassagem da lesão foi de 91,7% e a taxa de patência foi de 71% em um ano. Os bons resultados com o tratamento endovascular nas oclusões das artérias ilíacas, com baixas taxas de morbidade e mortalidade, sugerem a inclusão deste procedimento no arsenal terapêutico.

Heritability of ambulatory and office blood pressure in the Swiss population.

BACKGROUND: Blood pressure (BP) is known to aggregate in families. Yet, heritability estimates are population-specific and no Swiss data have been published so far. We estimated the heritability of ambulatory and office BP in a Swiss population-based sample. METHODS: The Swiss Kidney Project on Genes in Hypertension is a population-based family study focusing on BP genetics. Office and ambulatory BP were measured in 1009 individuals from 271 nuclear families. Heritability was estimated for SBP, DBP, and pulse pressure using a maximum likelihood method implanted in the Statistical Analysis in Genetic Epidemiology software. RESULTS: The 518 women and 491 men included in this analysis had a mean (±SD) age of 48.3 (±17.4) and 47.3 (±17.7) years, and a mean BMI of 23.8 (±4.2) and 25.9 (±4.1) kg/m, respectively. Narrow-sense heritability estimates (±standard error) for ambulatory SBP, DBP, and pulse pressure were 0.37 ± 0.07, 0.26 ± 0.07, and 0.29 ± 0.07 for 24-h BP; 0.39 ± 0.07, 0.28 ± 0.07, and 0.27 ± 0.07 for day BP; and 0.25 ± 0.07, 0.20 ± 0.07, and 0.30 ± 0.07 for night BP, respectively (all P < 0.001). Heritability estimates for office SBP, DBP, and pulse pressure were 0.21 ± 0.08, 0.25 ± 0.08, and 0.18 ± 0.07 (all P < 0.01). CONCLUSIONS: We found significant heritability estimates for both ambulatory and office BP in this Swiss population-based study. Our findings justify the ongoing search for the genetic determinants of BP.

Achados de imagem da revascularização do miocárdio pela tomografia computadorizada por múltiplos detectores: onde estão os enxertos? Ensaio iconográfico

A angiotomografia por multidetectores de coronárias constitui um método preciso para avaliação dos enxertos venosos e arteriais pós-revascularização coronariana e vem substituindo em parte o cateterismo, o qual é um método invasivo e de maior custo. Este ensaio iconográfico tem como objetivo a demonstração anatômica dos enxertos mais comumente utilizados, como diferenciar enxertos venosos e arteriais e como localizá-los. Os exames foram realizados em aparelhos de tomografia computadorizada multislice de 64 fileiras de detectores, com apneia, frequência cardíaca controlada e protocolos adequados com posterior reconstruções MPR, MIP e 3D, de acordo com o eletrocardiograma. A localização dos enxertos e anastomoses em tomografias computadorizadas direcionadas para as artérias coronárias e para o tórax pode dificultar a análise do exame pelo radiologista não familiarizado, sendo que o conhecimento das técnicas cirúrgicas utilizadas e dos possíveis trajetos das pontes de safena e enxertos arteriais ajuda na análise de ambos os exames, evitando também erros diagnósticos.

Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population.

BACKGROUND AND OBJECTIVES: Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology Collaboration formula and by 24-hour creatinine clearance. RESULTS: In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29-57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR<90 ml/min per 1.73 m(2). CONCLUSION: Age, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population.