ABSTRACT
Using proteomics and complexome profiling, we evaluated in a year-long study longitudinal variations in the plasma proteome of kidney failure patients, prior to and after a kidney transplantation. The post-transplant period was complicated by bacterial infections, resulting in dramatic changes in the proteome, attributed to an acute phase response (APR). As positive acute phase proteins (APPs), being elevated upon inflammation, we observed the well-described C-reactive protein and Serum Amyloid A (SAA), but also Fibrinogen, Haptoglobin, Leucine-rich alpha-2-glycoprotein, Lipopolysaccharide-binding protein, Alpha-1-antitrypsin, Alpha-1-antichymotrypsin, S100, and CD14. As negative APPs, being downregulated upon inflammation, we identified the well-documented Serotransferrin and Transthyretin, but added Kallistatin, Heparin cofactor 2, and interalpha-trypsin inhibitor heavy chain H1 and H2 (ITIH1, ITIH2). For the patient with the most severe APR, we performed plasma complexome profiling by SEC-LC-MS on all longitudinal samples. We observed that several plasma proteins displaying alike concentration patterns coelute and form macromolecular complexes. By complexome profiling, we expose how SAA1 and SAA2 become incorporated into high-density lipid particles, replacing largely Apolipoprotein (APO)A1 and APOA4. Overall, our data highlight that the combination of in-depth longitudinal plasma proteome and complexome profiling can shed further light on correlated variations in the abundance of several plasma proteins upon inflammatory events.
Subject(s)
Blood Proteins , Kidney Transplantation , Proteome , Humans , Kidney Transplantation/adverse effects , Proteome/analysis , Proteome/metabolism , Longitudinal Studies , Blood Proteins/analysis , Blood Proteins/metabolism , Acute-Phase Proteins/metabolism , Middle Aged , Male , Proteomics/methods , Female , Renal Insufficiency/blood , Acute-Phase Reaction/blood , AdultABSTRACT
Introduction: We aimed to investigate the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels, lupus nephritis (LN) disease activity, and the degree of renal injury (based on the estimated glomerular filtration rate [eGFR]) in patients with LN. Methods: We selected 40 healthy control participants and 102 patients with LN who were treated in the Second Hospital of Jilin University, China, for inclusion in this study. Patients with LN were classified into LN with high-eGFR and LN with low-eGFR groups. Nrf2 protein levels were measured in the serum and renal tissues of the participants in both groups to assess the correlation between Nrf2 protein levels and different LN disease states. Results: There was a significantly positive correlation between serum Nrf2 protein levels, the degree of renal injury, and systemic lupus erythematosus disease activity index (SLEDAI) scores in patients with LN. Nrf2 protein levels were higher in the LN with high-eGFR group than in the healthy control and LN with low-eGFR groups. In follow-up patients in the LN high eGFR group, Nrf2 protein levels decreased significantly after remission of disease activity. Conclusion: Nrf2 protein expression has a dual role in patients with LN. Nrf2 protein levels not only correlate with disease activity in patients with LN, but also with the degree of kidney injury. Before implementing targeted therapy for Nrf2, evaluating both Nrf2 protein expression and the disease state in patients with LN is necessary to better identify and place each patient in an appropriate patient group.
Subject(s)
Lupus Nephritis , NF-E2-Related Factor 2 , Renal Insufficiency , Humans , Biomarkers/blood , Kidney/pathology , Lupus Nephritis/blood , Lupus Nephritis/pathology , NF-E2-Related Factor 2/blood , Renal Insufficiency/blood , Renal Insufficiency/pathologyABSTRACT
Variation in DNA methylation (DNAmet) in white blood cells and other cells/tissues has been implicated in the etiology of progressive diabetic kidney disease (DKD). However, the specific mechanisms linking DNAmet variation in blood cells with risk of kidney failure (KF) and utility of measuring blood cell DNAmet in personalized medicine are not clear. We measured blood cell DNAmet in 277 individuals with type 1 diabetes and DKD using Illumina EPIC arrays; 51% of the cohort developed KF during 7 to 20 years of follow-up. Our epigenome-wide analysis identified DNAmet at 17 CpGs (5'-cytosine-phosphate-guanine-3' loci) associated with risk of KF independent of major clinical risk factors. DNAmet at these KF-associated CpGs remained stable over a median period of 4.7 years. Furthermore, DNAmet variations at seven KF-associated CpGs were strongly associated with multiple genetic variants at seven genomic regions, suggesting a strong genetic influence on DNAmet. The effects of DNAmet variations at the KF-associated CpGs on risk of KF were partially mediated by multiple KF-associated circulating proteins and KF-associated circulating miRNAs. A prediction model for risk of KF was developed by adding blood cell DNAmet at eight selected KF-associated CpGs to the clinical model. This updated model significantly improved prediction performance (c-statistic = 0.93) versus the clinical model (c-statistic = 0.85) at P = 6.62 × 10-14. In conclusion, our multiomics study provides insights into mechanisms through which variation of DNAmet may affect KF development and shows that blood cell DNAmet at certain CpGs can improve risk prediction for KF in T1D.
Subject(s)
DNA Methylation , Diabetes Mellitus, Type 1 , Genetic Variation , Humans , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , DNA Methylation/genetics , Male , Female , Renal Insufficiency/genetics , Renal Insufficiency/blood , MicroRNAs/genetics , MicroRNAs/blood , Adult , CpG Islands/genetics , Diabetic Nephropathies/genetics , Diabetic Nephropathies/blood , Risk FactorsABSTRACT
Abstract Introduction: Renal function is an independent risk factor for mortality among on-pump coronary bypass grafting (ONCABG) patients. This association is well known in the international literature, but there is a lack of knowledge of how admission creatinine (AC) levels modulate each cardiovascular risk factor. Objective: The aim of this paper was to assess the effect of different AC levels on mortality among ONCABG patients. Methods: 1,599 patients who underwent ONCABG between December 1999 and February 2006 at Hospital de Base in São José do Rio Preto/SP-Brazil were included. They were divided into quartiles according to their AC levels (QI: 0.2 ≤AC < 1.0 mg/dL; QII: 1.0 ≤ AC < 1.2 mg/dL; QIII: 1.2 ≤ AC < 1.4 mg/dL; and QIV: 1.4 ≤ AC ≤ 2.6 mg/dL). Seven risk factors were then evaluated in each stratum. Results: Mortality was higher in the QIV group than QI or QII groups. Factors such as age (≥ 65 years) and cardiopulmonary bypass (CPB) time (≥ 115 minutes) in QIV, as well preoperative hospital stay (≥ 5 days) in QIII, were associated with higher mortality rates. Creatinine variation greater than or equal to 0.4 mg/dL increased mortality rates in all groups. The use of intra-aortic balloon pump and dialysis increased mortality rates in all groups except for QII. Type I neurological dysfunction increased the mortality rate in the QII and III groups. Conclusion: Creatinine levels play an important role in ONCABG mortality. The combination of selected risk factors and higher AC values leads to a worse prognosis. On the other hand, lower AC values were associated with a protective effect, even among elderly patients and those with a high CPB time.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Coronary Artery Bypass/mortality , Creatinine/blood , Preoperative Period , Prognosis , Reference Values , Time Factors , Brazil , Logistic Models , Retrospective Studies , Risk Factors , Risk Assessment , Renal Insufficiency/mortality , Renal Insufficiency/blood , Length of StayABSTRACT
Regucalcin is a soluble protein that is principally expressed in hepatocytes. Studies of regucalcin have mainly been conducted in animals due to a lack of commercially available kits. We aimed to develop an enzyme-linked immunosorbent assay (ELISA) to quantify serum regucalcin in patients with hepatitis B virus (HBV)-related disease. High-titer monoclonal antibodies and a polyclonal antibody to regucalcin were produced, a double-antibody sandwich ELISA method was established, and serum regucalcin was determined in 47 chronic hepatitis B (CHB) patients, 91 HBV-related acute-on-chronic liver failure (HBV-ACLF) patients, and 33 healthy controls. The ELISA demonstrated an appropriate linear range, and high levels of reproducibility, sensitivity, specificity, accuracy, and stability. The median serum regucalcin concentrations in HBV-ACLF and CHB patients were 5.46 and 3.76 ng/mL, respectively (P<0.01), which were much higher than in healthy controls (1.72 ng/mL, both P<0.01). For the differentiation of CHB patients and healthy controls, the area under curve (AUC) was 0.86 with a cut-off of 2.42 ng/mL, 85.7% sensitivity, and 78.8% specificity. In contrast, the AUC of alanine aminotransferase (ALT) was lower (AUC=0.80, P=0.01). To differentiate ACLF from CHB, the AUC was 0.72 with a cut-off of 4.26 ng/mL, 77.0% sensitivity, and 61.2% specificity while the AUC of ALT was 0.41 (P=0.07). Thus, we have developed an ELISA that is suitable for measuring serum regucalcin and have shown that serum regucalcin increased with the severity of liver injury due to HBV-related diseases, such that it appears to be more useful than ALT as a marker of liver injury.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Calcium-Binding Proteins/blood , Hepatitis B, Chronic/blood , Renal Insufficiency/blood , Severity of Illness Index , Enzyme-Linked Immunosorbent Assay/methods , Biomarkers/blood , Case-Control Studies , Reproducibility of Results , Sensitivity and Specificity , Hepatitis B, Chronic/virology , Renal Insufficiency/virology , Antibodies, Viral/immunologyABSTRACT
Abstract Introduction: It is unclear whether residual renal function (RRF) in dialysis patients can attenuate the metabolic impact of the long 68-hour interdialytic interval, in which water, acid, and electrolyte accumulation occurs. Objective: to evaluate serum electrolyte levels, water balance, and acid-base status in dialytic patients with and without RRF over the long interdialytic interval (LII). Methodology: this was a single-center, cross-sectional, and analytical study that compared patients with and without RRF, defined by diuresis above 200 mL in 24 hours. Patients were weighed and serum samples were collected for biochemical and gasometric analysis at the beginning and at the end of the LII. Results: 27 and 24 patients with and without RRF were evaluated, respectively. Patients without RRF had a higher increase in serum potassium during the LII (2.67 x 1.14 mEq/L, p < 0.001), reaching higher values at the end of the study (6.8 x 5.72 mEq/L, p < 0.001) and lower pH value at the beginning of the interval (7.40 x 7.43, p = 0.018). More patients with serum bicarbonate < 18 mEq/L (50 x 14.8%, p = 0.007) and mixed acid-base disorder (57.7 x 29.2%, p = 0.042), as well as greater interdialytic weight gain (14.67 x 8.87 mL/kg/h, p < 0.001) and lower natremia (137 x 139 mEq/L, p = 0.02) at the end of the interval. Calcemia and phosphatemia were not different between the groups. Conclusion: Patients with RRF had better control of serum potassium, sodium, acid-base status, and volemia throughout the LII.
Resumo Introdução: Não se sabe ao certo se a função renal residual (FRR) de pacientes dialíticos pode atenuar o impacto metabólico do maior intervalo interdialítico (MII) de 68 horas, no qual ocorre acúmulo de volume, ácidos e eletrólitos. Objetivo: Avaliar os níveis séricos de eletrólitos, balanço hídrico e status ácido-básico de pacientes dialíticos com e sem FRR ao longo do MII. Metodologia: Tratou-se de estudo unicêntrico, transversal e analítico, que comparou pacientes com e sem FRR, definida como diurese acima de 200 mL em 24 horas. Para tal, os pacientes foram pesados e submetidos à coleta de amostras séricas para análise bioquímica e gasométrica no início e fim do MII. Resultados: Foram avaliados 27 e 24 pacientes com e sem FRR, respectivamente. Pacientes sem FRR apresentaram maior aumento de potássio sérico durante o MII (2,67 x 1,14 mEq/L, p < 0,001) atingindo valores mais elevados no fim (6,8 x 5,72 mEq/L, p < 0,001); menor valor de pH no início do intervalo (7,40 x 7,43, p = 0,018), maior proporção de pacientes com bicarbonato sérico < 18 mEq/L (50 x 14,8 %, p = 0,007) e distúrbio ácido-básico misto (70,8 x 42,3 %, p = 0,042), além de maior ganho de peso interdialítico (14,67 x 8,87 mL/kg/h, p < 0,001) e menor natremia (137 x 139 mEq/L, p = 0,02) no fim do intervalo. A calcemia e fosfatemia não foram diferentes entre os grupos. Conclusão: Pacientes com FRR apresentaram melhor controle dos níveis séricos de potássio, sódio, status ácido-básico e da volemia ao longo do MII.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Water-Electrolyte Balance/physiology , Renal Dialysis/adverse effects , Renal Insufficiency/blood , Kidney/physiopathology , Phosphates/blood , Potassium/blood , Sodium/blood , Acid-Base Imbalance/physiopathology , Bicarbonates/blood , Weight Gain , Calcium/blood , Cross-Sectional Studies , Disease Progression , Renal Insufficiency/physiopathology , Renal Insufficiency/urine , Renal Insufficiency/therapy , Kidney/metabolism , Kidney/chemistry , Kidney Function Tests/methodsABSTRACT
El dabigatrán etexilato (inhibidor directo de trombina) es eficaz en la prevención tromboembólica en pacientes con fibrilación auricular. No requiere control rutinario de laboratorio, pero dada su eliminación renal, sería importante medirlo ante el deterioro de la función renal. Los objetivos del trabajo fueron verificar la calidad analítica del ensayo tiempo de trombina diluido para medición de la concentración plasmática (cc) de dabigatrán, correlacionar las cc con las pruebas básicas de coagulación tiempo de protrombina (TP) y tiempo de tromboplastina parcial activada (APTT) y evaluarlas de acuerdo al clearance de creatinina (CLCr). Se utilizaron muestras de plasma de 40 pacientes que recibían dabigatrán 150 (n = 19) o 110 (n = 21) mg/12 horas, colectadas 10-14 horas después de la última toma. Los ensayos de trombina diluida HemosIL DTI para la medición de dabigatrán, TP y APTT (IL), fueron realizados en coagulómetros fotoópticos ACL TOP 300 y 500 (IL). El DTI presentó coeficiente de variación intraensayo < 5.4% e interensayo < 6.0%, rango de linealidad 0-493 ng/ml; cc medidas en pacientes: mediana 83 (4-945) ng/ml. Individuos con CLCr en tercil inferior (< 46.1 ml/min) presentaron cc significativamente más elevadas, 308 (49-945), que los de tercilos medio, 72 (12-190), y superior, 60 (4-118) ng/ml. Las correlaciones cc vs. APTT o TP fueron moderadas, r2 = 0.59, -0.66, p < 0.0001, respectivamente. La prueba ensayada permitió cuantificar el nivel de dabigatrán plasmático tanto en pacientes con función renal normal como deteriorada, representando una herramienta útil en situaciones clínicas como deterioro de la función renal, pre cirugía o emergencias.
Dabigatran etexilate (direct thrombin inhibitor) is effective in preventing embolic stroke in patients with atrial fibrillation. It does not require laboratory control, but given the high renal elimination, its measurement in plasma is important in renal failure. The objectives of the study were to verify the analytical quality of the diluted thrombin time assay for measurement of dabigatran plasma concentration (cc), correlate cc with classic coagulation assays, prothrombin time (PT) and activated partial thromboplastin time (APTT), and evaluate them according to the creatinine clearance (CLCr). Forty plasma samples of patients (34 consecutive and 6 suspected of drug accumulation) receiving dabigatran at 150 (n = 19) or 110 (n = 21) mg/12 hours were collected. Blood samples were drawn at 10-14 hours of the last intake. Dabigatran concentration was determined by diluted thrombin time (HemosIl DTI, Instrumentation Laboratory (IL). PT and APTT (IL) were performed on two fotooptical coagulometers, ACL TOP 300 and 500 (IL). DTI presented intra-assay coefficient of variation < 5.4% and inter-assay < 6%, linearity range 0-493 ng/ml. Patients´ cc: median 83 (4-945) ng/ml. Individuals with CLCr in the lowest tertile (22.6-46.1 ml/min) showed significantly higher median cc: 308 (49-945), compared to the average 72 (12-190) and highest tertile, 60 (4-118) ng/ml. Correlation between cc and APTT or PT were moderate, r2 = 0.59 and -0.66, p < 0.0001, respectively. DTI test allowed us to quantify plasma dabigatran levels, both in patients with normal or altered renal function, representing a useful tool in clinical situations such as renal failure, pre surgery or emergencies.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Antithrombins/blood , Creatinine/blood , Dabigatran/blood , Partial Thromboplastin Time , Thrombin Time , Drug Monitoring , Renal Insufficiency/blood , Kidney Function TestsABSTRACT
Abstract Background: Renal dysfunction is an independent predictor of morbidity and mortality in cardiac surgery. For a better assessment of renal function, calculation of creatinine clearance (CC) may be necessary. Objective: To objectively evaluate whether CC is a better risk predictor than serum creatinine (SC) in patients undergoing cardiac surgery. Methods: Analysis of 3,285 patients registered in a prospective, consecutive and mandatory manner in the Sao Paulo Registry of Cardiovascular Surgery (REPLICCAR) between November 2013 and January 2015. Values of SC, CC (Cockcroft-Gault) and EuroSCORE II were obtained. Association analysis of SC and CC with morbidity and mortality was performed by calibration and discrimination tests. Independent multivariate models with SC and CC were generated by multiple logistic regression to predict morbidity and mortality following cardiac surgery. Results: Despite the association between SC and mortality, it did not calibrate properly the risk groups. There was an association between CC and mortality with good calibration of risk groups. In mortality risk prediction, SC was uncalibrated with values > 1.35 mg /dL (p < 0.001). The ROC curve showed that CC is better than SC in predicting both morbidity and mortality risk. In the multivariate model without CC, SC was the only predictor of morbidity, whereas in the model without SC, CC was not only a mortality predictor, but also the only morbidity predictor. Conclusion: Compared with SC, CC is a better parameter of renal function in risk stratification of patients undergoing cardiac surgery.
Resumo Fundamentos: Disfunção renal é preditor independente de morbimortalidade após cirurgia cardíaca. Para uma melhor avaliação da função renal, o cálculo do clearance de creatinina (CC) pode ser necessário. Objetivo: Avaliar objetivamente se o CC é melhor que a creatinina sérica (CS) para predizer risco nos pacientes submetidos à cirurgia cardíaca. Métodos: Análise em 3285 pacientes do Registro Paulista de Cirurgia Cardiovascular (REPLICCAR) incluídos de forma prospectiva, consecutiva e mandatória entre novembro de 2013 e janeiro de 2015. Foram obtidos valores de CS, CC (Cockcroft-Gault) e do EuroSCORE II. Análise de associações da CS e do CC com morbimortalidade foi realizada mediante testes de calibração e discriminação. Por regressão logística múltipla, foram criados modelos multivariados independentes com CS e com CC para predição de risco de morbimortalidade após cirurgia cardíaca. Resultados: Apesar da associação entre a CS e morbimortalidade, essa não calibrou adequadamente os grupos de risco. Houve associação entre o CC e morbimortalidade com boa calibração dos grupos de risco. Na predição do risco de mortalidade, a CS ficou descalibrada com valores >1,35 mg/dL (p < 0,001). A curva ROC revelou que o CC é superior à CS na predição de risco de morbimortalidade. No modelo multivariado sem CC, a CS foi a única preditora de morbidade, enquanto que no modelo sem a CS, o CC foi preditor de mortalidade e o único preditor de morbidade. Conclusão: Para avaliação da função renal, o CC é superior que a CS na estratificação de risco dos pacientes submetidos a cirurgia cardíaca.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Risk Assessment/methods , Creatinine/blood , Renal Insufficiency/mortality , Renal Insufficiency/blood , Glomerular Filtration Rate/physiology , Cardiac Surgical Procedures/mortality , Reference Standards , Reference Values , Calibration , Logistic Models , Cross-Sectional Studies , Prospective Studies , Reproducibility of Results , Risk Factors , Morbidity , Sensitivity and SpecificityABSTRACT
OBJECTIVE: Kidney dysfunction is a major complication in the postoperative cardiac surgery setting. Operative risk factors for its development are cardiopulmonary bypass, anemia, antifibrinolytic drugs and blood transfusion. The objective of this study was to identify the risk factors for developing kidney dysfunction in patients undergoing cardiac surgery. METHODS: Ninety-seven patients were studied and 84 were analyzed. The sample was stratified into two groups. A serum creatinine higher than 30% compared to the preoperative period was considered for the kidney dysfunction group (n=9; 10.71%). There also was a control group when the increase in serum creatinine remained lower than 30% (n=75; 89.28%). RESULTS: It was observed that intraoperative transfusion of fresh frozen plasma in the control group was 2.05 ± 0.78 units and 3.80 ± 2.16 units in the kidney dysfunction group with P= 0.032. CONCLUSION: It was possible to associate that fresh frozen plasma transfusion is a risk factor for postoperative kidney dysfunction after cardiovascular surgery.
OBJETIVO: A disfunção renal é uma complicação importante no cenário de pós-operatório de cirurgia cardiovascular. Como fatores de risco conhecidos no intraoperatório para o seu desenvolvimento destacam-se a circulação extracorpórea, a hemodiluição, drogas antifibrinolíticos e a transfusão sanguínea. O objetivo deste estudo é identificar os fatores de risco na transfusão de sangue e derivados para o desenvolvimento de disfunção renal em pacientes submetidos à cirurgia cardiovascular. MÉTODOS: Noventa e sete pacientes foram estudados e 84 foram analisados. A amostra foi estratificada em dois grupos, sendo que o incremento de 30% na creatinina sérica no pós-operatório foi considerado para o grupo com disfunção renal (n = 9; 10,71%). O grupo não disfunção renal foi caracterizado pela creatinina sérica, que permaneceu inferior a aumento de 30% no pós-operatório (n = 75; 89,28%). RESULTADOS: Foi observado que a transfusão de plasma fresco congelado no grupo não disfunção renal foi de 2,05 ± 0,78 unidades e 3,80 ± 2,16 unidades no grupo disfunção renal com P= 0,032. CONCLUSÃO: Foi possível associar, nesta série de pacientes, que a transfusão de plasma fresco congelado foi um fator de risco para disfunção renal pós-operatório de cirurgia cardiovascular.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Blood Transfusion/adverse effects , Cardiovascular Surgical Procedures/adverse effects , Plasma , Renal Insufficiency/etiology , Chi-Square Distribution , Creatinine/blood , Postoperative Period , Postoperative Complications/etiology , Risk Factors , Renal Insufficiency/blood , Statistics, NonparametricABSTRACT
FUNDAMENTO: O efeito renoprotetor dos inibidores da ECA vem sendo questionado no caso de diminuição do volume circulante efetivo, como na insuficiência cardíaca crônica direita ou biventricular. Objetivo: Detectar os preditores clínicos de agravamento renal na população de pacientes com ICC, caracterizado por dois tipos de regime de dosagem de inibidores da ECA. MÉTODOS: De acordo com um desenho de coorte retrospectiva, seguimos dois grupos de pacientes com ICC - tanto direita quanto biventricular -, todos na classe III da NYHA, tratados com inibidores da ECA (enalapril ou lisinopril), e com fração de ejeção do ventrículo esquerdo (FEVE) < 50 por cento, por meio de distinção em sua dosagem de inibidor da ECA: média-baixa (< 10 mg por dia) ou dosagem "alta" (> 10 mg por dia) de enalapril ou lisinopril. A disfunção renal agravada (ARD) foi definida pelo aumento de Cr > 30 por cento com relação ao segmento basal. O modelo de risco proporcional de Cox foi utilizado para identificar os preditores da ARD entre as seguintes variáveis: os inibidores da ECA com "alta" dosagem, idade, FEVE basal, histórico de repetidas terapias intensivas com diuréticos de alça por via intravenosa (diurético intravenoso), diabete, Cr basal, histórico de hipertensão, pressão arterial sistólica < 100 mmHg. RESULTADOS: Cinquenta e sete pacientes foram recrutados, dos quais 15 foram tratados com inibidor da ECA com dosagem "alta". Durante um seguimento médio de 718 dias, a ARD ocorreu em 17 pacientes (29,8 por cento). Apenas o inibidor da ECA com "alta" dosagem (RR: 12,4681 IC: 2,1614 - 71,9239 p = 0,0050) e Cr basal (RR:1,2344 IC: 1,0414 - 1,4632 p = 0,0157) foi demonstrado ser preditor da ARD. Além disso, demonstrou-se que o inibidor da ECA com dosagens "altas" não previu ARD em ICC sem diurético intravenoso e ICC com diabete. CONCLUSÃO: Na ICC de classe III da NYHA, o inibidor da ECA com "altas" dosagens e um maior Cr basal foi preditor da ARD. A nefrotoxicidade relacionada com inibidores da ECA em "altas" dosagens foi aumentada com o diurético intravenoso, ao passo que, em pacientes com ICC com diabete, aquela não foi detectada.
BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50 percent, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30 percent from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8 percent) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.
Subject(s)
Aged , Female , Humans , Male , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Creatinine/blood , Diabetes Mellitus/drug therapy , Heart Failure/drug therapy , Renal Insufficiency/chemically induced , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/blood , Chronic Disease , Drug Therapy, Combination , Diabetes Mellitus/blood , Diuretics/therapeutic use , Epidemiologic Methods , Enalapril/administration & dosage , Enalapril/adverse effects , Enalapril/blood , Lisinopril/administration & dosage , Lisinopril/adverse effects , Lisinopril/blood , Reference Values , Risk Factors , Renal Insufficiency/blood , Renal Insufficiency/prevention & controlABSTRACT
FUNDAMENTO: A interpretação dos resultados de troponina em pacientes com síndromes coronarianas agudas (SCA) e doença renal é dificultada pelo fato de que a disfunção renal aumenta os níveis de troponina, independente da necrose miocárdica. Embora tenha sido demonstrado que a doença renal em estágio terminal está associada com níveis elevados de troponina T cardíaca (TnT), ainda não é conhecido se esse biomarcador é alterado por níveis menos graves de disfunção renal. OBJETIVO: Avaliar se disfunção renal moderada está associada com elevação dos níveis de TnT em pacientes com SCA. MÉTODOS: Um total de 145 indivíduos com SCA e clearance de creatinina > 30 ml/min foram estudados. O clearance de creatinina foi estimado através da fórmula de Cockcroft-Gault e a TnT foi medida na admissão hospitalar. Disfunção renal moderada foi definida como clearance de creatinina de 30-59 ml/min e TnT positiva como níveis > 0,01 ug/l. RESULTADOS: Nenhuma correlação foi observada entre o clearance de creatinina e TnT (r = - 0,06, P=0,45). Os níveis de TnT foram similares entre indivíduos no primeiro (mediana=0,05 ug/l), segundo (mediana=0 ug/l), terceiro (mediana=0,07 ug/l) e quarto quartis (mediana=0 ug/l) de clearance de creatinina - P=0,63. De forma similar, não houve diferença nos valores de troponina entre indivíduos com disfunção renal moderada (mediana=0,02 ug/l) e indivíduos com função renal normal/quase normal (mediana=0,03 ug/l) - P=0.63. A prevalência de TnT positiva foi similar entre indivíduos com disfunção renal moderada e função renal normal/quase normal (55 por cento vs 52 por cento, P=0,65). CONCLUSÃO: Disfunção renal moderada não está associada com elevação dos níveis de TnT em pacientes com SCA. (Arq Bras Cardiol 2010; 95(5): 600-605).
BACKGROUND: Interpretation of troponin results in patients with acute coronary syndromes (ACS) and renal disease is confused by the fact that renal dysfunction increases troponin levels, regardless of myocardial necrosis. Although it has been demonstrated that end-stage renal disease is associated with elevated cardiac troponin T (cTnT) levels, it is not known whether this biomarker is altered by less than severe degrees of renal impairment. OBJECTIVE: To evaluate whether moderate renal dysfunction is associated with cTnT elevation in patients with ACS. METHODS: One hundred, forty-five individuals with ACS and creatinine clearance > 30 ml/min were studied. Creatinine clearance was estimated by the Cockcroft-Gault formula and cTnT was measured at hospital admission. Moderate renal dysfunction was defined as a creatinine clearance of 30-59 ml/min and positive cTnT as levels > 0.01 ug/l. RESULTS: No correlation was observed between creatinine clearance and cTnT (r = - 0.06, P=0.45). The levels of cTnT were similar among individuals in the first (median=0.05 ug/l), second (median=0 ug/l), third (median=0.07 ug/l) and fourth quartiles (median=0 ug/l) of creatinine clearance - P=0.63. Similarly, there was no difference in troponin values between individuals with moderate renal dysfunction (median=0.02 ug/l) and individuals with normal/near normal function (median=0.03 ug/l) - P=0.63. The prevalence of positive cTnT was similar between individuals with moderate renal dysfunction and normal/near normal renal function (55 percent vs 52 percent, P=0.65). CONCLUSION: Moderate renal dysfunction is not associated with cTnT elevation in patients with ACS. (Arq Bras Cardiol 2010; 95(5): 600-605).
FUNDAMENTO: La interpretación de los resultados de troponina en pacientes con síndromes coronarias agudas (SCA) y enfermedad renal es dificultada debido al hecho de que la disfunción renal aumenta los niveles de troponina, independientemente de la necrosis miocárdica. Aunque se haya sido evidenciada la enfermedad renal en fase terminal está asociada con niveles elevados de troponina T cardíaca (TnT), aún no se conoce si este biomarcador es alterado por niveles menos severos de disfunción renal. OBJETIVOS: Evaluar si la disfunción renal moderada está asociada con la elevación de los niveles de TnT en pacientes con SCA. MÉTODOS: Un total de 145 individuos con SCA y clearance de creatinina > 30 ml/min fueron estudiados. El clearance de creatinina se estimó a través de la fórmula de Cockcroft-Gault y la TnT se midió en la admisión hospitalaria. Disfunción renal moderada se definió como clearance de creatinina de 30-59 ml/min y TnT positiva como niveles > 0,01 ug/L. RESULTADOS: No se observó alguna correlación entre el clearance de creatinina y TnT (r = - 0,06, P=0,45). Los niveles de TnT fueron similares entre individuos en el primero (mediana=0,05 ug/L), segundo (mediana=0 ug/L), tercero (mediana=0,07 ug/L) y cuarto cuartiles (mediana=0 ug/L) de clearance de creatinina - P=0,63. De forma similar, no hubo diferencia en los valores de troponina entre individuos con disfunción renal moderada (mediana=0,02 ug/L) y individuos con función renal normal/casi normal (mediana=0,03 ug/L) - P=0.63. La prevalencia de TnT positiva fue similar entre individuos con disfunción renal moderada y función renal normal/casi normal (55 por ciento vs 52 por ciento, P=0,65). CONCLUSIÓN: Disfunción renal moderada no está asociada con la elevación de los niveles de TnT en pacientes con SCA. (Arq Bras Cardiol 2010;95(5):600-605).
Subject(s)
Aged , Female , Humans , Male , Acute Coronary Syndrome/blood , Creatinine/blood , Renal Insufficiency/blood , Troponin T/blood , Biomarkers/blood , Case-Control Studies , Kidney/physiology , Reference ValuesABSTRACT
BACKGROUND: renal insufficiency (RI) is a frequent complication in patients with cirrhosis and ascites. OBJECTIVE: to assess the incidence, causes, predictive factors and prognosis of RI in cirrhotic patients with ascites. PATIENT AND METHODS: descriptive study of cases and controls. Clinical histories of 162 admissions in 103 patients during 3 years were reviewed. It was considered RI when there was an increase of creatininemia > 1.5 mg/dl. The predictive factors, clinical features, and mortality of the patients with and without RI were compared. RESULTS: a diagnosis of RI was made in 35 cases (21.6%). Hospital mortality rate was 18.5%: with RI 57.1%, controls 7.8% (p<0.01). Etiology: reversible prerrenal failure (54.3%), SHR 1 (14.2%) and 2 (5.7%), septic shock by spontaneous bacterial peritonitis (SBP) (11.4%), NTA (8.5%). The patients with and without RI had a Child-Pügh score average (+/-DS): 12.8 (1.8) and 11.4 (1.9) (p=0.0002) respectively. The patients with RI had higher values of total bilirubin, AST, ALT, white blood cells, time prothrombin, and minors values of serum sodium, Hto, Hb, protein, albumin and cholinesterase that controls (p<0.05). The clinical variables associated with RI included infections (OR 1.4), SBP (OR 4) and hepatic encephalopathy (OR 2.4). In the multivariate analysis, the independent predictive factors for RI were hyponatremia, bilirubinemia greater to 10 mg/dl and SPB. CONCLUSION: in cirrhotic patients RI have high mortality. The most frequent cause was reversible prerrenal failure. The risk of RI was increased significantly in patients with hyponatremia, marked hyperbilirubinemia and SPB.
Background: renal insufficiency (RI) is a frequent complication in patients with cirrhosis and ascites. Objective: to assess the incidence, causes, predictive factors and prognosis of RI in cirrhotic patients with ascites. Patient and methods: descriptive study of cases andcontrols. Clinical histories of 162 admissions in 103 patients during 3 years were reviewed. It was consideredRI when there was an increase of creatininemia > 1,5 mg/dl. The predictive factors, clinical features, andmortality of the patients with and without RI were compared. Results: a diagnosis of RI was made in 35 cases (21.6%). Hospital mortality rate was 18.5%: with RI 57.1%, controls 7.8% (p< 0.01). Etiology: reversible prerrenal failure (54.3%), SHR 1 (14.2%) and 2 (5.7%), septic shock by spontaneous bacterial peritonitis (SBP) (11.4%), NTA (8.5%). The patientswith and without RI had a Child-Pügh score average (± DS): 12.8 (1.8) and 11,4 (1.9) (p=0.0002) respectively.The patients with RI had higher values of total bilirubin, AST, ALT, white blood cells, time prothrombin, and minors values of serum sodium, Hto, Hb, protein,albumin and cholinesterase that controls (p<0.05). The clinical variables associated with RI included infections (OR 1.4), SBP (OR 4) and hepatic encephalopathy (OR 2.4). In the multivariate analysis, the independent predictive factors for RI were hyponatremia, bilirubinemia greater to 10 mg/dl and SPB. Conclusion: in cirrhotic patients RI have high mortality.The most frequent cause was reversible prerrenal failure. The risk of RI was increased significantly in patients with hyponatremia, marked yperbilirubinemiaand SPB.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Ascites/complications , Fibrosis/complications , Renal Insufficiency/etiology , Renal Insufficiency/blood , Renal Insufficiency/mortality , Biomarkers/blood , Epidemiologic Methods , Prognosis , Hepatorenal Syndrome/complicationsABSTRACT
Se presentan aquí los niveles de los marcadores tempranos de activación de la coagulación y del TNF-alpha en 12 niños con la forma epidémica del síndrome urémico hemolítico, de 16 meses de edad, (12-18) (mediana y rango) Todos los pacientes se recuperaron de las enfermedad dentro de las 2 a 4 semanas de evolución. Se tomaron cuatro muestras de sangre: al ingreso al hospital, luego en la primera y segunda semana y en la remisión. Las determinaciones del F1+2 TAT y TNF-alpha se realizaron por técnicas de ELISA comerciales, mientras que el factor von Willebrand se determinó por el método de Laurell. Los valores de F1+2 y del TAT al ingreso fueron 7.8 nM (3.7-12.3) y 22.7 ng/ml (8-76) respectivamente. Además, se encontró correlación significativa entre los niveles de F1+2 vs creatinina sérica, r:0.47 p < 0.001; F1+2 vs úrea sérica, r:0.66 p < 0.001; TAT vs creatinina sérica, r:0.77 p < 0.001; TAT vs urea , r:0.59 p <0.001. La mediana del FvW al ingreso en 11/12 niños fue de 260 por ciento (170-420). Los niveles del FvW se correlacionaron con los del F1+2; r:0.77 p < 0.001 y con los del TAT, r:0.41 p < 0.01. Los valores de estos marcadores séricos tendieron a normalizarse con la mejoría de la enfermedad. Se encontró una correlación negativa entre el recuento plaquetario y los niveles del F1+2, r:-0.64 p<0.001. Los niveles de TNF-alpha estuvieron aumentados en 5 niños, 22.2 pg/ml (17.2-53.7). Los resultados sugieren que estas anormalidades pueden ser atribuidas a un estímulo común sobre células endoteliales.
Subject(s)
Humans , Infant , Child, Preschool , Antithrombins/analysis , Hemolytic-Uremic Syndrome/blood , Prothrombin/analysis , Renal Insufficiency/blood , Thrombin/biosynthesis , Tumor Necrosis Factor-alpha/analysis , Biomarkers , Creatinine/blood , Urea/blood , von Willebrand Factor/analysisABSTRACT
El infarto renal puede definirse como la muerte de tejido renal debido a interferencia con su circulación sanguínea. Se presenta el caso de un paciente masculino, de nueve años de edad, con cefalea universal, vómitos de contenido gástrico y una tensión arterial (TA) de 140/100 mmHg. Su renina plasmática periférica fue de 7.4 ng/mL/h (normal hasta 2.5 ng/mL/h). La arteriografía renal indicó infarto parenquimatoso en polo superior de riñón derecho. Actualmente, está controlado con una tensión arterial de 110/70 mmHg, para lo cual recibe 1 mg/kg/día de captopril complementado con dieta hiposódica.