Dejaldo M. J. Christofalo

Effects of Low Birth Weight in 8- to 13-Year-Old Children: Implications in Endothelial Function and Uric Acid Levels

Low birth weight has been associated with an increased incidence of adult cardiovascular disease. Endothelial dysfunction and high levels of serum uric acid are associated with hypertension. In this study, we have determined whether uric acid is related to blood pressure and vascular function in children with low birth weight. We evaluated vascular function using high-resolution ultrasound, blood pressure, and uric acid levels in 78 children (35 girls, 43 boys, aged 8 to 13 years). Increasing levels of uric acid and systolic blood pressure were observed in children with low birth weight. Birth weight was inversely associated with both systolic blood pressure and uric acid; on the other hand, uric acid levels were directly correlated with systolic blood pressure in children of the entire cohort. Low birth weight was associated with reduced flow-mediated dilation (r=0.427, P<0.001). Because the children with low birth weight had elevated uric acid as well as higher systolic blood pressure levels, we evaluated the correlation between these variables. In the low birth weight group, multiple regression analysis revealed that uric acid (&bgr;=−2.886; SE=1.393; P=0.040) had a graded inverse relationship with flow-mediated dilation, which was not affected in a model adjusting for race and gender. We conclude that children with a history of low birth weight show impaired endothelial function and increased blood pressure and uric acid levels. These findings may be early expressions of vascular compromise, contributing to susceptibility to disease in adult life.

Intima-Media Thickness Is Associated with Inflammation and Traditional Cardiovascular Risk Factors in Non-Dialysis-Dependent Patients with Chronic Kidney Disease

Background: Mortality due to cardiovascular causes is high in chronic kidney disease (CKD). Intima-media thickness (IMT) and inflammation are early atherosclerosis markers, although data are lacking about their association in the CKD non-dialysis-dependent (CKD-NDD) population. The aim of the present study was to evaluate the association between IMT, inflammation and other cardiovascular risk factors in such patients. Methods: CKD-NDD patients (n = 122) were subjected to measurements of carotid IMT and inflammatory marker levels in a cross-sectional study. Results: Mean patient age was 55.2 ± 11.3 years (61.5% males). Median C-reactive protein (CRP) was 0.28 mg/dl (0.03–14.2). The median interleukin (IL)-6 count was 4.75 pg/ml (0.7–243), the mean adiponectin was 27.8 ± 7.3 ng/ml and the mean IMT was 0.61 ± 0.19 mm. Four (3.3%) patients had IMT above the normal range. IMT was higher in males (p < 0.001), patients with estimated glomerular filtration rate <60 ml/min (p = 0.030), inflammation (p = 0.005) and higher IL-6 levels (p = 0.023). IMT was correlated with age (R = 0.538; p < 0.001), waist circumference (R = 0.235; p = 0.016), CRP (R = 0.191; p = 0.035) and systolic blood pressure (R = 0.181; p = 0.048). In a multiple regression analysis, the independent determinants of IMT were age (β = 0.512; p < 0.001) and CRP levels (β = 0.159; p = 0.041). Conclusion: The present study demonstrated that although the IMT values were within the normal range, there was a clear association of IMT with age, as well as with inflammation in an asymptomatic CKD-NDD population.

Effect of rosuvastatin and sevelamer on the progression of coronary artery calcification in chronic kidney disease: a pilot study.

INTRODUCTION Coronary artery calcification (CAC) is highly prevalent among chronic kidney disease (CKD) patients and its strong association with mortality has been recognized early in the course of CKD. The aim of the present study was to test the effect of rosuvastatin and sevelamer hydrochloride on the progression of CAC in nondialyzed CKD patients. METHODS An open-label, randomized and controlled pilot study was conducted including 117 CKD patients (62% men, 56.9 ± 11.2 years, eGFR 36 ± 16.5 ml/min). Patients were randomly assigned to rosuvastatin (n = 38; 10 mg/day), to sevelamer hydrochloride (n = 38; 2,400 mg/day) and to control (n = 41) groups. CAC (by multislice computed tomography) and biochemical analyses were performed at baseline and after 24 months. RESULTS At baseline, CAC was observed in 55%, 58% and 61% of patients in the rosuvastatin, sevelamer hydrochloride and control groups, respectively (p = 0.87). Calcium score at baseline as well as its absolute and relative changes during 24 months were similar among the groups. Low density lipoprotein cholesterol (LDL-c) was higher and decreased significantly in the rosuvastatin group (p < 0.01). The analysis adjusting for LDL-c showed that the drug regimens were not associated with the progression of CAC (drug effect p = 0.85; time-effect p < 0.001; interaction p = 0.76). CONCLUSIONS Treatment with rosuvastatin and sevelamer hydrochloride may not delay the progression of CAC in non-dialysis dependent CKD patients.

Efeitos de diferentes graus de sensibilidade a insulina na função endotelial de pacientes obesos

BACKGROUND Obesity derived from intra-abdominal fat deposition tends to increase hormonal and cytokine production, thus worsening insulin sensitivity and leading to endothelial dysfunction. Hyperinsulinemia is considered an independent risk factor for ischemic heart disease and cause of endothelial dysfunction in healthy individuals. OBJECTIVE To assess the impact of different degrees of insulin resistance, measured by HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), on endothelial function in obese, non-diabetic patients without prior history of cardiovascular events and different metabolic syndrome components. METHODS Forty obese individuals were submitted to anthropometric measurements, BP measurements at office and ABPM and laboratory tests, in addition to non-invasive ultrasound assessment of endothelial function. Patients were divided into 3 groups according to the level of insulin resistance: patients with HOMA-IR values from 0.590 to 1.082 were assigned to Group 1 (n=13), from 1.083 to 1.410 to Group 2 (n=14) and from 1.610 to 2.510 to Group 3 (n=13). RESULTS We found a significant difference in flow-mediated dilation in group 3 compared to group 1 (9.2 ± 7.0 vs 18.0 ± 7.5 %, p=0.006). There was a negative correlation between endothelial function and insulin, HOMA-IR and triglycerides. CONCLUSION Our data suggest that mild changes in insulin resistance levels assessed by HOMA-IR may have an impact on vasodilatatory endothelial function in uncomplicated obese individuals with different cardiovascular risk factors.FUNDAMENTO: A obesidade derivada da deposicao de gordura intra-abdominal tende a aumentar a producao de hormonios e citoquinas, piorando a sensibilidade a insulina e levando a disfuncao endotelial. A hiperinsulinemia e considerada um fator de risco independente para doenca isquemica cardiaca e e uma causa de disfuncao endotelial em individuos saudaveis. OBJETIVO: Avaliar o impacto de diferentes graus de resistencia a insulina, medida pelo HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), sobre a funcao endotelial de obesos, pacientes nao diabeticos, sem historia previa de eventos cardiovasculares e diversos componentes da sindrome metabolica. METODOS: Um total de 40 individuos obesos foi submetido a medidas antropometricas, pressao arterial de consultorio, MAPA e exames laboratoriais, alem de avaliacao ultrassonografica nao invasiva da funcao endotelial. Os pacientes foram divididos em tres grupos de acordo com o grau de resistencia a insulina: pacientes com valores de HOMA-IR entre 0,590 e 1,082 foram incluidos no Grupo 1 (n = 13); entre 1,083 e 1,410 no Grupo 2 (n = 14); e entre 1,610 e 2,510 no Grupo 3 (n = 13). RESULTADOS: Encontramos uma diferenca significativa na vasodilatacao mediada por fluxo no Grupo 3 em relacao ao Grupo 1 (9,2 ± 7,0 vs 18,0 ± 7,5 %, p = 0,006). Houve uma correlacao negativa entre a funcao endotelial e insulina, HOMA-IR e triglicerides. CONCLUSAO: Nosso estudo sugere que leves alteracoes nos niveis de resistencia a insulina avaliada pelo HOMA-IR podem causar algum impacto sobre a funcao vasodilatadora do endotelio em individuos obesos nao complicados com diferentes fatores de risco cardiovascular.

Effects of different degrees of insulin sensitivity on endothelial function in obese patients.

BACKGROUND Obesity derived from intra-abdominal fat deposition tends to increase hormonal and cytokine production, thus worsening insulin sensitivity and leading to endothelial dysfunction. Hyperinsulinemia is considered an independent risk factor for ischemic heart disease and cause of endothelial dysfunction in healthy individuals. OBJECTIVE To assess the impact of different degrees of insulin resistance, measured by HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), on endothelial function in obese, non-diabetic patients without prior history of cardiovascular events and different metabolic syndrome components. METHODS Forty obese individuals were submitted to anthropometric measurements, BP measurements at office and ABPM and laboratory tests, in addition to non-invasive ultrasound assessment of endothelial function. Patients were divided into 3 groups according to the level of insulin resistance: patients with HOMA-IR values from 0.590 to 1.082 were assigned to Group 1 (n=13), from 1.083 to 1.410 to Group 2 (n=14) and from 1.610 to 2.510 to Group 3 (n=13). RESULTS We found a significant difference in flow-mediated dilation in group 3 compared to group 1 (9.2 ± 7.0 vs 18.0 ± 7.5 %, p=0.006). There was a negative correlation between endothelial function and insulin, HOMA-IR and triglycerides. CONCLUSION Our data suggest that mild changes in insulin resistance levels assessed by HOMA-IR may have an impact on vasodilatatory endothelial function in uncomplicated obese individuals with different cardiovascular risk factors.FUNDAMENTO: A obesidade derivada da deposicao de gordura intra-abdominal tende a aumentar a producao de hormonios e citoquinas, piorando a sensibilidade a insulina e levando a disfuncao endotelial. A hiperinsulinemia e considerada um fator de risco independente para doenca isquemica cardiaca e e uma causa de disfuncao endotelial em individuos saudaveis. OBJETIVO: Avaliar o impacto de diferentes graus de resistencia a insulina, medida pelo HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), sobre a funcao endotelial de obesos, pacientes nao diabeticos, sem historia previa de eventos cardiovasculares e diversos componentes da sindrome metabolica. METODOS: Um total de 40 individuos obesos foi submetido a medidas antropometricas, pressao arterial de consultorio, MAPA e exames laboratoriais, alem de avaliacao ultrassonografica nao invasiva da funcao endotelial. Os pacientes foram divididos em tres grupos de acordo com o grau de resistencia a insulina: pacientes com valores de HOMA-IR entre 0,590 e 1,082 foram incluidos no Grupo 1 (n = 13); entre 1,083 e 1,410 no Grupo 2 (n = 14); e entre 1,610 e 2,510 no Grupo 3 (n = 13). RESULTADOS: Encontramos uma diferenca significativa na vasodilatacao mediada por fluxo no Grupo 3 em relacao ao Grupo 1 (9,2 ± 7,0 vs 18,0 ± 7,5 %, p = 0,006). Houve uma correlacao negativa entre a funcao endotelial e insulina, HOMA-IR e triglicerides. CONCLUSAO: Nosso estudo sugere que leves alteracoes nos niveis de resistencia a insulina avaliada pelo HOMA-IR podem causar algum impacto sobre a funcao vasodilatadora do endotelio em individuos obesos nao complicados com diferentes fatores de risco cardiovascular.

Association of Urinary N-Domain Angiotensin I-Converting Enzyme with Plasma Inflammatory Markers and Endothelial Function

The aim of this study was to investigate the association between urinary 90 kDa N-domain Angiotensin I-converting enzyme (ACE) form with C-reactive protein (CRP) and homocysteine plasma levels (Hcy), urinary nitric oxide (NOu), and endothelial function (EF) in normotensive subjects. Forty healthy subjects were evaluated through brachial Doppler US to test the response to reactive hyperemia and a panel of blood tests to determine CRP and Hcy levels, NOu, and urinary ACE. They were divided into groups according to the presence (ACE90+) or absence (ACE90−) of the 90 kDa ACE, the presence (FH+) or absence (FH−) of family history of hypertension, and the presence or absence of these two variables FH+/ACE90+ and FH−/ACE90−. We found an impaired endothelial dilatation in subjects who presented the 90 kDa N-domain ACE as follows: 11.4% ± 5.3% in ACE90+ compared with 17.6% ± 7.1% in ACE90− group and 12.4% ± 5.6% in FH+/ACE90+ compared with 17.7% ± 6.2% in FH−/ACE90− group, P < 0.05. Hcy and CRP levels were statistically significantly lower in FH+/ACE90+ than in FH−/ACE90− group, as follows: 10.0 ± 2.3 µM compared with 12.7 ± 1.5 µM, and 1.3 ± 1.8 mg/L compared with 3.6 ± 2.0 mg/L, respectively. A correlation between flow-mediated dilatation (FMD) and CRP, Hcy, and NOu levels was not found. Our study suggests a reduction in the basal NO production confirmed by NOu analysis in subjects with the 90 kDa N-domain ACE isoform alone or associated with a family history of hypertension. Our data suggest that the presence of the 90 kDa N-domain ACE itself may have a negative impact on flow-mediated dilatation stimulated by reactive hyperemia.

Association of urinary 90 kDa angiotensin- converting enzyme with family history of hypertension and endothelial function in normotensive individuals.

We described angiotensin-I-converting enzyme (ACE) isoforms with molecular masses of 190, 90, and 65 kDa in the urine of normotensive offspring of hypertensive subjects. Since they did not appear in equal amounts, we suggested that 90 kDa ACE might be a marker for hypertension. We evaluated the endothelial response in normotensive offspring with or without family history of hypertension and its association with the 90 kDa ACE in urine. Thirty-five normotensive subjects with a known family history of hypertension and 20 subjects without a family history of hypertension, matched for age, sex, body weight, and blood pressure, were included in the study. Endothelial function was assessed by ultrasound and a sample of urine was collected for determination of ACE isoforms. In the presence of a family history of hypertension and detection of 90 kDa ACE, we noted a maximal flow mediated dilation of 12.1 +/- 5.0 vs 16.1 +/- 6.0% in those without a previous history of hypertension and lacking urinary 90 kDa ACE (P < 0.05). In subjects with a family history of hypertension and presenting 90 kDa ACE, there were lower levels of HDL-cholesterol (P < 0.05) and higher levels of triglycerides (P < 0.05). Subjects with 90 kDa ACE irrespective of hypertensive history presented a trend for higher levels of triglycerides and HDL-cholesterol (P = 0.06) compared to subjects without 90 kDa ACE. Our data suggest that the 90 kDa ACE may be a marker for hypertension which may be related to the development of early atherosclerotic changes.

Assessment of Factors Determining Graft Size in Transplant of Cadaver Kidneys From Child Donors

BACKGROUND Kidneys from child donors are very efficient at adapting to the recipient organism. This research aims to verify the size of kidney grafts from pediatric donors after transplant and to identify factors responsible for the size attained by these kidneys. Moreover, it aims to seek relationships between size and function of the transplanted pediatric kidney. METHODS Seventy-seven renal transplants performed at least 6 months earlier, with cadaver donor 15 years old or younger, had ultrasound measurements of the graft and renal function assessment. Potential factors for graft volume were analyzed using bivariate analysis, followed by multiple linear regression. RESULTS After a follow up of 4.2+/-3.3 years posttransplant, the grafts presented the following range of measures: length 10.61+/-1.13 cm, width 4.67+/-0.84 cm, and depth 4.76+/-0.99 cm. Graft volumes were 126.62+/-47.76 cm. Bivariate analysis showed that (1) age of both donor and recipient at transplantation; (2) sex of recipient; (3) occurrence of acute rejection episodes were statistically significant. After multivariate analysis, age and sex of recipients were the only significant factors influencing graft volume; child kidneys reached greater volumes when transplanted into adult and male individuals. Larger volume kidneys presented significantly more proteinuria. No difference was evident with regard to creatinine clearance values or urinary retinol binding protein among kidneys of differing sizes. CONCLUSIONS The size of the recipient (age and sex) is the main factor responsible for volumes achieved by kidneys from pediatric donors. The volume attained by these kidneys demonstrated no relationship with glomerular or tubular function of the organ.

Efectos de diferentes grados de sensibilidad a la insulina en la función endotelial de pacientes obesos

BACKGROUND Obesity derived from intra-abdominal fat deposition tends to increase hormonal and cytokine production, thus worsening insulin sensitivity and leading to endothelial dysfunction. Hyperinsulinemia is considered an independent risk factor for ischemic heart disease and cause of endothelial dysfunction in healthy individuals. OBJECTIVE To assess the impact of different degrees of insulin resistance, measured by HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), on endothelial function in obese, non-diabetic patients without prior history of cardiovascular events and different metabolic syndrome components. METHODS Forty obese individuals were submitted to anthropometric measurements, BP measurements at office and ABPM and laboratory tests, in addition to non-invasive ultrasound assessment of endothelial function. Patients were divided into 3 groups according to the level of insulin resistance: patients with HOMA-IR values from 0.590 to 1.082 were assigned to Group 1 (n=13), from 1.083 to 1.410 to Group 2 (n=14) and from 1.610 to 2.510 to Group 3 (n=13). RESULTS We found a significant difference in flow-mediated dilation in group 3 compared to group 1 (9.2 ± 7.0 vs 18.0 ± 7.5 %, p=0.006). There was a negative correlation between endothelial function and insulin, HOMA-IR and triglycerides. CONCLUSION Our data suggest that mild changes in insulin resistance levels assessed by HOMA-IR may have an impact on vasodilatatory endothelial function in uncomplicated obese individuals with different cardiovascular risk factors.FUNDAMENTO: A obesidade derivada da deposicao de gordura intra-abdominal tende a aumentar a producao de hormonios e citoquinas, piorando a sensibilidade a insulina e levando a disfuncao endotelial. A hiperinsulinemia e considerada um fator de risco independente para doenca isquemica cardiaca e e uma causa de disfuncao endotelial em individuos saudaveis. OBJETIVO: Avaliar o impacto de diferentes graus de resistencia a insulina, medida pelo HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), sobre a funcao endotelial de obesos, pacientes nao diabeticos, sem historia previa de eventos cardiovasculares e diversos componentes da sindrome metabolica. METODOS: Um total de 40 individuos obesos foi submetido a medidas antropometricas, pressao arterial de consultorio, MAPA e exames laboratoriais, alem de avaliacao ultrassonografica nao invasiva da funcao endotelial. Os pacientes foram divididos em tres grupos de acordo com o grau de resistencia a insulina: pacientes com valores de HOMA-IR entre 0,590 e 1,082 foram incluidos no Grupo 1 (n = 13); entre 1,083 e 1,410 no Grupo 2 (n = 14); e entre 1,610 e 2,510 no Grupo 3 (n = 13). RESULTADOS: Encontramos uma diferenca significativa na vasodilatacao mediada por fluxo no Grupo 3 em relacao ao Grupo 1 (9,2 ± 7,0 vs 18,0 ± 7,5 %, p = 0,006). Houve uma correlacao negativa entre a funcao endotelial e insulina, HOMA-IR e triglicerides. CONCLUSAO: Nosso estudo sugere que leves alteracoes nos niveis de resistencia a insulina avaliada pelo HOMA-IR podem causar algum impacto sobre a funcao vasodilatadora do endotelio em individuos obesos nao complicados com diferentes fatores de risco cardiovascular.