URIC ACID LEVELS CORRELATES WITH INFLAMMATORY MARKERS AND ADHESION MOLECULES IN HEMODIALYSIS PATIENTS

Elevated serum uric acid has been associated to a variety of cardiovascular disease states and with systemic inflammation. The aim of this study was to analyze the association between uric acid levels and inflammatory markers in hemodialysis (HD) patients. This cross-sectional study included 50HD patients (62% men, 54.3±12.6 yrs, BMI 24.4±4Kg/m2) and 21 healthy individuals (45% men, 50.7±15.7 yrs, BMI 25.5±4.0Kg/m2). Uric acid was measured using uricase-PAP method, inflammatory (TNF-α, IL-6 and CRP) and atherosclerosis markers (ICAM-1, VCAM-1, MCP-1 and PAI-1) were measured by a multiplexed particle-based flow cytometric assay. There was a positive correlation between serum uric acid and inflammatory markers, IL-6 (r=0.30, p=0.01), CRP (r=0.37, p=0.003), TNF-α (r=0.40, p=0.001) and adhesion molecules levels, ICAM-1 (r=0.53, p=0.0001), and VCAM-1 (r=0.45, p=0.0001)ParametersHD PatientsHealthy individualsCRP (mg/mL)0.32 ± 0.30*0.11 ± 0.12TNF-α (pg/mL)5.5 ± 2.1*2.4 ± 1.1IL-6 (pg/mL)4.1 ± 1.6*2.7 ± 0.4PAI-1 (ng/mL)7.0 ± 2.76.2 ± 2.1MCP-1 (pg/ml)47.6 ± 24.237.3 ± 19.0VCAM-1 (ng/mL)48.5 ± 8.5*23.8 ± 5.5ICAM-1 (ng/mL)20.5 ± 15.9*7.2 ± 1.2⁎p<0.05In conclusion, these original data suggest that uric acid may have a role in inflammation and atherosclerosis in HD patient

Electronegative LDL in chronic renal patients under hemodialysis and peritoneal dialysis and its relationship with nutritional status

A modificação oxidativa da LDL possui um papel crucial na patogênese da aterosclerose que é uma das principais causas de mortalidade nos pacientes renais crônicos. Uma subfração de LDL modificada in vivo, denominada LDL eletronegativa (LDL-), é formada a partir de modificações da parte protéica (ApoB100) e lipídica (fosfolípides, triglicérides e colesterol) da LDL induzidas por diversos mecanismos. A LDL (-) tem menor afinidade pelos receptores da LDL, é citotóxica para células endoteliais e apresenta atividade pró-inflamatória, quando comparada à LDL nativa. Com o objetivo de investigar as alterações do estado nutricional relacionadas à formação da LDL(-) nos pacientes renais crônicos, analisou-se neste estudo as concentrações plasmáticas de LDL(-), anticorpos IgG anti-LDL(-) e seus imunocomplexos em pacientes sob hemodiálise (HD, n=25) ou sob diálise peritoneal (DP, n=11) e indivíduos saudáveis (grupo controle, n=10), relacionando-as ao perfil lipídico e às concentrações plasmáticas de &#945;-tocoferol e ascorbato. Os resultados mostraram que a concentração de LDL(-) foi maior (p&#60;0.01) nos pacientes hemodialisados (575,6&#177;233,1&#181;g/mL) quando comparados aos pacientes submetidos à diálise peritoneal (223,4&#177;117,5 &#181;g/mL) e aos controles (54,9&#177;33,3&#181;g/mL). Os níveis de anticorpos IgG anti-LDL(-) foram mais elevados (p&#60;0,00001) nos controles (O,36&#177;0,09&#181;g/mL), quando comparados aos pacientes DP (0,28&#177;0,12&#181;g/mL) e HD (0,2&#177;0,1 &#181;g/mL). As concentrações dos imunocomplexos no grupo controle (0,35&#177;0,20&#181;g/mL) foram significativamente maiores comparadas às dos grupos HD (0,15&#177;0,07&#181;g/mL) e DP (0,22&#177;0,07&#181;g/mL). Não houve diferença das concentrações plasmáticas de ascorbato e de alfa-tocoferol (normalizada pela concentração de colesterol) nos grupos estudados. A maioria da população estudada estava eutrófica, segundo o índice de massa corpórea (IMG). Conclui-se que as concentração de LDL(-) nos pacientes HD e DP foram significativamente mais elevadas, enquanto os níveis de anticorpos IgG anti-LDL(-) foram menores, nos pacientes HD e DP comparados ao grupo controle. As análises de correlação demonstraram que os valores de prega cutânea tricipital (PCT) se correlacionaram diretamente com as concentrações plasmáticas dos imunocomlexos (r= 0,37; p= 0,01) e inversamente com as concentrações plasmáticas de LDL(-) (r= - 0.37; p= 0,018). As concentrações plasmáticas dos anticorpos anti-LDL(-) se correlacionaram diretamente com os valores do IMC (r= 0,83 p=0,00001) e da circunferência da cintura (r= 0,75 p= 0,0001).A minimally modified form of LDL, with structural ApoB100 modification and lower affinity by LDL receptors, has been described in blood plasma. This circulating modified form of LDL, named electronegative LDL, LDL(-), has increased negative charge, higher cytotoxicity and pro-inflammatory activity as compared to the native LDL. This LDL-is poorly described in hemodialysis and there is no study in peritoneal dialysis patients. Thus, the purpose of this study was to evaluate the relation of the nutritional status with the amount of electronegative LDL (LDL-), its autoantibodies and immune complexes (IC) in dialysed patients. LDL(-), its autoantibodies and IC were determined by ELISA in chronic kidney disease (CKD) patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) and compared to subjects without CKD (controls). Nutritional status, lipid profile and plasma concentrations of alpha-tocopherol, ascorbate and immune complexes (IC) were also evaluated. Results are expressed as median of LDL-(&#181;g/mL) and anti-LDL(-) IgG (OD405 nm). The concentrations of LDL(-) were higher in HD patients (575.6&#177;233.1 &#181;g/mL) as compared to PD (223.4&#177;117.5&#181;g/mL) and control groups (54.9&#177;33.3&#181;g/mL) (p&#60;0.01). The anti-LDL(-) IgG auto-antibodies were elevated in controls (0.36&#177;0.09&#181;g/mL) in relation to PD patients (0.28&#177;0.12&#181;g/mL) and HD patients (0.2&#177;0.1 &#181;g/mL) , (p&#60;0.00001). A negative correlation was observed between anti¬-LDL(-)lgG and LDL(-) levels (r = -0.43; P = 0.003) in the studied groups. The concentrations of le in the control group (0.35&#177;0.20&#181;g/mL) were higher compared with HD (0.15&#177;0.07&#181;g/mL) and PD (0.22&#177;0.07&#181;g/mL) groups. No differences were found for the plasma levels of ascorbate and alpha-tocopherol (normalized by cholesterol concentration) among the studied groups The body mass index (BMI) was normal in the majority of the studied subjects. The highest LDL(-) concentrations were found in HD patients, and for the first time, we showed that PD patients also have high levels of LDL(-) when compared with non-CKD subjects. The levels of anti-LDL(-) IgG in CKD patients were lower compared to controls. The correlation analysis showed that the values for triceps skin fold were positively correlated with blood plasma concentrations of IC (r= 0.37; p=0.01) and negatively correlated with LDL(-) concentrations (r= - 0.37; P 0.018). The concentrations of anti-LDL(-) autoantibodies were directly ·correlated with BMI (r= 0.83 p=0.00001) and waist circunference (r= 0.75 p= 0.0001)

Electronegative LDL in chronic renal patients under hemodialysis and peritoneal dialysis and its relationship with nutritional status

A modificação oxidativa da LDL possui um papel crucial na patogênese da aterosclerose que é uma das principais causas de mortalidade nos pacientes renais crônicos. Uma subfração de LDL modificada in vivo, denominada LDL eletronegativa (LDL-), é formada a partir de modificações da parte protéica (ApoB100) e lipídica (fosfolípides, triglicérides e colesterol) da LDL induzidas por diversos mecanismos. A LDL (-) tem menor afinidade pelos receptores da LDL, é citotóxica para células endoteliais e apresenta atividade pró-inflamatória, quando comparada à LDL nativa. Com o objetivo de investigar as alterações do estado nutricional relacionadas à formação da LDL(-) nos pacientes renais crônicos, analisou-se neste estudo as concentrações plasmáticas de LDL(-), anticorpos IgG anti-LDL(-) e seus imunocomplexos em pacientes sob hemodiálise (HD, n=25) ou sob diálise peritoneal (DP, n=11) e indivíduos saudáveis (grupo controle, n=10), relacionando-as ao perfil lipídico e às concentrações plasmáticas de &#945;-tocoferol e ascorbato. Os resultados mostraram que a concentração de LDL(-) foi maior (p&#60;0.01) nos pacientes hemodialisados (575,6&#177;233,1&#181;g/mL) quando comparados aos pacientes submetidos à diálise peritoneal (223,4&#177;117,5 &#181;g/mL) e aos controles (54,9&#177;33,3&#181;g/mL). Os níveis de anticorpos IgG anti-LDL(-) foram mais elevados (p&#60;0,00001) nos controles (O,36&#177;0,09&#181;g/mL), quando comparados aos pacientes DP (0,28&#177;0,12&#181;g/mL) e HD (0,2&#177;0,1 &#181;g/mL). As concentrações dos imunocomplexos no grupo controle (0,35&#177;0,20&#181;g/mL) foram significativamente maiores comparadas às dos grupos HD (0,15&#177;0,07&#181;g/mL) e DP (0,22&#177;0,07&#181;g/mL). Não houve diferença das concentrações plasmáticas de ascorbato e de alfa-tocoferol (normalizada pela concentração de colesterol) nos grupos estudados. A maioria da população estudada estava eutrófica, segundo o índice de massa corpórea (IMG). Conclui-se que as concentração de LDL(-) nos pacientes HD e DP foram significativamente mais elevadas, enquanto os níveis de anticorpos IgG anti-LDL(-) foram menores, nos pacientes HD e DP comparados ao grupo controle. As análises de correlação demonstraram que os valores de prega cutânea tricipital (PCT) se correlacionaram diretamente com as concentrações plasmáticas dos imunocomlexos (r= 0,37; p= 0,01) e inversamente com as concentrações plasmáticas de LDL(-) (r= - 0.37; p= 0,018). As concentrações plasmáticas dos anticorpos anti-LDL(-) se correlacionaram diretamente com os valores do IMC (r= 0,83 p=0,00001) e da circunferência da cintura (r= 0,75 p= 0,0001).A minimally modified form of LDL, with structural ApoB100 modification and lower affinity by LDL receptors, has been described in blood plasma. This circulating modified form of LDL, named electronegative LDL, LDL(-), has increased negative charge, higher cytotoxicity and pro-inflammatory activity as compared to the native LDL. This LDL-is poorly described in hemodialysis and there is no study in peritoneal dialysis patients. Thus, the purpose of this study was to evaluate the relation of the nutritional status with the amount of electronegative LDL (LDL-), its autoantibodies and immune complexes (IC) in dialysed patients. LDL(-), its autoantibodies and IC were determined by ELISA in chronic kidney disease (CKD) patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) and compared to subjects without CKD (controls). Nutritional status, lipid profile and plasma concentrations of alpha-tocopherol, ascorbate and immune complexes (IC) were also evaluated. Results are expressed as median of LDL-(&#181;g/mL) and anti-LDL(-) IgG (OD405 nm). The concentrations of LDL(-) were higher in HD patients (575.6&#177;233.1 &#181;g/mL) as compared to PD (223.4&#177;117.5&#181;g/mL) and control groups (54.9&#177;33.3&#181;g/mL) (p&#60;0.01). The anti-LDL(-) IgG auto-antibodies were elevated in controls (0.36&#177;0.09&#181;g/mL) in relation to PD patients (0.28&#177;0.12&#181;g/mL) and HD patients (0.2&#177;0.1 &#181;g/mL) , (p&#60;0.00001). A negative correlation was observed between anti¬-LDL(-)lgG and LDL(-) levels (r = -0.43; P = 0.003) in the studied groups. The concentrations of le in the control group (0.35&#177;0.20&#181;g/mL) were higher compared with HD (0.15&#177;0.07&#181;g/mL) and PD (0.22&#177;0.07&#181;g/mL) groups. No differences were found for the plasma levels of ascorbate and alpha-tocopherol (normalized by cholesterol concentration) among the studied groups The body mass index (BMI) was normal in the majority of the studied subjects. The highest LDL(-) concentrations were found in HD patients, and for the first time, we showed that PD patients also have high levels of LDL(-) when compared with non-CKD subjects. The levels of anti-LDL(-) IgG in CKD patients were lower compared to controls. The correlation analysis showed that the values for triceps skin fold were positively correlated with blood plasma concentrations of IC (r= 0.37; p=0.01) and negatively correlated with LDL(-) concentrations (r= - 0.37; P 0.018). The concentrations of anti-LDL(-) autoantibodies were directly ·correlated with BMI (r= 0.83 p=0.00001) and waist circunference (r= 0.75 p= 0.0001)

Há associação entre acyl-grelina e inflamação em pacientes em hemodiálise?

INTRODUÇÃO E OBJETIVOS: Pacientes com doença renal crônica (DRC) apresentam um quadro de anorexia que pode estar relacionado com o processo inflamatório crônico, característico desta população. Assim, o presente estudo teve como objetivo avaliar se há associação entre inflamação e o hormônio orexígeno, acyl-grelina, em pacientes com DRC em hemodiálise (HD). MÉTODOS: Foram estudados 36 pacientes (61,1% homens; 46,7 ± 14,9 anos; IMC 22,9 ± 3,9 kg/m²) em programa regular de HD (65,0 ± 46,8 meses em HD). Os níveis plasmáticos de acyl-grelina e dos marcadores inflamatórios (TNF-α, IL-6 e PCR) foram medidos com o uso do método imunoenzimático (ELISA, Enzyme Linked Immunosorbent Assay). Dados antropométricos foram coletados para avaliação do estado nutricional e a ingestão alimentar foi analisada por meio de recordatório alimentar de 24h de 2 dias. RESULTADOS: Os pacientes apresentaram elevados níveis de IL-6 (83 ± 10 pg/mL), TNF-α (21,06 pg/mL [20,6-40,0]) e PCR (2,7 pg/mL [1,7-3,4]) quando comparados a valores normais. Os níveis plasmáticos de acyl-grelina (18,0 pg/mL [1,3-77,7 pg/mL]) foram baixos comparados com valores de indivíduos saudáveis. Porém, pacientes com elevado IMC (> 25 kg/m²) apresentaram menores concentrações plasmáticas de acyl-grelina (13,6 [1,3-30,5] pg/mL) em relação aos pacientes com IMC < 25 kg/m² (21,7 [7,4-77,7] pg/mL (p < 0,05). Houve correlação negativa entre o IMC e acyl-grelina (r = -0,38; p = 0,02), porém, não houve correlação significativa entre acyl-grelina e os marcadores inflamatórios. CONCLUSÃO: Apesar dos pacientes em HD apresentarem baixas concentrações de acyl-grelina e uma provável resistência a este hormônio, não houve associação entre inflamação e acyl-grelina

Is there association between acyl-ghrelin and inflammation in hemodialysis patients?

INTRODUÇÃO E OBJETIVOS: Pacientes com doença renal crônica (DRC) apresentam um quadro de anorexia que pode estar relacionado com o processo inflamatório crônico, característico desta população. Assim, o presente estudo teve como objetivo avaliar se há associação entre inflamação e o hormônio orexígeno, acyl-grelina, em pacientes com DRC em hemodiálise (HD). MÉTODOS: Foram estudados 36 pacientes (61,1% homens; 46,7 ± 14,9 anos; IMC 22,9 ± 3,9 kg/m²) em programa regular de HD (65,0 ± 46,8 meses em HD). Os níveis plasmáticos de acyl-grelina e dos marcadores inflamatórios (TNF-α, IL-6 e PCR) foram medidos com o uso do método imunoenzimático (ELISA, Enzyme Linked Immunosorbent Assay). Dados antropométricos foram coletados para avaliação do estado nutricional e a ingestão alimentar foi analisada por meio de recordatório alimentar de 24h de 2 dias. RESULTADOS: Os pacientes apresentaram elevados níveis de IL-6 (83 ± 10 pg/mL), TNF-α (21,06 pg/mL [20,6-40,0]) e PCR (2,7 pg/mL [1,7-3,4]) quando comparados a valores normais. Os níveis plasmáticos de acyl-grelina (18,0 pg/mL [1,3-77,7 pg/mL]) foram baixos comparados com valores de indivíduos saudáveis. Porém, pacientes com elevado IMC (> 25 kg/m²) apresentaram menores concentrações plasmáticas de acyl-grelina (13,6 [1,3-30,5] pg/mL) em relação aos pacientes com IMC < 25 kg/m² (21,7 [7,4-77,7] pg/mL (p < 0,05). Houve correlação negativa entre o IMC e acyl-grelina (r = -0,38; p = 0,02), porém, não houve correlação significativa entre acyl-grelina e os marcadores inflamatórios. CONCLUSÃO: Apesar dos pacientes em HD apresentarem baixas concentrações de acyl-grelina e uma provável resistência a este hormônio, não houve associação entre inflamação e acyl-grelina

Apelin in hemodialysis patients: is there relationship with oxidative and inflammation markers?

Inflammation and oxidative stress are importante features associated with pathogenesis of cardiovascular disease in hemodialysis (HD) patients. Apelin is a bioactive peptide involved in a variety of physiological functions that has been associated with inflammation, however; little is known about apelin in chronic kidney disease (CKD). Thus, the purpose of this study was to analyse apelin plasma levels in HD patients and verify if there is any relationship with inflammation and oxidative markers. Twenty-four HD patients (53.6±14.4 years of age, 14 men and body mass index (BMI) of 25.0±4.2 kg/m2) were studied and compared to 15 healthy subjects (51.3±13.5 years of age, 7 men and BMI of 26.3±3.7 kg/m2). Plasma apelin-12 and -36 were measured using the enzyme immunometric assay (EIA) method. Plasma electronegative low density lipoprotein (LDL-) levels were measured using ELISA method. The levels of tumor-necrosis factor-α (TNF-α), interleukin-6, leptin and plasminogen activator inhibitor-1 were measured by a multiplex assay kit and C-reactive protein (CRP) by immunoturbidimetry. There was no difference between apelin-36 levels in HD patients (0.82±0.60 ng/mL) and healthy subjects (0.83±0.23 ng/mL). In contrast, apelin-12 levels were significantly higher in patients, 0.34 ±0.15 ng/mL than in healthy subjects, 0.24± 0.13ng/mL. Inflammation (TNF-α and CRP) and oxidative markers levels (LDL-) were higher in HD patients (5.4±1.3 pg/mL, 0.15 (0.33) mg/dL and 0.19±0.13U/L, respectively); however, there was not correlation among apelin-12 or -36 and inflammatory or oxidative markers. In conclusion, plasma apelin seems to be not associated with inflammatory and oxidative status in HD patients

Association Between Circulating Electronegative Low-Density Lipoproteins and Serum Ferritin in Hemodialysis Patients: A Pilot Study

Background: Iron supplementation is a common recommendation to chronic kidney disease patients undergoing hemodialysis (HD). However, iron excess is closely associated with lipid peroxidation and, it is well known that electronegative low-density lipoproteins (LDL[-]) are present at higher plasma concentrations in diseases with high cardiovascular risk such as chronic kidney disease. Thus, the aim of this study was to investigate whether ferritin levels are associated with LDL(-) levels in HD patients. Design: This was a cross-sectional study. Setting: This study was conducted from a private clinic in Rio de Janeiro, Brazil. Patients: The study included 27 HD patients and 15 healthy subjects. Methods and Procedures: Twenty-seven HD patients (14 men, 58.6 +/- 10 years, 62.2 +/- 51.4 months on dialysis, and body mass index: 24.4 +/- 4.2 kg/m(2)) were studied and compared with 15 healthy individuals (6 men, 53.8 +/- 15.4 years, body mass index: 24.5 +/- 4.3 kg/m(2)). Serum LDL(-) levels were measured using the enzyme-linked immunosorbent assay method; ferritin levels by commercially available kits, and tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein-1, and plasminogen activator inhibitor-1 were determined with a multiplex assay kit manufactured by R&D Systems. Results: The HD patients presented higher LDL(-) and tumor necrosis factor-alpha levels (0.15 +/- 0.13 U/L and 5.9 +/- 2.3 pg/mL, respectively) than healthy subjects (0.07 +/- 0.05 U/L and 2.3 +/- 1.3 pg/mL, respectively) (P = .0001). The mean ferritin level in HD patients was 1,117.5 +/- 610.4 ng/mL, and 90% of patients showed ferritin levels exceeding 500 ng/mL. We found a positive correlation between LDL(-) and ferritin in the patients (r = 0.48; P = .01), and ferritin was a significant contributor to LDL(-) concentrations independent of inflammation. Conclusions: Excess body iron stores for HD patients was associated with signs of increased oxidative stress, as reflected by increased LDL(-) levels in HD patients. (C) 2012 by the National Kidney Foundation, Inc. All rights reserved.FAPERJFAPERJCNPqCNPqNational Institutes of Health (Fogarty International CenterNIHUSA)National Institutes of Health (Fogarty International Center-NIH-USA) [1D43TW00640

Use of tranexamic acid for controlling bleeding in thoracolumbar scoliosis surgery with posterior instrumentation

OBJECTIVE: Scoliosis surgery involves major blood loss and frequently requires blood transfusion. The cost and risks involved in using allogeneic blood have motivated investigation of methods capable of reducing patients' bleeding during operations. One of these methods is to use antifibrinolytic drugs, and tranexamic acid is among these. The aim of this study was to assess the use of this drug for controlling bleeding in surgery to treat idiopathic scoliosis.METHODS: This was a retrospective study in which the medical files of 40 patients who underwent thoracolumbar arthrodesis by means of a posterior route were analyzed. Of these cases, 21 used tranexamic acid and were placed in the test group. The others were placed in the control group. The mean volumes of bleeding during and after the operation and the need for blood transfusion were compared between the two groups.RESULTS: The group that used tranexamic acid had significantly less bleeding during the operation than the control group. There was no significant difference between the groups regarding postoperative bleeding and the need for blood transfusion.CONCLUSIONS: Tranexamic acid was effective in reducing bleeding during the operation, as demonstrated in other studies. The correlation between its use and the reduction in the need for blood transfusion is multifactorial and could not be established in this study. We believe that tranexamic acid may be a useful resource and that it deserves greater attention in randomized double-blind prospective series, with proper control over variables that directly influence blood loss