Selenium plasma levels in hemodialysis patients: comparison between North and Southeast of Brazil.

INTRODUCTION: Patients with chronic kidney disease present selenium (Se) plasma deficiency which is an essential trace element with important biological functions and, the best known biological role is attributed to its presence in the antioxidant enzyme, glutathione peroxidase (GPx). The Se content of foods depends on soil and some authors have suggested that Amazon soil (North Brazilian region) has high Se concentrations when compared to other regions of Brazil. OBJECTIVE: The objective of this work was to compare the Se status in hemodialysis (HD) patients from North and Southeast of Brazil. METHODS: Thirty-eight patients from Southeast region (22 men and 16 women, 15% diabetic, 53.5 ± 26.4 yrs) were compared to 40 patients from North region (28 men and 12 women, 22.5% diabetic, 63.5 ± 11.9 yrs). Se in plasma was determined through atomic absorption spectrophotometry with hydride generation. RESULTS: The plasma Se levels in patients from Southeast region were significantly lower (17.5 ± 11.9 µg/L) when compared to patients from the North (37.1 ± 15.8 µg/L) (p < 0.001). However, both patient groups presented low Se plasma levels when compared to recommended values (60- 120 µg/L). There was no correlation between plasma Se levels and analyzed parameters. CONCLUSION: We concluded that patients from North (Amazon) region present higher plasma Se levels when compared to the patients from Southeast of Brazil. However, independently of the region, HD patients presented Se deficiency.

Selenium plasma levels in hemodialysis patients: Comparison between North and Southeast of Brazil / Níveis de selênio plasmático em pacientes em hemodiálise: Comparação entre Norte e Sudeste do Brasil

Introduction: Patients with chronic kidney disease present selenium (Se) plasma deficiency which is an essential trace element with important biological functions and, the best known biological role is attributed to its presence in the antioxidant enzyme, glutathione peroxidase (GPx). The Se content of foods depends on soil and some authors have suggested that Amazon soil (North Brazilian region) has high Se concentrations when compared to other regions of Brazil. Objective: The objective of this work was to compare the Se status in hemodialysis (HD) patients from North and Southeast of Brazil. Methods: Thirty-eight patients from Southeast region (22 men and 16 women, 15% diabetic, 53.5 ± 26.4 yrs) were compared to 40 patients from North region (28 men and 12 women, 22.5% diabetic, 63.5 ± 11.9 yrs). Se in plasma was determined through atomic absorption spectrophotometry with hydride generation. Results: The plasma Se levels in patients from Southeast region were significantly lower (17.5 ± 11.9 μg/L) when compared to patients from the North (37.1 ± 15.8 μg/L) (p < 0.001). However, both patient groups presented low Se plasma levels when compared to recommended values (60- 120 μg/L). There was no correlation between plasma Se levels and analyzed parameters. Conclusion: We concluded that patients from North (Amazon) region present higher plasma Se levels when compared to the patients from Southeast of Brazil. However, independently of the region, HD patients presented Se deficiency. .

Introdução: Pacientes com Doença Renal Crônica apresentam deficiência de selênio (Se), um elemento essencial, com importantes funções biológicas, como a de ser componente da enzima antioxidante glutationa peroxidase (GPx). A concentração de Se nos alimentos depende de sua concentração no solo e autores relatam que o solo da Amazônia possui elevados níveis de Se. Objetivo: O objetivo do trabalho foi comparar o estado nutricional do Se em pacientes em hemodiálise (HD) das regiões Norte e Sudeste do Brasil. Métodos: Trinta e oito pacientes da região Sudeste (22 homens e 16 mulheres, 15% diabéticos, 53,5 ± 26,4 anos) foram comparados com 40 pacientes da região Norte (28 homens e 12 mulheres, 22,5% diabéticos, 63,5 ± 11,9 anos). O Se no plasma foi determinado por espectrofotometria de absorção atômica por geração de hidretos acoplados a cela de quartzo. Resultados: Os níveis de Se dos pacientes em HD da região Sudeste foram significativamente menores (17,5 ± 11,9 μg/L) comparados aos pacientes da região Norte (37,1 ± 15,8 μg/L) (p < 0,001). Entretanto, ambos os grupos apresentaram níveis de Se abaixo da recomendação (60-120 μg/L). Não houve associação entre os níveis de Se e os parâmetros analisados. Conclusão: Com base nos resultados, concluímos que os pacientes da região Norte apresentaram elevados níveis de Se quando comparados com os pacientes da região Sudeste do Brasil. Entretanto, independentemente da região, ambos os grupos apresentaram deficiência com relação ao estado nutricional do Se. .

Brazil nut (Bertholletia excelsa, H.B.K.) improves oxidative stress and inflammation biomarkers in hemodialysis patients.

Cumulative evidence indicates that oxidative stress and inflammation frequently occurs in patients undergoing maintenance hemodialysis (HD) and as a result of overproduction of reactive oxygen species (ROS) and a decrease of antioxidant defenses such as selenium (Se). Previous studies in our laboratory showed that the supplementation of 1 unit of Brazil nut (the richest known food source of Se) a day during 3 months is effective to improve Se status and increase glutathione peroxidase (GPx) levels in HD patients. The aim of this study was to evaluate the effect of Brazil nut supplementation on oxidative stress and inflammation markers in HD patients. Forty HD patients from Rio de Janeiro, Brazil were studied. All patients received one nut per day for 3 months. The Se plasma levels and GPx, 8-isoprostane, 8-hydroxy-2-deoxyguanosine (8-OHdG), and cytokine (TNF-α and IL-6) levels and lipid profile were determined before and after 3 months of supplementation. The plasma Se and GPx activity increased, while cytokines, 8-OHdG, and 8-isoprostane plasma levels decreased significantly after 3 months supplementation. HDL-c levels increased and LDL-c levels decreased significantly. These data suggest that the consumption of only one Brazil nut per day during 3 months was effective to reduce the inflammation, oxidative stress markers, and the atherogenic risk, thereby increasing the antioxidant defenses in HD patients. Our results indicate that Brazil nut as Se source plays an important role as an anti-inflammatory and antioxidant agent in HD patients.

Reduced plasma zinc levels, lipid peroxidation, and inflammation biomarkers levels in hemodialysis patients: implications to cardiovascular mortality.

Despite the fact that low plasma zinc (Zn) levels play important roles in the oxidative stress, the relationships between lipid peroxidation and inflammation biomarkers with low plasma Zn levels have not been investigated in chronic kidney disease (CKD) patients. The aim of this study was to evaluate the Zn plasma levels, electronegative LDL [LDL(-)] levels, and inflammation markers as predictors of cardiovascular (CV) mortality in hemodialysis (HD) patients. Forty-five HD patients (28 men, 54.2 ± 12.7 years, 62.2 ± 51.4 months on dialysis and BMI 24.3 ± 4.1 kg/m(2)) were studied and compared to 20 healthy individuals (9 men, 51.6 ± 15.6 years, BMI 25.2 ± 3.9 kg/m(2)) and followed for 24 months to investigate the risks for CV mortality. LDL(-) levels were measured by ELISA, plasma Zn levels by atomic absorption spectrophotometry, C-reactive protein (CRP) level by immunoturbidimetric method, and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1) levels by a multiplex assay kit. HD patients presented low plasma Zn levels (54.9 ± 16.1 µg/dL) and high-LDL(-) (0.18 ± 0.12 U/L) and TNF-α (5.5 ± 2.2 pg/mL) levels when compared to healthy subjects (78.8 ± 9.4µ g/dL, 0.10 ± 0.08U/L, 2.4 ± 1.1 pg/mL, respectively, p < 0.05). Zn plasma levels were negatively correlated to TNF-α (r = -0.49; p = 0.0001) and LDL(-) (r = -0.33; p = 0.008). During the 2 years, 24.4% of the patients died, all due to CV disease. Analysis by the Cox model showed that high CRP, TNF-α, IL-6 levels, and long duration of HD were significant predictors of mortality. In conclusion, reduced Zn levels were associated with lipid peroxidation and inflammation, and we confirm here in a Brazilian cohort of HD patients that inflammation markers are strong predictors of CV death.

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-α, 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-α 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.

Increased electronegative LDL and decreased antibodies against electronegative LDL levels correlate with inflammatory markers and adhesion molecules in hemodialysed patients.

BACKGROUND: Chronic Kidney Disease (CKD) patients present high levels of electronegative LDL (LDL-) that can modulate the expression of molecules involved in inflammation and it is closely linked to atherosclerosis. We investigated the association between LDL(-) and inflammatory markers in patients undergoing hemodialysis (HD). METHODS: Forty-seven HD patients from a private clinic in Rio de Janeiro, Brazil were studied and compared with 20 age matched healthy individuals. Serum LDL(-) and anti-LDL(-) autoantibody levels were measured by ELISA; TNF-α, IL-6, VCAM-1 and ICAM-1 were determined by a multiplex assay kit. RESULTS: HD patients presented higher IL-6 and TNF-α concentrations (4.1 ± 1.6 and 5.5 ± 2.1 pg/ml, respectively) than healthy subjects (2.6 ± 0.2 and 2.4 ± 1.1 pg/ml, respectively) (p=0.0001). In addition, they presented higher VCAM-1 and ICAM-1 levels and, LDL(-) concentrations were also increased (0.18 ± 0.12 U/l) when compared to healthy individuals (0.10 ± 0.08 U/l) (p<0.02). In contrast, the anti-LDL(-) autoantibody levels were lower in HD patients (0.02 ± 0.01 mg/l) than in healthy subjects (0.05 ± 0.03 mg/l) (p<0.001). There was a positive correlation between LDL(-) and IL-6 (r=0.25, p=0.004) and ICAM-1 (r=0.36; p=0.003). There was also a negative correlation between anti-LDL(-) autoantibodies and TNF-α (r=-0.37; p=0.003) and VCAM-1 (r=-0.50; p=0.0001). CONCLUSIONS: The association between LDL(-) and inflammation and the lower levels of anti-LDL(-) autoantibodies are important risk factors related to atherosclerosis in CKD.

Impact of serum albumin and body-mass index on survival in hemodialysis patients.

A low body mass index (BMI) and serum albumin are associated with increased risk of mortality in patients with chronic kidney disease (CKD). The purpose of this study was to evaluate BMI and serum albumin as predictors of all-cause and cardiovascular (CV) mortality in hemodialysed (HD) patients. We describe the results of a five-year retrospective observational study with 187 HD patients (54.9 +/- 15.6 years old, 54% men, and 46% suffering from diabetes) from RenalCor Clinic in Rio de Janeiro, Brazil. The influence of serum albumin levels and BMI (determined every three months) over all-cause mortality was examined using a Cox model, while the influence of the same factors over CV mortality among all-cause mortality was modeled through a logistic regression. During the five years, 26.7% of the patients died, 62% of which due to CV disease (CVD). Analysis by the Cox model showed that low serum albumin and low BMI were significant predictors of mortality. Patients with higher BMI had a lower hazard of death for all-cause mortality (hazard ratio [HR] = 0.92; P ( )= 0.035) and a 1 g/l increase in serum albumin was associated with significantly lower hazard of death (hazard ratio = 0.9679; P < 0.001). The highest BMI value (>30 kg/m(2)) was significantly associated with an increase of odds of CV mortality (odds ratio = 1.22, P = 0.03). We confirm here in a Brazilian cohort of hemodialysis patients that both low BMI (<19 kg/m(2)) and hypoalbuminemia are strong predictors of death.

O papel do tecido adiposo na doença renal crônica: [revisão] / The role of adipose tissue in the chronic kidney disease: [review]

A obesidade em termos epidemiológicos é um fator de risco de mortalidade da população em geral. Todavia, experimentos realizados com pacientesdialisados revelam que a obesidade (índice de massa corporal elevado) pode estar associada à maior sobrevida desses pacientes. Esse fenômeno temsido conceituado como “Epidemiologia Reversa”. Em outra direção, estudos indicam que o tecido adiposo é um órgão complexo com várias outras funçõesalém do armazenamento de energia, pois, secreta um número significante de adipocinas que podem estar envolvidas em processos inflamatórios. Destaforma, o aumento de tecido adiposo pode estar associado à inflamação subclínica e/ou sistêmica nesses pacientes. Se confrontarmos os dados dos estudos sobre obesidade em pacientes renais, percebemos que ainda há muitas controvérsias a respeito da “Epidemiologia Reversa”, pois estes estudos avaliam obesidade apenas pelo IMC, o que não distingue massa magra e massa gorda. Enquanto o efeito de um aumento do IMC determinado por aumento da massa muscular poderia ser protetor, o determinado por aumento do tecido adiposo, ao contrário, poderia associar-se a um maior processo inflamatório.Assim, fica evidente com esta revisão, a necessidade de mais estudos nesta área para se ter um consenso sobre o papel deste tecido na doença renalcrônica.

Although obesity confers an increased risk of mortality in the general population, observational reports on the dialysis population have suggested that obesityis associated with improved survival. Then, the association of high body mass index (BMI) with better survival in chronic kidney disease (CKD) has beenconsidered a "risk factor paradox" or "reverse epidemiology". Adipose tissue is a complex organ with functions far beyond the mere storage of energy and secretes a number of adipokines that could be involved with inflammatory process. It has been proposed that adipose tissue may be a significant contributorto increased systemic and/or low grade inflammation. Until now, there are many controversies about the "reverse epidemiology", because the diagnosis ofobesity in uremic patients is based in a high BMI (a parameter that does not differ between muscle mass or adipose tissue). A raise in BMI due to a musclemass increase could be protective while the one determined by an increase of adipose tissue could be adverse due to the associated low gradeinflammation. In conclusion, more studies are needed in this area before reaching a consensus as to the role of adipose tissue in the chronic kidney disease.