Julie Calixto Lobo

Role of altered intestinal microbiota in systemic inflammation and cardiovascular disease in chronic kidney disease

The normal intestinal microbiota plays a major role in the maintenance of health and disease prevention. In fact, the alteration of the intestinal microbiota has been shown to contribute to the pathogenesis of several pathological conditions, including obesity and insulin resistance, among others. Recent studies have revealed profound alterations of the gut microbial flora in patients and animals with chronic kidney disease (CKD). Alterations in the composition of the microbiome in CKD may contribute to the systemic inflammation and accumulation of gut-derived uremic toxins, which play a central role in the pathogenesis of accelerated cardiovascular disease and numerous other CKD-associated complications. This review is intended to provide a concise description of the potential role of the CKD-associated changes in the gut microbiome and its potential role the pathogenesis of inflammation and uremic toxicity. In addition, the potential efficacy of pre- and pro-biotics in the restoration of the microbiome is briefly described.

Alpha-tocopherol supplementation decreases electronegative low-density lipoprotein concentration [LDL(−)] in haemodialysis patients

BACKGROUNDnOxidative stress is a significant contributor to cardiovascular diseases (CVD) in haemodialysis (HD) patients, predisposing to the generation of oxidized low-density lipoprotein (oxLDL) or electronegatively charged LDL subfraction. Antioxidant therapy such as alpha-tocopherol acts as a scavenger of lipid peroxyl radicals attenuating the oxidative stress, which decreases the formation of oxLDL. The present study was designed to investigate the influence of the alpha-tocopherol supplementation on the concentration of electronegative low-density lipoprotein [LDL(-)], a minimally oxidized LDL, which we have previously described to be high in HD patients.nnnMETHODSnBlood samples were collected before and after 120 days of supplementation by alpha-tocopherol (400 UI/day) in 19 stable HD patients (50 +/- 7.8 years; 9 males). The concentrations of LDL(-) in blood plasma [using an anti-LDL- human monoclonal antibody (mAb)] and the anti-LDL(-) IgG auto-antibodies were determined by ELISA. Calculation of body mass index (BMI) and measurements of waist circumference (WC), triceps skin folds (TSF) and arm muscle area (AMA) were performed.nnnRESULTSnThe plasma alpha-tocopherol levels increased from 7.9 microM (0.32-18.4) to 14.2 microM (1.22-23.8) after the supplementation (P = 0.02). The mean concentration of LDL(-) was reduced from 570.9 microg/mL (225.6-1241.0) to 169.1 microg/mL (63.6-621.1) (P < 0.001). The anti-LDL(-) IgG auto-antibodies did not change significantly after the supplementation. The alpha-tocopherol supplementation also reduced the total cholesterol and LDL-C levels in these patients, from 176 +/- 42.3 mg/dL to 120 +/- 35.7 mg/dL (P < 0.05) and 115.5 +/- 21.4 mg/dL to 98.5 +/- 23.01 mg/dL (P < 0.001), respectively.nnnCONCLUSIONnThe oral administration of alpha-tocopherol in HD patients resulted in a significant decrease in the LDL(-), total cholesterol and LDL-C levels. This effect may favour a reduction in cardiovascular risk in these patients, but a larger study is required to confirm an effect in this clinical setting.

Electronegative LDL and Lipid Abnormalities in Patients Undergoing Hemodialysis and Peritoneal Dialysis

Background: Oxidative modification of low-density lipoprotein (LDL) has been demonstrated in patients with end-stage renal disease, where it is associated with oxidative stress and plays a key role in the pathogenesis of atherosclerosis. In this context, the generation of minimally oxidized LDL, also called electronegative LDL [LDL(–)], has been associated with active disease, and is a detectable sign of atherogenic tendencies. The purpose of this study was to evaluate serum LDL(–) levels and anti-LDL(–) IgG autoantibodies in end-stage renal disease patients on dialysis, comparing patients on hemodialysis (HD), peritoneal dialysis (PD) and a control group. In addition, the serum lipid profile, nutritional status, biochemical data and parameters of mineral metabolism were also evaluated. Methods: The serum levels of LDL(–) and anti-LDL(–) IgG autoantibodies were measured in 25 patients undergoing HD and 11 patients undergoing PD at the Centro Integrado de Nefrologia, Rio de Janeiro, Brazil. Ten healthy subjects served as a control group. Serum levels of albumin, total cholesterol, triglycerides and lipoproteins were measured. Calculations of subjects’ body mass index and measurements of waist circumference, triceps skin fold and arm muscle area were performed. Measurements of hematocrit, serum blood urea nitrogen, creatinine, parathyroid hormone, phosphorus and calcium were taken. Results: Levels of LDL(–) were higher in HD patients (575.6 ± 233.1 µg/ml) as compared to PD patients (223.4 ± 117.5 µg/ml, p < 0.05), which in turn were higher than in the control group (54.9 ± 33.3 µg/ml, p < 0.01). The anti-LDL(–) IgG autoantibodies were increased in controls (0.36 ± 0.09 µg/ml) as compared to PD (0.28 ± 0.12 µg/ml, p < 0.001) and HD patients (0.2 ± 0.1 µg/ml, p < 0.001). The mean values of total cholesterol and LDL were considered high in the PD group, whereas the mean triceps skin fold was significantly lower in the HD group. Conclusion: Levels of LDL(–) are higher in renal patients on dialysis than in normal individuals, and are reciprocally related to IgG autoantibodies. LDL(–) may be a useful marker of oxidative stress, and this study suggests that HD patients are more susceptible to cardiovascular risk due to this condition. Moreover, autoantibodies reactive to LDL(–) may have protective effects in chronic kidney disease.

Zinc deficiency in chronic kidney disease: is there a relationship with adipose tissue and atherosclerosis?

Cardiovascular complications caused by an accelerated atherosclerotic disease consist the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). These patients present multiple atherosclerotic risk factors, considered traditional, as well as nontraditional risk factors such as inflammation and oxidative stress. These complications are also seen in obesity, in which endothelial dysfunction is one of the early stages of atherosclerosis. The impact of trace metal deficiencies on this process is not well studied in patients with CKD and in obese people, although the influence of trace elements depletion, particularly zinc (Zn), may have significant clinical implications. This brief review describes the functions of Zn as well as the respective role of this trace element in atherosclerosis processes, with a particular emphasis on obese patients with chronic kidney disease.

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 3xa0months 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 3xa0months. 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 3xa0months of supplementation. The plasma Se and GPx activity increased, while cytokines, 8-OHdG, and 8-isoprostane plasma levels decreased significantly after 3xa0months 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 3xa0months 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.

Zinc-α2-Glycoprotein: Is There Association between This New Adipokine and Body Composition in Hemodialysis Patients?

Peptides involved in the regulation of body composition are of interest in hemodialysis (HD) patients because protein wasting associated with high fat mass (FM) is present in these patients. Zinc-α2-glycoprotein (ZAG), a new adipokine, is involved in the regulation of lipid metabolism, adiposity, and energy balance. The purpose of this study was to evaluate ZAG levels and its relationship with body composition and dietary intake in HD patients. Forty-nine HD patients (28 men, 53.1 ± 12.5 years, and BMI 24.0 ± 4.3 kg/m2) were studied and compared with 20 healthy subjects (9 men, 49.5 ± 15.2 years, and BMI 25.6 ± 4.1 kg/m2). Plasma ZAG levels were measured using the ELISA methods and body composition was evaluated through anthropometric data. Dietary intake was assessed 3 days by 24-hour food recall. Although most of the HD patients (59.2%) were eutrophic according to BMI, 92.3% presented high percentage of body fat (BF), and 43.5%, reduced fat-free mass according to midarm muscle circumference values. ZAG levels were ∼2.5-fold higher in HD patients (135.9 ± 40.9 mg/L) compared with healthy individuals (54.6 ± 23.0 mg/L) (p < 0.0001). Circulating ZAG was not associated with dietary intake; however, this peptide was negatively correlated with %BF and, for each 1% reduction in BF, ZAG levels increased by 2.4 mg/L (p = 0.02). In summary, circulating ZAG is increased and inversely correlated with adiposity in HD patients; however, in spite of its higher plasma levels, the majority of HD patients did not show low BF.

Linking Zinc and Leptin in Chronic Kidney Disease: Future Directions

Anorexia is a common complication in patients with chronic kidney disease (CKD) and is associated with the development of malnutrition and an increased risk of mortality. Several compounds are linked to anorexia in these patients; however, the mechanisms are unknown. Zinc (Zn) deficiency is associated with decreased food intake and has been observed in CKD patients. In addition, leptin is an anorexigenic peptide, and patients with CKD present generally high levels of this hormone. Studies have suggested an association between Zn and leptin status in human and rats; however, the results are inconsistent. Some claimed that Zn supplementation does not change leptin release or that there is no significant relationship between Zn and leptin. Others have reported that Zn might be a mediator of leptin production. CKD patients have hyperleptinemia and hypozincemia, but the relationship between Zn deficiency and leptin levels in CKD patients has been poorly understood until now. The aim of this review is to integrate knowledge on leptin and Zn actions to provide a cohesive clinical perspective regarding their interactions in CKD patients.

Effects of resistance exercise training on acyl-ghrelin and obestatin levels in hemodialysis patients.

Abstract Background: Patients undergoing hemodialysis (HD) present altered levels of appetite hormones such as acyl-ghrelin (orexigenic) and obestatin (anorexigenic), which may contribute to anorexia. Physical exercise may affect these hormones and improve appetite in these patients. Objectives: The objective of this study is to evaluate the effects of a resistance exercise program in appetite hormones, body composition, and nutritional status in HD patients. Design: Intervention study with the control group. Subjects: Fifty-two patients on regular HD program were enrolled into two groups: 37 patients performed exercises (56.7% male, 45u2009±u200912.8 years, 57 (9–192) months on HD) and 15 patients comprised the control group (66.7% men, 50u2009±u200910.6 years, 57 (11–153) months on HD). Measurements: Exercise program (performed with elastic bands and ankle cuffs in both lower limbs) was supervised three times a week during 6 months (72 sessions). Patients had their blood drawn in a regular HD day after overnight fasting, before and after 6 months of exercise program. Obestatin, acyl-ghrelin, routine biochemical parameters, quality of life, and anthropometric data were collected and analyzed before and after 6 months. Results: After 6 months of exercise, obestatin levels reduced [from 3.0u2009ng/mL (2.3–3.4) to 1.9u2009ng/mL (0.6–3.4)] and acyl-ghrelin levels increased [from 21.5u2009pg/mL (1.3–77.7) to 37.2u2009pg/mL (16.7–94.1)] and the control group presented no significant differences in both plasma levels of hormones. Body composition and physical functional assessed by SF-36 and albumin levels (3.7u2009±u20090.3 to 3.9u2009±u20090.2, pu2009<u20090.05) improved after exercises. Conclusion: Six months of resistance exercises contributed to changes in plasma appetite hormones, body composition, and nutritional status in hemodialysis patients.

Fructose intake: is there an association with uric acid levels in nondialysis-dependent chronic kidney disease patients?

INTRODUCTIONnFructose intake has increased dramatically in consequence of the consumption of fructose-based sweetened foods and beverages. Research suggests that high fructose intake has a strong association with uric acid (UA) levels and worse prognosis of chronic kidney disease (CKD).nnnOBJECTIVEnThe aim of this study was to investigate the influence of fructose intake on plasma UA levels in nondialysis- dependent CKD patients.nnnMETHODSnFifty-two patients on stages 3-5 (64.2 ± 9.6 years, 24 men, glomerular filtration rate of 30.5 ± 10.3 ml/ min) were divided into two groups: high fructose intake (>50 g/d, n=29, 61.7 ± 9.3 years) and low fructose intake (