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.

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/m(2)). 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.

The relationship between apelin and parathyroid hormone in hemodialysis patients.

Both apelin and parathyroid hormone (PTH) are endogenous ligands for G-protein-coupled receptors. Apelin acts as a mitogenic agent for osteoblasts, and metabolic bone abnormalities are frequently seen in hemodialysis (HD) patients because of hyperparathyroidism. The aim of this study was to analyze plasma apelin levels in HD patients and to determine whether they are related to PTH concentrations. A total of 23 HD patients [15 men and 8 women, with a mean (SD) age of 54.2 (4.4) years and a mean body mass index (BMI) of 25.0 (4.1) kg/m(2)] were studied and compared with 15 healthy subjects [6 men and 9 women, with a mean (SD) age of 51.3 (13.6) years and a BMI of 27.0 (4.3) kg/m(2)]. Plasma apelin-36 was measured using an enzyme immunometric assay method and PTH was measured by ELISA. There was no significant difference in apelin levels between the patients [0.80 (0.6) ng/mL] and the healthy subjects [0.83 (0.23) ng/mL]. There was a positive correlation between apelin and PTH (r = 0.66, p = 0.0001). The patients with PTH >300 pg/mL had significantly higher plasma apelin levels [1.17 (0.7) ng/mL] compared with the patients with PTH <300 pg/mL [0.50 (0.15) ng/mL] (p = 0.003). In conclusion, HD patients with secondary hyperparathyroidism have high plasma apelin levels, which suggest that apelin may protect bone in HD patients by acting as an osteoblastic factor.

Is a body mass index of 23 kg/m² a reliable marker of protein-energy wasting in hemodialysis patients?

OBJECTIVE: To evaluate the body composition and inflammatory status in patients on hemodialysis (HD) according to the cutoff of 23 kg/m² for the body mass index (BMI). METHODS: Forty-seven patients (30 men, 11 diabetics, 53.8 ± 12.2 y of age, 58.2 ± 50.9 mo on HD) were studied. Anthropometric data and handgrip strength were evaluated. C-reactive protein, tumor necrosis factor-α, leptin, and interleukin-6 were measured. Mortality was assessed after 24 mo of follow-up. RESULTS: Nineteen patients (40.4%) presented BMI values lower than 23 kg/m² and leptin levels, midarm muscle area, and free-fat mass were significantly lower in these patients. The prevalence of functional muscle loss according to handgrip strength was not different between the BMI groups. The sum of skinfold thicknesses, the percentage of body fat, fat mass, the fat mass/free-fat mass ratio, and waist circumference were significantly lower in patients with a BMI lower than 23 kg/m², but the mean values did not indicate energy wasting. Patients with a BMI higher than 23 kg/m² presented a higher prevalence of inflammation and higher waist circumference and body fat values. The adiposity parameters were correlated with C-reactive protein and leptin. A Cox multivariate regression analysis demonstrated that C-reactive protein, tumor necrosis factor-α, and interleukin-6 predict cardiovascular mortality. CONCLUSION: Patients on HD with a BMI lower than 23 kg/m² did not present signs of energy wasting, whereas those with a BMI higher than 23 kg/m² had more inflammation, probably because of a greater adiposity. Thus, the BMI value of 23 kg/m² does not seem to be a reliable marker of protein-energy wasting in patients on HD.

Apelin: a peptide involved in cardiovascular risk in hemodialysis patients?

Inflammation, oxidative stress, and obesity are important features associated with pathogenesis of cardiovascular disease, a major contributor to the mortality of hemodialysis (HD) patients. Apelin is an adipokine involved in a variety of physiological functions; however, little is known about apelin in chronic kidney disease (CKD). Thus, the purpose of this study was to analyze apelin plasma levels in HD patients and verify whether there is any relationship with inflammation, oxidative markers, and obesity. Twenty-four HD patients [53.6 ± 14.4 years, 14 men, and body mass index (BMI) of 25.0 ± 4.2 kg/m(2)] were studied and compared with 15 healthy subjects (51.3 ± 13.5 years, 7 men, and BMI of 26.3 ± 3.7 kg/m(2)). Plasma apelin-12 and -36 were measured using the enzyme immunometric assay method. Plasma electronegative low-density lipoprotein [LDL(-)] levels were measured using ELISA method, and tumor necrosis factor-α, interleukin-6, leptin, and plasminogen activator inhibitor-1 levels were measured by a multiplex assay kit. C-Reactive protein (CRP) was determined by immunoturbidimetry. Anthropometric data were also evaluated. 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 vs. 0.24 ± 0.13 ng/mL in healthy subjects). TNF-α, CRP, and LDL(-) levels were higher in patients; however, there was no correlation among apelin-12 or -36 and inflammatory or oxidative markers. The adiposity parameters were also not associated with apelin-12 or -36. In conclusion, plasma apelin seems to be not associated with cardiovascular risk in HD patients.

Is zinc-α2-glycoprotein a cardiovascular protective factor for patients undergoing hemodialysis?

BACKGROUND: Zinc-α2-glycoprotein (ZAG) is a lipid mobilizing factor. Its anti-inflammatory action and expression pattern suggest that ZAG could act by protecting against the obesity-associated disorders. In hemodialysis (HD) patients, ZAG levels were described to be elevated but its effects on markers of inflammation and LDL oxidation are still unclear. We investigated the relationship between ZAG and markers of systemic inflammation and LDL atherogenic modification profile in HD patients. METHODS: Forty-three patients regularly on HD were studied and compared to 20 healthy subjects. Plasma ZAG, adiponectin, electronegative LDL [LDL(-)], an atherosclerotic negatively charged LDL subfraction, and anti-LDL(-) autoantibodies levels were measured by ELISA. Markers of inflammation and atherogenic cell recruitment (TNF-α, interleukin-6, VCAM-1, ICAM-1, MCP-1 and PAI-1) were also determined. RESULTS: Inflammatory markers and atherogenic cell recruitment were higher in HD patients when compared to healthy subjects. ZAG levels were also higher in HD patients (151.5 ± 50.1 mg/l vs 54.6 ± 23.0 mg/l; p<0.0001) and its levels were negatively correlated with TNF-α (r=-0.39; p=0.001) and VCAM-1 (r=-0.52; p<0.0001) and, positively correlated with anti-LDL(-) autoantibodies (r=0.38; p=0.016). On multivariate analyses, plasma ZAG levels were independently associated with VCAM-1 (p=0.01). CONCLUSION: ZAG is inversely associated with markers of pro-atherogenic factors linked to systemic inflammation and oxidative stress. Thus, this adipokine may constitute a novel marker of a favorable metabolic profile regarding cardiovascular risk factors in HD population.