Chronic alteration of circadian rhythm is related to impaired lung function and immune response.

BACKGROUND: Alterations of the circadian rhythm negatively impact several aspects of the health, including the lung function. Chronic shiftwork scale classically induces alterations in the circadian rhythm. However, its effects on pulmonary immune response are unknown. AIMS: To evaluate the impact of chronic alteration of circadian rhythm on pulmonary function and immune response. METHODS: In this context, a 12 × 24 hours and 12 × 48 hours work scale in shiftwork scale policemen (n = 25; 38.73 ± 6.92 years old) were compared with fixed work scale (8 h/d) civil men (n = 25; 34.00 ± 9.60 years old) who were evaluated for perceived stress, sleepiness, physical activity levels, anthropometric characteristics, lung function, pulmonary and systemic cellular and humoral immune response. RESULTS: Policemen presented increased levels of perceived stress (P < .0008), impaired sleepiness (P < .04) and lung function as demonstrated by reduced forced vital capacity (FVC) (P < .053) and FEV1 (P < .043) when compared with civil men. In addition, increased levels of exhaled nitric oxide (P < .037) and of IL-2 (P < .0046) in the breath condensate revealed that policemen presented chronic lung inflammation compared with civil men. Although the whole blood analysis did not showed any differences between the two groups concerning the number of leucocytes, the humoral response revealed that policemen presented increased levels of IL-2 (P < .002) and lower levels of IL-10 (P < .001), clearly displaying a clinical status of low-grade inflammation. CONCLUSIONS: Chronic alteration of circadian rhythm in shiftwork scale policemen results in impaired lung function, beyond to impair pulmonary and systemic immune function.

Protein-Bound Uremic Toxins from Gut Microbiota and Inflammatory Markers in Chronic Kidney Disease.

OBJECTIVE: Protein-bound uremic toxins from gut microbiota tend to accumulate in chronic kidney disease (CKD) patients and are poorly removed by current dialysis techniques. These toxins induce inflammation and are associated with cardiovascular disease (CVD). The aim of this study was to report the relationship between uremic toxins and inflammatory and cardiovascular markers in CKD patients. DESIGN: This was a cross sectional study. SUBJECTS: Twenty-one nondialysis patients were included (43% men, 63.0 ± 7.8 years, glomerular filtration rate: 34.4 ± 12.5 mL/min) as well as 29 hemodialysis (HD) patients [58% men, 52.7 ± 10.3 years, time on dialysis 54 (31-94.5 months)]. MAIN OUTCOME MEASURE: Total levels of uremic toxins (IS, p-CS, and IAA) were assessed by high-performance liquid chromatography with fluorescence detection. C-reactive protein, Interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and calprotectin plasma levels were determined by immunometric assays. RESULTS: HD patients presented higher inflammatory markers and uremic toxins levels than nondialysis patients. IL-6 levels were positively correlated with IS (r = 0.49; P = .03), p-CS (r = 0.35; P = .04) and IAA (r = 0.36; P = .03). A positive correlation was also observed between MCP-1 levels with IS (r = 0.72; P = .001), p-CS (r = 0.48; P = .001) and IAA (r = 0.75; P = .0001). Linear regression showed that IS was an independent predictor for IL-6 and MCP-1 levels after adjustment. CONCLUSION: Plasma uremic toxins were associated with higher IL-6 and MCP-1 levels in CKD patients, potentially playing a role in the development of CVD.

Effects of acute resistance exercise on acyl-ghrelin and obestatin levels in hemodialysis patients: a pilot study.

Chronic physical exercises may be beneficial to modulate appetite hormones as acyl-ghrelin (orexigenic) and obestatin (anorexigenic) in chronic kidney disease (CKD) patients; however, there are no data about the effects of acute exercises on these hormones. Thus, the aim of the present study was to assess the effect of acute resistance exercise on appetite hormones (acyl-ghrelin and obestatin) of patients undergoing hemodialysis (HD). Twenty-five patients (44.7 ± 12.9 years, 68% women) on regular HD program were enrolled into two groups, 16 patients performed exercises and 9 patients comprised the control group. The patients performed the exercises in both lower limbs with ankle-cuffs and elastic bands, 30 min after the initiation of hemodialysis session. Blood samples of both the groups were drawn in the morning before and after 30 min with exercise session (exercise group) and, before and after the same time without exercise (control group). Acyl-ghrelin and obestatin plasma levels were measured using an enzyme immunometric assay. Acyl-ghrelin plasma levels did not change in both the groups. However, when stratified by gender the acyl-ghrelin increased significantly right after exercise in men [32.1 pg/mL (25.6-41.2) to 46.0 pg/mL (39.0-59.5)] (p = 0.04). Obestatin plasma levels reduced after a single bout of exercise and changes remained significantly when the sample was stratified by gender. There was no change in obestatin plasma levels in control group. A single bout of resistance exercise seems to modulate the levels of appetite hormones in HD patients.

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

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, 45 ± 12.8 years, 57 (9-192) months on HD) and 15 patients comprised the control group (66.7% men, 50 ± 10.6 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 3.0 ng/mL (2.3-3.4) to 1.9 ng/mL (0.6-3.4)] and acyl-ghrelin levels increased [from 21.5 pg/mL (1.3-77.7) to 37.2 pg/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 (3.7 ± 0.3 to 3.9 ± 0.2, p < 0.05) improved after exercises. CONCLUSION: Six months of resistance exercises contributed to changes in plasma appetite hormones, body composition, and nutritional status in hemodialysis patients.

Is there interaction between gut microbial profile and cardiovascular risk in chronic kidney disease patients?

AIM: To evaluate the gut microbial profile in chronic kidney disease (CKD) patients and evaluate the possible relationship with inflammation and cardiovascular risk. PATIENTS & METHODS: Markers inflammation plasma and bacterial community profile (denaturing gradient gel electrophoresis) were analyzed. RESULTS: The average number of bands was not different in healthy individuals and CKD patients. The number of bands was negatively associated with plasma levels of VCAM-1 in patients. Flavobacteriaceae bacterium and Listeria monocytogenes were found in patients and Lachnospiraceae bacterium and Butyrivibrio crossotus in healthy individuals. CONCLUSION: Although CKD patients did not present altered gut microbial profile, the sequencing of bands suggested a different microbiota between groups. The result suggests a possible relationship between gut microbiota and cardiovascular risk in CKD patients.

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.

Acyl-ghrelin and obestatin plasma levels in different stages of chronic kidney disease.

OBJECTIVE: This study assessed acyl-ghrelin and obestatin plasma levels in nondialysis chronic kidney disease (CKD) and hemodialysis (HD) patients compared with healthy volunteers. DESIGN: This was a cross-sectional study conducted at Renal Vida Clinic (Rio de Janeiro, Brazil) and Renal Nutrition Ambulatory (Niterói, Brazil). SUBJECTS: Sixty-four subjects were studied: 29 HD patients (55.4 ± 10.5 years, body mass index [BMI], 24.4 ± 3.9 kg/m(2), 17 men); 19 nondialysis patients (59.8 ± 7.5 years, BMI, 26.3 ± 4.8 kg/m(2), glomerular filtration rate, 28.8 ± 10.5 mL/minute/1.73 m(2), 5 men), and 16 healthy volunteers (53.8 ± 5.4 years, BMI, 24.6 ± 2.7 kg/m(2), 7 men). MAIN OUTCOME MEASURE: Acyl-ghrelin and obestatin were assessed using enzyme immunometric assays. Body weight, height, waist circumference (WC), and skinfold were measurement, and body fat percentage, arm muscle area, BMI, and conicity index were calculated. The average daily intake of calories and protein were estimated using a 3-day, 24-hour dietary recall, and the appetite was assessed by the first question of the Hemodialysis Study Appetite Questionnaire. RESULTS: The highest serum acyl-ghrelin (34.1 ± 13.0 pg/mL) and acyl-ghrelin/obestatin ratio (34.0 [6.7-90.2]) were found in nondialysis CKD patients who also presented with the lowest obestatin levels (0.8 [0.30-2.7] ng/mL) when compared with HD patients and healthy volunteers. HD patients presented the highest obestatin plasma levels (3.0 [2.7-3.4] ng/mL) and the lowest acyl-ghrelin/obestatin ratio (P < .05). Obestatin levels inversely correlated with WC (r = -0.6, P < .04) and BMI (r = -0.56, P < .04) in healthy volunteers. CONCLUSION: Although no correlation was found for appetite and food intake with acyl-ghrelin and obestatin in CKD patients, HD patients have the most important alteration of acyl-ghrelin and obestatin plasma levels and had a more impaired nutritional status than nondialysis CKD individuals.

Dietary protein metabolism by gut microbiota and its consequences for chronic kidney disease patients.

The breakdown of proteins and peptides by colonic microorganisms yields a great diversity of end products, including short-chain fatty acids, ammonia, amines, phenols, indoles, thiols, CO2, H2 and H2S, many of which have toxic properties. An increase of the dietary protein load in healthy individuals results in enhanced generation of these toxins, many of which are rapidly cleared by the kidneys. In this regard, the impact upon the colonic microbiota of controlled changes in the dietary protein has not been examined in chronic kidney disease patients. This review focuses on the impact of dietary proteins on the intestinal microbiota and its possible consequences for chronic kidney disease patients.