Bruna Guida

Early Changes in Bioelectrical Estimates of Body Composition in Chronic Kidney Disease

The aim of this study was to detect the potential occurrence of early abnormalities of body composition in patients with chronic kidney disease (CKD) at first referral to an outpatient nephrology clinic. Eighty-four patients with CKD (49 men and 35 women) were compared with 604 healthy control subjects (298 men and 306 women). Anthropometry and bioelectrical impedance analysis (BIA) were performed in all participants, whereas renal function, laboratory tests for nutritional status, and nutrient intake were assessed in the CKD group only. Creatinine clearance was 27.8 +/- 13.8 and 27.4 +/- 13.0 ml/min per 1.73 m(2) in male and female patients with CKD, respectively. No patient showed peripheral edema; frank malnutrition, defined by presence of serum albumin <3.5 g/dl plus body mass index <20 kg/m(2); or protein intake <0.6 g/kg per d. At the BIA, patients with CKD showed lower resistance (R) and abnormal mean impedance vectors for the bivariate normal distribution of R/height and reactance/height. Phase angle also was reduced (-22%), especially in patients with diabetes. When BIA-derived data were considered, total body water was slightly higher (+4.3% in men; +3.5% in women) and body cell mass was lower (-6.7% in men; -7.7% in women) in patients with CKD. No difference in either BIA parameters or nutritional indexes was observed among various CKD stages. Despite the absence of overt malnutrition, patients with CKD exhibit altered BIA variables from the early phases of renal disease. These alterations are related to the renal dysfunction, are more marked in the presence of diabetes, and mainly indicate the presence of overhydration in the absence of edema. Therefore, BIA represents an attractive clinical tool to detect impairment of body composition from the early stages of CKD.

Effect of short-term synbiotic treatment on plasma p-cresol levels in patients with chronic renal failure: A randomized clinical trial

BACKGROUND AND AIMS In patients with chronic kidney disease (CKD), alterations in gut microbiome are posited to be responsible for gastrointestinal symptoms and generation of p-cresol, a uremic toxin that has been associated with CKD progression and cardiovascular mortality. This pilot study investigated whether Probinul-neutro®, a synbiotic that normalizes intestinal microflora, may lower plasma p-cresol concentrations and reduce gastrointestinal symptoms in non-dialyzed CKD patients. METHODS AND RESULTS This was a double-blind, randomized placebo-controlled trial. Thirty patients on 3-4 CKD stages were randomized to receive either Probinul neutro® or placebo for 4 weeks. Total plasma p-cresol concentration was assessed at baseline, and 15 and 30 days after treatment start. At the same study times, ease and frequency of defecation, upper and lower abdominal pain, stool shape, borborygmi, and flatus were quantified by subjective assessment questionnaires. Compared to baseline total plasma p-cresol median concentrations on 15th and 30th day were significantly lower in patients receiving Probinul-neutro® (2.31 and 0.78 vs. 3.05 μg/ml, p < 0.05; n = 18); no changes of plasma p-cresol concentrations were recorded in placebo-treated patients. No significant changes in gastrointestinal symptoms were observed during the study both in Probinul-neutro®-treated and placebo-treated patients. CONCLUSION Probinul-neutro® lowered total plasma p-cresol concentrations but did not ameliorate gastrointestinal symptoms in non-dialyzed CKD patients. Because high plasma concentrations of p-cresol in early phases of CKD are predictive of progression to end-stage renal disease, the results of our study suggest that synbiotics deserve attention as possible tools to delay CKD progression towards end-stage renal disease (ESRD). CLINICALTRIALSGOV IDENTIFIER NCT02008331.

Myocardial fibrosis and diastolic dysfunction in patients on chronic haemodialysis

BACKGROUND Left ventricular (LV) diastolic dysfunction is linked to myocardial collagen content in many cardiac diseases. There are no data regarding such relationship in patients with end-stage renal disease (ESRD) undergoing haemodialysis. METHODS Twenty-five patients with ESRD undergoing haemodialysis were studied by echocardiography. LV diastolic function was investigated by Doppler echocardiography, by analysing LV filling velocities at rest and during loading manoeuvres, which represent an estimate of LV filling pressure. According to the Doppler pattern, LV filling pressure in a given patient was judged to be normal or slightly increased or to be moderately or severely increased. The presence of myocardial fibrosis was estimated by ultrasound tissue characterization with integrated backscatter, which in diastole correlates with the collagen content of the myocardium. RESULTS Integrated backscatter was higher in patients with moderate or severely increased than in patients with normal or slightly increased LV filling pressure (integrated backscatter: 51.0 +/- 9.8 vs 41.6 +/- 5.6%; P = 0.008). Integrated backscatter was a strong and independent determinant of diastolic dysfunction (odds ratio = 1.212; P = 0.040). CONCLUSION Our data support the hypothesis that, in a selected population of patients with ESRD undergoing haemodialysis, myocardial fibrosis is associated with LV diastolic myocardial properties.

Growth hormone status in morbidly obese subjects and correlation with body composition

Morbidly obese subjects are characterized by multiple endocrine abnormalities and these are paralleled by unfavorable changes in body composition. In obese individuals, either 24-h spontaneous or stimulated GH secretion is impaired without an organic pituitary disease and the severity of the secretory defect is proportional to the degree of obesity. The GHRH+arginine (GHRH+ARG) test is likely to be the overall test of choice in clinical practice to differentiate GH deficiency (GHD) patients. Similarly to other provocative tests, GHRH+ARG is influenced by obesity per se. Therefore, a new cut-off limit of peak GH response of 4.2 µg/l in obese subjects has been recently assumed. The aim of the present study was to investigate the reciprocal influence between decreased GH secretion and body composition in a group of 110 morbidly obese subjects, using the new cut-off limit of peak GH response to GHRH+ARG test for these subjects. In our study, GHD was identified in 27.3% of the obese subjects, without gender difference. In GDH obese subjects body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), fat mass (FM), and resistance (R) were higher while reactance (Xc), phase angle, body cell mass (BCM), IGF-I, or IGF-I z-scores were lower than in normal responders (p<0.001). In all obese subjects, GH peak levels showed a negative correlation with age, BMI, waist circumference and FM, and a positive correlation with IGF-I. In the stepwise multiple linear regression, waist circumference and FM were the major determinants of GH peak levels and IGF-I. In conclusion, using the new cut-off limit of peak GH response to GHRH+ARG test for obese subjects, about 1/3 morbidly obese subjects were GHD. GHD subjects showed a significantly different body composition compared with normal responders, and the secretory defect was correlated to different anthropometric variables with waist circumference and FM as the major determinants.

Energy-restricted, n-3 polyunsaturated fatty acids-rich diet improves the clinical response to immuno-modulating drugs in obese patients with plaque-type psoriasis: a randomized control clinical trial

BACKGROUND & AIMS Low-grade systemic inflammation associated with obesity may worsen the clinical course of psoriasis. This study aimed to assess the effectiveness of an energy-restricted diet, enriched in n-3 polyunsaturated fatty acids (PUFAs) and poor in n-6 PUFAs, on metabolic markers and clinical outcome of obese patients with psoriasis. METHODS Forty-four obese patients with mild-to-severe plaque-type psoriasis treated with immuno-suppressive drugs were randomized to assume for six months either their usual diet or an energy-restricted diet (20 kcal/kg/ideal body weight/day) enriched of n-3 PUFAs (average 2.6 g/d). All patients continued their immuno-modulating therapy throughout the study. RESULTS At 3 and 6 months, a significant clinical improvement was observed in patients assuming the low-calorie high n-3 PUFAs diet respect to controls. Specifically Psoriasis Area Score Index (7.7 ± 3.7, 5.3 ± 4.3 and 2.6 ± 3.0, respectively; p < 0.05), itch scores (15.4 ± 13.5, 12.3 ± 12.1 and 1.8 ± 5.9, respectively; p < 0.05) and Dermatological Life Quality Index (19.5 ± 1.9, 11.4 ± 3.5 and 5.1 ± 1.6; respectively, p < 0.05) all decreased respect to baseline. In these subjects but not in controls, a significant decrease in body weight (93.8 ± 10.1, 85.8 ± 11.4 and 83.1 ± 12.1 kg, respectively; p < 0.05), waist circumference (112.7 ± 7.2, 106.1 ± 10.3 and 101.9 ± 10.4 cm; p < 0.05), serum triglycerides (141.8 ± 51.1, 100.5 ± 26.6 and 90.2 ± 34.5 mg/dL; respectively, p < 0.05), serum total cholesterol (198.3 ± 31.7, 171.4 ± 29.0 and 176.5 ± 20.5 mg/dL; respectively, p < 0.05) and n-6/n-3 ratio intake also occurred (5.1 ± 0.9, 2.0 ± 0.9 and 2.3 ± 1.1; respectively, p < 0.05). CONCLUSIONS In obese psoriatic patients, an energy-restricted diet designed to increase n-3 and reduce n-6 PUFAs, ameliorated the metabolic profile and, by increasing the response to immuno-modulating therapy, improved the clinical outcomes of the disease (ClinicalTrials.gov identifier: NCT01876875).

Impedance vector distribution by body mass index and conventional bioelectrical impedance analysis in obese women.

BACKGROUND AND AIM To compare the body fluid status assessments provided by conventional bioelectrical impedance analysis (BIA) and vector BIA in moderate and severe obesity. METHODS AND RESULTS We studied 516 normotensive Caucasian women (mean age: 48 +/- 9.2 years), who were age-matched and divided into four groups on the basis of their body mass index (BMI): 99 normal weight women with a BMI of 19-25 Kg/m2; 228 preobese overweight women with a BMI of 25-30 Kg/m2; 132 women with class I-II obesity (BMI: 30-35 Kg/m2), and 57 women with class III obesity (BMI: 40-64 Kg/m2). Single-frequency (50 kHz) tetrapolar (hand-foot) bioelectrical impedance measurements were made, and total body water (TBW) and extracellular water (ECW) were estimated using conventional BIA regression equations. The RXc graph method was used for vector BIA, with the set of 327 women with a BMI of 19-30 Kg/m2 being adopted as the reference population. Mean vector displacement followed a definite pattern, with progressive vector shortening as the BMI increased, and along a fixed phase angle. This pattern indicates more TBW due to a greater soft tissue mass with average normal hydration. Short and downsloping vectors indicating fluid overload were more frequent in the group with class III obesity than in the group with class I obesity (19 vs 5%). The absolute values of TBW and ECW were significantly higher in the obese and overweight subjects than in those with normal weight subjects. TBW as a percentage of body weight was significantly lower in the obese subjects. CONCLUSIONS BMI influenced the impedance vector distribution pattern, which proved to be consistent up to a BMI of 64 Kg/m2. Obese women with an altered body composition can be identified and monitored using vector BIA.

NOX signaling in molecular cardiovascular mechanisms involved in the blood pressure homeostasis

Blood pressure homeostasis is maintained by several mechanisms regulating cardiac output, vascular resistances, and blood volume. At cellular levels, reactive oxygen species (ROS) signaling is involved in multiple molecular mechanisms controlling blood pressure. Among ROS producing systems, NADPH oxidases (NOXs), expressed in different cells of the cardiovascular system, are the most important enzymes clearly linked to the development of hypertension. NOXs exert a central role in cardiac mechanosensing, endothelium-dependent relaxation, and Angiotensin-II (Ang-II) redox signaling regulating vascular tone. The central role of NOXs in redox-dependent cardiovascular cell functions renders these enzymes a promising pharmacological target for the treatment of cardiovascular diseases, including hypertension. The aim of the present review is to focus on the physiological role of the cardiovascular NOX-generating ROS in the molecular and cellular mechanisms affecting blood pressure.

Plasma p-Cresol Lowering Effect of Sevelamer in Peritoneal Dialysis Patients: Evidence from a Cross-Sectional Observational Study

p-Cresol is a by-product of the metabolism of aromatic aminoacid operated by resident intestinal bacteria. In patients with chronic kidney disease, the accumulation of p-cresol and of its metabolite p-cresyl-sulphate causes endothelial dysfunction and ultimately increases the cardiovascular risk of these patients. Therapeutic strategies to reduce plasma p-cresol levels are highly demanded but not available yet. Because it has been reported that the phosphate binder sevelamer sequesters p-cresol in vitro we hypothesized that it could do so also in peritoneal dialysis patients. To explore this hypothesis we measured total cresol plasma concentrations in 57 patients with end-stage renal disease on peritoneal dialysis, 29 receiving sevelamer for the treatment of hyperphosphatemia and 28 patients not assuming this drug. Among the patients not assuming sevelamer, 16 were treated with lanthanum whereas the remaining 12 received no drug because they were not hyperphosphatemic. Patients receiving sevelamer had plasma p-cresol and serum high sensitivity C-reactive protein concentrations significantly lower than those receiving lanthanum or no drug. Conversely, no difference was observed among the different groups either in residual glomerular filtration rate, total weekly dialysis dose, total clearance, urine volume, protein catabolic rate, serum albumin or serum phosphate levels. Multiple linear regression analysis showed that none of these variables predicted plasma p-cresol concentrations that, instead, negatively correlated with the use of sevelamer. These results suggest that sevelamer could be an effective strategy to lower p-cresol circulating levels in peritoneal dialysis patients in which it could also favorably affect cardiovascular risk because of its anti-inflammatory effect.

Evidence on the prevalence and geographic distribution of major cardiovascular risk factors in Italy.

OBJECTIVE To assess the prevalence and geographic distribution of major cardiovascular risk factors in a large community-wide sample of the Italian population. DESIGN A cross-sectional survey. Standardized methods were used to collect and measure cardiovascular risk factors. Data were adjusted for survey weightings. Qualitative and quantitative variables were compared with parametric and non-parametric tests, as appropriate. SETTING Towns (n 193) across different Italian regions. SUBJECTS Unselected adults (n 24 213; 12 626 men; 11 587 women) aged 18-98 years (mean age 56·9 (sd 15·3) years), who volunteered to participate in a community-wide screening programme over a 2 d period in 2007. RESULTS Overall, the prevalence of major cardiovascular risk factors was: obesity, 22·7 % (women 18·9 %, men 26·1 %); overweight, 44·7 % (women 31·6 %, men 56·7 %); hypertension, 59·6 % (women 48·3 %, men 70·0 %); dyslipidaemia, 59·1 % (women 57·7 %, men 60·3 %); diabetes, 15·3 % (women 11·2 %, men 19·0 %) and smoking, 19·8 % (women 14·0 %, men 25·2 %). We found a high prevalence of unhealthy eating habits; fruit and vegetable consumption was below the recommended range in 60 % of the study population. Ninety per cent of the study population had more than one cardiovascular risk factor and 84 % had between two and five cardiovascular risk factors. There were differences among Italian macro-areas mainly for obesity, hypertension, dyslipidaemia and diabetes. CONCLUSIONS The study provides alarming evidence on current prevalence data for major cardiovascular risk factors in a large sample of the Italian population. Particularly, obesity and hypertension represent a relevant public health problem. There is a pressing need for effective preventive health measures which must also take into account the differences among Italian macro-areas.

Role of dehydroepiandrosterone sulfate levels on body composition after laparoscopic adjustable gastric banding in pre-menopausal morbidly obese women

In humans, dehydroepiandrosterone (DHEAS) has been postulated to have anabolic and lipolytic properties that could potentially counteract the catabolic effect of cortisol. DHEAS secretion is reduced in morbid obesity, likely due to hyperinsulinemia, and laparoscopic adjustable gastric banding (LASGB), by inducing considerable and rapid weight loss, reduces insulin levels. To investigate the role of decreased insulin levels after LASGB-induced weight loss on DHEAS levels and on body composition changes, we studied 30 pre-menopausal morbidly obese women (BMI ranging 37–62 kg/m2) before, 6, 12 and 24 months after LASGB. Total body water (TBW), fat-free mass (FFM) and fat mass (FM) were measured by bioelectrical impedance analysis; tissue hydration was also assessed by impedance vector analysis. At study ending, the subjects had a total weight loss of 28% of baseline body weight (15% after 6 months). After LASGB, weight loss was mainly due to decreased FM, and TBW, FFM, and body hydration were not significantly reduced. Weight loss was associated with an 82% rise in serum DHEAS already after 6 months while cortisol, cortisol/DHEAS molar ratio, and insulin levels fell by 5.5, 62 and 50%, respectively, after 6, 12 and 24 months (p<0.05). Conclusions: LASGB associated with a well balanced low-calorie diet permits a satisfactory 2-yr weight loss, sparing FFM and without body fluid alterations. As the result of a stable weight reduction program weight loss is associated to decrease in cortisol, cortisol/DHEAS molar ratio, and insulin plasma levels with marked rise in DHEAS. Higher cortisol/DHEAS molar ratio values at baseline are also associated to lower weight loss after LASGB, with lower decrease in FM and higher reduction in FFM and body cell mass, in spite of no differences in dietary regimes. Cortisol/DHEAS molar ratio is likely to represent a reliable marker of favourable modifications in body composition.