Effetti a lungo termine di una dieta a basso versus una dieta a moderato contenuto proteico sulla progressione della insufficienza renale cronica

Background: Whether low protein diet (LPD) regimens as opposed to moderate protein restrictions (MPR) improve long-term survival of Chronic Kidney Disease (CKD) patients or induce protein caloric malnutrition (PCM) remains unknown. Study Design: Intention-to-treat analysis of follow-up data from a randomized controlled trial on the metabolic effects of LPD v MPR (0.55 v 0.80 g/kg/day). Setting & Participants: 423 CKD (Stage 4-5) patients were randomized between January 1999 and January 2003, and followed until December 2006 or death. Outcomes: PCM, dialysis, death or composite outcome of dialysis and death. Measurements: Cox regression was used to model time to dialysis initiation and death as a function of protein regimen while taking into account biochemical and clinical data. Results: The average protein intakes were 0.73±0.04 g/kg/day (Gr-0.55) and 0.9±0.06 g/kg/day (Gr-0.80). After an average follow-up of 32 months (median 30 months, 1st and 3rd quartile: 21 to 39) only three patients met the criteria for PCM. The cumulative incidence of death or dialysis start were unaffected by the diet regimen, with 113 patients reaching the composite outcome: 56 (26%) patients in the Gr-0.55 and 57 (27%) patients in the Gr-0.80. Only 11% of participants died during the study, with 66% and 64% remaining dialysis and death free in the Gr-0.55 and Gr-0.80 respectively. Limitations: Secondary analysis of trial data. Conclusions: Our study shows that (1) the prescription of a low protein diet does not lead to protein wasting; (2) most patients, regularly followed in CKD clinics, remain acceptably compliant to the prescribed dietary protein intake restrictions; and (3) low protein diet does not seem to impact patient outcomes

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

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, that represents more than 95% of circulating p-cresol, causes endothelial dysfunction and ultimately increases the cardiovascular risk of these patients. Therapeutic strategies able to reduce plasma p-cresol levels are highly demanded but unfortunately not available yet. Because it has been reported that the phosphate binder sevelamer also 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 patients, 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. When we compared total p-cresol plasma concentrations in these different groups of patients, we, we found that plasma p-cresol levels were significantly lower in patients receiving sevelamer than in subjects receiving lanthanum or no drug. Patients assuming sevelamer had also lower high sensitivity C-reactive protein serum concentrations compared to patients not assuming this drug. Multiple linear regression analysis showed that Conversely, no difference either in residual glomerular filtration rate, total weekly dialysis dose or serum phosphate levels were observed among the different groups. 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 the cardiovascular risk because of its anti-inflammatory effect

Human Mature Adipocytes Express Albumin and This Expression Is Not Regulated by Inflammation

Aims. Our group investigated albumin gene expression in human adipocytes, its regulation by inflammation and the possible contribution of adipose tissue to albumin circulating levels. Methods. Both inflamed and healthy subjects provided adipose tissue samples. RT-PCR, Real-Time PCR, and Western Blot analysis on homogenates of adipocytes and pre-adipocytes were performed. In sixty-three healthy subjects and fifty-four micro-inflamed end stage renal disease (ESRD) patients circulating levels of albumin were measured by nephelometry; all subjects were also evaluated for body composition, calculated from bioelectrical measurements and an thropometric data. Results. A clear gene expression of albumin was showed in pre-adipocytes and, for the first time, in mature adipocytes. Albumin gene expression resulted significantly higher in pre-adipocytes than in adipocytes. No significant difference in albumin gene expression was showed between healthy controls and inflamed patients. A significant negative correlation was observed between albumin levels and fat mass in both healthy subjects and inflamed ESRD patients. Conclusions. In the present study we found first time evidence that human adipocytes express albumin. Our results also showed that systemic inflammation does not modulate albumin gene expression. The negative correlation between albumin and fat mass seems to exclude a significant contributing role of adipocyte in plasma albumin

Poikiloderma With Neutropenia and Mastocytosis: A Case Report and a Review of Dermatological Signs

Poikiloderma with neutropenia (PN) is a very rare genetic disorder mainly characterized by poikiloderma and congenital neutropenia, which explains the recurrence of respiratory infections and risk of developing bronchiectasis. Patients are also prone to develop hematological and skin cancers. Here, we present the case of a patient, the only child of apparently unrelated Serbian parents, affected by PN resulting from the homozygous mutation NM_024598.3:c.243G>A (p.Trp81Ter) of USB1; early onset of poikiloderma (1 year of age) was associated with cutaneous mastocytosis. We also provide a review of the literature on this uncommon condition with a focus on dermatological findings

Progression of coronary artery calcification and cardiac events in patients with chronic renal disease not receiving dialysis

We tested for the presence of coronary calcifications in patients with chronic renal disease not on dialysis and studied its progression in 181 consecutive non-dialyzed patients who were followed for a median of 745 days. Coronary calcifications (calcium score) were tallied in Agatston units by computed tomography, and the patients were stratified into two groups by their baseline calcium score (100 U or less and over 100 U). Survival was measured by baseline calcium score and its progression. Cardiac death and myocardial infarction occurred in 29 patients and were significantly more frequent in those patients with calcium scores over 100 U (hazard ratio of 4.11). With a calcium score of 100 U or less, the hazard ratio for cardiac events was 0.41 and 3.26 in patients with absent and accelerated progression, respectively. Thus, in non-dialyzed patients, the extent of coronary calcifications was associated to cardiac events, and progression was an independent predictive factor of cardiac events mainly in less calcified patients. Hence, assessment of coronary calcifications and progression might be useful for earlier management of risk factors and guiding decisions for prevention of cardiac events in this patient population

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

SARS-CoV-2 Infections and COVID-19 Fatality: Estimation of Infection Fatality Ratio and Current Prevalence

COVID-19 is one of the most important problems for public health, according to the number of deaths associated to this pathology reported so far. However, from the epidemiological point of view, the dimension of the problem is still unknown, since the number of actual cases of SARS-CoV-2 infected people is underestimated, due to limited testing. This paper aims at estimating the actual Infection Fatality Ratio (number of deaths with respect to the number of infected people) and the actual current prevalence (number of infected people with respect to the entire population), both in a specific population and all over the world. With this aim, this paper proposes a method to estimate Infection Fatality Ratio of a still ongoing infection, based on a daily estimation, and on the relationship between this estimation and the number of tests performed per death. The method has been applied using data about COVID-19 from Italy. Results show a fatality ratio of about 0.9%, which is lower than previous findings. The number of actual infected people in Italy is also estimated, and results show that (i) infection started at the end of January 2020; (ii) a maximum number of about 100,000 new cases in one day was reached at the beginning of March 2020; (iii) the estimated cumulative number of infections at the beginning of October 2020 is about 4.2 million cases in Italy (more than 120 million worldwide, if a generalization is conjectured as reasonable). Therefore, the prevalence at the beginning of October 2020 is estimated at about 6.9% in Italy (1.6% worldwide, if a generalization is conjectured)

Effects of phosphorus-restricted diet and phosphate-binding therapy on outcomes in patients with chronic kidney disease

Abstract Background Phosphorus is associated with mortality in patients with chronic kidney disease (CKD) not on dialysis, possibly through phosphorus-dependent vascular calcification. Although a phosphorus-restricted diet reduces serum phosphorus, it is unlikely that it reduces vascular calcification progression in CKD. This study evaluated whether a combined strategy of phosphorus-restricted diet and phosphate-binding therapy can reduce the risk of allcause mortality and/or dialysis initiation by attenuating coronary artery calcification (CAC) progression in nondialysis CKD patients. Methods This was a post hoc analysis of a subgroup of patients from a study that evaluated the impact of two phosphorus binder regimens on hard outcomes in CKD. Patients (n = 113) with stage 3–4 CKD and evidence of CAC on a phosphorus-restricted diet were randomized to receive either calcium carbonate or sevelamer added to their phosphorus-restricted diet. End-points were death for any cause and initiation of dialysis. Patients were monitored to the first event or to conclusion of the 36-month follow-up. Results Overall, treatment with calcium carbonate was associated with increased CAC progression and occurrence of all-cause mortality, dialysis initiation, and the composite end-point. After adjustment for confounders, sevelamer use was the only independent predictive factor of reduced risk of each endpoint but only if CAC progression was either absent or moderate. Accelerated progression (annual CAC increase[75th percentile of the study cohort) increased the risk of all-cause mortality and composite end-point (p = 0.01) independently of the use of sevelamer. Conclusions A significant reduction in all-cause mortality, dialysis initiation, and composite end-point risk was achieved by combining phosphorus-restricted diet and sevelamer in non-dialysis CKD patients with absent or moderate but not accelerated CAC progression. Future studies should investigate the role of serum phosphorus, the usefulness of a phosphorus- restricted diet, and the appropriateness of current normal ranges of serum phosphorus concentration in relation to events in non-dialyzed CKD patients

EFFECT OF PHOSPHATE BINDER THERAPY ON MORTALITY IN PRE-DIALYSIS PATIENTS

INTRODUCTION AND AIMS Coronary artery calcifications ( CAC ) are prevalent and severe in all stages of chronic kidney disease. In pre-dialysis patients (NDD-CKD ), CAC display an accelerated progression that is strongly associated to poor outcomes such as cardiovascular events and faster inception to dialysis. Despite the clinical relevance of the latter findings, there is no study aimed at establishing improvement of outcomes by reducing CAC progression in NDD-CKD. The main aim of the present study was to ascertain whether outcomes may be ameliorated by reducing CAC progression in NDD-CKD patients treated with either sevelamer or calcium carbonate. METHODS: This study has been performed in a sub-group of outpatients from a larger multicenter, prospective, randomized study. Inclusion criteria were: age > 18 years, CKD stage 2-4, presence of CAC. Exclusion criteria were: heart failure and/or coronary artery disease, history of myocardial infarction, coronary bypass, angioplasty, stroke, arrhythmia. Patients were treated either with calcium carbonate or sevelamer. Routine blood chemistry was assessed at enrollment and every six months. Clinicians were instructed to control parameters of mineral metabolism according to their everyday practice; targets taken in account were those suggested by K/DOQI guidelines that were available at the start of the study. Recorded events were: sudden death, fatal and not fatal myocardial infarction, other-cause mortality, and inception of dialysis. The scheduled follow-up for evaluation of events was 36-month long. Coronary Calcium Score (CAC-Score) was assessed by computed tomography at study entry, on 6th, 12th, 24th month. Progression of CAC was evaluated as (1) absolute change of CAC-score (change between 24th month and baseline) and (2) annualized progression that take in account the time between scans. Patients were defined progressors when the difference between the last and the baseline CAC-score was ≥ 15%. Data are expressed as mean ± standard deviation. Kaplan-Meier survival curves were created and a long-rank test used for comparisons. Multivariable Cox regression analysis was performed to assess factors significantly associated to events risk. RESULTS: Enrolled patient were n. 113 (n.47 and n. 66 treated with calcium and sevelamer, respectively). Baseline CAC-score was 388±413 and 306±382 AU in calcium and sevelamertreated patients, respectively; p=0.27). CAC-score did not progress in n.1 and in n. 22 patients treated with calcium and sevelamer, respectively; p=0.0001). All survival curves were significantly (p=0.001) worse in calcium-treated patients