Giuseppe Dalfino

Microbiota and metabolome associated with immunoglobulin A nephropathy (IgAN).

This study aimed at investigating the fecal microbiota, and the fecal and urinary metabolome of non progressor (NP) and progressor (P) patients with immunoglobulin A nephropathy (IgAN). Three groups of volunteers were included in the study: (i) sixteen IgAN NP patients; (ii) sixteen IgAN P patients; and (iii) sixteen healthy control (HC) subjects, without known diseases. Selective media were used to determine the main cultivable bacterial groups. Bacterial tag-encoded FLX-titanium amplicon pyrosequencing of the 16S rDNA and 16S rRNA was carried out to determine total and metabolically active bacteria, respectively. Biochrom 30 series amino acid analyzer and gas-chromatography mass spectrometry/solid-phase microextraction (GC-MS/SPME) analyses were mainly carried out for metabolomic analyses. As estimated by rarefaction, Chao and Shannon diversity index, the lowest microbial diversity was found in P patients. Firmicutes increased in the fecal samples of NP and, especially, P patients due to the higher percentages of some genera/species of Ruminococcaceae, Lachnospiraceae, Eubacteriaceae and Streptococcaeae. With a few exceptions, species of Clostridium, Enterococcus and Lactobacillus genera were found at the highest levels in HC. Bacteroidaceae, Porphyromonadaceae, Prevotellaceae and Rikenellaceae families differed among NP, P and HC subjects. Sutterellaceae and Enterobacteriaceae species were almost the highest in the fecal samples of NP and/or P patients. Compared to HC subjects, Bifidobacterium species decreased in the fecal samples of NP and P. As shown by multivariate statistical analyses, the levels of metabolites (free amino acids and organic volatile compounds) from fecal and urinary samples markedly differentiated NP and, especially, P patients.

What Would You Like to Eat, Mr CKD Microbiota? A Mediterranean Diet, please!

In this review we elucidate the role of gut microbiota as the plausible missing link between food and health, focusing on chronic kidney disease (CKD). Microbiota, the microbial community harboured in the large intestine, is considered a symbiotic “supplementary organ”. It contributes to digestion, mainly through two catabolic pathways: saccharolytic (fermentation) or proteolytic (putrefaction). It also interacts with host influencing immunity, metabolism, and health status. It is believed that a balanced healthy microbiota is primarily saccharolytic and diet has a deep effect on its composition. Mediterranean Diet, UNESCO “Intangible Cultural Heritage of Humanity”, prevents cardiovascular and metabolic systemic diseases, thanks to the high supply of fibres and antioxidants. Mediterranean Diet also favours the prevalence of saccharolytic species, while Western Diet promotes the shift towards a proteolytic profile (dysbiosis). Emerging evidences highlight the association between a wide range of diseases and dysbiosis. In CKD a vicious circle exists, in which proteolytic-derived microbial metabolites (p-cresol and indoxyl sulphate), represent the main circulating uremic toxins: their accumulation worsens dysbiosis and promotes CKD progression. Gut microbiota shaping through non-pharmacologic nutritional treatments, based on Mediterranean Diet, represents an innovative approach in CKD, potentially restoring microbiota balance, ameliorating CKD conditions and slowing down disease progression.

Serum fetuin a in hemodialysis: a link between derangement of calcium-phosphorus homeostasis and progression of atherosclerosis?

BACKGROUND Fetuin A, a circulating inhibitor of ectopic calcification, is downregulated in hemodialysis and has been shown to predict cardiovascular mortality in this setting. The association of altered calcium-phosphorus with serum fetuin A levels is still a matter of debate. Although carotid intima-media thickness (cIMT) is a strong predictor of major cardiovascular events, its association with serum fetuin A levels is poorly defined. STUDY DESIGN Cohort study. PARTICIPANTS & SETTINGS 174 uremic patients on long-term hemodialysis therapy enrolled in 4 university hospitals. PREDICTORS Serum fetuin A levels at the beginning of the study (T0) and after 12 months (T12). OUTCOMES Progression of atherosclerosis assessed by means of cIMT measurements at 24 months (T24); cardiovascular morbidity and mortality at 36 months. RESULTS Serum fetuin A concentrations at T0 and T12 were 282.3 +/- 79.4 and 290.0 +/- 92.2 microg/mL, respectively. Mean T0 and T24 cIMT values were 1.02 +/- 0.2 and 1.06 +/- 0.2 mm, respectively (P < 0.001). Fatal and nonfatal cardiovascular disease occurred in 36 and 86 patients by 36 months, respectively. In multivariate logistic regression, higher calcium-phosphorus product was associated with lower serum fetuin A level (odds ratio, 0.96; 95% confidence interval [CI], 0.93 to 1.00; P = 0.02). Multiple regression analysis showed that T0 serum fetuin A level was associated with T24 cIMT (P = 0.01) after adjustments for age, cholesterol level, high-sensitivity C-reactive protein level, previous cardiovascular events, and T0 cIMT. In a multivariate Cox regression analysis, cardiovascular mortality was independently associated with a 1-tertile lower T0 serum fetuin A level, and a 1-tertile higher T0 cIMT value was independently associated with greater cardiovascular mortality (hazard ratio, 0.45; 95% CI, 0.15 to 0.65; P = 0.007 and hazard ratio, 10.00; 95% CI, 3.16 to 31.73; P < 0.001, respectively) after adjustment for age and previous cardiovascular events. LIMITATION Length of follow-up. CONCLUSION Calcium-phosphorus product in hemodialysis patients inversely correlated with serum fetuin A level, which, in turn, was associated inversely with progression of atherosclerotic lesions and cardiovascular mortality in this study population.

Beta-Glucans Supplementation Associates with Reduction in P-Cresyl Sulfate Levels and Improved Endothelial Vascular Reactivity in Healthy Individuals

Background Oat and barley beta-glucans are prebiotic fibers known for their cholesterol-lowering activity, but their action on the human gut microbiota metabolism is still under research. Although the induction of short-chain fatty acids (SCFA) following their ingestion has previously been reported, no study has investigated their effects on proteolytic uremic toxins p-cresyl sulfate (pCS) and indoxyl sulfate (IS) levels, while others have failed to demonstrate an effect on the endothelial function measured through flow-mediated dilation (FMD). Objective The aim of our study was to evaluate whether a nutritional intervention with a functional pasta enriched with beta-glucans could promote a saccharolytic shift on the gut microbial metabolism and improve FMD. Methods We carried out a pilot study on 26 healthy volunteers who underwent a 2-month dietary treatment including a daily administration of Granoro “Cuore Mio” pasta enriched with barley beta-glucans (3g/100g). Blood and urine routine parameters, serum pCS/IS and FMD were evaluated before and after the dietary treatment. Results The nutritional treatment significantly reduced LDL and total cholesterol, as expected. Moreover, following beta-glucans supplementation we observed a reduction of serum pCS levels and an increase of FMD, while IS serum levels remained unchanged. Conclusions We demonstrated that a beta-glucans dietary intervention in healthy volunteers correlates with a saccharolytic shift on the gut microbiota metabolism, as suggested by the decrease of pCS and the increase of SCFA, and associates with an improved endothelial reactivity. Our pilot study suggests, in addition to cholesterol, novel pCS-lowering properties of beta-glucans, worthy to be confirmed in large-scale trials and particularly in contexts where the reduction of the microbial-derived uremic toxin pCS is of critical importance, such as in chronic kidney disease.

Pentraxin 3 and complement cascade activation in the failure of arteriovenous fistula

OBJECTIVE Pentraxin-3 (PTX3) has been suggested to play a role in the development of vascular pathology. Stenosis of arteriovenous fistula (AVF) leading to its failure is the major cause of morbidity in hemodialysis patients. To date, little is known on the pathogenesis of AVF stenosis. The aim of the present study was to investigate the potential role of PTX3 in this setting. METHODS AND RESULTS A sample of venous wall was collected at the time of AVF formation in 44 patients with end stage renal disease. Ten patients developed AVF stenosis and from these patients a second portion of the venous wall was obtained during surgical revision of the AVF. Confocal laser scanning microscopy demonstrated that PTX3 immunostaining, hardly detectable in native AVF, was significantly increased in failed AVF, showing a specific co-localization with endothelial cell markers. Circulating mononuclear cells isolated at the time of AVF revision presented a significantly higher PTX3 mRNA expression than those collected during AVF creation. Interestingly, a significant deposition of C5b-9 on endothelial cells, co-localizing with PTX3, was observed in stenotic AVF. CONCLUSION The present study demonstrates for the first time a close association between PTX3 deposition and complement activation at the endothelial cell level in failed AVF and suggests a role for PTX3 in modulating innate immunity in the pathogenesis of AVF stenosis.

Neural Network Classification of Blood Vessels and Tubules Based on Haralick Features Evaluated in Histological Images of Kidney Biopsy

In this paper, we present a Computer Aided Diagnosis that implements a supervised approach to discriminate vessels versus tubules that are two different types of structural elements in images of biopsy tissue. In particular, in this work we formerly describe an innovative preliminary step to segment region of interest, then the procedure to extract from them significant features and finally present and discuss the Back Propagation Neural Network binary classifier performance that shows Precision 91 % and Recall 91 %.

Monitoring of Lifestyle and Cognitive Status in Seniors at Risk of Dementia: The SmartAging Program

Lifestyle and risk factors affect the development of diseases, cognitive decline and loss of autonomy during ageing. In the Italian Smart Health 2.0 project, we developed the SmartAging program offering innovative ICT solutions, grounded upon the Italian Telecom platform (“Nuvola Italian Home Doctor”), to contrast cognitive decline and support “active” ageing. Specifically, the SmartAging program includes tools for daily telemonitoring at subjects’ home of: (i) eating behaviour, (ii) physical exercise, (iii) tobacco consumption, (iv) cultural, social and relational activities, (v) cognitive functions, (vi) weight, temperature, and blood pressure. Furthermore, a Point of Care device and a Self-Assessment Health Station (i.e. health medical equipment), in proximity to the subjects’ home, allowed periodic measures of blood biomarkers and physiological indices. To demonstrate the feasibility of this program, we performed a clinical proof of concept study for 16 weeks on 10 elderly subjects (5 being oncological long-term survivors). All subjects expressed a need for education and assistance concerning a healthy lifestyle. Most of them expressed a preference for ICT-based home programs to improve the lifestyle over institutional programs. All expressed satisfaction with the SmartAging program in terms of simplicity, clarity, adequacy and reported a positive impact on their quality of life. These results suggest that the SmartAging program fulfills all the requirements to be considered an innovative technological approach for the lifestyle education and telemonitoring of seniors, to prevent dementing disorders. Some concepts of the SmartAging program have been further developing in the H2020-MSCA-ITN-ETN BBDiag project.

Mediterranean diet for patients with polycystic kidney disease

The changes that have occurred in peoples eating habits and lifestyle from the second half of the 20th century have modified the state of health of the general population. Extensive scientific evidence indicates the need of reconsidering the eating habits, reverting to the typical foods of the Mediterranean diet. The Mediterranean diet, together with physical activity, abstention from smoking and other addictions, and with conviviality can have an effect not only on the progression of chronic degenerative diseases but also, certainly, on quality of life. It is well known that a high-protein diet with high sodium content, combined with alcohol abuse, is an important cause of the worsening of renal diseases. By contrast, following a Mediterranean diet, rich in fruits, vegetables, legumes, cereals, and olive oil with a moderate consumption of animal proteins and alcohol, plays a protective role on renal function. The Medi¬terranean diet has proved to contribute to the reduction of cardiovascular diseases and oxidative stress. Hence, there are the conditions to assess whether the Mediterranean diet is able to significantly reduce the activation of the oxidative stress and, therefore, the cardio-vascular risk in patients with ADPKD.